Comparison of patella bone strain between females with and without patellofemoral pain: a finite element analysis study.

PubMed

Ho, Kai-Yu; Keyak, Joyce H; Powers, Christopher M

2014-01-03

Elevated bone principal strain (an indicator of potential bone injury) resulting from reduced cartilage thickness has been suggested to contribute to patellofemoral symptoms. However, research linking patella bone strain, articular cartilage thickness, and patellofemoral pain (PFP) remains limited. The primary purpose was to determine whether females with PFP exhibit elevated patella bone strain when compared to pain-free controls. A secondary objective was to determine the influence of patella cartilage thickness on patella bone strain. Ten females with PFP and 10 gender, age, and activity-matched pain-free controls participated. Patella bone strain fields were quantified utilizing subject-specific finite element (FE) models of the patellofemoral joint (PFJ). Input parameters for the FE model included (1) PFJ geometry, (2) elastic moduli of the patella bone, (3) weight-bearing PFJ kinematics, and (4) quadriceps muscle forces. Using quasi-static simulations, peak and average minimum principal strains as well as peak and average maximum principal strains were quantified. Cartilage thickness was quantified by computing the perpendicular distance between opposing voxels defining the cartilage edges on axial plane magnetic resonance images. Compared to the pain-free controls, individuals with PFP exhibited increased peak and average minimum and maximum principal strain magnitudes in the patella. Additionally, patella cartilage thickness was negatively associated with peak minimum principal patella strain and peak maximum principal patella strain. The elevated bone strain magnitudes resulting from reduced cartilage thickness may contribute to patellofemoral symptoms and bone injury in persons with PFP. © 2013 Published by Elsevier Ltd.

Microcomputed tomographic and histomorphometric analyses of novel titanium mesh membranes for guided bone regeneration: a study in rat calvarial defects.

PubMed

Rakhmatia, Yunia Dwi; Ayukawa, Yasunori; Furuhashi, Akihiro; Koyano, Kiyoshi

2014-01-01

The objective of this study was to evaluate the optimal thickness and porosity of novel titanium mesh membranes to enhance bone augmentation, prevent soft tissue ingrowth, and prevent membrane exposure. Six types of novel titanium meshes with different thicknesses and pore sizes, along with three commercially available membranes, were used to cover surgically created calvarial defects in 6-week-old Sprague-Dawley rats. The animals were killed after 4 or 8 weeks. Microcomputed tomographic analyses were performed to analyze the three-dimensional bone volume and bone mineral density. Soft tissue ingrowth was also evaluated histologically and histomorphometrically. The novel titanium membranes used in this study were as effective at augmenting bone in the rat calvarial defect model as the commercially available membranes. The greatest bone volume was observed on 100-μm-thick membranes with larger pores, although these membranes promoted growth of bone with lower mineral density. Soft tissue ingrowth when 100-μm membranes were used was increased at 4 weeks but decreased again by 8 weeks to a level not statistically significantly different from other membranes. Membrane thickness affects the total amount of new bone formation, and membrane porosity is an essential factor for guided bone regeneration, especially during the initial healing period, although the final bone volume obtained is essentially the same. Newly developed titanium mesh membranes of 100 μm in thickness and with large pores appear to be optimal for guided bone regeneration.

Comparison of dental implant stabilities by impact response and resonance frequencies using artificial bone.

PubMed

Kim, Dae-Seung; Lee, Woo-Jin; Choi, Soon-Chul; Lee, Sam-Sun; Heo, Min-Suk; Huh, Kyung-Hoe; Kim, Tae-Il; Yi, Won-Jin

2014-06-01

We compared implant stability as determined by the peak frequency from the impact response with the implant stability quotient (ISQ) by resonance frequency analysis (RFA) in various artificial bone conditions. The clinical bone conditions were simulated using an artificial bone material with different cortical thicknesses and trabecular densities. The artificial bone material was solid, rigid polyurethane. The polyurethane foam of 0.8g/cm(3) density was used for the cortical bone layer, and that of 0.08, 0.16, 0.24, 0.32, and 0.48g/cm(3) densities for the trabecular bone layer. The cortical bone material of 4 different thicknesses (1.4, 1.6, 1.8, and 2.0mm) was attached to the trabecular bone with varying density. Two types of dental implants (10 and 13mm lengths of 4.0mm diameter) were placed into the artificial bone blocks. An inductive sensor was used to measure the vibration caused by tapping the adapter-implant assembly. The peak frequency of the power spectrum of the impact response was used as the criterion for implant stability. The ISQ value was also measured for the same conditions. The stability, as measured by peak frequency (SPF) and ISQ value, increased as the trabecular density and the cortical density increased in linear regression analysis. The SPF and ISQ values were highly correlated with each other when the trabecular bone density and cortical bone thickness changed (Pearson correlation=0.90, p<0.01). The linear regression of the SPF with the cortical bone thickness showed higher goodness of fit (R(2) measure) than the ISQ value with the cortical bone thickness. The SPF could differentiate implantation conditions as many as the ISQ value when the trabecular bone density and the cortical density changed. However, the ISQ value was not consistent with the general stability tendency in some conditions. The SPF showed better consistency and differentiability with implant stability than the ISQ value by resonance frequency analysis in the various implantation conditions. Copyright © 2013 IPEM. Published by Elsevier Ltd. All rights reserved.

Running exercise alleviates trabecular bone loss and osteopenia in hemizygous β-globin knockout thalassemic mice.

PubMed

Thongchote, Kanogwun; Svasti, Saovaros; Teerapornpuntakit, Jarinthorn; Krishnamra, Nateetip; Charoenphandhu, Narattaphol

2014-06-15

A marked decrease in β-globin production led to β-thalassemia, a hereditary anemic disease associated with bone marrow expansion, bone erosion, and osteoporosis. Herein, we aimed to investigate changes in bone mineral density (BMD) and trabecular microstructure in hemizygous β-globin knockout thalassemic (BKO) mice and to determine whether endurance running (60 min/day, 5 days/wk for 12 wk in running wheels) could effectively alleviate bone loss in BKO mice. Both male and female BKO mice (1-2 mo old) showed growth retardation as indicated by smaller body weight and femoral length than their wild-type littermates. A decrease in BMD was more severe in female than in male BKO mice. Bone histomorphometry revealed that BKO mice had decreases in trabecular bone volume, trabecular number, and trabecular thickness, presumably due to suppression of osteoblast-mediated bone formation and activation of osteoclast-mediated bone resorption, the latter of which was consistent with elevated serum levels of osteoclastogenic cytokines IL-1α and -1β. As determined by peripheral quantitative computed tomography, running increased cortical density and thickness in the femoral and tibial diaphyses of BKO mice compared with those of sedentary BKO mice. Several histomorphometric parameters suggested an enhancement of bone formation (e.g., increased mineral apposition rate) and suppression of bone resorption (e.g., decreased osteoclast surface), which led to increases in trabecular bone volume and trabecular thickness in running BKO mice. In conclusion, BKO mice exhibited pervasive osteopenia and impaired bone microstructure, whereas running exercise appeared to be an effective intervention in alleviating bone microstructural defect in β-thalassemia. Copyright © 2014 the American Physiological Society.

Quantifying bone thickness, light transmission, and contrast interrelationships in transcranial photoacoustic imaging

NASA Astrophysics Data System (ADS)

Lediju Bell, Muyinatu A.; Ostrowski, Anastasia K.; Li, Ke; Kaanzides, Peter; Boctor, Emad

2015-03-01

We previously introduced photoacoustic imaging to detect blood vessels surrounded by bone and thereby eliminate the deadly risk of carotid artery injury during endonasal, transsphenoidal surgeries. Light would be transmitted through an optical fiber attached to the surgical drill, while a transcranial probe placed on the temporal region of the skull receives photoacoustic signals. This work quantifies changes in photoacoustic image contrast as the sphenoid bone is drilled. Frontal bone from a human adult cadaver skull was cut into seven 3 cm x 3 cm chips and sanded to thicknesses ranging 1-4 mm. For 700-940 nm wavelengths, the average optical transmission through these specimens increased from 19% to 44% as bone thickness decreased, with measurements agreeing with Monte Carlo simulations within 5%. These skull specimens were individually placed in the optical pathway of a 3.5 mm diameter, cylindrical, vessel-mimicking photoacoustic target, as the laser wavelength was varied between 700-940 nm. The mean optical insertion loss and photoacoustic image contrast loss due to the bone specimens were 56-80% and 46-79%, respectively, with the majority of change observed when the bone was <=2 mm thick. The decrease in contrast is directly proportional to insertion loss over this thickness range by factors of 0.8-1.1 when multiple wavelengths are considered. Results suggest that this proportional relationship may be used to determine the amount of bone that remains to be drilled when the thickness is 2 mm or less.

Intracranial volume, cranial thickness, and hyperostosis frontalis interna in the elderly.

PubMed

May, Hila; Mali, Yael; Dar, Gali; Abbas, Janan; Hershkovitz, Israel; Peled, Nathan

2012-01-01

According to the "brain reserve hypothesis," a larger premorbid brain protects against the development of dementia. The aim of this study was to reveal a possible pathophysiology of brain degenerative diseases by studying intracranial bone lesions that act to reduce intracranial volume (ICV), such as hyperostosis frontalis interna (HFI). Three hundred and eighty postmenopausal females (aged 60+) who had undergone a head computerized tomography scan (Brilliance 64, Philips Healthcare, Cleveland, OH) at the Carmel Medical Center, Haifa, Israel, before the study were included. The subjects were divided into four groups according to their degree of HFI. Six measurements of the skull and brain were taken. As HFI becomes more severe, the cranial bone thickness and cranial bone volume increase. This process is accompanied by a decrease in ICV. In none of the HFI groups studied there was a significant association between ICV and cranial bone thickness. The inter-relationships between the various thickness parameters are not disturbed by the degree of HFI. HFI is accompanied by an increase in thickness of all calvarial bones and reduced ICV. In addition, the thickening process initiated by HFI is synchronized among the calvarial bones. Presence of HFI suggests a decrease in brain volume and has a major clinical significance as it may indicate the beginning of degenerative processes of the brain. In addition, as females age, their skulls tend to develop more robust characteristics. Copyright © 2012 Wiley Periodicals, Inc.

SU-F-T-360: Dosimetric Impacts On the Mucosa and Bone in Radiotherapy with Unflattened Photon Beams

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chow, J; Owrangi, A

Purpose: This study investigated the dosimetric impacts on the mucosa and bone when using the unflattened photon beams in radiotherapy. Dose calculations were carried out by Monte Carlo simulation. Methods: Heterogeneous phantoms containing water (soft tissue and mucosa), air and bone, with mucosa thicknesses varying from 0.5 – 3 mm were irradiated by the 6 MV unflattened and flattened photon beams (field size = 10 × 10 cm{sup 2}), produced by a Varian TrueBEAM linear accelerator. The photon energy spectra of the beams, mean bone and mucosal doses with different mucosa thicknesses were calculated using the EGSnrc Monte Carlo code.more » Results: It is found that the flattened photon beams had higher mean bone doses (1.3% and 2% for upper and lower bone regarding the phantom geometry, respectively) than the unflattened beams, and the mean bone doses of both beams did not vary significantly with the mucosa thickness. Similarly, flattened photon beams had higher mucosal dose (0.9% and 1.6% for upper and lower mucosa, respectively) than the unflattened beams. This is due to the larger slope of the depth dose for the unflattened photon beams compared to the flattened. The mucosal doses of both beams were found increased with the mucosa thickness. Moreover, the mucosal dose differences between the unflattened and flattened beams increased with the mucosa thickness. For photon energy spectra on the mucosal layers, it is found that the unflattened photon beams contained a larger portion of lowenergy photons than the flattened beams. The photon energy spectra did not change significantly with the mucosa thickness. Conclusion: It is concluded that the mucosal and bone dose for the unflattened photon beams were not more than 2% lower than the flattened beams, though the flattening filter free beams contained larger portion of low-energy photons than the flattened beams.« less

Soft Tissue Alterations in Esthetic Postextraction Sites: A 3-Dimensional Analysis.

PubMed

Chappuis, V; Engel, O; Shahim, K; Reyes, M; Katsaros, C; Buser, D

2015-09-01

Dimensional alterations of the facial soft and bone tissues following tooth extraction in the esthetic zone play an essential role to achieve successful outcomes in implant therapy. This prospective study is the first to investigate the interplay between the soft tissue dimensions and the underlying bone anatomy during an 8-wk healing period. The analysis is based on sequential 3-dimensional digital surface model superimpositions of the soft and bone tissues using digital impressions and cone beam computed tomography during an 8-wk healing period. Soft tissue thickness in thin and thick bone phenotypes at extraction was similar, averaging 0.7 mm and 0.8 mm, respectively. Interestingly, thin bone phenotypes revealed a 7-fold increase in soft tissue thickness after an 8-wk healing period, whereas in thick bone phenotypes, the soft tissue dimensions remained unchanged. The observed spontaneous soft tissue thickening in thin bone phenotypes resulted in a vertical soft tissue loss of only 1.6 mm, which concealed the underlying vertical bone resorption of 7.5 mm. Because of spontaneous soft tissue thickening, no significant differences were detected in the total tissue loss between thin and thick bone phenotypes at 2, 4, 6, and 8 wk. More than 51% of these dimensional alterations occurred within 2 wk of healing. Even though the observed spontaneous soft tissue thickening in thin bone phenotypes following tooth extraction conceals the pronounced underlying bone resorption pattern by masking the true bone deficiency, spontaneous soft tissue thickening offers advantages for subsequent bone regeneration and implant therapies in sites with high esthetic demand (Clinicaltrials.gov NCT02403700). © International & American Associations for Dental Research.

Statistical analysis of biomechanical properties of the adult skull and age-related structural changes by sex in a Japanese forensic sample.

PubMed

Torimitsu, Suguru; Nishida, Yoshifumi; Takano, Tachio; Koizumi, Yoshinori; Makino, Yohsuke; Yajima, Daisuke; Hayakawa, Mutsumi; Inokuchi, Go; Motomura, Ayumi; Chiba, Fumiko; Otsuka, Katsura; Kobayashi, Kazuhiro; Odo, Yuriko; Iwase, Hirotaro

2014-01-01

The purpose of this research was to investigate the biomechanical properties of the adult human skull and the structural changes that occur with age in both sexes. The heads of 94 Japanese cadavers (54 male cadavers, 40 female cadavers) autopsied in our department were used in this research. A total of 376 cranial samples, four from each skull, were collected. Sample fracture load was measured by a bending test. A statistically significant negative correlation between the sample fracture load and cadaver age was found. This indicates that the stiffness of cranial bones in Japanese individuals decreases with age, and the risk of skull fracture thus probably increases with age. Prior to the bending test, the sample mass, the sample thickness, the ratio of the sample thickness to cadaver stature (ST/CS), and the sample density were measured and calculated. Significant negative correlations between cadaver age and sample thickness, ST/CS, and the sample density were observed only among the female samples. Computerized tomographic (CT) images of 358 cranial samples were available. The computed tomography value (CT value) of cancellous bone which refers to a quantitative scale for describing radiodensity, cancellous bone thickness and cortical bone thickness were measured and calculated. Significant negative correlation between cadaver age and the CT value or cortical bone thickness was observed only among the female samples. These findings suggest that the skull is substantially affected by decreased bone metabolism resulting from osteoporosis. Therefore, osteoporosis prevention and treatment may increase cranial stiffness and reinforce the skull structure, leading to a decrease in the risk of skull fractures. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Bisphosphonates Improve Trabecular Bone Mass and Normalize Cortical Thickness in Ovariectomized, Osteoblast Connexin43 Deficient Mice

PubMed Central

Watkins, Marcus P.; Norris, Jin Yi; Grimston, Susan K.; Zhang, Xiaowen; Phipps, Roger J.; Ebetino, Frank H.; Civitelli, Roberto

2012-01-01

The gap junction protein, connexin43 (Cx43) controls both bone formation and osteoclastogenesis via osteoblasts and/or osteocytes. Cx43 has also been proposed to mediate an anti-apoptotic effect of bisphosphonates, potent inhibitors of bone resorption. We studied whether bisphosphonates are effective in protecting mice with a conditional Cx43 gene deletion in osteoblasts and osteocytes (cKO) from the consequences of ovariectomy on bone mass and strength. Ovariectomy resulted in rapid loss of trabecular bone followed by a slight recovery in wild type (WT) mice, and a similar degree of trabecular bone loss, albeit slightly delayed, occurred in cKO mice. Treatment with either risedronate (20µg/kg) or alendronate (40µg/kg) prevented ovariectomy-induced bone loss in both genotypes. In basal conditions, bones of cKO mice have larger marrow area, higher endocortical osteoclast number, and lower cortical thickness and strength relative to WT. Ovariectomy increased endocortical osteoclast number in WT but not in cKO mice. Both bisphosphonates prevented these increases in WT mice, and normalized endocortical osteoclast number, cortical thickness and bone strength in cKO mice. Thus, lack of osteoblast/osteocyte Cx43 does not alter bisphosphonate action on bone mass and strength in estrogen deficiency. These results support the notion that one of the main functions of Cx43 in cortical bone is to restrain osteoblast and/or osteocytes from inducing osteoclastogenesis at the endocortical surface. PMID:22750450

Finite element analysis of stress-breaking attachments on maxillary implant-retained overdentures.

PubMed

Tanino, Fuminori; Hayakawa, Iwao; Hirano, Shigezo; Minakuchi, Shunsuke

2007-01-01

The purpose of this study was to examine the effect of stress-breaking attachments at the connections between maxillary palateless overdentures and implants. Three-dimensional finite element models were used to reproduce an edentulous human maxilla with an implant-retained overdenture. Two-implant models (in the canine tooth positions on both sides) and four-implant models (in the canine and second premolar tooth positions on both sides) were examined. Stress-breaking material connecting the implants and denture was included around each abutment. Axial loads of 100 N were applied to the occlusal surface at the left first molar tooth positions. In each model, the influence of the stress-breaking attachments was compared by changing the elastic modulus from 1 to 3,000 MPa and the thickness of the stress-breaking material from 1 to 3 mm. Maximum stress at the implant-bone interface and stress at the cortical bone surface just under the loading point were calculated. In all models, maximum stress at the implant-bone interface with implants located in the canine tooth position was generated at the peri-implant bone on the loading side. As the elastic modulus of the stress-breaking materials increased, the stress increased at the implant-bone interface and decreased at the cortical bone surface. Moreover, stress at the implant-bone interface with 3-mm-thick stress-breaking material was smaller than that with 1-mm-thick material. Within the limitations of this experiment, stress generated at the implant-bone interface could be controlled by altering the elastic modulus and thickness of the stress-breaking materials.

Effect of rhythmic gymnastics on volumetric bone mineral density and bone geometry in premenarcheal female athletes and controls.

PubMed

Tournis, S; Michopoulou, E; Fatouros, I G; Paspati, I; Michalopoulou, M; Raptou, P; Leontsini, D; Avloniti, A; Krekoukia, M; Zouvelou, V; Galanos, A; Aggelousis, N; Kambas, A; Douroudos, I; Lyritis, G P; Taxildaris, K; Pappaioannou, N

2010-06-01

Weight-bearing exercise during growth exerts positive effects on the skeleton. Our objective was to test the hypothesis that long-term elite rhythmic gymnastics exerts positive effects on volumetric bone mineral density and geometry and to determine whether exercise-induced bone adaptation is associated with increased periosteal bone formation or medullary contraction using tibial peripheral quantitative computed tomography and bone turnover markers. We conducted a cross-sectional study at a tertiary center. We studied 26 elite premenarcheal female rhythmic gymnasts (RG) and 23 female controls, aged 9-13 yr. We measured bone age, volumetric bone mineral density, bone mineral content (BMC), cortical thickness, cortical and trabecular area, and polar stress strength index (SSIp) by peripheral quantitative computed tomography of the left tibia proximal to the distal metaphysis (trabecular) at 14, 38 (cortical), and 66% (muscle mass) from the distal end and bone turnover markers. The two groups were comparable according to height and chronological and bone age. After weight adjustment, cortical BMC, area, and thickness at 38% were significantly higher in RG (P < 0.005-0.001). Periosteal circumference, SSIp, and muscle area were higher in RG (P < 0.01-0.001). Muscle area was significantly associated with cortical BMC, area, and SSIp, whereas years of training showed positive association with cortical BMC, area, and thickness independent of chronological age. RG in premenarcheal girls may induce positive adaptations on the skeleton, especially in cortical bone. Increased duration of exercise is associated with a positive response of bone geometry.

Analysis of stress on mucosa and basal bone underlying complete dentures with different reliner material thicknesses: a three-dimensional finite element study.

PubMed

Lima, J B G; Orsi, I A; Borie, E; Lima, J H F; Noritomi, P Y

2013-10-01

The aim of this study was to determine the optimal thickness of reliner material that provides the least amount of stress on thin mucosa and supporting bone in patients with complete removable dentures using a three-dimensional finite element analyses. The model was obtained from two CT scans of edentulous mandibles with dentures supported by the alveolar ridge. After virtual reconstruction, the three-dimensional models were exported to the solidworks cad software and divided into six groups based on the thickness of the reliner material as follows: (i) without material, (ii) 0·5 mm, (iii) 1 mm, (iv) 1·5 mm, (v) 2 mm and (vi) 2·5 mm. The applied load was 60 N and perpendicular to the long axis of the alveolar ridge of all the prosthetic teeth, and the mucosal thickness used was 1 mm. The analyses were based on the maximum principal stress in the fibromucosa and the minimum principal stress in the basal bone. Stress concentration was observed in the anterior zone of the mandible in the mucosa and in the bone. The maximum and minimum principal stress in the mucosa and bone, respectively, decreased, whereas the thickness of the reliner material increased until 2 mm, which transmitted the lowest stress, compared with the control. Reliner materials with a thickness of 2·5 mm showed higher stress values than those with a thickness of 2 mm. In conclusion, reliner material with a thickness of 2 mm transmitted the lowest amount of stress to the mucosa and bone in 1 mm of mucosa thickness. © 2013 John Wiley & Sons Ltd.

Osteomesopyknosis: report of a new case with bone histology.

PubMed

Hardouin, P; Flautre, B; Sutter, B; Leclet, H; Grardel, B; Fauquert, P

1994-01-01

A new case of osteomesopyknosis, a rare autosomal dominant axial osteosclerosis is reported, with 4 affected members of the same family. Biochemical investigations, bone mineral content (BMC) measurement, 99mTc HMDP bone scan and microscopy of iliac crest bone and femoral head have been performed on 1 subject. A marked increase of BMC was found, without abnormality of biochemical data. Microscopy of bone showed an increase of trabecular thickness, and a low rate of bone turnover. No abnormality of mineralization was found on microradiographs.

Adaptations in tibial cortical thickness and total volumetric bone density in postmenopausal South Asian women with small bone size.

PubMed

Darling, Andrea L; Hakim, Ohood A; Horton, Khim; Gibbs, Michelle A; Cui, Liang; Berry, Jacqueline L; Lanham-New, Susan A; Hart, Kathryn H

2013-07-01

There is some evidence that South Asian women may have an increased risk of osteoporosis compared with Caucasian women, although whether South Asians are at increased risk of fracture is not clear. It is unknown whether older South Asian women differ from Caucasian women in bone geometry. This is the first study, to the authors' knowledge, to use peripheral Quantitative Computed Tomography (pQCT) to measure radial and tibial bone geometry in postmenopausal South Asian women. In comparison to Caucasian women, Asian women had smaller bone size at the 4% (-18% p<0.001) and 66% radius (-15% p=0.04) as well as increased total density at the 4% (+13% p=0.01) radius. For the tibia, they had a smaller bone size at the 4% (-16% p=0.005) and 14% (-38% p=0.002) sites. Also, Asians had increased cortical thickness (-17% p=0.04) at the 38% tibia, (in proportion to bone size (-30% p=0.003)). Furthermore, at the 4% and 14% tibia there were increased total densities (+12% to +29% p<0.01) and at the 14% tibia there was increased cortical density (+5% p=0.005) in Asians. These differences at the 14% and 38% (but not 4%) remained statistically significant after adjustment for Body Mass Index (BMI). These adaptations are similar to those seen previously in Chinese women. Asian women had reduced strength at the radius and tibia, evidenced by the 20-40% reduction in both polar Strength Strain Index (SSIp) and fracture load (under bending). Overall, the smaller bone size in South Asians is likely to be detrimental to bone strength, despite some adaptations in tibial cortical thickness and tibial and radial density which may partially compensate for this. Copyright © 2013 Elsevier Inc. All rights reserved.

Evaluation of bone microstructure in CRPS-affected upper limbs by HR-pQCT.

PubMed

Mussawy, Haider; Schmidt, Tobias; Rolvien, Tim; Rüther, Wolfgang; Amling, Michael

2017-01-01

Complex regional pain syndrome (CRPS) is a major complication after trauma, surgery, and/or immobilization of an extremity. The disease often starts with clinical signs of local inflammation and develops into a prolonged phase that is characterized by trophic changes and local osteoporosis and sometimes results in functional impairment of the affected limb. While the pathophysiology of CRPS remains poorly understood, increased local bone resorption plays an undisputed pivotal role. The aim of this retrospective clinical study was to assess the bone microstructure in patients with CRPS. Patients with CRPS type I of the upper limb whose affected and unaffected distal radii were analyzed by high-resolution peripheral quantitative computed tomography (HR-pQCT) were identified retrospectively. The osteology laboratory data and dual-energy X-ray absorptiometry (DXA) images of the left femoral neck and lumbar spine, which were obtained on the same day as HR-pQCT, were extracted from the medical records. Five patients were identified. The CRPS-affected upper limbs had significantly lower trabecular numbers and higher trabecular thicknesses than the unaffected upper limbs. However, the trabecular bone volume to total bone volume and cortical thickness values of the affected and unaffected sides were similar. Trabecular thickness tended to increase with time since disease diagnosis. CRPS associated with significant alterations in the bone microstructure of the affected upper limb that may amplify as the duration of disease increases.

[Alveolar bone thickness in A point area : how to avoid periodontal failures in front of upper incisors].

PubMed

Chevalier, Émilie; Philip-Alliez, Camille; Le Gall, Michel

2016-03-01

Studies on orthodontic-periodontics relationships are numerous but few have benefited from the contribution of new 3D imaging techniques that emphasize iatrogenic effects that orthodontics may have on the periodontium. Periodontal risk in terms of fenestration, bone dehiscences next maxillary incisors are real during or after orthodontic treatment. The accurate assessment of the initial situation in terms of bone quantity in this dental arch anterior segment is thus very important. Our study aimed to evaluate the reliability of conventional lateral cephalograms to quantify alveolar bone thickness in relation to the maxillary incisors by comparing it with data from CT scans. The second objective was to identify an at risk patient profile by assessing possible correlations between this thickness and dysmorphia components. The results revealed a half of assessment error in the estimation of bone thickness and increased risk in case of hyperdivergence typology, Class III skeletal relationships and dento-alveolar protrusion. Finally, in view of these data, we discussed the clinical procedures to avoid such periodontal failures in this anterior segment of the dental arch. © EDP Sciences, SFODF, 2016.

Subchondral bone histology and grading in osteoarthritis

PubMed Central

Aho, Olli-Matti; Finnilä, Mikko; Thevenot, Jerome; Saarakkala, Simo; Lehenkari, Petri

2017-01-01

Objective Osteoarthritis (OA) has often regarded as a disease of articular cartilage only. New evidence has shifted the paradigm towards a system biology approach, where also the surrounding tissue, especially bone is studied more vigorously. However, the histological features of subchondral bone are only poorly characterized in current histological grading scales of OA. The aim of this study is to specifically characterize histological changes occurring in subchondral bone at different stages of OA and propose a simple grading system for them. Design 20 patients undergoing total knee replacement surgery were randomly selected for the study and series of osteochondral samples were harvested from the tibial plateaus for histological analysis. Cartilage degeneration was assessed using the standardized OARSI grading system, while a novel four-stage grading system was developed to illustrate the changes in subchondral bone. Subchondral bone histology was further quantitatively analyzed by measuring the thickness of uncalcified and calcified cartilage as well as subchondral bone plate. Furthermore, internal structure of calcified cartilage-bone interface was characterized utilizing local binary patterns (LBP) based method. Results The histological appearance of subchondral bone changed drastically in correlation with the OARSI grading of cartilage degeneration. As the cartilage layer thickness decreases the subchondral plate thickness and disorientation, as measured with LBP, increases. Calcified cartilage thickness was highest in samples with moderate OA. Conclusion The proposed grading system for subchondral bone has significant relationship with the corresponding OARSI grading for cartilage. Our results suggest that subchondral bone remodeling is a fundamental factor already in early stages of cartilage degeneration. PMID:28319157

Effect of exercise on thicknesses of mature hyaline cartilage, calcified cartilage, and subchondral bone of equine tarsi.

PubMed

Tranquille, Carolyne A; Blunden, Antony S; Dyson, Sue J; Parkin, Tim D H; Goodship, Allen E; Murray, Rachel C

2009-12-01

OBJECTIVE-To investigate effects of exercise on hyaline cartilage (HC), calcified cartilage (CC), and subchondral bone (SCB) thickness patterns of equine tarsi. SAMPLE POPULATION-30 tarsi from cadavers of horses with known exercise history. PROCEDURES-Tarsi were assigned to 3 groups according to known exercise history as follows: pasture exercise only (PE tarsi), low-intensity general-purpose riding exercise (LE tarsi), and high-intensity elite competition riding exercise (EE tarsi). Osteochondral tissue from distal tarsal joints underwent histologic preparation. Hyaline cartilage, CC, and SCB thickness were measured at standard sites at medial, midline, and lateral locations across joints with a histomorphometric technique. RESULTS-HC, CC, and SCB thickness were significantly greater at all sites in EE tarsi, compared with PE tarsi; this was also true when LE tarsi were compared with PE tarsi. At specific sites, HC, CC, and SCB were significantly thicker in EE tarsi, compared with LE tarsi. Along the articular surface of the proximal aspect of the third metatarsal bone, SCB was thickest in EE tarsi and thinnest in LE tarsi; increases were greatest at sites previously reported to undergo peak strains and osteochondral damage. CONCLUSIONS AND CLINICAL RELEVANCE-Increased exercise was associated with increased HC, CC, and SCB thickness in mature horses. At sites that undergo high compressive strains, with a reported predisposition to osteoarthritic change, there was increased CC and SCB thickness. These results may provide insight into the interaction between adaptive response to exercise and pathological change.

Mechanical competence of ovariectomy-induced compromised bone after single or combined treatment with high-frequency loading and bisphosphonates

PubMed Central

Camargos G. V.; Bhattacharya P.; van Lenthe G. H.; Del Bel Cury A. A.; Naert I.; Duyck J.; Vandamme K.

2015-01-01

Osteoporosis leads to increased bone fragility, thus effective approaches enhancing bone strength are needed. Hence, this study investigated the effect of single or combined application of high-frequency (HF) loading through whole body vibration (WBV) and alendronate (ALN) on the mechanical competence of ovariectomy-induced osteoporotic bone. Thirty-four female Wistar rats were ovariectomized (OVX) or sham-operated (shOVX) and divided into five groups: shOVX, OVX-shWBV, OVX-WBV, ALN-shWBV and ALN-WBV. (Sham)WBV loading was applied for 10 min/day (130 to 150 Hz at 0.3g) for 14 days and ALN at 2 mg/kg/dose was administered 3x/week. Finite element analysis based on micro-CT was employed to assess bone biomechanical properties, relative to bone micro-structural parameters. HF loading application to OVX resulted in an enlarged cortex, but it was not able to improve the biomechanical properties. ALN prevented trabecular bone deterioration and increased bone stiffness and bone strength of OVX bone. Finally, the combination of ALN with HF resulted in an increased cortical thickness in OVX rats when compared to single treatments. Compared to HF loading, ALN treatment is preferred for improving the compromised mechanical competence of OVX bone. In addition, the association of ALN with HF loading results in an additive effect on the cortical thickness. PMID:26027958

Estimation of in vivo cortical bone thickness using ultrasonic waves.

PubMed

Mano, Isao; Horii, Kaoru; Hagino, Hiroshi; Miki, Takami; Matsukawa, Mami; Otani, Takahiko

2015-07-01

To verify the measurement of cortical bone thickness at the distal radius in vivo using an ultrasonic method. The method for estimating cortical bone thickness was derived from experiments with in vitro bovine specimens. Propagation time of echo waves and propagation time of slow waves were used for the estimation. The outside diameter of cortical bone and the cortical bone thickness at the distal 5.5 % site of radius were measured with the new ultrasonic bone measurement system, and the results were compared with X-ray pQCT clinical measurements. There was a high positive correlation (r: 0.76) between the cortical bone thickness measured by the new ultrasonic system and the X-ray pQCT results. We will be able to measure not only cancellous bone density but also cortical bone thickness in vivo using ultrasonic waves (without X-ray) safely and repeatedly.

Monocyte chemotactic protein-1 deficiency attenuates and high-fat diet exacerbates bone loss in mice with Lewis lung carcinoma.

PubMed

Yan, Lin; Nielsen, Forrest H; Sundaram, Sneha; Cao, Jay

2017-04-04

Bone loss occurs in obesity and cancer-associated complications including wasting. This study determined whether a high-fat diet and a deficiency in monocyte chemotactic protein-1 (MCP-1) altered bone structural defects in male C57BL/6 mice with Lewis lung carcinoma (LLC) metastases in lungs. Compared to non-tumor-bearing mice, LLC reduced bone volume fraction, connectivity density, trabecular number, trabecular thickness and bone mineral density and increased trabecular separation in femurs. Similar changes occurred in vertebrae. The high-fat diet compared to the AIN93G diet exacerbated LLC-induced detrimental structural changes; the exacerbation was greater in femurs than in vertebrae. Mice deficient in MCP-1 compared to wild-type mice exhibited increases in bone volume fraction, connectivity density, trabecular number and decreases in trabecular separation in both femurs and vertebrae, and increases in trabecular thickness and bone mineral density and a decrease in structure model index in vertebrae. Lewis lung carcinoma significantly decreased osteocalcin but increased tartrate-resistant acid phosphatase 5b (TRAP 5b) in plasma. In LLC-bearing mice, the high-fat diet increased and MCP-1 deficiency decreased plasma TRAP 5b; neither the high-fat diet nor MCP-1 deficiency resulted in significant changes in plasma concentration of osteocalcin. In conclusion, pulmonary metastasis of LLC is accompanied by detrimental bone structural changes; MCP-1 deficiency attenuates and high-fat diet exacerbates the metastasis-associated bone wasting.

Using modern human cortical bone distribution to test the systemic robusticity hypothesis.

PubMed

Baab, Karen L; Copes, Lynn E; Ward, Devin L; Wells, Nora; Grine, Frederick E

2018-06-01

The systemic robusticity hypothesis links the thickness of cortical bone in both the cranium and limb bones. This hypothesis posits that thick cortical bone is in part a systemic response to circulating hormones, such as growth hormone and thyroid hormone, possibly related to physical activity or cold climates. Although this hypothesis has gained popular traction, only rarely has robusticity of the cranium and postcranial skeleton been considered jointly. We acquired computed tomographic scans from associated crania, femora and humeri from single individuals representing 11 populations in Africa and North America (n = 228). Cortical thickness in the parietal, frontal and occipital bones and cortical bone area in limb bone diaphyses were analyzed using correlation, multiple regression and general linear models to test the hypothesis. Absolute thickness values from the crania were not correlated with cortical bone area of the femur or humerus, which is at odds with the systemic robusticity hypothesis. However, measures of cortical bone scaled by total vault thickness and limb cross-sectional area were positively correlated between the cranium and postcranium. When accounting for a range of potential confounding variables, including sex, age and body mass, variation in relative postcranial cortical bone area explained ∼20% of variation in the proportion of cortical cranial bone thickness. While these findings provide limited support for the systemic robusticity hypothesis, cranial cortical thickness did not track climate or physical activity across populations. Thus, some of the variation in cranial cortical bone thickness in modern humans is attributable to systemic effects, but the driving force behind this effect remains obscure. Moreover, neither absolute nor proportional measures of cranial cortical bone thickness are positively correlated with total cranial bone thickness, complicating the extrapolation of these findings to extinct species where only cranial vault thickness has been measured. Copyright © 2018 Elsevier Ltd. All rights reserved.

Human parathyroid hormone-(1-38) restores cancellous bone to the immobilized, osteopenic proximal tibial metaphysis in rats

NASA Technical Reports Server (NTRS)

Ma, Y. F.; Jee, W. S.; Ke, H. Z.; Lin, B. Y.; Liang, X. G.; Li, M.; Yamamoto, N.

1995-01-01

The purpose of this study was to determine if human parathyroid hormone-(1-38) (hPTH(1-38)) can restore cancellous bone mass to the established osteopenic, immobilized proximal tibial metaphyses of female rats. The right hindlimbs of 6-month-old female Sprague-Dawley rats were immobilized by bandaging the right hindlimbs to the abdomen. After 30 days of right hindlimb immobilization, the rats were subcutaneously injected with 200 micrograms hPTH(1-38)/kg/day for 15 days (short-term treatment) or 75 days (longer-term treatment). Static bone histomorphometry was performed on the primary spongiosa, and both static and dynamic histomorphometry were performed on the secondary spongiosa of the right proximal tibial metaphyses. Immobilization for 30 days without treatment decreased trabecular bone area, number, and thickness in both primary and secondary spongiosa, and induced an increase in eroded perimeter and a decrease in tissue referent-bone formation rate in the secondary spongiosa. These changes reached a new steady state thereafter. Treatment with 200 micrograms hPTH(1-38)/kg/day for 15 days, beginning 30 days after immobilization, significantly increased trabecular bone area, thickness, and number in both primary and secondary spongiosa despite continuous immobilization when compared with controls. The short-term PTH treatment (15 days) significantly increased labeling perimeter, mineral apposition rate, and tissue referent-bone formation rate in the secondary spongiosa and stimulated longitudinal bone growth as compared with the controls. Longer PTH treatment (75 days) further increased trabecular bone area, thickness, and number as compared with controls and groups given short-term PTH treatment (15 days). The bone formation indices in the secondary spongiosa of the longer-term treated rats were lower than those of the short-term treated group, but they were still higher than those of controls. Our findings indicate that PTH treatment stimulates cancellous bone formation, and restores and adds extra cancellous bone to the established, disuse-osteopenic proximal tibial metaphysis of female rats with continuously immobilized right hindlimbs. These results suggest that PTH may be useful in treating disuse-induced osteoporosis in humans.

Evaluation of bone microstructure in CRPS-affected upper limbs by HR-pQCT

PubMed Central

Mussawy, Haider; Schmidt, Tobias; Rolvien, Tim; Rüther, Wolfgang; Amling, Michael

2017-01-01

Summary Introduction Complex regional pain syndrome (CRPS) is a major complication after trauma, surgery, and/or immobilization of an extremity. The disease often starts with clinical signs of local inflammation and develops into a prolonged phase that is characterized by trophic changes and local osteoporosis and sometimes results in functional impairment of the affected limb. While the pathophysiology of CRPS remains poorly understood, increased local bone resorption plays an undisputed pivotal role. The aim of this retrospective clinical study was to assess the bone microstructure in patients with CRPS. Methods Patients with CRPS type I of the upper limb whose affected and unaffected distal radii were analyzed by high-resolution peripheral quantitative computed tomography (HR-pQCT) were identified retrospectively. The osteology laboratory data and dual-energy X-ray absorptiometry (DXA) images of the left femoral neck and lumbar spine, which were obtained on the same day as HR-pQCT, were extracted from the medical records. Results Five patients were identified. The CRPS-affected upper limbs had significantly lower trabecular numbers and higher trabecular thicknesses than the unaffected upper limbs. However, the trabecular bone volume to total bone volume and cortical thickness values of the affected and unaffected sides were similar. Trabecular thickness tended to increase with time since disease diagnosis. Discussion CRPS associated with significant alterations in the bone microstructure of the affected upper limb that may amplify as the duration of disease increases. PMID:28740526

Establishing a method to measure bone structure using spectral CT

NASA Astrophysics Data System (ADS)

Ramyar, M.; Leary, C.; Raja, A.; Butler, A. P. H.; Woodfield, T. B. F.; Anderson, N. G.

2017-03-01

Combining bone structure and density measurement in 3D is required to assess site-specific fracture risk. Spectral molecular imaging can measure bone structure in relation to bone density by measuring macro and microstructure of bone in 3D. This study aimed to optimize spectral CT methodology to measure bone structure in excised bone samples. MARS CT with CdTe Medipix3RX detector was used in multiple energy bins to calibrate bone structure measurements. To calibrate thickness measurement, eight different thicknesses of Aluminium (Al) sheets were scanned one in air and the other around a falcon tube and then analysed. To test if trabecular thickness measurements differed depending on scan plane, a bone sample from sheep proximal tibia was scanned in two orthogonal directions. To assess the effect of air on thickness measurement, two parts of the same human femoral head were scanned in two conditions (in the air and in PBS). The results showed that the MARS scanner (with 90μm voxel size) is able to accurately measure the Al (in air) thicknesses over 200μm but it underestimates the thicknesses below 200μm because of partial volume effect in Al-air interface. The Al thickness measured in the highest energy bin is overestimated at Al-falcon tube interface. Bone scanning in two orthogonal directions gives the same trabecular thickness and air in the bone structure reduced measurement accuracy. We have established a bone structure assessment protocol on MARS scanner. The next step is to combine this with bone densitometry to assess bone strength.

Human parathyroid hormone-(1-38) restores cancellous bone to the immobilized, osteopenic proximal tibial metaphysis in rats

NASA Technical Reports Server (NTRS)

Ma, Y. F.; Jee, W. S. S.; Ke, H. Z.; Lin, B. Y.; Liang, X. G.; Li, M.; Yamamoto, N.

1994-01-01

The purpose of this study was to determine if human parathyroid hormone-(1-38) (PTH) can restore cancellous bone mass to the established osteopenic, immobilized proximal tibial metaphyses (PTM) of female rats. The right hindlimbs of six-month-old female Sprague-Dawley rats were immobilized by bandaging the right hindlimbs to the abdomen. After 30 days of right hindlimb immobilization (RHLI), the rats were subcutaneously injected with 200 microgram hPTH(1-38)/kg/day for 15 (short-term) or 75 (longer-term) days. Static bone histomorphometry was performed on the primary spongiosa, while both static and dynamic histomorphometry were performed on the secondary spongiosa of the right PTM. Immobilization for 30 days without treatment decreased trabecular bone area, number and thickness in both primary and secondary spongiosa, and induced an increase in eroded perimeter and a decrease in tissue referent-bone formation rate (BFR/TV) in the secondary spongios. These changes reached a new steady state thereafter. Treatment with 200 microgram hPTH(1-38)/kg/day for 15 days, beginning at 30 days post immobilization (IM), significantly increased trabecular bone area, thickness and number in both primary and secondary spongiosa despite continuous IM when compared to the age-related and IM controls. The short-term (15 days) PTH treatment significantly increased labeling perimeter, mineral apposition rate and BFR/TV in the secondary spongiosa and stimulated longitudinal bone growth as compared to the age-related and IM controls. PTH treatment for longer-term (75 days) further increased trabecular bone area, thickness and number as compared to aging and IM controls and short-term (15 days) PTH treated groups. The bone formation indices in the secondary spongiosa of these longer-term treated rats were lower than that of short-term (15 days) PTH treated group, but they were still higher than those of IM and age-related controls. Our findings indicate that PTH treatment stimulates cancellous bone formation, restores and adds extra cancellous bone to the established, disuse-osteopenic proximal tibial metaphysis of continuously RHLI female rats. These results suggest that PTH may be a useful agent in treatment disuse-induced osteoporosis in humans.

Evaluation of Bone Thickness and Density in the Lower Incisors' Region in Adults with Different Types of Skeletal Malocclusion using Cone-beam Computed Tomography.

PubMed

Al-Masri, Maram M N; Ajaj, Mowaffak A; Hajeer, Mohammad Y; Al-Eed, Muataz S

2015-08-01

To evaluate the bone thickness and density in the lower incisors' region in orthodontically untreated adults, and to examine any possible relationship between thickness and density in different skeletal patterns using cone-beam computed tomography (CBCT). The CBCT records of 48 patients were obtained from the archive of orthodontic department comprising three groups of malocclusion (class I, II and III) with 16 patients in each group. Using OnDemand 3D software, sagittal sections were made for each lower incisor. Thicknesses and densities were measured at three levels of the root (cervical, middle and apical regions) from the labial and lingual sides. Accuracy and reliability tests were undertaken to assess the intraobserver reliability and to detect systematic error. Pearson correlation coefficients were calculated and one-way analysis of variance (ANOVA) was employed to detect significant differences among the three groups of skeletal malocclusion. Apical buccal thickness (ABT) in the four incisors was higher in class II and I patients than in class III patients (p < 0.05). There were significant differences between buccal and lingual surfaces at the apical and middle regions only in class II and III patients. Statistical differences were found between class I and II patients for the cervical buccal density (CBD) and between class II and III patients for apical buccal density (ABD). Relationship between bone thickness and density values ranged from strong at the cervical regions to weak at the apical regions. Sagittal skeletal patterns affect apical bone thickness and density at buccal surfaces of the four lower incisors' roots. Alveolar bone thickness and density increased from the cervical to the apical regions.

Effect of epimedium pubescen flavonoid on bone mineral status and bone turnover in male rats chronically exposed to cigarette smoke

PubMed Central

2012-01-01

Background Epimedii herba is one of the most frequently used herbs in formulas that are prescribed for the treatment of osteoporosis in China and its main constituent is Epimedium pubescen flavonoid (EPF). However, it is unclear whether EPF during chronic exposure to cigarette smoke may have a protective influence on the skeleton. The present study investigated the effect of EPF on bone mineral status and bone turnover in a rat model of human relatively high exposure to cigarette smoke. Methods Fifty male Wistar rats were randomized into five groups: controls, passive smoking groups and passive smoking rats administered EPF at three dosage levels (75, 150 or 300 mg/kg/day) in drinking water for 4 months. A rat model of passive smoking was prepared by breeding male rats in a cigarette-smoking box. Bone mineral content (BMC), bone mineral density (BMD), bone turnover markers, bone histomorphometric parameters and biomechanical properties were examined. Results Smoke exposure decreased BMC and BMD, increased bone turnover (inhibited bone formation and stimulated its resorption), affected bone histomorphometry (increased trabecular separation and osteoclast surface per bone surface; decreased trabecular bone volume, trabecular thickness, trabecular number, cortical thickness, bone formation rate and osteoblast surface per bone surface), and reduced mechanical properties. EPF supplementation during cigarette smoke exposure prevented smoke-induced changes in bone mineral status and bone turnover. Conclusion The results suggest that EPF can prevent the adverse effects of smoke exposure on bone by stimulating bone formation and inhibiting bone turnover and bone resorption. PMID:22713117

Effect of epimedium pubescen flavonoid on bone mineral status and bone turnover in male rats chronically exposed to cigarette smoke.

PubMed

Gao, Shu-guang; Cheng, Ling; Li, Kang-hua; Liu, Wen-He; Xu, Mai; Jiang, Wei; Wei, Li-Cheng; Zhang, Fang-jie; Xiao, Wen-feng; Xiong, Yi-lin; Tian, Jian; Zeng, Chao; Sun, Jin-peng; Xie, Qiang; Lei, Guang-hua

2012-06-19

Epimedii herba is one of the most frequently used herbs in formulas that are prescribed for the treatment of osteoporosis in China and its main constituent is Epimedium pubescen flavonoid (EPF). However, it is unclear whether EPF during chronic exposure to cigarette smoke may have a protective influence on the skeleton. The present study investigated the effect of EPF on bone mineral status and bone turnover in a rat model of human relatively high exposure to cigarette smoke. Fifty male Wistar rats were randomized into five groups: controls, passive smoking groups and passive smoking rats administered EPF at three dosage levels (75, 150 or 300 mg/kg/day) in drinking water for 4 months. A rat model of passive smoking was prepared by breeding male rats in a cigarette-smoking box. Bone mineral content (BMC), bone mineral density (BMD), bone turnover markers, bone histomorphometric parameters and biomechanical properties were examined. Smoke exposure decreased BMC and BMD, increased bone turnover (inhibited bone formation and stimulated its resorption), affected bone histomorphometry (increased trabecular separation and osteoclast surface per bone surface; decreased trabecular bone volume, trabecular thickness, trabecular number, cortical thickness, bone formation rate and osteoblast surface per bone surface), and reduced mechanical properties. EPF supplementation during cigarette smoke exposure prevented smoke-induced changes in bone mineral status and bone turnover. The results suggest that EPF can prevent the adverse effects of smoke exposure on bone by stimulating bone formation and inhibiting bone turnover and bone resorption.

Transgenic Expression of Osteoactivin/gpnmb Enhances Bone Formation In Vivo and Osteoprogenitor Differentiation Ex Vivo.

PubMed

Frara, Nagat; Abdelmagid, Samir M; Sondag, Gregory R; Moussa, Fouad M; Yingling, Vanessa R; Owen, Thomas A; Popoff, Steven N; Barbe, Mary F; Safadi, Fayez F

2016-01-01

Initial identification of osteoactivin (OA)/glycoprotein non-melanoma clone B (gpnmb) was demonstrated in an osteopetrotic rat model, where OA expression was increased threefold in mutant bones, compared to normal. OA mRNA and protein expression increase during active bone regeneration post-fracture, and primary rat osteoblasts show increased OA expression during differentiation in vitro. To further examine OA/gpnmb as an osteoinductive agent, we characterized the skeletal phenotype of transgenic mouse overexpressing OA/gpnmb under the CMV-promoter (OA-Tg). Western blot analysis showed increased OA/gpnmb in OA-Tg osteoblasts, compared to wild-type (WT). In OA-Tg mouse femurs versus WT littermates, micro-CT analysis showed increased trabecular bone volume and thickness, and cortical bone thickness; histomorphometry showed increased osteoblast numbers, bone formation and mineral apposition rates in OA-Tg mice; and biomechanical testing showed higher peak moment and stiffness. Given that OA/gpnmb is also over-expressed in osteoclasts in OA-Tg mice, we evaluated bone resorption by ELISA and histomorphometry, and observed decreased serum CTX-1 and RANK-L, and decreased osteoclast numbers in OA-Tg, compared to WT mice, indicating decreased bone remodeling in OA-Tg mice. The proliferation rate of OA-Tg osteoblasts in vitro was higher, compared to WT, as was alkaline phosphatase staining and activity, the latter indicating enhanced differentiation of OA-Tg osteoprogenitors. Quantitative RT-PCR analysis showed increased TGF-β1 and TGF-β receptors I and II expression in OA-Tg osteoblasts, compared to WT. Together, these data suggest that OA overexpression has an osteoinductive effect on bone mass in vivo and stimulates osteoprogenitor differentiation ex vivo. © 2015 Wiley Periodicals, Inc.

Dipeptidyl Peptidase-4 Inhibitor, Vildagliptin, Improves Trabecular Bone Mineral Density and Microstructure in Obese, Insulin-Resistant, Pre-diabetic Rats.

PubMed

Charoenphandhu, Narattaphol; Suntornsaratoon, Panan; Sa-Nguanmoo, Piangkwan; Tanajak, Pongpan; Teerapornpuntakit, Jarinthorn; Aeimlapa, Ratchaneevan; Chattipakorn, Nipon; Chattipakorn, Siriporn

2018-02-02

Obese insulin resistance and type 2 diabetes mellitus profoundly impair bone mechanical properties and bone quality. However, because several antidiabetes drugs, especially thiazolidinediones, further aggravate bone loss in individuals with diabetes, diabetic osteopathy should not be treated by using simply any glucose-lowering agents. Recently, incretins have been reported to affect osteoblast function positively. The present study aimed to investigate the effects of vildagliptin, an inhibitor of dipeptidyl peptidase-4, on bone of rats with high-fat-diet-induced prediabetes. Male rats were fed a high-fat diet for 12 weeks to induce obese insulin resistance and then treated with vildagliptin for 4 weeks. The effects of the drug on bone were determined by microcomputed tomography and bone histomorphometry. Vildagliptin markedly improved insulin resistance in these obese insulin-resistant rats. It also significantly increased volumetric bone mineral density. Specifically, vildagliptin-treated obese insulin-resistant rats exhibited higher trabecular volumetric bone mineral density than vehicle-treated obese insulin-resistant rats, whereas cortical volumetric bone mineral density, cortical thickness and area were not changed. Bone histomorphometric analysis in a trabecular-rich area (i.e. tibial metaphysis) revealed greater trabecular bone volume and number and less trabecular separation without change in trabecular thickness, osteocyte lacunar area or cortical thickness in the vildagliptin-treated group. Vildagliptin had a beneficial effect on the bone of obese insulin-resistant rats with prediabetes, particularly at the trabecular site. Such benefit probably results from enhanced bone formation rather than from suppressed bone resorption. Copyright © 2018 Diabetes Canada. Published by Elsevier Inc. All rights reserved.

Mice lacking bone sialoprotein (BSP) lose bone after ovariectomy and display skeletal site-specific response to intermittent PTH treatment.

PubMed

Wade-Gueye, Ndéye Marième; Boudiffa, Maya; Laroche, Norbert; Vanden-Bossche, Arnaud; Fournier, Carole; Aubin, Jane E; Vico, Laurence; Lafage-Proust, Marie-Hélène; Malaval, Luc

2010-11-01

Bone sialoprotein (BSP) belongs to the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family, whose members play multiple and distinct roles in the development, turnover, and mineralization of bone and dentin. The functions of BSP in bone remodeling are not yet well established. We previously showed that BSP knockout (BSP(-/-)) mice exhibit a higher trabecular bone volume, concomitant with lower bone remodeling, than wild-type (BSP(+/+)) mice. To determine whether bone turnover can be stimulated in the absence of BSP, we subjected BSP(+/+) and BSP(-/-) mice to catabolic [ovariectomy (OVX)] or anabolic (intermittent PTH administration) hormonal challenges. BSP(-/-) mice progressively develop hypocalcemia and high serum PTH between 2 and 4 months of age. Fifteen and 30 d after OVX, microtomography analysis showed a significant decrease of trabecular bone volume in tibiae of both genotypes. Histomorphometric parameters of bone formation and resorption were significantly increased by OVX. PTH treatment resulted in an increase of trabecular thickness and both bone formation and resorption parameters at all skeletal sites in both genotypes and a decrease of trabecular bone volume in tibiae of BSP(+/+) but not BSP(-/-) mice. PTH increased cortical thickness and bone area in BSP(+/+) but not BSP(-/-) mice and stimulated the bone formation rate specifically in the endosteum of BSP(+/+) mice and the periosteum of BSP(-/-) mice. PTH enhanced the expression of RANKL, MEPE, and DMP1 in both genotypes but increased OPG and OPN expression only in BSP(-/-) mice. In conclusion, despite the low basal turnover, both catabolic and anabolic challenges increase bone formation and resorption in BSP(-/-) mice, suggesting that compensatory pathways are operative in the skeleton of BSP-deficient mice. Although up-regulation of one or several other SIBLINGs is a possible mechanism, further studies are needed to analyze the interplay and cross-regulation involved in compensating for the absence of BSP.

Hydroxyapatite paste Ostim, without elevation of full-thickness flaps, improves alveolar healing stimulating BMP- and VEGF-mediated signal pathways: an experimental study in humans.

PubMed

Canuto, R A; Pol, R; Martinasso, G; Muzio, G; Gallesio, G; Mozzati, M

2013-08-01

Tooth extraction is considered as the starting point of jaw atrophy via osteoclast activity stimulation. The maintenance of dental alveolar bone depends on surgery procedure and use of materials to maintain prior space favoring bone regeneration. Among substitutes used in dentistry to fill bone defects, Ostim-Pastes (Ostim) is a nanocrystalline paste tested for treatment of severe clinical conditions. This research first investigated the effect of Ostim on alveolar healing, comparing in the same healthy subjects, an Ostim-filled socket with a not-filled one. Moreover, it also proposed a new surgical protocol for the post-extractive socket treatment using the graft materials without elevation of full-thickness flaps. Fourteen patients were enrolled to bilateral maxillary or mandibular extraction that was performed without elevation of full-thickness flaps. In each patient, one socket was filled using Ostim, and the other one was allowed to undergo natural healing. No suture was carried out. Clinical and biologic parameters were screened at 1, 7, and 14 days. Obtained results evidenced that nanocrystalline hydroxyapatite supports bone regeneration, increasing the synthesis of pro-osteogenic factors as bone morphogenetics protein (BMP)-4, BMP-7, alkaline phosphatase, and osteocalcin. Moreover, filling post-extractive socket with nanocrystalline hydroxyapatite paste leads to a complete epithelialization already at 7 days after extraction, despite the fact that the teeth were extracted without elevation of full-thickness flaps . The improved epithelialization is mediated by increased vascular endothelial growth factor (VEGF) expression. No significant change was observed in inflammatory parameters, with exception of an early and transient IL-1β induction, that could trigger and improve alveolar healing. Clinical and biomolecular observations of this explorative study evidenced that nanocrystalline hydroxyapatite improves alveolar socket healing, increasing angiogenesis, epithelialization, and osteogenesis, also in absence of elevation of full-thickness flaps. © 2011 John Wiley & Sons A/S.

The effects of cortical bone thickness and trabecular bone strength on noninvasive measures of the implant primary stability using synthetic bone models.

PubMed

Hsu, Jui-Ting; Fuh, Lih-Jyh; Tu, Ming-Gene; Li, Yu-Fen; Chen, Kuan-Ting; Huang, Heng-Li

2013-04-01

This study investigated how the primary stability of a dental implant as measured by the insertion torque value (ITV), Periotest value (PTV), and implant stability quotient (ISQ) is affected by varying thicknesses of cortical bone and strengths of trabecular bone using synthetic bone models. Four synthetic cortical shells (with thicknesses of 0, 1, 2, and 3 mm) were attached to four cellular rigid polyurethane foams (with elastic moduli of 137, 47.5, 23, and 12.4 MPa) and one open-cell rigid polyurethane foam which mimic the osteoporotic bone (with an elastic modulus 6.5 MPa), to represent the jawbones with various cortical bone thicknesses and strengths of trabecular bone. A total of 60 bone specimens accompanied with implants was examined by a torque meter, Osstell resonance frequency analyzer, and Periotest electronic device. All data were statistically analyzed by two-way analysis of variance. In addition, second-order nonlinear regression was utilized to assess the correlations of the primary implant stability with the four cortex thicknesses and five strengths of trabecular bone. ITV, ISQ, and PTV differed significantly (p < .05) and were strongly correlated with the thickness of cortical bone (R(2) > 0.9) and the elastic modulus of trabecular bone (R(2) = 0.74-0.99). The initial stability at the time of implant placement is influenced by both the cortical bone thickness and the strength of trabecular bone; however, these factors are mostly nonlinearly correlated with ITV, PTV, and ISQ. Using ITV and PTV seems more suitable for identifying the primary implant stability in osteoporotic bone with a thin cortex. © 2011 Wiley Periodicals, Inc.

A high-fat diet increases body weight and circulating estradiol concentrations but does not improve bone structural properties in ovariectomized mice.

PubMed

Cao, Jay J; Gregoire, Brian R

2016-04-01

Bone health is influenced by body mass and estrogen. The objective of the study was to determine whether high-fat diet-induced obesity affects bone structure and alters markers of bone turnover in ovariectomized (OVX) mice. We hypothesized that a high-fat diet would increase body weight gain and serum estradiol levels in OVX mice but would not improve bone structural parameter in OVX mice. Thirty-five C57BL/6 mice were either sham operated or OVX at the age of 4 months and then fed either a normal-fat diet (10% energy as fat) or a high-fat diet (45% energy as fat with extra fat from lard) ad libitum for 11 weeks. Ovariectomy increased body weight, serum tartrate-resistant acid phosphatase concentration, and expression of cathepsin K in bone; decreased serum estradiol concentration; and induced significant bone loss manifested by decreased bone volume/total volume (BV/TV), connectivity density (Conn.D), trabecular number, and trabecular thickness with increased trabecular separation and structural model index (P < .01). The high-fat diet increased body weight (P < .01) in OVX mice and nonsignificantly decreased BV/TV (P = .08) and Conn.D (P = .10). Despite having similar serum estradiol concentrations and higher body weight, OVX mice consuming the high-fat diet had lower BV/TV, Conn.D, trabecular number, trabecular thickness, and higher structural model index and trabecular separation than did sham mice fed the normal-fat diet. These findings indicate that increased body weight and elevated serum estradiol concentration induced by a high-fat diet do not mitigate ovariectomy-induced bone loss in mice. Published by Elsevier Inc.

Comparing the influence of crestal cortical bone and sinus floor cortical bone in posterior maxilla bi-cortical dental implantation: a three-dimensional finite element analysis.

PubMed

Yan, Xu; Zhang, Xinwen; Chi, Weichao; Ai, Hongjun; Wu, Lin

2015-05-01

This study aimed to compare the influence of alveolar ridge cortical bone and sinus floor cortical bone in sinus areabi-cortical dental implantation by means of 3D finite element analysis. Three-dimensional finite element (FE) models in a posterior maxillary region with sinus membrane and the same height of alveolar ridge of 10 mm were generated according to the anatomical data of the sinus area. They were either with fixed thickness of crestal cortical bone and variable thickness of sinus floor cortical bone or vice versa. Ten models were assumed to be under immediate loading or conventional loading. The standard implant model based on the Nobel Biocare implant system was created via computer-aided design software. All materials were assumed to be isotropic and linearly elastic. An inclined force of 129 N was applied. Von Mises stress mainly concentrated on the surface of crestal cortical bone around the implant neck. For all the models, both the axial and buccolingual resonance frequencies of conventional loading were higher than those of immediate loading; however, the difference is less than 5%. The results showed that bi-cortical implant in sinus area increased the stability of the implant, especially for immediately loading implantation. The thickness of both crestal cortical bone and sinus floor cortical bone influenced implant micromotion and stress distribution; however, crestal cortical bone may be more important than sinus floor cortical bone.

Cortical bone thickening in Type A posterior atlas arch defects: experimental report.

PubMed

Sanchis-Gimeno, Juan A; Llido, Susanna; Guede, David; Martinez-Soriano, Francisco; Ramon Caeiro, Jose; Blanco-Perez, Esther

2017-03-01

To date, no information about the cortical bone microstructural properties in atlas vertebrae with posterior arch defects has been reported. To test if there is an increased cortical bone thickening in atlases with Type A posterior atlas arch defects in an experimental model. Micro-computed tomography (CT) study on cadaveric atlas vertebrae. We analyzed the cortical bone thickness, the cortical volume, and the medullary volume (SkyScan 1172 Bruker micro-CT NV, Kontich, Belgium) in cadaveric dry vertebrae with a Type A atlas arch defect and normal control vertebrae. The micro-CT study revealed significant differences in cortical bone thickness (p=.005), cortical volume (p=.003), and medullary volume (p=.009) values between the normal and the Type A vertebrae. Type A congenital atlas arch defects present a cortical bone thickening that may play a protective role against atlas fractures. Copyright © 2016 Elsevier Inc. All rights reserved.

Creating a normative database of age-specific 3D geometrical data, bone density, and bone thickness of the developing skull: a pilot study.

PubMed

Delye, Hans; Clijmans, Tim; Mommaerts, Maurice Yves; Sloten, Jos Vnder; Goffin, Jan

2015-12-01

Finite element models (FEMs) of the head are used to study the biomechanics of traumatic brain injury and depend heavily on the use of accurate material properties and head geometry. Any FEM aimed at investigating traumatic head injury in children should therefore use age-specific dimensions of the head, as well as age-specific material properties of the different tissues. In this study, the authors built a database of age-corrected skull geometry, skull thickness, and bone density of the developing skull to aid in the development of an age-specific FEM of a child's head. Such a database, containing age-corrected normative skull geometry data, can also be used for preoperative surgical planning and postoperative long-term follow-up of craniosynostosis surgery results. Computed tomography data were processed for 187 patients (age range 0-20 years old). A 3D surface model was calculated from segmented skull surfaces. Skull models, reference points, and sutures were processed into a MATLAB-supported database. This process included automatic calculation of 2D measurements as well as 3D measurements: length of the coronal suture, length of the lambdoid suture, and the 3D anterior-posterior length, defined as the sum of the metopic and sagittal suture. Skull thickness and skull bone density calculations were included. Cephalic length, cephalic width, intercoronal distance, lateral orbital distance, intertemporal distance, and 3D measurements were obtained, confirming the well-established general growth pattern of the skull. Skull thickness increases rapidly in the first year of life, slowing down during the second year of life, while skull density increases with a fast but steady pace during the first 3 years of life. Both skull thickness and density continue to increase up to adulthood. This is the first report of normative data on 2D and 3D measurements, skull bone thickness, and skull bone density for children aged 0-20 years. This database can help build an age-specific FEM of a child's head. It can also help to tailor preoperative virtual planning in craniosynostosis surgery toward patient-specific normative target values and to perform objective long-term follow-up in craniosynostosis surgery.

A Bone-Thickness Map as a Guide for Bone-Anchored Port Implantation Surgery in the Temporal Bone

PubMed Central

Guignard, Jérémie; Arnold, Andreas; Weisstanner, Christian; Caversaccio, Marco; Stieger, Christof

2013-01-01

The bone-anchored port (BAP) is an investigational implant, which is intended to be fixed on the temporal bone and provide vascular access. There are a number of implants taking advantage of the stability and available room in the temporal bone. These devices range from implantable hearing aids to percutaneous ports. During temporal bone surgery, injuring critical anatomical structures must be avoided. Several methods for computer-assisted temporal bone surgery are reported, which typically add an additional procedure for the patient. We propose a surgical guide in the form of a bone-thickness map displaying anatomical landmarks that can be used for planning of the surgery, and for the intra-operative decision of the implant’s location. The retro-auricular region of the temporal and parietal bone was marked on cone-beam computed tomography scans and tridimensional surfaces displaying the bone thickness were created from this space. We compared this method using a thickness map (n = 10) with conventional surgery without assistance (n = 5) in isolated human anatomical whole head specimens. The use of the thickness map reduced the rate of Dura Mater exposition from 100% to 20% and suppressed sigmoid sinus exposures. The study shows that a bone-thickness map can be used as a low-complexity method to improve patient’s safety during BAP surgery in the temporal bone. PMID:28788390

A Bone-Thickness Map as a Guide for Bone-Anchored Port Implantation Surgery in the Temporal Bone.

PubMed

Guignard, Jérémie; Arnold, Andreas; Weisstanner, Christian; Caversaccio, Marco; Stieger, Christof

2013-11-19

The bone-anchored port (BAP) is an investigational implant, which is intended to be fixed on the temporal bone and provide vascular access. There are a number of implants taking advantage of the stability and available room in the temporal bone. These devices range from implantable hearing aids to percutaneous ports. During temporal bone surgery, injuring critical anatomical structures must be avoided. Several methods for computer-assisted temporal bone surgery are reported, which typically add an additional procedure for the patient. We propose a surgical guide in the form of a bone-thickness map displaying anatomical landmarks that can be used for planning of the surgery, and for the intra-operative decision of the implant's location. The retro-auricular region of the temporal and parietal bone was marked on cone-beam computed tomography scans and tridimensional surfaces displaying the bone thickness were created from this space. We compared this method using a thickness map ( n = 10) with conventional surgery without assistance ( n = 5) in isolated human anatomical whole head specimens. The use of the thickness map reduced the rate of Dura Mater exposition from 100% to 20% and suppressed sigmoid sinus exposures. The study shows that a bone-thickness map can be used as a low-complexity method to improve patient's safety during BAP surgery in the temporal bone.

Kit W-sh Mutation Prevents Cancellous Bone Loss during Calcium Deprivation.

PubMed

Lotinun, Sutada; Suwanwela, Jaijam; Poolthong, Suchit; Baron, Roland

2018-01-01

Calcium is essential for normal bone growth and development. Inadequate calcium intake increases the risk of osteoporosis and fractures. Kit ligand/c-Kit signaling plays an important role in regulating bone homeostasis. Mice with c-Kit mutations are osteopenic. The present study aimed to investigate whether impairment of or reduction in c-Kit signaling affects bone turnover during calcium deprivation. Three-week-old male WBB6F1/J-Kit W /Kit W-v /J (W/W v ) mice with c-Kit point mutation, Kit W-sh /HNihrJaeBsmJ (W sh /W sh ) mice with an inversion mutation in the regulatory elements upstream of the c-Kit promoter region, and their wild-type controls (WT) were fed either a normal (0.6% calcium) or a low calcium diet (0.02% calcium) for 3 weeks. μCT analysis indicated that both mutants fed normal calcium diet had significantly decreased cortical thickness and cancellous bone volume compared to WT. The low calcium diet resulted in a comparable reduction in cortical bone volume and cortical thickness in the W/W v and W sh /W sh mice, and their corresponding controls. As expected, the low calcium diet induced cancellous bone loss in the W/W v mice. In contrast, W sh /W sh cancellous bone did not respond to this diet. This c-Kit mutation prevented cancellous bone loss by antagonizing the low calcium diet-induced increase in osteoblast and osteoclast numbers in the W sh /W sh mice. Gene expression profiling showed that calcium deficiency increased Osx, Ocn, Alp, type I collagen, c-Fms, M-CSF, and RANKL/OPG mRNA expression in controls; however, the W sh mutation suppressed these effects. Our findings indicate that although calcium restriction increased bone turnover, leading to osteopenia, the decreased c-Kit expression levels in the W sh /W sh mice prevented the low calcium diet-induced increase in cancellous bone turnover and bone loss but not the cortical bone loss.

Comparative cortical bone thickness between the long bones of humans and five common non-human mammal taxa.

PubMed

Croker, Sarah L; Reed, Warren; Donlon, Denise

2016-03-01

The task of identifying fragments of long bone shafts as human or non-human is difficult but necessary, for both forensic and archaeological cases, and a fast simple method is particularly useful. Previous literature suggests there may be differences in the thickness of the cortical bone between these two groups, but this has not been tested thoroughly. The aim of this study was not only to test this suggestion, but also to provide data that could be of practical assistance for future comparisons. The major limb bones (humerus, radius, femur and tibia) of 50 Caucasoid adult skeletons of known age and sex were radiographed, along with corresponding skeletal elements from sheep, pigs, cattle, large dogs and kangaroos. Measurements were taken from the radiographs at five points along the bone shaft, of shaft diameter, cortical bone thickness, and a cortical thickness index (sum of cortices divided by shaft diameter) in both anteroposterior and mediolateral orientations. Each variable for actual cortical bone thickness as well as cortical thickness indices were compared between the human group (split by sex) and each of the non-human groups in turn, using Student's t-tests. Results showed that while significant differences did exist between the human groups and many of the non-human groups, these were not all in the same direction. That is, some variables in the human groups were significantly greater than, and others were significantly less than, the corresponding variable in the non-human groups, depending on the particular non-human group, sex of the human group, or variable under comparison. This was the case for measurements of both actual cortical bone thickness and cortical thickness index. Therefore, for bone shaft fragments for which the skeletal element is unknown, the overlap in cortical bone thickness between different areas of different bones is too great to allow identification using this method alone. However, by providing extensive cortical bone thickness data for a range of bones, this study may be able to assist in the identification of some bone fragments by providing another piece of evidence that, used in conjunction with other clues, can provide a likely determination of the origin of a bone fragment. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Influence of mesh density, cortical thickness and material properties on human rib fracture prediction.

PubMed

Li, Zuoping; Kindig, Matthew W; Subit, Damien; Kent, Richard W

2010-11-01

The purpose of this paper was to investigate the sensitivity of the structural responses and bone fractures of the ribs to mesh density, cortical thickness, and material properties so as to provide guidelines for the development of finite element (FE) thorax models used in impact biomechanics. Subject-specific FE models of the second, fourth, sixth and tenth ribs were developed to reproduce dynamic failure experiments. Sensitivity studies were then conducted to quantify the effects of variations in mesh density, cortical thickness, and material parameters on the model-predicted reaction force-displacement relationship, cortical strains, and bone fracture locations for all four ribs. Overall, it was demonstrated that rib FE models consisting of 2000-3000 trabecular hexahedral elements (weighted element length 2-3mm) and associated quadrilateral cortical shell elements with variable thickness more closely predicted the rib structural responses and bone fracture force-failure displacement relationships observed in the experiments (except the fracture locations), compared to models with constant cortical thickness. Further increases in mesh density increased computational cost but did not markedly improve model predictions. A ±30% change in the major material parameters of cortical bone lead to a -16.7 to 33.3% change in fracture displacement and -22.5 to +19.1% change in the fracture force. The results in this study suggest that human rib structural responses can be modeled in an accurate and computationally efficient way using (a) a coarse mesh of 2000-3000 solid elements, (b) cortical shells elements with variable thickness distribution and (c) a rate-dependent elastic-plastic material model. Copyright © 2010 IPEM. Published by Elsevier Ltd. All rights reserved.

The effect of the heights and thicknesses of the remaining root segments on buccal bone resorption in the socket-shield technique: An experimental study in dogs.

PubMed

Tan, Zhen; Kang, Jian; Liu, Wenjia; Wang, Hang

2018-06-01

To date only a few studies have been done on the use of the socket-shield technique for preserving the resorption of the buccal bone in aesthetically sensitive sites. Besides, there have been no further studies on the effect of the heights and thicknesses of the remaining root segments on buccal bone resorption when using this method. The aim of this study was to evaluate the effect of different heights and thicknesses of the remaining root segments on bone resorption in the socket-shield technique. Four healthy female beagle dogs were used in this study. The third premolar (P3) and the fourth premolar (P4) on both sides of the mandible were hemisected in the buccal-lingual direction, and the clinical crown of the distal root was beheaded. In the experimental groups, the roots were worn down in the apical direction until they were located at the buccal crestal level (Group A) or 1 mm higher than that level (Group B). In the control group, the distal root segments were extracted. Then, implant placement was performed into the distal root. After 3 months of healing, the specimens were prepared for histological diagnosis. There was no difference between Group A and Group B when using the socket-shield technique, but the results of both groups were better than those of the control group. The height of the root segments has little effect on the bone absorption of alveolar bone, while the bone absorption was strongly influenced by the thickness of the root segments. More precisely, the absorption may decrease if the thickness of the root fragment increases, when the thickness of the root plate is in the 0.5-1.5 mm range. © 2018 Wiley Periodicals, Inc.

Dependences of mucosal dose on photon beams in head-and-neck intensity-modulated radiation therapy: a Monte Carlo study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chow, James C.L., E-mail: james.chow@rmp.uhn.on.ca; Department of Radiation Oncology, University of Toronto, Toronto, Ontario; Department of Physics, Ryerson University, Toronto, Ontario

2012-07-01

Dependences of mucosal dose in the oral or nasal cavity on the beam energy, beam angle, multibeam configuration, and mucosal thickness were studied for small photon fields using Monte Carlo simulations (EGSnrc-based code), which were validated by measurements. Cylindrical mucosa phantoms (mucosal thickness = 1, 2, and 3 mm) with and without the bone and air inhomogeneities were irradiated by the 6- and 18-MV photon beams (field size = 1 Multiplication-Sign 1 cm{sup 2}) with gantry angles equal to 0 Degree-Sign , 90 Degree-Sign , and 180 Degree-Sign , and multibeam configurations using 2, 4, and 8 photon beams inmore » different orientations around the phantom. Doses along the central beam axis in the mucosal tissue were calculated. The mucosal surface doses were found to decrease slightly (1% for the 6-MV photon beam and 3% for the 18-MV beam) with an increase of mucosal thickness from 1-3 mm, when the beam angle is 0 Degree-Sign . The variation of mucosal surface dose with its thickness became insignificant when the beam angle was changed to 180 Degree-Sign , but the dose at the bone-mucosa interface was found to increase (28% for the 6-MV photon beam and 20% for the 18-MV beam) with the mucosal thickness. For different multibeam configurations, the dependence of mucosal dose on its thickness became insignificant when the number of photon beams around the mucosal tissue was increased. The mucosal dose with bone was varied with the beam energy, beam angle, multibeam configuration and mucosal thickness for a small segmental photon field. These dosimetric variations are important to consider improving the treatment strategy, so the mucosal complications in head-and-neck intensity-modulated radiation therapy can be minimized.« less

In Vivo Evaluation of Immediately Loaded Stainless Steel and Titanium Orthodontic Screws in a Growing Bone

PubMed Central

Gritsch, Kerstin; Laroche, Norbert; Bonnet, Jeanne-Marie; Exbrayat, Patrick; Morgon, Laurent; Rabilloud, Muriel; Grosgogeat, Brigitte

2013-01-01

The present work intends to evaluate the use of immediate loaded orthodontic screws in a growing model, and to study the specific bone response. Thirty-two screws (half of stainless steel and half of titanium) were inserted in the alveolar bone of 8 growing pigs. The devices were immediately loaded with a 100 g orthodontic force. Two loading periods were assessed: 4 and 12 weeks. Both systems of screws were clinically assessed. Histological observations and histomorphometric analysis evaluated the percent of “bone-to-implant contact” and static and dynamic bone parameters in the vicinity of the devices (test zone) and in a bone area located 1.5 cm posterior to the devices (control zone). Both systems exhibit similar responses for the survival rate; 87.5% and 81.3% for stainless steel and titanium respectively (p = 0.64; 4-week period), and 62.5% and 50.0% for stainless steel and titanium respectively (p = 0.09; 12-week period). No significant differences between the devices were found regarding the percent of “bone-to-implant contact” (p = 0.1) or the static and dynamic bone parameters. However, the 5% threshold of “bone-to-implant contact” was obtained after 4 weeks with the stainless steel devices, leading to increased survival rate values. Bone in the vicinity of the miniscrew implants showed evidence of a significant increase in bone trabecular thickness when compared to bone in the control zone (p = 0.05). In our study, it is likely that increased trabecular thickness is a way for low density bone to respond to the stress induced by loading. PMID:24124540

Joint cartilage thickness and automated determination of bone age and bone health in juvenile idiopathic arthritis.

PubMed

Twilt, Marinka; Pradsgaard, Dan; Spannow, Anne Helene; Horlyck, Arne; Heuck, Carsten; Herlin, Troels

2017-08-10

BoneXpert is an automated method to calculate bone maturation and bone health index (BHI) in children with juvenile idiopathic arthritis (JIA). Cartilage thickness can also be seen as an indicator for bone health and arthritis damage. The objective of this study was to evaluate the relation between cartilage thickness, bone maturation and bone health in patients with JIA. Patients with JIA diagnosed according ILAR criteria included in a previous ultrasonography (US) study were eligible if hand radiographs were taken at the same time as the US examination. Of the 95 patients 67 met the inclusion criteria. Decreased cartilage thickness was seen in 27% of the examined joints. Decreased BHI was seen in half of the JIA patient, and delayed bone maturation was seen in 33% of patients. A combination of decreased BHI and bone age was seen in 1 out of 5 JIA patients. Decreased cartilage thickness in the knee, wrist and MCP joint was negatively correlated with delayed bone maturation but not with bone health index. Delayed bone maturation and decreased BHI were not related to a thinner cartilage, but a thicker cartilage. No relation with JADAS 10 was found. The rheumatologist should remain aware of delayed bone maturation and BHI in JIA patients with cartilage changes, even in the biologic era.

Spine Trabecular Bone Score as an Indicator of Bone Microarchitecture at the Peripheral Skeleton in Kidney Transplant Recipients.

PubMed

Luckman, Matthew; Hans, Didier; Cortez, Natalia; Nishiyama, Kyle K; Agarawal, Sanchita; Zhang, Chengchen; Nikkel, Lucas; Iyer, Sapna; Fusaro, Maria; Guo, Edward X; McMahon, Donald J; Shane, Elizabeth; Nickolas, Thomas L

2017-04-03

Studies using high-resolution peripheral quantitative computed tomography showed progressive abnormalities in cortical and trabecular microarchitecture and biomechanical competence over the first year after kidney transplantation. However, high-resolution peripheral computed tomography is a research tool lacking wide availability. In contrast, the trabecular bone score is a novel and widely available tool that uses gray-scale variograms of the spine image from dual-energy x-ray absorptiometry to assess trabecular quality. There are no studies assessing whether trabecular bone score characterizes bone quality in kidney transplant recipients. Between 2009 and 2010, we conducted a study to assess changes in peripheral skeletal microarchitecture, measured by high-resolution peripheral computed tomography, during the first year after transplantation in 47 patients managed with early corticosteroid-withdrawal immunosuppression. All adult first-time transplant candidates were eligible. Patients underwent imaging with high-resolution peripheral computed tomography and dual-energy x-ray absorptiometry pretransplantation and 3, 6, and 12 months post-transplantation. We now test if, during the first year after transplantation, trabecular bone score assesses the evolution of bone microarchitecture and biomechanical competence as determined by high-resolution peripheral computed tomography. At baseline and follow-up, among the 72% and 78%, respectively, of patients having normal bone mineral density by dual-energy x-ray absorptiometry, 53% and 50%, respectively, were classified by trabecular bone score as having high fracture risk. At baseline, trabecular bone score correlated with spine, hip, and ultradistal radius bone mineral density by dual-energy x-ray absorptiometry and cortical area, density, thickness, and porosity; trabecular density, thickness, separation, and heterogeneity; and stiffness and failure load by high-resolution peripheral computed tomography. Longitudinally, each percentage increase in trabecular bone score was associated with increases in trabecular number (0.35%±1.4%); decreases in trabecular thickness (-0.45%±0.15%), separation (-0.40%±0.15%), and network heterogeneity (-0.48%±0.20%); and increases in failure load (0.22%±0.09%) by high-resolution peripheral computed tomography (all P <0.05). Trabecular bone score may be a useful method to assess and monitor bone quality and strength and classify fracture risk in kidney transplant recipients. Copyright © 2017 by the American Society of Nephrology.

Spine Trabecular Bone Score as an Indicator of Bone Microarchitecture at the Peripheral Skeleton in Kidney Transplant Recipients

PubMed Central

Luckman, Matthew; Hans, Didier; Cortez, Natalia; Nishiyama, Kyle K.; Agarawal, Sanchita; Zhang, Chengchen; Nikkel, Lucas; Iyer, Sapna; Fusaro, Maria; Guo, Edward X.; McMahon, Donald J.; Shane, Elizabeth

2017-01-01

Background and objectives Studies using high-resolution peripheral quantitative computed tomography showed progressive abnormalities in cortical and trabecular microarchitecture and biomechanical competence over the first year after kidney transplantation. However, high-resolution peripheral computed tomography is a research tool lacking wide availability. In contrast, the trabecular bone score is a novel and widely available tool that uses gray-scale variograms of the spine image from dual-energy x-ray absorptiometry to assess trabecular quality. There are no studies assessing whether trabecular bone score characterizes bone quality in kidney transplant recipients. Design, settings, participants, & measurements Between 2009 and 2010, we conducted a study to assess changes in peripheral skeletal microarchitecture, measured by high-resolution peripheral computed tomography, during the first year after transplantation in 47 patients managed with early corticosteroid–withdrawal immunosuppression. All adult first-time transplant candidates were eligible. Patients underwent imaging with high-resolution peripheral computed tomography and dual-energy x-ray absorptiometry pretransplantation and 3, 6, and 12 months post-transplantation. We now test if, during the first year after transplantation, trabecular bone score assesses the evolution of bone microarchitecture and biomechanical competence as determined by high-resolution peripheral computed tomography. Results At baseline and follow-up, among the 72% and 78%, respectively, of patients having normal bone mineral density by dual-energy x-ray absorptiometry, 53% and 50%, respectively, were classified by trabecular bone score as having high fracture risk. At baseline, trabecular bone score correlated with spine, hip, and ultradistal radius bone mineral density by dual-energy x-ray absorptiometry and cortical area, density, thickness, and porosity; trabecular density, thickness, separation, and heterogeneity; and stiffness and failure load by high-resolution peripheral computed tomography. Longitudinally, each percentage increase in trabecular bone score was associated with increases in trabecular number (0.35%±1.4%); decreases in trabecular thickness (−0.45%±0.15%), separation (−0.40%±0.15%), and network heterogeneity (−0.48%±0.20%); and increases in failure load (0.22%±0.09%) by high-resolution peripheral computed tomography (all P<0.05). Conclusions Trabecular bone score may be a useful method to assess and monitor bone quality and strength and classify fracture risk in kidney transplant recipients. PMID:28348031

Thickness and resistivity variations over the upper surface of the human skull.

PubMed

Law, S K

1993-01-01

A study of skull thickness and resistivity variations over the upper surface was made for an adult human skull. Physical measurements of thickness and qualitative analysis of photographs and CT scans of the skull were performed to determine internal and external features of the skull. Resistivity measurements were made using the four-electrode method and ranged from 1360 to 21400 Ohm-cm with an overall mean of 7560 +/- 4130 Ohm-cm. The presence of sutures was found to decrease resistivity substantially. The absence of cancellous bone was found to increase resistivity, particularly for samples from the temporal bone. An inverse relationship between skull thickness and resistivity was determined for trilayer bone (n = 12, p < 0.001). The results suggest that the skull cannot be considered a uniform layer and that local resistivity variations should be incorporated into realistic geometric and resistive head models to improve resolution in EEG. Influences of these variations on head models, methods for determining these variations, and incorporation into realistic head models, are discussed.

Increased frequency of temporal acoustic window failure in rheumatoid arthritis: a manifestation of altered bone metabolism?

PubMed

Kardos, Zsófia; Oláh, Csaba; Sepsi, Mariann; Sas, Attila; Kostyál, László; Bóta, Tünde; Bhattoa, Harjit Pal; Hodosi, Katalin; Kerekes, György; Tamási, László; Bereczki, Dániel; Szekanecz, Zoltán

2018-05-01

Assessment of intracranial vessels includes transcranial Doppler (TCD). TCD performance requires intact temporal acoustic windows (TAW). Failure of TAW (TAWF) is present in 8-20% of people. There have been no reports on TAWF in rheumatoid arthritis (RA). Altogether, 62 female RA patients were included. Among them, 20 were MTX-treated and biologic-free, 20 received infliximab, and 22 tocilizumab. The controls included 60 non-RA women. TAWF, temporal bone thickness, and texture were determined by ultrasound and CT. BMD and T-scores of multiple bones were determined by DEXA. Several bone biomarkers were assessed by ELISA. In RA, 54.8% of the patients had TAWF on at least one side. Neither TAW could be identified in 34% of RA subjects. In contrast, only 20.0% of control subjects had TAWF on either or both sides (p < 0.001). In RA vs controls, 53.0 vs 2.9% of subjects exerted the trilayer, "sandwich-like" structure of TAW (p < 0.001). Finally, in RA vs controls, the mean temporal bone thickness values of the right TAW were 3.58 ± 1.43 vs 2.92 ± 1.22 mm (p = NS), while those of the left TAW were 4.16 ± 1.56 vs 2.90 ± 1.16 mm (p = 0.001). There was close association between TAWF, bone thickness, and texture (p < 0.05). These TAW parameters all correlated with age; however, TAW failure and texture also correlated with serum osteoprotegerin. TAW bone thickness inversely correlated with hip BMD (p < 0.05). TAWF, thicker, and heterogeneous temporal bones were associated with RA. These features have been associated with bone loss and OPG production. Bone loss seen in RA may result in OPG release and stimulation of bone formation around TAW.

Dynamic histomorphometric evaluation of human fetal bone formation.

PubMed

Glorieux, F H; Salle, B L; Travers, R; Audra, P H

1991-01-01

We have evaluated dynamic and static parameters of bone formation in femoral metaphyses collected from two human fetuses at 19 weeks of gestation. Tetracycline was administered to the mother at set intervals (2-5-2 day schedule) before interruption of pregnancy. Labels were distinct and sharply linear, suggesting a well organized calcification front at this early stage of mineralization. Mineral apposition rate (MAR) was fastest (4.1 +/- 0.3 microns/d) in the periosteal (Ps) envelope, and about half that value in the endosteal envelopes (endocortical: 2.5 +/- 0.1, cancellous 2.1 +/- 0.1 microns/d). Because cellular activities may vary throughout the metaphyseal area, sections were arbitrarily separated in 0.75 mm layers starting from the growth plate. Three measured parameters decreased rapidly with increasing distance from the physis: Ps MAR: 4.9 to 2.3 microns/d, trabecular osteoid thickness: 5.9 to 1.2 microns, and cartilage volume (CgV/TV): 5.4% to 1.2%. Others did not vary significantly along the metaphysis. Comparison of several static parameters with those measured in five autopsy specimens from full-term infants showed that bone and cartilage volume, and trabecular thickness increased while osteoid thickness and parameters of resorption decreased in the second half of the gestation period. The study indicates that fetal bone matrix mineralization is already highly organized at mid-gestation, and validates the use of histomorphometry to assess bone maturation during early skeletal development.

The effects of orally administered diacerein on cartilage and subchondral bone in an ovine model of osteoarthritis.

PubMed

Hwa, S Y; Burkhardt, D; Little, C; Ghosh, P

2001-04-01

An ovine model of osteoarthritis (OA) induced by bilateral lateral meniscectomy (BLM) was used to evaluate in vivo effects of the slow acting antiarthritic drug diacerein (DIA) on degenerative changes in cartilage and subchondral bone of the operated joints. Twenty of 30 adult age matched Merino wethers were subjected to BLM in the knee joints and the remainder served as non-operated controls (NOC). Half of the BLM group (n = 10) were given DIA (25 mg/kg orally) daily for 3 mo, then 50 mg/kg daily for a further 6 mo. The remainder of the meniscectomized (MEN) group served as OA controls. Five DIA, 5 MEN, and 5 NOC animals were sacrificed at 3 mo and the remainder at 9 mo postsurgery. One knee joint of each animal was used for bone mineral density (BMD) studies. Osteochondral slabs from the lateral femoral condyle and lateral tibial plateau were cut from the contralateral joint and were processed for histological and histomorphometric examination to assess the cartilage and subchondral bone changes. No significant difference was observed in the modified Mankin scores for cartilage from the DIA and MEN groups at 3 or 9 mo. However, in animals treated with DIA, the thickness of cartilage (p = 0.05) and subchondral bone (p = 0.05) in the lesion (middle) zone of the lateral tibial plateau were decreased relative to the corresponding zone of the MEN group at 3 mo (p = 0.05). At 9 mo subchondral bone thickness in this zone remained the same as NOC but BMD, which included both subchondral and trabecular bone, was significantly increased relative to the NOC group (p = 0.01). In contrast, the subchondral bone thickness of the outer zone of lateral tibial plateau and lateral femoral condyle of both MEN and DIA groups increased after 9 mo, while BMD remained the same as in the NOC. DIA treatment of meniscectomized animals mediated selective responses of cartilage and subchondral bone to the altered mechanical stresses induced across the joints by this procedure. While subchondral bone thickness in tibial lesion sites was reduced, cartilage and bone proliferation at the outer joint margins, a region where osteophyte formation occurred, were enhanced, suggesting that DIA supported the processes of repair and endochondral ossification.

Effect of porosity, tissue density, and mechanical properties on radial sound speed in human cortical bone

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eneh, C. T. M., E-mail: chibuzor.eneh@uef.fi, E-mail: markus.malo@uef.fi, E-mail: janne.karjalainen@boneindex.fi, E-mail: jukka.liukkonen@gmail.com, E-mail: juha.toyras@uef.fi; Töyräs, J., E-mail: chibuzor.eneh@uef.fi, E-mail: markus.malo@uef.fi, E-mail: janne.karjalainen@boneindex.fi, E-mail: jukka.liukkonen@gmail.com, E-mail: juha.toyras@uef.fi; Jurvelin, J. S., E-mail: jukka.jurvelin@uef.fi

Purpose: The purpose of this study was to investigate the effect of simultaneous changes in cortical porosity, tissue mineral density, and elastic properties on radial speed of sound (SOS) in cortical bone. The authors applied quantitative pulse-echo (PE) ultrasound techniques that hold much potential especially for screening of osteoporosis at primary healthcare facilities. Currently, most PE measurements of cortical thickness, a well-known indicator of fracture risk, use a predefined estimate for SOS in bone to calculate thickness. Due to variation of cortical bone porosity, the use of a constant SOS value propagates to an unknown error in cortical thickness assessmentmore » by PE ultrasound. Methods: The authors conducted 2.25 and 5.00 MHz focused PE ultrasound time of flight measurements on femoral diaphyses of 18 cadavers in vitro. Cortical porosities of the samples were determined using microcomputed tomography and related to SOS in the samples. Additionally, the effect of cortical bone porosity and mechanical properties of the calcified matrix on SOS was investigated using numerical finite difference time domain simulations. Results: Both experimental measurements and simulations demonstrated significant negative correlation between radial SOS and cortical porosity (R{sup 2} ≥ 0.493, p < 0.01 and R{sup 2} ≥ 0.989, p < 0.01, respectively). When a constant SOS was assumed for cortical bone, the error due to variation of cortical bone porosity (4.9%–16.4%) was about 6% in the cortical thickness assessment in vitro. Conclusions: Use of a predefined, constant value for radial SOS in cortical bone, i.e., neglecting the effect of measured variation in cortical porosity, propagated to an error of 6% in cortical thickness. This error can be critical as characteristic cortical thinning of 1.10% ± 1.06% per yr decreases bending strength of the distal radius and results in increased fragility in postmenopausal women. Provided that the cortical porosity can be estimated in vivo, the relationship between radial SOS and cortical porosity can be utilized and a porosity based radial SOS estimate could be implemented to determine cortical thickness. This would constitute a step toward individualized quantitative ultrasound diagnostics of osteoporosis.« less

What lies beneath: sub-articular long bone shape scaling in eutherian mammals and saurischian dinosaurs suggests different locomotor adaptations for gigantism.

PubMed

Bonnan, Matthew F; Wilhite, D Ray; Masters, Simon L; Yates, Adam M; Gardner, Christine K; Aguiar, Adam

2013-01-01

Eutherian mammals and saurischian dinosaurs both evolved lineages of huge terrestrial herbivores. Although significantly more saurischian dinosaurs were giants than eutherians, the long bones of both taxa scale similarly and suggest that locomotion was dynamically similar. However, articular cartilage is thin in eutherian mammals but thick in saurischian dinosaurs, differences that could have contributed to, or limited, how frequently gigantism evolved. Therefore, we tested the hypothesis that sub-articular bone, which supports the articular cartilage, changes shape in different ways between terrestrial mammals and dinosaurs with increasing size. Our sample consisted of giant mammal and reptile taxa (i.e., elephants, rhinos, sauropods) plus erect and non-erect outgroups with thin and thick articular cartilage. Our results show that eutherian mammal sub-articular shape becomes narrow with well-defined surface features as size increases. In contrast, this region in saurischian dinosaurs expands and remains gently convex with increasing size. Similar trends were observed in non-erect outgroup taxa (monotremes, alligators), showing that the trends we report are posture-independent. These differences support our hypothesis that sub-articular shape scales differently between eutherian mammals and saurischian dinosaurs. Our results show that articular cartilage thickness and sub-articular shape are correlated. In mammals, joints become ever more congruent and thinner with increasing size, whereas archosaur joints remained both congruent and thick, especially in sauropods. We suggest that gigantism occurs less frequently in mammals, in part, because joints composed of thin articular cartilage can only become so congruent before stress cannot be effectively alleviated. In contrast, frequent gigantism in saurischian dinosaurs may be explained, in part, by joints with thick articular cartilage that can deform across large areas with increasing load.

What Lies Beneath: Sub-Articular Long Bone Shape Scaling in Eutherian Mammals and Saurischian Dinosaurs Suggests Different Locomotor Adaptations for Gigantism

PubMed Central

Bonnan, Matthew F.; Wilhite, D. Ray; Masters, Simon L.; Yates, Adam M.; Gardner, Christine K.; Aguiar, Adam

2013-01-01

Eutherian mammals and saurischian dinosaurs both evolved lineages of huge terrestrial herbivores. Although significantly more saurischian dinosaurs were giants than eutherians, the long bones of both taxa scale similarly and suggest that locomotion was dynamically similar. However, articular cartilage is thin in eutherian mammals but thick in saurischian dinosaurs, differences that could have contributed to, or limited, how frequently gigantism evolved. Therefore, we tested the hypothesis that sub-articular bone, which supports the articular cartilage, changes shape in different ways between terrestrial mammals and dinosaurs with increasing size. Our sample consisted of giant mammal and reptile taxa (i.e., elephants, rhinos, sauropods) plus erect and non-erect outgroups with thin and thick articular cartilage. Our results show that eutherian mammal sub-articular shape becomes narrow with well-defined surface features as size increases. In contrast, this region in saurischian dinosaurs expands and remains gently convex with increasing size. Similar trends were observed in non-erect outgroup taxa (monotremes, alligators), showing that the trends we report are posture-independent. These differences support our hypothesis that sub-articular shape scales differently between eutherian mammals and saurischian dinosaurs. Our results show that articular cartilage thickness and sub-articular shape are correlated. In mammals, joints become ever more congruent and thinner with increasing size, whereas archosaur joints remained both congruent and thick, especially in sauropods. We suggest that gigantism occurs less frequently in mammals, in part, because joints composed of thin articular cartilage can only become so congruent before stress cannot be effectively alleviated. In contrast, frequent gigantism in saurischian dinosaurs may be explained, in part, by joints with thick articular cartilage that can deform across large areas with increasing load. PMID:24130690

Increase of cortical bone after a cementless long stem in periprosthetic fractures.

PubMed

García-Rey, Eduardo; García-Cimbrelo, Eduardo; Cruz-Pardos, Ana; Madero, Rosário

2013-12-01

Healing and functional recovery have been reported using an extensively porous-coated stem in Vancouver B2 and B3 periprosthetic fractures; however, loss of cortical bone has been observed when using these stems in revision surgery for aseptic loosening. However, it is unclear whether this bone loss influences subsequent loosening. We analyze the healing fracture rate and whether the radiographic changes observed around and extensively porous-coated stem used for periprosthetic fractures affect function or loosening. We retrospectively reviewed 35 patients with periprosthetic fractures (20 Vancouver B2 and 15 Vancouver B3). Patients' mean age at surgery was 80 years (range, 51-86 years). No cortical struts were used in this series. We evaluated radiographs for signs of loosening or subsidence. The cortical index and the femoral cortical width were measured at different levels on the immediate pre- and postoperative radiographs and at different periods of followup. The minimum followup was 3 years (mean, 8.3 years; range, 3-17 years). All fractures had healed, and all stems were clinically and radiographically stable at the end of followup. Nineteen hips showed nonprogressive radiographic subsidence during the first 3 postoperative months without clinical consequences. The cortical index and the lateral and medial cortical thickness increased over time. Increase of femoral cortex thicknesses was greater in cases with moderate preoperative osteoporosis and in cases with stems less than 16 mm in thickness. Our data suggest an extensively porous-coated stem for Vancouver B2 and B3 periprosthetic fractures leads to a high rate of union and stable fixation. Cortical index and lateral cortex thickness increased in these patients with periprosthetic fractures. Patients with moderate osteoporosis and those using thin stems showed a major increase in femoral cortex thickness over time.

Effect of Dietary Phytase Supplementation on Bone and Hyaline Cartilage Development of Broilers Fed with Organically Complexed Copper in a Cu-Deficient Diet.

PubMed

Muszyński, Siemowit; Tomaszewska, Ewa; Kwiecień, Małgorzata; Dobrowolski, Piotr; Tomczyk, Agnieszka

2018-04-01

Tibial mechanical, chemical, and histomorphometrical traits were investigated for growing male Ross 308 broiler chickens fed diets that had copper (Cu) from organic source at a lowered level of 25% of the daily requirement (4 mg kg -1 of a premix) with or without phytase. Dietary treatments were control non-copper, non-phytase group (0 Suppl); 4 mg kg -1 Cu non-phytase group (25%Cu); and 4 mg kg -1 Cu + 500 FTU kg -1 phytase group (25%Cu + phyt). The results show that birds fed with the addition of phytase exhibited improved weight gain and final body weight and had increased serum IGF-1 and osteocalcin concentrations. The serum concentration of Cu and P did not differ between groups; however, Ca concentration decreased in the 25%Cu + phyt group when compared to the 25%Cu group. Added Cu increased bone Ca, P, Cu, and ash content in Cu-supplemented groups, but bone weight and length increased only by the addition of phytase. Bone geometry, yield, and ultimate strengths were affected by Cu and phytase addition. A decrease of the elastic stress and ultimate stress of the tibia in Cu-supplemented groups was observed. The histomorphometric analysis showed a positive effect of Cu supplementation on real bone volume and trabecular thickness in the tibia metaphyseal trabeculae; additionally, phytase increased the trabeculea number. The supplementation with Cu significantly increased the total articular cartilage and growth plate cartilage thickness; however, the changes in thickness of particular zones were dependent upon phytase addition. In summary, dietary Cu supplements given to growing broilers with Cu in their diet restricted to 25% of the daily requirement had a positive effect on bone metabolism, and phytase supplementation additionally improved cartilage development.

Bone geometry, volumetric bone mineral density, microarchitecture and estimated bone strength in Caucasian females with systemic lupus erythematosus. A cross-sectional study using HR-pQCT.

PubMed

Hansen, Stinus; Gudex, Claire; Åhrberg, Fabian; Brixen, Kim; Voss, Anne

2014-12-01

Patients with systemic lupus erythematosus (SLE) have an increased risk of fracture. We used high resolution peripheral quantitative computed tomography (HR-pQCT) to measure bone geometry, volumetric bone mineral density (vBMD), cortical and trabecular microarchitecture and estimated bone strength by finite element analysis (FEA) at the distal radius and tibia to assess bone characteristics beyond BMD that may contribute to the increased risk of fracture. Thirty-three Caucasian women with SLE (median age 48, range 21-64 years) and 99 controls (median age 45, range 21-64 years) were studied. Groups were comparable in radius regarding geometry and vBMD, but SLE patients had lower trabecular number (-7%, p < 0.05), higher trabecular separation (13%, p < 0.05) and lower FEA-estimated failure load compared to controls (-10%, p < 0.05). In tibia, SLE patients had lower total vBMD (-11%, p < 0.01), cortical area (-14%, p < 0.001) and cortical thickness (-16%, p < 0.001) and higher trabecular area (8%, p < 0.05). In subgroup analyses of the premenopausal participants (SLE n = 21, controls n = 63), SLE patients had significantly lower trabecular bone volume fraction [(BV/TV); -17%, p < 0.01], trabecular number (-9%, p < 0.01), trabecular thickness (-9%, p < 0.05) and higher trabecular separation (13%, p < 0.01) and trabecular network inhomogeneity (14%, p < 0.05) in radius along with lower BV/TV (-15%, p < 0.01) and higher trabecular separation (11%, p < 0.05) in tibia. FEA-estimated bone strength was lower in both radius (-11%, p < 0.01) and tibia (-10%, p < 0.05). In conclusion, Caucasian women with SLE compared to controls had fewer and more widely separated trabeculae and lower estimated bone strength in radius and lower total vBMD, cortical area and thickness in tibia.

Evaluation of cortical bone mass, thickness and density by z-scores in osteopenic conditions and in relation to menopause and estrogen treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meema, S.; Meema, H.E.

1982-08-01

Z-scores express, differences from normals in standard deviation units, and are particularly useful for comparison of changes where normal values are age- and sex-dependent. We determined z-scores for bone mineral mass, cortical thickness, and bone mineral density in the radius in various conditions and diseases in both sexes. In the males, z-scores were calculated for age, but in the females z-scores for menopausal status (years postmenopausal exclusive of years on estrogen treatment) were found to be more appropriate. With few exceptions, changes in a disease were of a similar order in both sexes. For bone minerals mass few mean z-scoresmore » were significantly increased, but diseases with significantly decreased mean z-scores were numerous. The usefulness of z-scores in diagnosis and study of metabolic bone disease is discussed.« less

Female Mice Lacking Estrogen Receptor-α in Hypothalamic Proopiomelanocortin (POMC) Neurons Display Enhanced Estrogenic Response on Cortical Bone Mass.

PubMed

Farman, H H; Windahl, S H; Westberg, L; Isaksson, H; Egecioglu, E; Schele, E; Ryberg, H; Jansson, J O; Tuukkanen, J; Koskela, A; Xie, S K; Hahner, L; Zehr, J; Clegg, D J; Lagerquist, M K; Ohlsson, C

2016-08-01

Estrogens are important regulators of bone mass and their effects are mainly mediated via estrogen receptor (ER)α. Central ERα exerts an inhibitory role on bone mass. ERα is highly expressed in the arcuate (ARC) and the ventromedial (VMN) nuclei in the hypothalamus. To test whether ERα in proopiomelanocortin (POMC) neurons, located in ARC, is involved in the regulation of bone mass, we used mice lacking ERα expression specifically in POMC neurons (POMC-ERα(-/-)). Female POMC-ERα(-/-) and control mice were ovariectomized (OVX) and treated with vehicle or estradiol (0.5 μg/d) for 6 weeks. As expected, estradiol treatment increased the cortical bone thickness in femur, the cortical bone mechanical strength in tibia and the trabecular bone volume fraction in both femur and vertebrae in OVX control mice. Importantly, the estrogenic responses were substantially increased in OVX POMC-ERα(-/-) mice compared with the estrogenic responses in OVX control mice for cortical bone thickness (+126 ± 34%, P < .01) and mechanical strength (+193 ± 38%, P < .01). To test whether ERα in VMN is involved in the regulation of bone mass, ERα was silenced using an adeno-associated viral vector. Silencing of ERα in hypothalamic VMN resulted in unchanged bone mass. In conclusion, mice lacking ERα in POMC neurons display enhanced estrogenic response on cortical bone mass and mechanical strength. We propose that the balance between inhibitory effects of central ERα activity in hypothalamic POMC neurons in ARC and stimulatory peripheral ERα-mediated effects in bone determines cortical bone mass in female mice.

The Effect of Naturally Occurring Chronic Kidney Disease on the Micro-Structural and Mechanical Properties of Bone

PubMed Central

Meltzer, Hagar; Milrad, Moran; Brenner, Ori; Atkins, Ayelet; Shahar, Ron

2014-01-01

Chronic kidney disease (CKD) is a growing public health concern worldwide, and is associated with marked increase of bone fragility. Previous studies assessing the effect of CKD on bone quality were based on biopsies from human patients or on laboratory animal models. Such studies provide information of limited relevance due to the small size of the samples (biopsies) or the non-physiologic CKD syndrome studied (rodent models with artificially induced CKD). Furthermore, the type, architecture, structure and biology of the bone of rodents are remarkably different from human bones; therefore similar clinicopathologic circumstances may affect their bones differently. We describe the effects of naturally occurring CKD with features resembling human CKD on the skeleton of cats, whose bone biology, structure and composition are remarkably similar to those of humans. We show that CKD causes significant increase of resorption cavity density compared with healthy controls, as well as significantly lower cortical mineral density, cortical cross-sectional area and cortical cross-sectional thickness. Young's modulus, yield stress, and ultimate stress of the cortical bone material were all significantly decreased in the skeleton of CKD cats. Cancellous bone was also affected, having significantly lower trabecular thickness and bone volume over total volume in CKD cats compared with controls. This study shows that naturally occurring CKD has deleterious effects on bone quality and strength. Since many similarities exist between human and feline CKD patients, including the clinicopathologic features of the syndrome and bone microarchitecture and biology, these results contribute to better understanding of bone abnormalities associated with CKD. PMID:25333360

Antiosteoporotic Effect of Combined Extract of Morus alba and Polygonum odoratum

PubMed Central

Sungkamanee, Sudarat; Thukham-mee, Wipawee

2014-01-01

Due to the limitation of osteoporosis therapy, the alternative therapies from natural sources have been considered. In this study, we aimed to determine the antiosteoporotic effect of the combined extract of Morus alba and Polygonum odoratum leaves. Ovariectomized rats, weighing 200–220 g, were orally given the combined extract at doses of 5, 150, and 300 mg·kg−1 BW for 3 months. At the end of study, blood was collected to determine serum osteocalcin, calcium, and alkaline phosphatase level. In addition, tibia bone was isolated to determine bone oxidative stress markers, cortical bone thickness, and density of osteoblast. The combined extract decreased oxidative stress and osteoclast density but increased osteoblast density and cortical thickness. The elevation of serum calcium, alkaline phosphatase, and osteocalcin was also observed. These results suggested the antiosteoporotic effect of the combined extract via the increased growth formation together with the suppression of bone resorption. However, further studies concerning chronic toxicity and the underlying mechanism are required. PMID:25478061

Cross-sex testosterone therapy in ovariectomized mice: addition of low-dose estrogen preserves bone architecture.

PubMed

Goetz, Laura G; Mamillapalli, Ramanaiah; Devlin, Maureen J; Robbins, Amy E; Majidi-Zolbin, Masoumeh; Taylor, Hugh S

2017-11-01

Cross-sex hormone therapy (XHT) is widely used by transgender people to alter secondary sex characteristics to match their desired gender presentation. Here, we investigate the long-term effects of XHT on bone health using a murine model. Female mice underwent ovariectomy at either 6 or 10 wk and began weekly testosterone or vehicle injections. Dual-energy X-ray absorptiometry (DXA) was performed (20 wk) to measure bone mineral density (BMD), and microcomputed tomography was performed to compare femoral cortical and trabecular bone architecture. The 6-wk testosterone group had comparable BMD with controls by DXA but reduced bone volume fraction, trabecular number, and cortical area fraction and increased trabecular separation by microcomputed tomography. Ten-week ovariectomy/XHT maintained microarchitecture, suggesting that estrogen is critical for bone acquisition during adolescence and that late, but not early, estrogen loss can be sufficiently replaced by testosterone alone. Given these findings, we then compared effects of testosterone with effects of weekly estrogen or combined testosterone/low-dose estrogen treatment after a 6-wk ovariectomy. Estrogen treatment increased spine BMD and microarchitecture, including bone volume fraction, trabecular number, trabecular thickness, and connectivity density, and decreased trabecular separation. Combined testosterone-estrogen therapy caused similar increases in femur and spine BMD and improved architecture (increased bone volume fraction, trabecular number, trabecular thickness, and connectivity density) to estrogen therapy and were superior compared with mice treated with testosterone only. These results demonstrate estradiol is critical for bone acquisition and suggest a new cross-sex hormone therapy adding estrogens to testosterone treatments with potential future clinical implications for treating transgender youth or men with estrogen deficiency. Copyright © 2017 the American Physiological Society.

Trabecular Bone Score (TBS)—A Novel Method to Evaluate Bone Microarchitectural Texture in Patients With Primary Hyperparathyroidism

PubMed Central

Boutroy, Stephanie; Zhang, Chiyuan; McMahon, Donald Jay; Zhou, Bin; Wang, Ji; Udesky, Julia; Cremers, Serge; Sarquis, Marta; Guo, Xiang-Dong Edward; Hans, Didier

2013-01-01

Context: In the milder form of primary hyperparathyroidism (PHPT), cancellous bone, represented by areal bone mineral density at the lumbar spine by dual-energy x-ray absorptiometry (DXA), is preserved. This finding is in contrast to high-resolution peripheral quantitative computed tomography (HRpQCT) results of abnormal trabecular microstructure and epidemiological evidence for increased overall fracture risk in PHPT. Because DXA does not directly measure trabecular bone and HRpQCT is not widely available, we used trabecular bone score (TBS), a novel gray-level textural analysis applied to spine DXA images, to estimate indirectly trabecular microarchitecture. Objective: The purpose of this study was to assess TBS from spine DXA images in relation to HRpQCT indices and bone stiffness in radius and tibia in PHPT. Design and Setting: This was a cross-sectional study conducted in a referral center. Patients: Participants were 22 postmenopausal women with PHPT. Main Outcome Measures: Outcomes measured were areal bone mineral density by DXA, TBS indices derived from DXA images, HRpQCT standard measures, and bone stiffness assessed by finite element analysis at distal radius and tibia. Results: TBS in PHPT was low at 1.24, representing abnormal trabecular microstructure (normal ≥1.35). TBS was correlated with whole bone stiffness and all HRpQCT indices, except for trabecular thickness and trabecular stiffness at the radius. At the tibia, correlations were observed between TBS and volumetric densities, cortical thickness, trabecular bone volume, and whole bone stiffness. TBS correlated with all indices of trabecular microarchitecture, except trabecular thickness, after adjustment for body weight. Conclusion: TBS, a measurement technology readily available by DXA, shows promise in the clinical assessment of trabecular microstructure in PHPT. PMID:23526463

Influence of residual bone thickness on primary stability of hybrid self-tapping and cylindric non-self-tapping implants in vitro.

PubMed

Divac, Marija; Stawarczyk, Bogna; Sahrmann, Philipp; Attin, Thomas; Schmidlin, Patrick R

2013-01-01

To assess the primary stability of a hybrid self-tapping implant and a cylindric non-self-tapping implant in an in vitro test model using polyurethane foam. Eighty standardized blocks of cellular rigid polyurethane foam, 2 cm long and 1 cm wide, with different thicknesses of 2, 4, 6, and 9 mm (n = 10 per group) were cut. Two implant systems--a hybrid self-tapping (Tapered Effect [TE], Straumann) and a cylindric non-self-tapping (Standard Plus [SP] Wide Neck, Straumann) were placed in the block specimens. Subsequently, resonance frequency analysis (RFA) was performed. The RFA measurements were made in triplicate on four aspects of each implant (mesial, distal, buccal, and oral), and the mean RFA value was calculated. Subsequently, the tensile load of the implants was determined by pull-out tests. The data were analyzed using one-way and two-way analysis of variance followed by a post hoc Scheffe test and a t test (α = .05). Additionally, the simple linear correlation between the RFA and tensile load values was evaluated. No statistically significant differences were found between TE and SP in terms of RFA at different bone thicknesses. Starting from a bone thickness of 4 mm, TE implants showed significantly higher tensile load compared to SP implants (P = .016 to .040). A correlation was found between the RFA measurements and tensile load. Mechanically stable placement is possible with TE and SP implants in a trabecular bone model. RFA and tensile load increased with greater bone thickness.

Microarchitecture of irradiated bone: comparison with healthy bone

NASA Astrophysics Data System (ADS)

Bléry, Pauline; Amouriq, Yves; Guédon, Jeanpierre; Pilet, Paul; Normand, Nicolas; Durand, Nicolas; Espitalier, Florent; Arlicot, Aurore; Malard, Olivier; Weiss, Pierre

2012-03-01

The squamous cell carcinomas of the upper aero-digestive tract represent about ten percent of cancers. External radiation therapy leads to esthetic and functional consequences, and to a decrease of the bone mechanical abilities. For these patients, the oral prosthetic rehabilitation, including possibilities of dental implant placement, is difficult. The effects of radiotherapy on bone microarchitecture parameters are not well known. Thus, the purpose of this study is to assess the effects of external radiation on bone micro architecture in an experimental model of 25 rats using micro CT. 15 rats were irradiated on the hind limbs by a single dose of 20 Grays, and 10 rats were non irradiated. Images of irradiated and healthy bone were compared. Bone microarchitecture parameters (including trabecular thickness, trabecular number, trabecular separation, connectivity density and tissue and bone volume) between irradiated and non-irradiated bones were calculated and compared using a Mann and Whitney test. After 7 and 12 weeks, images of irradiated and healthy bone are different. Differences on the irradiated and the healthy bone populations exhibit a statistical significance. Trabecular number, connectivity density and closed porosity are less important on irradiated bone. Trabecular thickness and separation increase for irradiated bone. These parameters indicate a decrease of irradiated bone properties. Finally, the external irradiation induces changes on the bone micro architecture. This knowledge is of prime importance for better oral prosthetic rehabilitation, including implant placement.

Fibroblast growth factor-21 restores insulin sensitivity but induces aberrant bone microstructure in obese insulin-resistant rats.

PubMed

Charoenphandhu, Narattaphol; Suntornsaratoon, Panan; Krishnamra, Nateetip; Sa-Nguanmoo, Piangkwan; Tanajak, Pongpun; Wang, Xiaojie; Liang, Guang; Li, Xiaokun; Jiang, Chao; Chattipakorn, Nipon; Chattipakorn, Siriporn

2017-03-01

Fibroblast growth factor (FGF)-21 is a potent endocrine factor that improves insulin resistance and obesity-associated metabolic disorders. However, concomitant activation of peroxisome proliferator-activated receptor-γ by FGF-21 makes bone susceptible to osteopenia and fragility fracture. Since an increase in body weight often induced adaptive change in bone by making it resistant to fracture, it was unclear whether FGF-21 would still induce bone defects in overweight rats. Therefore, the present study aimed to investigate bone microstructure and its mechanical properties in high fat diet (HF)-fed rats treated with 0.1 mg/kg/day FGF-21. Eighteen male rats were divided into two groups to receive either a normal diet or HF for 12 weeks. HF rats were then divided into two subgroups to receive either vehicle or FGF-21 for 4 weeks. The results showed that HF led to obesity, dyslipidemia and insulin resistance, as indicated by hyperinsulinemia with euglycemia. In HF rats, there was an increase in tibial yield displacement (an indicator of ability to be deformed without losing toughness, as determined by 3-point bending) without changes in tibial trabecular volumetric bone mineral density (vBMD) or cortical bone parameters, e.g., cortical thickness and bone area. FGF-21 treatment strongly improved the metabolic parameters and increased insulin sensitivity in HF rats. However, FGF-21-treated HF rats showed lower yield displacement, trabecular vBMD, trabecular bone volume, trabecular thickness, and osteoblast surface compared with vehicle-treated HF rats. These findings suggest that, despite being a potent antagonist of insulin resistance and visceral fat accumulation, FGF-21 is associated with bone defects in HF rats.

Review of vascularised bone tissue-engineering strategies with a focus on co-culture systems.

PubMed

Liu, Yuchun; Chan, Jerry K Y; Teoh, Swee-Hin

2015-02-01

Poor angiogenesis within tissue-engineered grafts has been identified as a main challenge limiting the clinical introduction of bone tissue-engineering (BTE) approaches for the repair of large bone defects. Thick BTE grafts often exhibit poor cellular viability particularly at the core, leading to graft failure and lack of integration with host tissues. Various BTE approaches have been explored for improving vascularisation in tissue-engineered constructs and are briefly discussed in this review. Recent investigations relating to co-culture systems of endothelial and osteoblast-like cells have shown evidence of BTE efficacy in increasing vascularization in thick constructs. This review provides an overview of key concepts related to bone formation and then focuses on the current state of engineered vascularized co-culture systems using bone repair as a model. It will also address key questions regarding the generation of clinically relevant vascularized bone constructs as well as potential directions and considerations for research with the objective of pursuing engineered co-culture systems in other disciplines of vascularized regenerative medicine. The final objective is to generate serious and functional long-lasting vessels for sustainable angiogenesis that will enable enhanced cellular survival within thick voluminous bone grafts, thereby aiding in bone formation and remodelling in the long term. However, more evidence about the quality of blood vessels formed and its associated functional improvement in bone formation as well as a mechanistic understanding of their interactions are necessary for designing better therapeutic strategies for translation to clinical settings. Copyright © 2012 John Wiley & Sons, Ltd.

Profile changes after conventional and chin shield genioplasty

PubMed Central

Singh, Stuti; Mehrotra, Divya; Mohammad, S.

2014-01-01

Introduction The aim of this study was to compare the profile changes after conventional and chin shield genioplasty. Material and method 20 patients with retruded chin were randomly allocated to two different groups. The experimental group had chin shield osteotomy with interposition of hydroxyapatite collagen graft soaked in platelet rich plasma, while the controls had a conventional genioplasty. The outcome variables evaluated were lip seal, chin thickness, mandibular base length, SNB, labiomental angle, anterior lower facial height, transverse chin shift, and complications. Results There was an increase in chin thickness among all, but a significant increase in anterior lower facial height was seen in the experimental group only. There was no statistically significant difference in satisfaction score in both groups. Conclusion Chin shield genioplasty provides horizontal as well as vertical lengthening of chin without deepening of the mentolabial fold. Hydroxyapatite collagen bone graft and platelet rich plasma promote healing, induce bone formation and reduce bone resorption. PMID:25737921

Profile changes after conventional and chin shield genioplasty.

PubMed

Singh, Stuti; Mehrotra, Divya; Mohammad, S

2014-01-01

The aim of this study was to compare the profile changes after conventional and chin shield genioplasty. 20 patients with retruded chin were randomly allocated to two different groups. The experimental group had chin shield osteotomy with interposition of hydroxyapatite collagen graft soaked in platelet rich plasma, while the controls had a conventional genioplasty. The outcome variables evaluated were lip seal, chin thickness, mandibular base length, SNB, labiomental angle, anterior lower facial height, transverse chin shift, and complications. There was an increase in chin thickness among all, but a significant increase in anterior lower facial height was seen in the experimental group only. There was no statistically significant difference in satisfaction score in both groups. Chin shield genioplasty provides horizontal as well as vertical lengthening of chin without deepening of the mentolabial fold. Hydroxyapatite collagen bone graft and platelet rich plasma promote healing, induce bone formation and reduce bone resorption.

In vivo microcomputed tomography evaluation of rat alveolar bone and root resorption during orthodontic tooth movement.

PubMed

Ru, Nan; Liu, Sean Shih-Yao; Zhuang, Li; Li, Song; Bai, Yuxing

2013-05-01

To observe the real-time microarchitecture changes of the alveolar bone and root resorption during orthodontic treatment. A 10 g force was delivered to move the maxillary left first molars mesially in twenty 10-week-old rats for 14 days. The first molar and adjacent alveolar bone were scanned using in vivo microcomputed tomography at the following time points: days 0, 3, 7, and 14. Microarchitecture parameters, including bone volume fraction, structure model index, trabecular thickness, trabecular number, and trabecular separation of alveolar bone, were measured on the compression and tension side. The total root volume was measured, and the resorption crater volume at each time point was calculated. Univariate repeated measures analysis of variance with Bonferroni corrections were performed to compare the differences in each parameter between time points with significance level at P < .05. From day 3 to day 7, bone volume fraction, structure model index, trabecular thickness, and trabecular separation decreased significantly on the compression side, but the same parameters increased significantly on the tension side from day 7 to day 14. Root resorption volume of the mesial root increased significantly on day 7 of orthodontic loading. Real-time root and bone resorption during orthodontic movement can be observed in 3 dimensions using in vivo micro-CT. Alveolar bone resorption and root resorption were observed mostly in the apical third on day 7 on the compression side; bone formation was observed on day 14 on the tension side during orthodontic tooth movement.

Skeletal site-specific effects of whole body vibration in mature rats: from deleterious to beneficial frequency-dependent effects.

PubMed

Pasqualini, Marion; Lavet, Cédric; Elbadaoui, Mohamed; Vanden-Bossche, Arnaud; Laroche, Norbert; Gnyubkin, Vasily; Vico, Laurence

2013-07-01

Whole body vibration (WBV) is receiving increasing interest as an anti-osteoporotic prevention strategy. In this context, selective effects of different frequency and acceleration magnitude modalities on musculoskeletal responses need to be better defined. Our aim was to investigate the bone effects of different vibration frequencies at constant g level. Vertical WBV was delivered at 0.7 g (peak acceleration) and 8, 52 or 90 Hz sinusoidal vibration to mature male rats 10 min daily for 5 days/week for 4 weeks. Peak accelerations measured by skin or bone-mounted accelerometers at L2 vertebral and tibia crest levels revealed similar values between adjacent skin and bone sites. Local accelerations were greater at 8 Hz compared with 52 and 90 Hz and were greater in vertebra than tibia for all the frequencies tested. At 52 Hz, bone responses were mainly seen in L2 vertebral body and were characterized by trabecular reorganization and stimulated mineral apposition rate (MAR) without any bone volume alteration. At 90 Hz, axial and appendicular skeletons were affected as were the cortical and trabecular compartments. Cortical thickness increased in femur diaphysis (17%) along with decreased porosity; trabecular bone volume increased at distal femur metaphysis (23%) and even more at L2 vertebral body (32%), along with decreased SMI and increased trabecular connectivity. Trabecular thickness increased at the tibia proximal metaphysis. Bone cellular activities indicated a greater bone formation rate, which was more pronounced at vertebra (300%) than at long bone (33%). Active bone resorption surfaces were unaffected. At 8 Hz, however, hyperosteoidosis with reduced MAR along with increased resorption surfaces occurred in the tibia; hyperosteoidosis and trend towards decreased MAR was also seen in L2 vertebra. Trabecular bone mineral density was decreased at femur and tibia. Thus the most favorable regimen is 90 Hz, while deleterious effects were seen at 8 Hz. We concluded that the skeleton is frequency-scalable, thus highlighting the importance of WBV regimen conditions and suggesting that cautions are required for frequencies less than 10 Hz, at least in rats. Copyright © 2013 Elsevier Inc. All rights reserved.

Effects of Skin Thickness on Cochlear Input Signal using Transcutaneous Bone Conduction Implants

PubMed Central

Mattingly, Jameson K.; Greene, Nathaniel T.; Jenkins, Herman A.; Tollin, Daniel J.; Easter, James R.; Cass, Stephen P.

2015-01-01

Hypothesis Intracochlear sound pressures (PIC) and velocity measurements of the stapes, round window, and promontory (VStap/RW/Prom) will show frequency dependent attenuation using magnet-based, transcutaneous bone-conduction implants (TCBCI) in comparison to direct-connect, skin-penetrating implants (DCBCI). Background TCBCIs have recently been introduced as alternatives to DCBCIs. Clinical studies have demonstrated elevated high-frequency thresholds for TCBCIs as compared to DCBCIs; however, little data exists examining the direct effect of skin thickness on the cochlear input signal using TCBCIs. Methods Using seven cadveric heads, PIC was measured in the scala vestibuli and tympani with fiber-optic pressure sensors concurrently with VStap/RW/Prom via laser Doppler vibrometry. Ipsilateral titanium implant fixtures were placed and connected to either a DCBCI or TCBCI. Soft tissue flaps with varying thicknesses (no flap, 3, 6, and 9 mm) were placed successively between the magnetic plate and sound processor magnet. A bone-conduction transducer coupled to custom software provided pure tone stimuli between 120 to 10240 Hz. Results Stimulation via the DCBCI produced the largest response magnitudes. The TCBCI showed similar PSV/ST and VStap/RW/Prom with no intervening flap, and a frequency-dependent, non-linear reduction of magnitude with increasing flap thickness. Phase shows a comparable dependence on transmission delay as the acoustic baseline, and the slope steepens at higher frequencies as flap thickness increases suggesting a longer group delay. Conclusions Proper soft tissue management is critical to optimize the cochlear input signal. The skin thickness related effects on cochlear response magnitudes should be taken into account when selecting patients for a TCBCI. PMID:26164446

Effects of Loading Duration and Short Rest Insertion on Cancellous and Cortical Bone Adaptation in the Mouse Tibia

PubMed Central

Yang, Haisheng; Embry, Rachel E.; Main, Russell P.

2017-01-01

The skeleton’s osteogenic response to mechanical loading can be affected by loading duration and rest insertion during a series of loading events. Prior animal loading studies have shown that the cortical bone response saturates quickly and short rest insertions between load cycles can enhance cortical bone formation. However, it remains unknown how loading duration and short rest insertion affect load-induced osteogenesis in the mouse tibial compressive loading model, and particularly in cancellous bone. To address this issue, we applied cyclic loading (-9 N peak load; 4 Hz) to the tibiae of three groups of 16 week-old female C57BL/6 mice for two weeks, with a different number of continuous load cycles applied daily to each group (36, 216 and 1200). A fourth group was loaded under 216 daily load cycles with a 10 s rest insertion after every fourth cycle. We found that as few as 36 load cycles per day were able to induce osteogenic responses in both cancellous and cortical bone. Furthermore, while cortical bone area and thickness continued to increase through 1200 cycles, the incremental increase in the osteogenic response decreased as load number increased, indicating a reduced benefit of the increasing number of load cycles. In the proximal metaphyseal cancellous bone, trabecular thickness increased with load up to 216 cycles. We also found that insertion of a 10 s rest between load cycles did not improve the osteogenic response of the cortical or cancellous tissues compared to continuous loading in this model given the age and sex of the mice and the loading parameters used here. These results suggest that relatively few load cycles (e.g. 36) are sufficient to induce osteogenic responses in both cortical and cancellous bone in the mouse tibial loading model. Mechanistic studies using the mouse tibial loading model to examine bone formation and skeletal mechanobiology could be accomplished with relatively few load cycles. PMID:28076363

Dietary Pseudopurpurin Improves Bone Geometry Architecture and Metabolism in Red-Bone Guishan Goats

PubMed Central

Han, TieSuo; Li, Peng; Wang, JianGuo; Liu, GuoWen; Wang, Zhe; Ge, ChangRong; Gao, ShiZheng

2012-01-01

Red-colored bones were found initially in some Guishan goats in the 1980s, and they were designated red-boned goats. However, it is not understood what causes the red color in the bone, or whether the red material changes the bone geometry, architecture, and metabolism of red-boned goats. Pseudopurpurin was identified in the red-colored material of the bone in red-boned goats by high-performance liquid chromatography–electrospray ionization–mass spetrometry and nuclear magnetic resonance analysis. Pseudopurpurin is one of the main constituents of Rubia cordifolia L, which is eaten by the goats. The assessment of the mechanical properties and micro-computed tomography showed that the red-boned goats displayed an increase in the trabecular volume fraction, trabecular thickness, and the number of trabeculae in the distal femur. The mean thickness, inner perimeter, outer perimeter, and area of the femoral diaphysis were also increased. In addition, the trabecular separation and structure model index of the distal femur were decreased, but the bone mineral density of the whole femur and the mechanical properties of the femoral diaphysis were enhanced in the red-boned goats. Meanwhile, expression of alkaline phosphatase and osteocalcin mRNA was higher, and the ratio of the receptor activator of the nuclear factor kappa B ligand to osteoprotegerin was markedly lower in the bone marrow of the red-boned goats compared with common goats. To confirm further the effect of pseudopurpurin on bone geometry, architecture, and metabolism, Wistar rats were fed diets to which pseudopurpurin was added for 5 months. Similar changes were observed in the femurs of the treated rats. The above results demonstrate that pseudopurpurin has a close affinity with the mineral salts of bone, and consequently a high level of mineral salts in the bone cause an improvement in bone strength and an enhancement in the structure and metabolic functions of the bone. PMID:22624037

A pilot study of laser energy transmission through bone and gingiva.

PubMed

Ng, Doreen Y; Chan, Ambrose K; Dalci, Oyku; Petocz, Peter; Papadopoulou, Alexandra K; Darendeliler, M Ali

2018-06-20

The use of low-level laser therapy is growing in the field of dentistry especially in orthodontics to speed up tooth movement and in implantology to aid osseointegration. In these dental applications, the laser energy needs to penetrate through the periodontium to the target site to stimulate photobiomodulation. The percentage of energy loss when laser is transmitted through the periodontium has not been previously studied. With the use of an 808-nanometer diode laser, the aim was to investigate the percentage loss of laser energy when transmitted through the periodontium to the extraction socket. The percentage energy loss of an 808-nm diode laser through the periodontium was measured in 27 tooth sockets by using a specifically designed photodiode ammeter. For each millimeter of increased bone thickness there was 6.81% reduction in laser energy (95% confidence interval, 5.02% to 8.60%). The gingival thickness had no statistically significant effect on energy penetration. Energy penetration depends markedly on bone thickness and is independent of gingival thickness. To the best of the authors' knowledge, this study is one of the first to investigate laser penetration through the periodontium. Evidence from this study showed that laser energy penetration through the periodontium is markedly affected by bone thickness but less so by gingival thickness. Clinicians need to be aware of the biological factors that could affect laser energy penetration to the target site and adjust their laser dosages accordingly. These findings may guide dental practitioners in selecting the appropriate laser dosage parameters for low-level laser therapy. Copyright © 2018 American Dental Association. Published by Elsevier Inc. All rights reserved.

A novel pyrazole derivative protects from ovariectomy-induced osteoporosis through the inhibition of NADPH oxidase

PubMed Central

Joo, Jung Hee; Huh, Jeong-Eun; Lee, Jee Hyun; Park, Doo Ri; Lee, Yoonji; Lee, Seul Gee; Choi, Sun; Lee, Hwa Jeong; Song, Seong-Won; Jeong, Yongmi; Goo, Ja-Il; Choi, Yongseok; Baek, Hye Kyung; Yi, Sun Shin; Park, Soo Jin; Lee, Ji Eun; Ku, Sae Kwang; Lee, Won Jae; Lee, Kee-In; Lee, Soo Young; Bae, Yun Soo

2016-01-01

Osteoclast cells (OCs) are differentiated from bone marrow-derived macrophages (BMMs) by activation of receptor activator of nuclear factor κB (NF-κB) ligand (RANKL). Activation of NADPH oxidase (Nox) isozymes is involved in RANKL-dependent OC differentiation, implicating Nox isozymes as therapeutic targets for treatment of osteoporosis. Here, we show that a novel pyrazole derivative, Ewha-18278 has high inhibitory potency on Nox isozymes. Blocking the activity of Nox with Ewha-18278 inhibited the responses of BMMs to RANKL, including reactive oxygen species (ROS) generation, activation of mitogen-activated protein (MAP) kinases and NF-κB, and OC differentiation. To evaluate the anti-osteoporotic function of Ewha-18278, the derivative was applied to estrogen-deficient ovariectomized (OVX) ddY mice. Oral administration of Ewha-18278 (10 mg/kg/daily, 4 weeks) into the mice recovered bone mineral density, trabecular bone volume, trabecular bone length, number and thickness, compared to control OVX ddY mice. Moreover, treatment of OVX ddY mice with Ewha-18278 increased bone strength by increasing cortical bone thickness. We provide that Ewha-18278 displayed Nox inhibition and blocked the RANKL-dependent cell signaling cascade leading to reduced differentiation of OCs. Our results implicate Ewha-18278 as a novel therapeutic agent for the treatment of osteoporosis. PMID:26975635

Mathematical simulations of photon interactions using Monte Carlo analysis to evaluate the uncertainty associated with in vivo K X-ray fluorescence measurements of stable lead in bone

NASA Astrophysics Data System (ADS)

Lodwick, Camille J.

This research utilized Monte Carlo N-Particle version 4C (MCNP4C) to simulate K X-ray fluorescent (K XRF) measurements of stable lead in bone. Simulations were performed to investigate the effects that overlying tissue thickness, bone-calcium content, and shape of the calibration standard have on detector response in XRF measurements at the human tibia. Additional simulations of a knee phantom considered uncertainty associated with rotation about the patella during XRF measurements. Simulations tallied the distribution of energy deposited in a high-purity germanium detector originating from collimated 88 keV 109Cd photons in backscatter geometry. Benchmark measurements were performed on simple and anthropometric XRF calibration phantoms of the human leg and knee developed at the University of Cincinnati with materials proven to exhibit radiological characteristics equivalent to human tissue and bone. Initial benchmark comparisons revealed that MCNP4C limits coherent scatter of photons to six inverse angstroms of momentum transfer and a Modified MCNP4C was developed to circumvent the limitation. Subsequent benchmark measurements demonstrated that Modified MCNP4C adequately models photon interactions associated with in vivo K XRF of lead in bone. Further simulations of a simple leg geometry possessing tissue thicknesses from 0 to 10 mm revealed increasing overlying tissue thickness from 5 to 10 mm reduced predicted lead concentrations an average 1.15% per 1 mm increase in tissue thickness (p < 0.0001). An anthropometric leg phantom was mathematically defined in MCNP to more accurately reflect the human form. A simulated one percent increase in calcium content (by mass) of the anthropometric leg phantom's cortical bone demonstrated to significantly reduce the K XRF normalized ratio by 4.5% (p < 0.0001). Comparison of the simple and anthropometric calibration phantoms also suggested that cylindrical calibration standards can underestimate lead content of a human leg up to 4%. The patellar bone structure in which the fluorescent photons originate was found to vary dramatically with measurement angle. The relative contribution of lead signal from the patella declined from 65% to 27% when rotated 30°. However, rotation of the source-detector about the patella from 0 to 45° demonstrated no significant effect on the net K XRF response at the knee.

Estrogens are essential for male pubertal periosteal bone expansion.

PubMed

Bouillon, Roger; Bex, Marie; Vanderschueren, Dirk; Boonen, Steven

2004-12-01

The skeletal response to estrogen therapy was studied in a 17-yr-old boy with congenital aromatase deficiency. As expected, estrogen therapy (1 mg estradiol valeriate/d from age 17 until 20 yr) normalized total and free testosterone and reduced the rate of bone remodeling. Dual-energy x-ray absorptiometry-assessed areal bone mineral density (BMD) of the lumbar spine and femoral neck increased significantly (by 23% and 14%, respectively), but peripheral quantitative computed tomography at the ultradistal radius revealed no gain of either trabecular or cortical volumetric BMD. The increase in areal BMD was thus driven by an increase in bone size. Indeed, longitudinal bone growth (height, +8.5%) and especially cross-sectional area of the radius (+46%) and cortical thickness (+12%), as measured by peripheral quantitative computed tomography, increased markedly during estrogen treatment. These findings demonstrate that androgens alone are insufficient, whereas estrogens are essential for the process of pubertal periosteal bone expansion typically associated with the male bone phenotype.

Significance of maxillary sinus mucosal thickening in patients with periodontal disease.

PubMed

Ren, Song; Zhao, Haijiao; Liu, Jingbo; Wang, Qingxuan; Pan, Yaping

2015-12-01

To characterise and measure the Schneiderian membranes of individuals with periodontal diseases in China and to analyse the factors impacting maxillary sinus mucosal thickness using cone-beam computed tomography (CBCT). A cohort of 221 patients with periodontal disease was subjected to cross-sectional CBCT examination. Various parameters, including age, sex, alveolar bone loss, furcation lesions and vertical infrabony pockets, were analysed as correlates of mucosal thickening (MT). Sinus mucosal thickness ≥ 2 mm qualified as MT. MT was detected in 103 (48.9%) patients, increasing in frequency as the degree of alveolar bone loss advanced (mild, 14.5%; moderate, 29.5%; severe, 87.9%). The association between MT and vertical infrabony pockets was statistically significant (P < 0.001). The likelihood of MT increased with moderate [odds ratio (OR) = 1.02] and severe (OR = 4.62) periodontal bone loss (P < 0.001), as well as with furcation lesions (OR = 2.76) and vertical infrabony pockets (OR = 13.58). Relative to the case in patients with periodontitis and normal mucosa, the probability of MT increased dramatically as alveolar bone loss worsened. Periodontal pathologies (i.e. furcation lesions and vertical infrabony pockets) were also more likely to coincide with MT. © 2015 FDI World Dental Federation.

Cortical bone is more sensitive to alcohol dose effects than trabecular bone in the rat.

PubMed

Maurel, Delphine B; Boisseau, Nathalie; Benhamou, Claude-Laurent; Jaffré, Christelle

2012-10-01

While chronic alcohol consumption is known to decrease bone mineral content (BMC), bone mineral density (BMD), and negatively modify trabecular bone microarchitecture, the impact of alcohol on cortical microarchitecture is still unclear. The aim of this study was to investigate the effects of various doses of alcohol on bone density, trabecular and cortical parameters and bone strength in rats. Forty-eight male Wistar rats were divided into four groups: control (C), alcohol 25% v/v (A25), alcohol 30% v/v (A30) and alcohol 35% v/v (A35). Rats in the alcohol groups were fed a solution composed of ethanol and water for 17 weeks while the control group drank only water. Bone quality and quantity were evaluated through the analysis of density, trabecular and cortical bone microarchitectural parameters, osteocalcin and N-Telopeptide concentrations and a 3-point bending test. Bone density along with trabecular and cortical thickness were lower in alcohol groups compared to C. BMD was lower in A35 vs. A30 and cortical thickness was lower in A35 vs. A25 and A30. Pore number was increased by alcohol and the porosity was greater in A35 compared to C. N-Telopeptide concentration was decreased in alcohol groups compared to control whereas no differences were observed in osteocalcin concentrations. Maximal energy to failure was lower in A25 and A35 compared to C. Chronic ethanol consumption increases cortical bone damage in rats and may have detrimental effects on bone strength. These effects were dose-dependent, with greater negative effects proportionate to greater alcohol doses. Copyright © 2011 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Alveolar bone changes after asymmetric rapid maxillary expansion.

PubMed

Akin, Mehmet; Baka, Zeliha Muge; Ileri, Zehra; Basciftci, Faruk Ayhan

2015-09-01

To quantitatively evaluate the effects of asymmetric rapid maxillary expansion (ARME) on cortical bone thickness and buccal alveolar bone height (BABH), and to determine the formation of dehiscence and fenestration in the alveolar bone surrounding the posterior teeth, using cone-beam computed tomography (CBCT). The CBCT records of 23 patients with true unilateral posterior skeletal crossbite (10 boys, 14.06 ± 1.08 years old, and 13 girls, 13.64 ± 1.32 years old) who had undergone ARME were selected from our clinic archives. The bonded acrylic ARME appliance, including an occlusal stopper, was used on all patients. CBCT records had been taken before ARME (T1) and after the 3-month retention period (T2). Axial slices of the CBCT images at 3 vertical levels were used to evaluate the buccal and palatal aspects of the canines, first and second premolars, and first molars. Paired samples and independent sample t-tests were used for statistical comparison. The results suggest that buccal cortical bone thickness of the affected side was significantly more affected by the expansion than was the unaffected side (P < .05). ARME significantly reduced the BABH of the canines (P < .01) and the first and second premolars (P < .05) on the affected side. ARME also increased the incidence of dehiscence and fenestration on the affected side. ARME may quantitatively decrease buccal cortical bone thickness and height on the affected side.

Site-specific adaptive remodeling of Greyhound metacarpal cortical bone subjected to asymmetrical cyclic loading.

PubMed

Johnson, K A; Skinner, G A; Muir, P

2001-05-01

To quantify geometric, inertial, and histomorphometric properties at the mid-diaphyseal level of left and right metacarpal bones (MCB) of racing Greyhounds. MCB from 7 racing Greyhounds euthanatized for reasons unrelated to MCB abnormalities. Mid-diaphyseal transverse sections of left and right MCB were stained with H&E or microradiographed. Images of stained sections were digitized, and cross-sectional area, cortical area, and maximum and minimum area moments of inertia of each bone were determined. Histomorphometric data (osteonal density, osteonal birefringence, and endosteal new lamellar bone thickness) were collected in 4 quadrants (dorsal, palmar, lateral, medial). Values were compared between limbs and among bones and quadrants. Cross-sectional area, cortical area, and maximum and minimum moments of inertia of left MCB-IV and -V were significantly greater, compared with contralateral bones. Overall osteonal densities in the dorsal quadrants of left MCB were greater, compared with lateral and medial quadrants. Also, percentage of birefringent osteons was significantly greater in the dorsal quadrant of left MCB-III, -IV, and -V, compared with the palmar quadrant. Thickness of new endosteal lamellar bone was not significantly influenced by limb, bone, or quadrant. Increased cortical thickness and geometric properties of left MCB-IV and -V of Greyhounds, together with altered turnover and orientation of osteons in the dorsal quadrants of left MCB, are site-specific adaptive responses associated with asymmetric cyclic loading as a result of racing on circular tracks. Site-specific adaptive remodeling may be important in the etiopathogenesis of fatigue fractures in racing Greyhounds.

Morphomic measurement of the temporalis muscle and zygomatic bone as novel predictors of hospital-based clinical outcomes in patients with mandible fracture.

PubMed

Lisiecki, Jeffrey; Zhang, Peng; Wang, Lu; Rinkinen, Jacob; De La Rosa, Sara; Enchakalody, Binu; Brownley, Robert Cameron; Wang, Stewart C; Buchman, Steven R; Levi, Benjamin

2013-09-01

Patients with mandibular fracture often have comorbidities and concomitant injuries making the decision for when and how to operate a challenge. Physicians describe "temporalis wasting" as a finding that indicates frailty; however, this is a subjective finding without quantitative values. In this study, we demonstrate that decreased morphomic values of the temporalis muscle and zygomatic bone are an objective measure of frailty associated with increased injury-induced morbidity as well as negative impact on overall hospital-based clinical outcomes in patients with mandible fracture. Computed tomographic (CT) scans from all patients with a diagnosis of a mandible fracture in the University of Michigan trauma registry and with a hospital admission were collected from the years 2004 to 2011. Automated, high-throughput CT analysis was used to reconstruct the anatomy and quantify morphomic values (temporalis volume, area and thickness, and zygomatic thickness) in these patients using MATLAB v13.0 (MathWorks Inc, Natick, MA, USA). Subsequently, a subset of 16 individuals with a Glasgow Coma Scale of 14 or 15 was analyzed to control for brain injury. Clinical data were obtained, and the association between morphomic measurements and clinical outcomes was evaluated using Pearson correlation for unadjusted analysis and multiple regression for adjusted analysis. The mean age of patients in the study was 47.1 years. Unadjusted analysis using Pearson correlation revealed that decreases in zygomatic bone thickness correlated strongly with increases in hospital, intensive care unit, and ventilator days (P < 0.0001, P = 0.0003, and P = 0.0017, respectively). Furthermore, we found that decreases in temporalis mean thickness correlated with increases in hospital and ventilator days (P = 0.0264 and P = 0.0306, respectively). Similarly, decreases in temporalis local mean thickness are significantly correlated with increases in hospital and ventilator days (P = 0.0232 and P = 0.0472, respectively). Decreased thicknesses of the zygomatic bone and temporalis muscle are significantly correlated with higher hospital, ventilator, and intensive care unit days in patients with mandibular fracture receiving reconstructive operations. This morphomic methodology provides an accurate, quantitative means to evaluate craniofacial trauma patient frailty, injury, and outcomes using routinely obtained CT scans. In the future, we plan to apply this approach to determine preoperative risk stratification and assist in surgical planning.

Structure of Clavicle In Relation to Weight Transmission

PubMed Central

Routatal, Rohini V

2015-01-01

Aims and Objectives It is a known fact that weight of upper limb is transmitted to the axial skeleton through clavicle. The present study is an attempt to correlate pattern of compact and trabecular bone of clavicle as a weight transmitting bone. Materials and Methods Sixty clavicles were studied from right and left sides of 30 cadavers donated to the Anatomy department, Pramukhswami Medical College, Karamsad, India. The study was focused on the thickness of compact bone of clavicle and trabecular pattern of this bone. Results Cancellous bone: Cancellous bone near both ends of clavicle presented meshwork of thin bony plates. Between the conoid tubercle and area for attachment of costo-clavicular ligament, cancellous bone showed a definite pattern. Thickness of compact bone The compact bone was thicker between conoid tubercle and area for attachment of costo-clavicular ligament. At midshaft point thickness of compact bone was maximum. Conclusion The structure of clavicle between conoid tubercle and area for costoclavicular ligament showed thick compact bone and definite pattern of cancellous bone. This structure of clavicle between conoid tubercle and area for attachment of costo-clavicular ligament transmits weight from lateral to medial direction and this knowledge of clavicular structure will also be useful to orthopedic surgeons to deal with clavicular fractures and other abnormalities. PMID:26393112

[Clinical auxiliary diagnosis value of high frequency ultrasonographic measurements of the thickness of transverse carpal ligaments in carpal tunnel syndrome patients].

PubMed

Xu, L; Chen, F M; Wang, L; Zhang, P X; Jiang, X R

2016-04-18

To evaluate the meaning and value of high-frequency ultrasound in the diagnosis of carpal tunnel syndrome (CTS). In this study, 48 patients (unilateral hand) with CTS were analyzed. The thickness of transverse carpal ligaments at the pisiform bone was measured using high-frequency ultrasound. Open carpal tunnel release procedure was performed in the 48 CTS patients, and the thickness of transverse carpal ligaments at the hamate hook bone measured using vernier caliper under direct vision. The accuracy of thickness of transverse carpal ligaments was evaluated using high-frequency ultrasound. high-frequency ultrasound measurement of thickness of transverse carpal ligaments at the hamate hook bone and pisiform bone, and determination of the diagnostic threshold measurement index using receiver operating characteristic (ROC) curve, sensitivity and specificity were performed and the correlation between the thickness of transverse carpal ligaments and nerve conduction study (NCS) analyzed. The thickness of transverse carpal ligaments in the CTS patients were (0.42±0.08) cm (high-frequency ultrasound) and (0.41±0.06) cm (operation) at hamate hook bone, and there was no significant difference between the two ways (t=0.672, P>0.05). The optimal cut-off value of the transverse carpal ligaments at hamate hook bone was 0.385 cm, the sensitivity 0.775, and the specificity 0.788. The optimal cut-off value of the transverse carpal ligaments at the pisiform bone was 0.315 cm, the sensitivity 0.950, and the specificity 1.000. The transverse carpal ligaments thickness and wrist-index finger sensory nerve conduction velocity (SCV), wrist-middle finger SCV showed a negative correlation. High frequency ultrasound measurements of thickness of transverse carpal ligaments is a valuable method for the diagnosis of CTS.

The Efficacy of Cyclic Injection of Bone Morphogenetic Protein-2 in Large-Scale Calvarial Bone Defects.

PubMed

Choi, Jin Mi; Jeong, Woo Shik; Park, Eun Jung; Choi, Jong Woo

2017-03-01

Bone morphogenetic protein-2 (BMP-2) appears to be one of the most potent growth factors thus far studied. However, recent publications on the clinical application of BMP-2 revealed that its correct control is the paramount issue in clinical practice. For improving BMP-2 delivery, the cyclic administration might be an alternative. Accordingly, the authors cyclically injected BMP-2 in a cyclic injection model of large cranial defects to maintain the proper dosage during the bone healing process. A 10-mm diameter calvarial bone defect was produced using a round drill in 8-week-old Sprague-Dawley rats. Silk-hydroxyapatite scaffolds soaked in the appropriate concentration of BMP-2 were implanted into the defect. The animals were split into 4 single-injection groups and 3 multiple-injection groups; the latter groups received weekly subcutaneous injections of BMP-2 solution (1, 5, and 10 μg/mL) for 4 weeks, whereas the former groups received a single injection of BMP-2 at these concentrations. Each rat underwent computed tomography at 8 weeks. In terms of total volumes of the new bone, the 5 μg/mL multiple-injection BMP-2 group had significantly greater increases in bone volume than the single-injection groups. In terms of bone thickness, the multiple-injection groups had better outcomes than the single-injection groups. Thus, the cyclic injection protocol restored the original thickness without overgrowth. Cyclic injection of BMP-2 permits more accurate dosage control than single injection and improves thickness and dense bone regeneration. Therefore, it may represent a promising approach for future clinical trials. Further investigation using a greater number of animals is required.

Changes in tibial bone microarchitecture in female recruits in response to 8 weeks of U.S. Army Basic Combat Training.

PubMed

Hughes, Julie M; Gaffney-Stomberg, Erin; Guerriere, Katelyn I; Taylor, Kathryn M; Popp, Kristin L; Xu, Chun; Unnikrishnan, Ginu; Staab, Jeffery S; Matheny, Ronald W; McClung, James P; Reifman, Jaques; Bouxsein, Mary L

2018-08-01

U.S. Army Basic Combat Training (BCT) is a physically-demanding program at the start of military service. Whereas animal studies have shown that increased mechanical loading rapidly alters bone structure, there is limited evidence of changes in bone density and structure in humans exposed to a brief period of unaccustomed physical activity. We aimed to characterize changes in tibial bone density and microarchitecture and serum-based biochemical markers of bone metabolism in female recruits as a result of 8 weeks of BCT. We collected high-resolution peripheral quantitative computed tomographic images of the distal tibial metaphysis and diaphysis (4% and 30% of tibia length from the distal growth plate, respectively) and serum markers of bone metabolism before and after BCT. Linear mixed models were used to estimate the mean difference for each outcome from pre- to post-BCT, while controlling for race/ethnicity, age, and body mass index. 91 female BCT recruits volunteered and completed this observational study (age = 21.5 ± 3.3 yrs). At the distal tibial metaphysis, cortical thickness, trabecular thickness, trabecular number, bone volume/total volume, and total and trabecular volumetric bone density (vBMD) increased significantly by 1-2% (all p < 0.05) over the BCT period, whereas trabecular separation, cortical tissue mineral density (TMD), and cortical vBMD decreased significantly by 0.3-1.0% (all p < 0.05). At the tibial diaphysis, cortical vBMD and cortical TMD decreased significantly (both -0.7%, p < 0.001). Bone strength, estimated by micro finite element analysis, increased by 2.5% and 0.7% at the distal tibial metaphysis and diaphysis, respectively (both p < 0.05). Among the biochemical markers of bone metabolism, sclerostin decreased (-5.7%), whereas bone alkaline phosphatase, C-telopeptide cross-links of type 1 collagen, tartrate-resistance acid phosphatase, and 25(OH)D increased by 10-28% (all p < 0.05). BCT leads to improvements in trabecular bone microarchitecture and increases in serum bone formation markers indicative of new bone formation, as well as increases in serum bone resorption markers and decreases in cortical vBMD consistent with intracortical remodeling. Together, these results demonstrate specific changes in trabecular and cortical bone density and microarchitecture following 8 weeks of unaccustomed physical activity in women. Copyright © 2018 Elsevier Inc. All rights reserved.

Computed tomography analysis of guinea pig bone: architecture, bone thickness and dimensions throughout development

PubMed Central

Witkowska, Agata; Alibhai, Aziza; Hughes, Chloe; Price, Jennifer; Klisch, Karl; Sturrock, Craig J.

2014-01-01

The domestic guinea pig, Cavia aperea f. porcellus, belongs to the Caviidae family of rodents. It is an important species as a pet, a source of food and in medical research. Adult weight is achieved at 8–12 months and life expectancy is ∼5–6 years. Our aim was to map bone local thickness, structure and dimensions across developmental stages in the normal animal. Guinea pigs (n = 23) that had died of natural causes were collected and the bones manually extracted and cleaned. Institutional ethical permission was given under the UK Home Office guidelines and the Veterinary Surgeons Act. X-ray Micro Computed Tomography (microCT) was undertaken on the left and right scapula, humerus and femur from each animal to ascertain bone local thickness. Images were also used to undertake manual and automated bone measurements, volumes and surface areas, identify and describe nutrient, supratrochlear and supracondylar foramina. Statistical analysis between groups was carried out using ANOVA with post-hoc testing. Our data mapped a number of dimensions, and mean and maximum bone thickness of the scapula, humerus and femur in guinea pigs aged 0–1 month, 1–3 months, 3–6 months, 6 months–1 year and 1–4 years. Bone dimensions, growth rates and local bone thicknesses differed between ages and between the scapula, humerus and femur. The microCT and imaging software technology showed very distinct differences between the relative local bone thickness across the structure of the bones. Only one bone showed a singular nutrient foramen, every other bone had between 2 and 5, and every nutrient canal ran in an oblique direction. In contrast to other species, a supratrochlear foramen was observed in every humerus whereas the supracondylar foramen was always absent. Our data showed the bone local thickness, bone structure and measurements of guinea pig bones from birth to 4 years old. Importantly it showed that bone development continued after 1 year, the point at which most guinea pigs have reached full weight. This study is the first to show the high abundance (100% in this study) of the supratrochlear foramen within the guinea pig humerus and the complete absence of a supracondylar foramen, which is different to many other species and may also affect potential fracture points and frequencies. Understanding bone morphology and growth is essential in not only understanding the requirements of the healthy guinea pig, but also necessary in order to investigate disease states. PMID:25289194

Computed tomography analysis of guinea pig bone: architecture, bone thickness and dimensions throughout development.

PubMed

Witkowska, Agata; Alibhai, Aziza; Hughes, Chloe; Price, Jennifer; Klisch, Karl; Sturrock, Craig J; Rutland, Catrin S

2014-01-01

The domestic guinea pig, Cavia aperea f. porcellus, belongs to the Caviidae family of rodents. It is an important species as a pet, a source of food and in medical research. Adult weight is achieved at 8-12 months and life expectancy is ∼5-6 years. Our aim was to map bone local thickness, structure and dimensions across developmental stages in the normal animal. Guinea pigs (n = 23) that had died of natural causes were collected and the bones manually extracted and cleaned. Institutional ethical permission was given under the UK Home Office guidelines and the Veterinary Surgeons Act. X-ray Micro Computed Tomography (microCT) was undertaken on the left and right scapula, humerus and femur from each animal to ascertain bone local thickness. Images were also used to undertake manual and automated bone measurements, volumes and surface areas, identify and describe nutrient, supratrochlear and supracondylar foramina. Statistical analysis between groups was carried out using ANOVA with post-hoc testing. Our data mapped a number of dimensions, and mean and maximum bone thickness of the scapula, humerus and femur in guinea pigs aged 0-1 month, 1-3 months, 3-6 months, 6 months-1 year and 1-4 years. Bone dimensions, growth rates and local bone thicknesses differed between ages and between the scapula, humerus and femur. The microCT and imaging software technology showed very distinct differences between the relative local bone thickness across the structure of the bones. Only one bone showed a singular nutrient foramen, every other bone had between 2 and 5, and every nutrient canal ran in an oblique direction. In contrast to other species, a supratrochlear foramen was observed in every humerus whereas the supracondylar foramen was always absent. Our data showed the bone local thickness, bone structure and measurements of guinea pig bones from birth to 4 years old. Importantly it showed that bone development continued after 1 year, the point at which most guinea pigs have reached full weight. This study is the first to show the high abundance (100% in this study) of the supratrochlear foramen within the guinea pig humerus and the complete absence of a supracondylar foramen, which is different to many other species and may also affect potential fracture points and frequencies. Understanding bone morphology and growth is essential in not only understanding the requirements of the healthy guinea pig, but also necessary in order to investigate disease states.

The effects of prostaglandin E2 in growing rats - Increased metaphyseal hard tissue and cortico-endosteal bone formation

NASA Technical Reports Server (NTRS)

Jee, W. S. S.; Ueno, K.; Deng, Y. P.; Woodbury, D. M.

1985-01-01

The role of in vivo prostaglandin E2 (PGE2) in bone formation is investigated. Twenty-five male Sprague-Dawley rats weighing between 223-267 g were injected subcutaneously with 0.3, 1.0, 3.0, and 6.0 mg of PGE2-kg daily for 21 days. The processing of the tibiae for observation is described. Radiographs and histomorphometric analyses are also utilized to study bone formation. Body weight, weights of soft tissues and bones morphometry are evaluated. It is observed that PGE2 depressed longitudinal bone growth, increased growth cartilage thickness, decreased degenerative cartilage cell size and cartilage cell production, and significantly increased proximal tibial metaphyseal hard tissue mass. The data reveal that periosteal bone formation is slowed down at higher doses of PGE2 and endosteal bone formation is slightly depressed less than 10 days post injection; however, here is a late increase (10 days after post injection) in endosteal bone formation and in the formation of trabecular bone in the marrow cavity of the tibial shaft. It is noted that the effects of PGE2 on bone formation are similar to the responses of weaning rats to PGE2.

The relationship between dental implant stability and trabecular bone structure using cone-beam computed tomography

PubMed Central

2016-01-01

Purpose The objective of this study was to investigate the relationships between primary implant stability as measured by impact response frequency and the structural parameters of trabecular bone using cone-beam computed tomography(CBCT), excluding the effect of cortical bone thickness. Methods We measured the impact response of a dental implant placed into swine bone specimens composed of only trabecular bone without the cortical bone layer using an inductive sensor. The peak frequency of the impact response spectrum was determined as an implant stability criterion (SPF). The 3D microstructural parameters were calculated from CT images of the bone specimens obtained using both micro-CT and CBCT. Results SPF had significant positive correlations with trabecular bone structural parameters (BV/TV, BV, BS, BSD, Tb.Th, Tb.N, FD, and BS/BV) (P<0.01) while SPF demonstrated significant negative correlations with other microstructural parameters (Tb.Sp, Tb.Pf, and SMI) using micro-CT and CBCT (P<0.01). Conclusions There was an increase in implant stability prediction by combining BV/TV and SMI in the stepwise forward regression analysis. Bone with high volume density and low surface density shows high implant stability. Well-connected thick bone with small marrow spaces also shows high implant stability. The combination of bone density and architectural parameters measured using CBCT can predict the implant stability more accurately than the density alone in clinical diagnoses. PMID:27127692

Quantifying the degradation of degradable implants and bone formation in the femoral condyle using micro-CT 3D reconstruction.

PubMed

Xu, Yichi; Meng, Haoye; Yin, Heyong; Sun, Zhen; Peng, Jiang; Xu, Xiaolong; Guo, Quanyi; Xu, Wenjing; Yu, Xiaoming; Yuan, Zhiguo; Xiao, Bo; Wang, Cheng; Wang, Yu; Liu, Shuyun; Lu, Shibi; Wang, Zhaoxu; Wang, Aiyuan

2018-01-01

Degradation limits the application of magnesium alloys, and evaluation methods for non-traumatic in vivo quantification of implant degradation and bone formation are imperfect. In the present study, a micro-arc-oxidized AZ31 magnesium alloy was used to evaluate the degradation of implants and new bone formation in 60 male New Zealand white rabbits. Degradation was monitored by weighing the implants prior to and following implantation, and by performing micro-computed tomography (CT) scans and histological analysis after 1, 4, 12, 24, 36, and 48 weeks of implantation. The results indicated that the implants underwent slow degradation in the first 4 weeks, with negligible degradation in the first week, followed by significantly increased degradation during weeks 12-24 (P<0.05), and continued degradation until the end of the 48-week experimental period. The magnesium content decreased as the implant degraded (P<0.05); however, the density of the material exhibited almost no change. Micro-CT results also demonstrated that pin volume, pin mineral density, mean 'pin thickness', bone surface/bone volume and trabecular separation decreased over time (P<0.05), and that the pin surface area/pin volume, bone volume fraction, trabecular thickness, trabecular number and tissue mineral density increased over time (P<0.05), indicating that the number of bones and density of new bone increased as magnesium degraded. These results support the positive effect of magnesium on osteogenesis. However, from the maximum inner diameter of the new bone loop and diameter of the pin in the same position, the magnesium alloy was not capable of creating sufficient bridges between the bones and biomaterials when there were preexisting gaps. Histological analyses indicated that there were no inflammatory responses around the implants. The results of the present study indicate that a micro-arc-oxidized AZ31 magnesium alloy is safe in vivo and efficiently degraded. Furthermore, the novel bone formation increased as the implant degraded. The findings concluded that micro-CT, which is useful for providing non-traumatic, in vivo , quantitative and precise data, has great value for exploring the degradation of implants and novel bone formation.

Peripheral cannabinoid receptor, CB2, regulates bone mass

PubMed Central

Ofek, Orr; Karsak, Meliha; Leclerc, Nathalie; Fogel, Meirav; Frenkel, Baruch; Wright, Karen; Tam, Joseph; Attar-Namdar, Malka; Kram, Vardit; Shohami, Esther; Mechoulam, Raphael; Zimmer, Andreas; Bab, Itai

2006-01-01

The endogenous cannabinoids bind to and activate two G protein-coupled receptors, the predominantly central cannabinoid receptor type 1 (CB1) and peripheral cannabinoid receptor type 2 (CB2). Whereas CB1 mediates the cannabinoid psychotropic, analgesic, and orectic effects, CB2 has been implicated recently in the regulation of liver fibrosis and atherosclerosis. Here we show that CB2-deficient mice have a markedly accelerated age-related trabecular bone loss and cortical expansion, although cortical thickness remains unaltered. These changes are reminiscent of human osteoporosis and may result from differential regulation of trabecular and cortical bone remodeling. The CB2–/– phenotype is also characterized by increased activity of trabecular osteoblasts (bone-forming cells), increased osteoclast (the bone-resorbing cell) number, and a markedly decreased number of diaphyseal osteoblast precursors. CB2 is expressed in osteoblasts, osteocytes, and osteoclasts. A CB2-specific agonist that does not have any psychotropic effects enhances endocortical osteoblast number and activity and restrains trabecular osteoclastogenesis, apparently by inhibiting proliferation of osteoclast precursors and receptor activator of NF-κB ligand expression in bone marrow-derived osteoblasts/stromal cells. The same agonist attenuates ovariectomy-induced bone loss and markedly stimulates cortical thickness through the respective suppression of osteoclast number and stimulation of endocortical bone formation. These results demonstrate that the endocannabinoid system is essential for the maintenance of normal bone mass by osteoblastic and osteoclastic CB2 signaling. Hence, CB2 offers a molecular target for the diagnosis and treatment of osteoporosis, the most prevalent degenerative disease in developed countries. PMID:16407142

In vivo cyclic compression causes cartilage degeneration and subchondral bone changes in mouse tibiae.

PubMed

Ko, Frank C; Dragomir, Cecilia; Plumb, Darren A; Goldring, Steven R; Wright, Timothy M; Goldring, Mary B; van der Meulen, Marjolein C H

2013-06-01

Alterations in the mechanical loading environment in joints may have both beneficial and detrimental effects on articular cartilage and subchondral bone, and may subsequently influence the development of osteoarthritis (OA). Using an in vivo tibial loading model, the aim of this study was to investigate the adaptive responses of cartilage and bone to mechanical loading and to assess the influence of load level and duration. Cyclic compression at peak loads of 4.5N and 9.0N was applied to the left tibial knee joint of adult (26-week-old) C57BL/6 male mice for 1, 2, and 6 weeks. Only 9.0N loading was utilized in young (10-week-old) mice. Changes in articular cartilage and subchondral bone were analyzed by histology and micro-computed tomography. Mechanical loading promoted cartilage damage in both age groups of mice, and the severity of joint damage increased with longer duration of loading. Metaphyseal bone mass increased with loading in young mice, but not in adult mice, whereas epiphyseal cancellous bone mass decreased with loading in both young and adult mice. In both age groups, articular cartilage thickness decreased, and subchondral cortical bone thickness increased in the posterior tibial plateau. Mice in both age groups developed periarticular osteophytes at the tibial plateau in response to the 9.0N load, but no osteophyte formation occurred in adult mice subjected to 4.5N peak loading. This noninvasive loading model permits dissection of temporal and topographic changes in cartilage and bone and will enable investigation of the efficacy of treatment interventions targeting joint biomechanics or biologic events that promote OA onset and progression. Copyright © 2013 by the American College of Rheumatology.

In vivo cyclic compression causes cartilage degeneration and subchondral bone changes in mouse tibiae

PubMed Central

Ko, Frank C.; Dragomir, Cecilia; Plumb, Darren A.; Goldring, Steven R.; Wright, Timothy M.; Goldring, Mary B.; van der Meulen, Marjolein C.H.

2013-01-01

Objectives Alterations in the mechanical loading environment in joints may have both beneficial and detrimental effects on articular cartilage and subchondral bone and subsequently influence the development of osteoarthritis (OA). We used an in vivo tibial loading model to investigate the adaptive responses of cartilage and bone to mechanical loading and to assess the influence of load level and duration. Methods We applied cyclic compression of 4.5 and 9.0N peak loads to the left tibia via the knee joint of adult (26-week-old) C57Bl/6 male mice for 1, 2, and 6 weeks. Only 9.0N loading was utilized in young (10-week-old) mice. The changes in articular cartilage and subchondral bone were analyzed by histology and microcomputed tomography. Results Loading promoted cartilage damage in both age groups, with increased damage severity dependent upon the duration of loading. Metaphyseal bone mass increased in the young mice, but not in the adult mice, whereas epiphyseal cancellous bone mass decreased with loading in both young and adult mice. Articular cartilage thickness decreased, and subchondral cortical bone thickness increased in the posterior tibial plateau in both age groups. Both age groups developed periarticular osteophytes at the tibial plateau in response to the 9.0N load, but no osteophyte formation occurred in adult mice subjected to 4.5N peak loading. Conclusion This non-invasive loading model permits dissection of temporal and topographical changes in cartilage and bone and will enable investigation of the efficacy of treatment interventions targeting joint biomechanics or biological events that promote OA onset and progression. PMID:23436303

Correlation between the thickness of the crestal and buccolingual cortical bone at varying depths and implant stability quotients

PubMed Central

Chatvaratthana, Kanthanat; Thaworanunta, Sita; Seriwatanachai, Dutmanee; Wongsirichat, Natthamet

2017-01-01

Background/purpose Resonance frequency analysis (RFA) is clinically used in dentistry to access the stiffness of dental implants in surrounding bone. However, the clear advantages and disadvantages of this method are still inconclusive. The aim of this study was to investigate and compare implant stability quotient (ISQ) values obtained from RFA with parameters obtained from a cone beam computed tomography (CBCT) scan of the same region. Materials and methods Nineteen implants (Conelog) were inserted in the posterior maxillary and mandibular partially edentulous regions of 16 patients. At the time of implant placement, the ISQ values were obtained using RFA (Osstell). CBCT was used to measure the thickness of the crestal, cortical, buccolingual cortical, and cancellous bone at 3, 6, and 9 mm below the crestal bone level, as indicated by radiographic markers. The ratio of the thickness of the cortical to cancellous bone at varying depths was also calculated and classified into 4 groups (Group 1–4). Results There was a strong correlation between the crestal cortical bone thickness and ISQ values (P<0.001). The thickness of the buccolingual cortical bone and ratio of the cortical to cancellous bone thickness at 3 mm were significantly related to the ISQ (P = 0.018 and P = 0.034, respectively). Furthermore, the ISQs in Group 1 were the highest compared with those in Group 2 and Group 3, whereas the CBCT parameters at 6 and 9 mm did not have any specific correlation with the ISQ values. Conclusion This study showed that the ISQ values obtained from RFA highly correlated with the quantity and quality of bone 3 mm below the crestal bone level. The correlation between the ISQ and bone surrounding the implant site was dependent on the depth of measurement. Therefore, RFA can help to predict the marginal bone level, as confirmed in this study. PMID:29281715

Uniform Deposition of Protein Incorporated Mineral Layer on Three-Dimensional Porous Polymer Scaffolds

PubMed Central

Segvich, Sharon; Smith, Hayes C.; Luong, Linh N.; Kohn, David H.

2009-01-01

Inorganic–organic hybrid materials designed to facilitate bone tissue regeneration use a calcium phosphate mineral layer to encourage cell adhesion, proliferation, and osteogenic differentiation. Mineral formed on porous materials is often discontinuous through the thickness of the scaffold. This study aimed to uniformly coat the pores of three-dimensional (3D) porous, polymer scaffolds with a bone-like mineral layer in addition to uniformly incorporating a model protein within this mineral layer. A filtration system designed to induce simulated body fluid flow through the interstices of 3D polylactic-co-glycolic acid scaffolds (10-mm diameter × 2-mm thickness) illustrated that a uniform, continuous mineral layer can be precipitated on the pore surfaces of a 3D porous structure within 5 days. MicroCT analysis showed increased mineral volume percent (MV%) (7.86 ± 3.25 MV%, p = 0.029) and continuous mineralization of filtered scaffolds compared with two static control groups (floating, 0.16 ± 0.26 MV% and submerged, 0.20 ± 0.01 MV%). Furthermore, the system was effective in coprecipitating a model protein, bone sialoprotein (BSA), within the mineral layer. A 10-fold increase in BSA incorporation was seen when coprecipitated filtered scaffolds (1308 ± 464 μg) were compared to a submerged static control group (139 ± 45 μg), p < 0.001. Confocal microscopy visually confirmed uniform coprecipitation of BSA throughout the thickness of the filtration scaffolds. The designed system enables 3D mineralization through the thickness of porous materials, and provides the option of including coprecipitated biomolecular cues within the mineral layer. This approach of providing a 3D conductive and osteoinductive environment could be conducive to bone tissue regeneration. PMID:17618505

Effect of Denosumab on Peripheral Compartmental Bone Density, Microarchitecture and Estimated Bone Strength in De Novo Kidney Transplant Recipients.

PubMed

Bonani, Marco; Meyer, Ursina; Frey, Diana; Graf, Nicole; Bischoff-Ferrari, Heike A; Wüthrich, Rudolf P

2016-01-01

In a randomized controlled clinical trial in kidney transplant recipients (NCT01377467) we have recently shown that RANKL inhibition with denosumab significantly improved areal bone mineral density (aBMD) when given during the first year after transplantation. The effect of denosumab on skeletal microstructure and bone strength in kidney transplant recipients is not known. The purpose of the present bone microarchitecture ancillary study was to investigate high-resolution peripheral quantitative computed tomography (HRpQCT) data from the distal tibia and distal radius in 24 study patients that had been randomized to receive either two injections of denosumab 60 mg at baseline and after 6 months (n=10) or no treatment (n=14). Consistent with the full trial findings, denosumab reduced biomarkers of bone turnover, and significantly increased aBMD at the lumbar spine (median difference of 4.7%; 95% confidence interval [CI] 2.6 - 7.8; p<0.001). Bone quality as assessed by total and cortical volumetric bone mineral density (Tot. vBMD, Ct.vBMD) and cortical thickness (Ct.Th) increased significantly at the tibia, while changes at the radius were less pronounced. The trabecular volumetric BMD (Tb.vBMD), thickness (Tb. Th), separation (Tb.Sp) and number (Tb.N) and the cortical porosity (Ct.Po) at the tibia and the radius did not significantly change in both treatment groups. Micro-finite element analysis (µFEA) showed that bone stiffness increased significantly at the tibia (median difference 5.6%; 95% CI 1.8% - 9.2%; p=0.002) but not at the radius (median difference 2.9%, 95% CI -3.7% - 9.1%; p=0.369). Likewise, failure load increased significantly at the tibia (median difference 5.1%; 95% CI 2.1% - 8.1%; p=0.002) but not at the radius (median difference 2.4%, 95% CI -3.2% - 8.5%; p=0.336). These findings demonstrate that denosumab improves bone density and bone quality in first-year kidney transplant recipients at risk to develop osteoporosis. © 2016 The Author(s) Published by S. Karger AG, Basel.

Therapeutic impact of low amplitude high frequency whole body vibrations on the osteogenesis imperfecta mouse bone☆

PubMed Central

Vanleene, Maximilien; Shefelbine, Sandra J.

2013-01-01

Osteogenesis imperfecta (OI) is characterized by extremely brittle bone. Currently, bisphosphonate drugs allow a decrease of fracture by inhibiting bone resorption and increasing bone mass but with possible long term side effects. Whole body mechanical vibrations (WBV) treatment may offer a promising route to stimulate bone formation in OI patients as it has exhibited health benefits on both muscle and bone mass in human and animal models. The present study has investigated the effects of WBV (45 Hz, 0.3 g, 15 minutes/days, 5 days/week) in young OI (oim) and wild type female mice from 3 to 8 weeks of age. Vibration therapy resulted in a significant increase in the cortical bone area and cortical thickness in the femur and tibia diaphysis of both vibrated oim and wild type mice compared to sham controls. Trabecular bone was not affected by vibration in the wild type mice; vibrated oim mice, however, exhibited significantly higher trabecular bone volume fraction in the proximal tibia. Femoral stiffness and yield load in three point bending were greater in the vibrated wild type mice than in sham controls, most likely attributed to the increase in femur cortical cross sectional area observed in the μCT morphology analyses. The vibrated oim mice showed a trend toward improved mechanical properties, but bending data had large standard deviations and there was no significant difference between vibrated and non-vibrated oim mice. No significant difference of the bone apposition was observed in the tibial metaphyseal trabecular bone for both the oim and wild type vibrated mice by histomorphometry analyses of calcein labels. At the mid diaphysis, the cortical bone apposition was not significantly influenced by the WBV treatment in both the endosteum and periosteum of the oim vibrated mice while a significant change is observed in the endosteum of the vibrated wild type mice. As only a weak impact in bone apposition between the vibrated and sham groups is observed in the histological sections, it is possible that WBV reduced bone resorption, resulting in a relative increase in cortical thickness. Whole body vibration appears as a potential effective and innocuous means for increasing bone formation and strength, which is particularly attractive for treating the growing skeleton of children suffering from brittle bone disease or low bone density pathologies without the long term disadvantages of current pharmacological therapies. PMID:23352925

High-resolution-cone beam tomography analysis of bone microarchitecture in patients with acromegaly and radiological vertebral fractures.

PubMed

Maffezzoni, Filippo; Maddalo, Michele; Frara, Stefano; Mezzone, Monica; Zorza, Ivan; Baruffaldi, Fabio; Doglietto, Francesco; Mazziotti, Gherardo; Maroldi, Roberto; Giustina, Andrea

2016-11-01

Vertebral fractures are an emerging complication of acromegaly but their prediction is still difficult occurring even in patients with normal bone mineral density. In this study we evaluated the ability of high-resolution cone-beam computed tomography to provide information on skeletal abnormalities associated with vertebral fractures in acromegaly. 40 patients (24 females, 16 males; median age 57 years, range 25-72) and 21 healthy volunteers (10 females, 11 males; median age 60 years, range: 25-68) were evaluated for trabecular (bone volume/trabecular volume ratio, mean trabecular separation, and mean trabecular thickness) and cortical (thickness and porosity) parameters at distal radius using a high-resolution cone-beam computed tomography system. All acromegaly patients were evaluated for morphometric vertebral fractures and for mineral bone density by dual-energy X-ray absorptiometry at lumbar spine, total hip, femoral neck, and distal radius. Acromegaly patients with vertebral fractures (15 cases) had significantly (p < 0.05) lower bone volume/trabecular volume ratio, greater mean trabecular separation, and higher cortical porosity vs. nonfractured patients, without statistically significant differences in mean trabecular thickness and cortical thickness. Fractured and nonfractured acromegaly patients did not have significant differences in bone density at either skeletal site. Patients with acromegaly showed lower bone volume/trabecular volume ratio (p = 0.003) and mean trabecular thickness (p < 0.001) and greater mean trabecular separation (p = 0.02) as compared to control subjects, without significant differences in cortical thickness and porosity. This study shows for the first time that abnormalities of bone microstructure are associated with radiological vertebral fractures in acromegaly. High-resolution cone-beam computed tomography at the distal radius may be useful to evaluate and predict the effects of acromegaly on bone microstructure.

Dentoalveolar mandibular changes with self-ligating versus conventional bracket systems: A CBCT and dental cast study

PubMed Central

de Almeida, Marcio Rodrigues; Futagami, Cristina; Conti, Ana Cláudia de Castro Ferreira; Oltramari-Navarro, Paula Vanessa Pedron; Navarro, Ricardo de Lima

2015-01-01

OBJECTIVE: The aim of the present study was to compare dentoalveolar changes in mandibular arch, regarding transversal measures and buccal bone thickness, in patients undergoing the initial phase of orthodontic treatment with self-ligating or conventional bracket systems. METHODS: A sample of 25 patients requiring orthodontic treatment was assessed based on the bracket type. Group 1 comprised 13 patients bonded with 0.022-in self-ligating brackets (SLB). Group 2 included 12 patients bonded with 0.022-in conventional brackets (CLB). Cone-beam computed tomography (CBCT) scans and a 3D program (Dolphin) assessed changes in transversal width of buccal bone (TWBB) and buccal bone thickness (BBT) before (T1) and 7 months after treatment onset (T2). Measurements on dental casts were performed using a digital caliper. Differences between and within groups were analyzed by Student's t-test; Pearson correlation coefficient was also calculated. RESULTS: Significant mandibular expansion was observed for both groups; however, no significant differences were found between groups. There was significant decrease in mandibular buccal bone thickness and transversal width of buccal bone in both groups. There was no significant correlation between buccal bone thickness and dental arch expansion. CONCLUSIONS: There were no significant differences between self-ligating brackets and conventional brackets systems regarding mandibular arch expansion and changes in buccal bone thickness or transversal width of buccal bone. PMID:26154456

Differences in trabecular bone of leptin-deficient ob/ob mice in response to biomechanical loading.

PubMed

Heep, Hansjoerg; Wedemeyer, Christian; Wegner, Alexander; Hofmeister, Sebastian; von Knoch, Marius

2008-06-15

It is known that bone mineral density (BMD) and the strength of bone is predicted by body mass. Fat mass is a significant predictor of bone mineral density which correlates with body weight. This suggests that body fat regulates bone metabolism first by means of hormonal factors and second that the effects of muscle and loading are signaling factors in mechanotransduction. Leptin, a peptide hormone produced predominantly by white fat cells, is one of these hormonal factors. The aim of this study was to investigate and measure by micro-CT the different effects of weight-bearing on trabecular bone formation in mice without the stimulation of leptin. Animals with an ad-libitum-diet (Group A) were found to increase body weight significantly at the age of six weeks in comparison with lean mice (Group B). From this point on, the difference increased constantly. At the age of twenty weeks the obese mice were almost twice as heavy as the lean mice. Significant statistical differences are shown between the two groups for body weight and bone mineral density. Examination of trabecular bone (BV/TV, trabecular number (Tb.N.), trabecular thickness (Tb.Th.)) revealed that the only statistically significant difference between the two groups was the Tb.N. for the proximal femur. High weight-bearing insignificantly improved all trabecular bone parameters in the obese mice. Compared with the control-diet Group B, the BV/TV and Tb.N. were slightly higher in the controlled-diet Group A, but not the Tb.Th.. However, correlation was found between Tb.N. and BMD on the one hand and body weight on the other hand. biomechanical loading led to decreased bone mineral density by a decrease in the number of trabeculae. Trabecular thickness was not increased by biomechanical loading in growing mice. Decreased body weight in leptin-deficient mice protects against bone loss. This finding is consistent with the principle of light-weight construction of bone. Differences in cortical and trabecular bone will be examined in later studies. It is not possible to conclude that these results also apply to human beings.

Accuracy of measuring the cortical bone thickness adjacent to dental implants using cone beam computed tomography.

PubMed

Razavi, Touraj; Palmer, Richard M; Davies, Jonathan; Wilson, Ron; Palmer, Paul J

2010-07-01

To assess the accuracy of measuring the cortical bone thickness adjacent to dental implants using two cone beam computed tomography (CBCT) systems. Ten 4 x 11 mm Astra Tech implants were placed at varying distances from the cortical bone in two prepared bovine ribs. Both ribs were scanned in a reproducible position using two different CBCT scanners. Ten examiners each carried out four measurements on all 10 implants using the two CBCT systems: vertical distance between the top of the implant and the alveolar crest (IT-AC), and thickness of the cortical bone from the outer surface of the implant threads at 3, 6 and 9 mm from the top of the implant. Ground sections were prepared and bone thickness was measured using a light microscope and a graticule to give a gold standard (GS) measurement. The examiner's measurements were significantly different between CBCT systems for the vertical and thickness dimensions (P<0.001) while measuring the cortical bone thickness between 0.3 and 3.7 mm. Within that range, i-CAT NG measurements were consistently underestimated in comparison with the GS. Accuitomo 3D60 FPD measurements closely approximated the GS, except when cortical bone thickness was <0.8 mm. The mean percentage errors from the GS at 3, 6 and 9 mm measurement levels were 68%, 28% and 18%, respectively, for i-CAT NG and 23%, 5% and 6%, respectively, for Accuitomo 3D60 FPD. Within the limitations of this study, it was concluded that i-CAT NG (voxel size 0.3) may not produce sufficient resolution of the thin cortical bone adjacent to dental implants and, therefore, the measurements may not be accurate; whereas, Accuitomo 3D60 FPD (voxel size 0.125) may produce better resolution and more accurate measurement of the thin bone.

Chronic Inhibition of ERK1/2 Signaling Improves Disordered Bone and Mineral Metabolism in Hypophosphatemic (Hyp) Mice

PubMed Central

Zhang, Martin Y. H.; Ranch, Daniel; Pereira, Renata C.; Armbrecht, Harvey J.; Portale, Anthony A.

2012-01-01

The X-linked hypophosphatemic (Hyp) mouse carries a loss-of-function mutation in the phex gene and is characterized by hypophosphatemia due to renal phosphate (Pi) wasting, inappropriately suppressed 1,25-dihydroxyvitamin D [1,25(OH)2D] production, and rachitic bone disease. Increased serum fibroblast growth factor-23 concentration is responsible for the disordered metabolism of Pi and 1,25(OH)2D. In the present study, we tested the hypothesis that chronic inhibition of fibroblast growth factor-23-induced activation of MAPK signaling in Hyp mice can reverse their metabolic derangements and rachitic bone disease. Hyp mice were administered the MAPK inhibitor, PD0325901 orally for 4 wk. PD0325901 induced a 15-fold and 2-fold increase in renal 1α-hydroxylase mRNA and protein abundance, respectively, and thereby higher serum 1,25(OH)2D concentrations (115 ± 13 vs. 70 ± 16 pg/ml, P < 0.05), compared with values in vehicle-treated Hyp mice. With PD0325901, serum Pi levels were higher (5.1 ± 0.5 vs. 3 ± 0.2 mg/dl, P < 0.05), and the protein abundance of sodium-dependent phosphate cotransporter Npt2a, was greater than in vehicle-treated mice. The rachitic bone disease in Hyp mice is characterized by abundant unmineralized osteoid bone volume, widened epiphyses, and disorganized growth plates. In PD0325901-treated Hyp mice, mineralization of cortical and trabecular bone increased significantly, accompanied by a decrease in unmineralized osteoid volume and thickness, as determined by histomorphometric analysis. The improvement in mineralization in PD0325901-treated Hyp mice was confirmed by microcomputed tomography analysis, which showed an increase in cortical bone volume and thickness. These findings provide evidence that in Hyp mice, chronic MAPK inhibition improves disordered Pi and 1,25(OH)2D metabolism and bone mineralization. PMID:22334725

Chronic inhibition of ERK1/2 signaling improves disordered bone and mineral metabolism in hypophosphatemic (Hyp) mice.

PubMed

Zhang, Martin Y H; Ranch, Daniel; Pereira, Renata C; Armbrecht, Harvey J; Portale, Anthony A; Perwad, Farzana

2012-04-01

The X-linked hypophosphatemic (Hyp) mouse carries a loss-of-function mutation in the phex gene and is characterized by hypophosphatemia due to renal phosphate (Pi) wasting, inappropriately suppressed 1,25-dihydroxyvitamin D [1,25(OH)₂D] production, and rachitic bone disease. Increased serum fibroblast growth factor-23 concentration is responsible for the disordered metabolism of Pi and 1,25(OH)₂D. In the present study, we tested the hypothesis that chronic inhibition of fibroblast growth factor-23-induced activation of MAPK signaling in Hyp mice can reverse their metabolic derangements and rachitic bone disease. Hyp mice were administered the MAPK inhibitor, PD0325901 orally for 4 wk. PD0325901 induced a 15-fold and 2-fold increase in renal 1α-hydroxylase mRNA and protein abundance, respectively, and thereby higher serum 1,25(OH)₂D concentrations (115 ± 13 vs. 70 ± 16 pg/ml, P < 0.05), compared with values in vehicle-treated Hyp mice. With PD0325901, serum Pi levels were higher (5.1 ± 0.5 vs. 3 ± 0.2 mg/dl, P < 0.05), and the protein abundance of sodium-dependent phosphate cotransporter Npt2a, was greater than in vehicle-treated mice. The rachitic bone disease in Hyp mice is characterized by abundant unmineralized osteoid bone volume, widened epiphyses, and disorganized growth plates. In PD0325901-treated Hyp mice, mineralization of cortical and trabecular bone increased significantly, accompanied by a decrease in unmineralized osteoid volume and thickness, as determined by histomorphometric analysis. The improvement in mineralization in PD0325901-treated Hyp mice was confirmed by microcomputed tomography analysis, which showed an increase in cortical bone volume and thickness. These findings provide evidence that in Hyp mice, chronic MAPK inhibition improves disordered Pi and 1,25(OH)₂D metabolism and bone mineralization.

Role of TAF12 in the Increased VDR Activity in Paget’s Disease of Bone

DTIC Science & Technology

2014-10-01

DRIP205) and VDR interacting with the histone acetyltransferases (SRC1, CBBP etc) that control entry and activity of RNA polymerase II for TAF12...bone volume fraction (BV/TV, %), trabecular number (Tb.N, N /mm2), trabecular thickness (Tb.Th, mm), and trabecular bone spacing (Tb.Sp, mm). Cortical...mean SD ( n ¼ 4); p< 0.01, significantly different from OCLs formed with the same treatment in WT mouse cultures. (B) OCL formation by treatment of

Finite element study of human pelvis model in side impact for Chinese adult occupants.

PubMed

Ma, Zhengwei; Lan, Fengchong; Chen, Jiqing; Liu, Weiguo

2015-01-01

The occupant's pelvis is very vulnerable to side collision in road accidents. Finite element (FE) studies on pelvic injury help to design occupant protection devices to improve vehicle safety. This study was aimed to develop a highly biofidelic pelvis model of Chinese adults and assess its sensitivity to variations in pelvis cortical bone thickness, bone material properties, and loading conditions. In this study, 4 different FE models of the pelvis were developed from the computed tomography (CT) data of a volunteer representing the 50th percentile Chinese male. Two of them were meshed using entirely hexahedral elements with variable and constant cortical thickness distribution (the V-Hex and C-Hex models), and the others were modeled with hexahedral elements for cancellous bone and variable or constant thickness shell elements for cortical bone (the V-HS and C-HS models). In model developments, the semi-automatic multiblock meshing approach was employed to maintain the pelvis geometric curvature and generate a high-quality hexahedral mesh. Then, several simulations with postmortem human subjects (PMHS) tests were performed to obtain the most accurate model in predicting pelvic injury. Based on the most accurate model, sensitivity studies were conducted to analyze the effects of the cortex thickness, Young's modulus of the cortical and cancellous bone, impactor velocity, and impactor with or without padding on the biomechanical responses and injuries of pelvis. The results indicate that the models with variable cortical bone thickness can give more accurate predictions than those with constant cortical thickness. Both the V-Hex and V-HS models are favorable for simulating pelvic response and injury, but the simulation results of the V-Hex model agree with the tests better. The sensitivity study shows that pelvic response is more sensitive to alterations in the Young's modulus of cortical bone than cancellous bone. Compared to failure displacement, peak force is more sensitive to the cortical bone thickness. However, displacement is more sensitive to the Young's modulus of cancellous bone than peak force. The padding attached on the impactor plays a significant role in absorbing the impact energy and alleviating pelvic injury. The all-hex meshing method with variable cortical bone thickness has the highest accuracy but is time-consuming. The cortical bone plays a determining role in resisting pelvic fracture. Peak impact force appears to be a reasonable injury predictor for pelvic injury assessment. Some appropriate energy absorbers installed in the car door can significantly reduce pelvic injury and will be beneficial for occupant protection.

PTH [1-34]-induced alterations of the subchondral bone provoke early osteoarthritis.

PubMed

Orth, P; Cucchiarini, M; Wagenpfeil, S; Menger, M D; Madry, H

2014-06-01

To test the hypothesis that changes in the subchondral bone induced by parathyroid hormone (PTH [1-34]) reciprocally affect the integrity of the articular cartilage within a naïve osteochondral unit in vivo. Daily subcutaneous injections of 10 μg PTH [1-34]/kg were given to adult rabbits for 6 weeks, controls received saline. Blood samples were continuously collected to monitor renal function. The subchondral bone plate and subarticular spongiosa of the femoral heads were separately assessed by micro-computed tomography. Articular cartilage was evaluated by macroscopic and histological osteoarthritis scoring, polarized light microscopy, and immunohistochemical determination of type-I, type-II, type-X collagen contents, PTH [1-34] receptor and caspase-3 expression. Absolute and relative extents of hyaline and calcified articular cartilage layers were measured histomorphometrically. The correlation between PTH-induced changes in subchondral bone and articular cartilage was determined. PTH [1-34] enhanced volume, mineral density, and trabecular thickness within the subarticular spongiosa, and increased thickness of the calcified cartilage layer (all P < 0.05). Moreover, PTH [1-34] led to cartilage surface irregularities and reduced matrix staining (both P < 0.03). These early osteoarthritic changes correlated with and were ascribed to the increased thickness of the calcified cartilage layer (P = 0.026) and enhanced mineral density of the subarticular spongiosa (P = 0.001). Modifications of the subarticular spongiosa by PTH [1-34] cause broadening of the calcified cartilage layer, resulting in osteoarthritic cartilage degeneration. These findings identify a mechanism by which PTH-induced alterations of the normal subchondral bone microarchitecture may provoke early osteoarthritis. Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Hyperostosis frontalis interna in postmenopausal women-Possible relation to osteoporosis.

PubMed

Djonic, Danijela; Bracanovic, Djurdja; Rakocevic, Zoran; Ivovic, Miomira; Nikolic, Slobodan; Zivkovic, Vladimir; Djuric, Marija

2016-01-01

To improve our understanding of hyperostosis frontalis interna (HFI), we investigated whether HFI was accompanied by changes in the postcranial skeleton. Based on head CT scan analyses, 103 postmenopausal women were divided into controls without HFI and those with HFI, in whom we measured the thickness of frontal, occipital, and parietal bones. Women in the study underwent dual energy x-ray absorptiometry to analyze the bone density of the hip and vertebral region and external geometry of the proximal femora. Additionally, all of the women completed a questionnaire about symptoms and conditions that could be related to HFI. Women with HFI had a significantly higher prevalence of headaches, neurological and psychiatric disorders, and a significantly lower prevalence of having given birth. Increased bone thickness and altered bone structure in women with HFI was localized only on the skull, particularly on the frontal bone, probably due to specific properties of its underlying dura. Bone loss in the postcranial skeleton showed the same pattern in postmenopausal women with HFI as in those without HFI. Recording of HFI in medical records can be helpful in distinguishing whether reported disorders occur as a consequence of HFI or are related to other diseases, but does not appear helpful in identifying women at risk of bone loss.

The Effect of Changing Scan Mode on Trabecular Bone Score Using Lunar Prodigy.

PubMed

Chen, Weiwen; Slattery, Anthony; Center, Jacqueline; Pocock, Nicholas

2016-10-01

Trabecular bone score (TBS) is a measure of gray scale homogeneity that correlates with trabecular microarchitecture and is an independent predictor of fracture risk. TBS is being increasingly used in the assessment of patients at risk of osteoporosis and has recently been incorporated into FRAX ® . GE Lunar machines acquire spine scans using 1 of 3 acquisition modes depending on abdominal tissue thickness (thin, standard, and thick). From a database review, 30 patients (mean body mass index: 30.8, range 26.2-34.1) were identified who had undergone lumbar spine DXA scans (GE Lunar Prodigy, software 14.10; Lunar Radiation Corporation, Madison, WI) in both standard mode and thick mode, on the same day with no repositioning. Lumbar spine bone mineral density (L1-L4) and TBS were derived from the 30 paired spine scans. There was no significant difference in lumbar spine bone mineral density between the 2 scanning modes. There were, however, significant higher TBS values from the spine scans acquired in thick mode compared to the TBS values derived from spine acquisitions in standard mode (mean TBS difference: 0.24 [20%], standard deviation ±0.10). In conclusion, these preliminary data suggest that TBS values acquired in the GE Lunar Prodigy are dependent on the scanning mode used. Further evaluation is required to confirm the cause and develop appropriate protocols. Copyright © 2016 International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.

Photoperiod-Induced Increases in Bone Mineral Apposition Rate in Siberian Hamsters and the Involvement of Seasonal Leptin Changes

PubMed Central

Kokolski, Marie; Ebling, Francis J.; Henstock, James R.; Anderson, Susan I.

2017-01-01

The adipokine leptin regulates energy balance, appetite, and reproductive maturation. Leptin also acts on bone growth and remodeling, but both osteogenic and anti-osteogenic effects have been reported depending on experimental conditions. Siberian hamsters (Phodopus sungorus) have natural variation in circulating leptin concentrations, where serum leptin is significantly decreased during the short day (SD)-induced winter state. In summer long day (LD) photoperiods, appetite and body adiposity increase with associated central leptin insensitivity. This natural change in leptin secretion was exploited to investigate leptin’s effect on bone growth. Hamsters were injected with calcium-chelating fluorescent dyes to measure bone mineral apposition rate (MAR). Measurements were initially obtained from 5-week and 6-month-old animals maintained in low leptin (SD) or high leptin (LD) states. A further study investigated effects of chronic administration of recombinant mouse leptin to hamsters housed in SD and LD conditions; growth plate thickness and bone density were also assessed. As expected, a reduction in body mass was seen in hamsters exposed to SD, confirming the phenotype change in all studies. Serum leptin concentrations were significantly reduced in SD animals in all studies. MAR was reproducibly and significantly increased in the femurs of SD animals in all studies. Vitamin D and growth plate thickness were significantly increased in SD animals at 6 months. No effect on bone density was observed in any study. Taken together these data suggest that bone growth is associated with the low leptin, winter, lean state. In leptin-treated animals, there was a significant interaction effect of leptin and photoperiod. In comparison to their vehicle counterparts, SD animals had decreased and LD animals had increased MAR, which was not apparent prior to leptin administration. In conclusion, increased MAR was associated with low serum leptin levels in early life and sustained over 6 months, implying that leptin has a negative effect on bone growth in this model. The unexpected finding that MAR increased after peripheral leptin administration in LD suggests that leptin exerts different effects on bone growth dependent on initial leptin status. This adds further weight to the hypothesis that leptin-treated LD animals display central leptin resistance. PMID:29312147

Photoperiod-Induced Increases in Bone Mineral Apposition Rate in Siberian Hamsters and the Involvement of Seasonal Leptin Changes.

PubMed

Kokolski, Marie; Ebling, Francis J; Henstock, James R; Anderson, Susan I

2017-01-01

The adipokine leptin regulates energy balance, appetite, and reproductive maturation. Leptin also acts on bone growth and remodeling, but both osteogenic and anti-osteogenic effects have been reported depending on experimental conditions. Siberian hamsters ( Phodopus sungorus ) have natural variation in circulating leptin concentrations, where serum leptin is significantly decreased during the short day (SD)-induced winter state. In summer long day (LD) photoperiods, appetite and body adiposity increase with associated central leptin insensitivity. This natural change in leptin secretion was exploited to investigate leptin's effect on bone growth. Hamsters were injected with calcium-chelating fluorescent dyes to measure bone mineral apposition rate (MAR). Measurements were initially obtained from 5-week and 6-month-old animals maintained in low leptin (SD) or high leptin (LD) states. A further study investigated effects of chronic administration of recombinant mouse leptin to hamsters housed in SD and LD conditions; growth plate thickness and bone density were also assessed. As expected, a reduction in body mass was seen in hamsters exposed to SD, confirming the phenotype change in all studies. Serum leptin concentrations were significantly reduced in SD animals in all studies. MAR was reproducibly and significantly increased in the femurs of SD animals in all studies. Vitamin D and growth plate thickness were significantly increased in SD animals at 6 months. No effect on bone density was observed in any study. Taken together these data suggest that bone growth is associated with the low leptin, winter, lean state. In leptin-treated animals, there was a significant interaction effect of leptin and photoperiod. In comparison to their vehicle counterparts, SD animals had decreased and LD animals had increased MAR, which was not apparent prior to leptin administration. In conclusion, increased MAR was associated with low serum leptin levels in early life and sustained over 6 months, implying that leptin has a negative effect on bone growth in this model. The unexpected finding that MAR increased after peripheral leptin administration in LD suggests that leptin exerts different effects on bone growth dependent on initial leptin status. This adds further weight to the hypothesis that leptin-treated LD animals display central leptin resistance.

Mandibular bone changes in 24 years and skeletal fracture prediction.

PubMed

Jonasson, G; Sundh, V; Hakeberg, M; Hassani-Nejad, A; Lissner, L; Ahlqwist, M

2013-03-01

The objectives of the investigation were to describe changes in mandibular bone structure with aging and to compare the usefulness of cortical and trabecular bone for fracture prediction. From 1968 to 1993, 1,003 women were examined. With the help of panoramic radiographs, cortex thickness was measured and cortex was categorized as: normal, moderately, or severely eroded. The trabeculation was assessed as sparse, mixed, or dense. Visually, the mandibular compact and trabecular bone transformed gradually during the 24 years. The compact bone became more porous, the intertrabecular spaces increased, and the radiographic image of the trabeculae seemed less mineralized. Cortex thickness increased up to the age of 50 and decreased significantly thereafter. At all examinations, the sparse trabeculation group had more fractures (71-78 %) than the non-sparse group (27-31 %), whereas the severely eroded compact group showed more fractures than the less eroded groups only in 1992/1993, 24 years later. Sparse trabecular pattern was associated with future fractures both in perimenopausal and older women (relative risk (RR), 1.47-4.37) and cortical erosion in older women (RR, 1.35-1.55). RR for future fracture associated with a severely eroded cortex increased to 4.98 for cohort 1930 in 1992/1993. RR for future fracture associated with sparse trabeculation increased to 11.43 for cohort 1922 in 1992/1993. Dental radiographs contain enough information to identify women most at risk of future fracture. When observing sparse mandibular trabeculation, dentists can identify 40-69 % of women at risk for future fractures, depending on participant age at examination.

Blocking the expression of both bone sialoprotein (BSP) and osteopontin (OPN) impairs the anabolic action of PTH in mouse calvaria bone.

PubMed

Bouleftour, Wafa; Bouet, Guenaelle; Granito, Renata Neves; Thomas, Mireille; Linossier, Marie-Thérèse; Vanden-Bossche, Arnaud; Aubin, Jane E; Lafage-Proust, Marie-Hélène; Vico, Laurence; Malaval, Luc

2015-03-01

Osteopontin (OPN) and bone sialoprotein (BSP) are coexpressed in osteoblasts and osteoclasts, and display overlapping properties. We used daily injection of parathyroid hormone 1-84 (iPTH) over the calvaria of BSP knockout (-/-) mice to investigate further their functional specificity and redundancy. iPTH stimulated bone formation in both +/+ and -/- mice, increasing to the same degree periosteum, osteoid and total bone thickness. Expression of OPN, osterix, osteocalcin (OCN) and DMP1 was also increased by iPTH in both genotypes. In contrast to +/+, calvaria cell cultures from -/- mice revealed few osteoblast colonies, no mineralization and little expression of OCN, MEPE or DMP1. In contrast, OPN levels were 5× higher in -/- versus +/+ cultures. iPTH increased alkaline phosphatase (ALP) activity in cell cultures of both genotypes, with higher OCN and the induction of mineralization in -/- cultures. siRNA blocking of OPN expression did not alter the anabolic action of the hormone in BSP +/+ calvaria, while it blunted iPTH effects in -/- mice, reduced to a modest increase in periosteum thickness. In -/- (not +/+) cell cultures, siOPN blocked the stimulation by iPTH of ALP activity and OCN expression, as well as the induction of mineralization. Thus, full expression of either OPN or BSP is necessary for the anabolic effect of PTH at least in the ectopic calvaria injection model. This suggests that OPN may compensate for the lack of BSP in the response to this hormonal challenge, and provides evidence of functional overlap between these cognate proteins. © 2014 Wiley Periodicals, Inc., A Wiley Company.

Geometry reconstruction method for patient-specific finite element models for the assessment of tibia fracture risk in osteogenesis imperfecta.

PubMed

Caouette, Christiane; Ikin, Nicole; Villemure, Isabelle; Arnoux, Pierre-Jean; Rauch, Frank; Aubin, Carl-Éric

2017-04-01

Lower limb deformation in children with osteogenesis imperfecta (OI) impairs ambulation and may lead to fracture. Corrective surgery is based on empirical assessment criteria. The objective was to develop a reconstruction method of the tibia for OI patients that could be used as input of a comprehensive finite element model to assess fracture risks. Data were obtained from three children with OI and tibia deformities. Four pQCT scans were registered to biplanar radiographs, and a template mesh was deformed to fit the bone outline. Cortical bone thickness was computed. Sensitivity of the model to missing slices of pQCT was assessed by calculating maximal von Mises stress for a vertical hopping load case. Sensitivity of the model to ±5 % of cortical thickness measurements was assessed by calculating loads at fracture. Difference between the mesh contour and bone outline on the radiographs was below 1 mm. Removal of one pQCT slice increased maximal von Mises stress by up to 10 %. Simulated ±5 % variation of cortical bone thickness leads to variations of up to 4.1 % on predicted fracture loads. Using clinically available tibia imaging from children with OI, the developed reconstruction method allowed the building of patient-specific finite element models.

Morphologic evaluation of dentoalveolar structures of mandibular anterior teeth during augmented corticotomy-assisted decompensation.

PubMed

Ahn, Hyo-Won; Seo, Dong-Hwi; Kim, Seong-Hun; Park, Young-Guk; Chung, Kyu-Rhim; Nelson, Gerald

2016-10-01

Our aim in this study was to evaluate the effect of augmented corticotomy on the decompensation pattern of mandibular anterior teeth, alveolar bone, and surrounding periodontal tissues during presurgical orthodontic treatment. Thirty skeletal Class III adult patients were divided into 2 groups according to the application of augmented corticotomy labial to the anterior mandibular roots: experimental group (with augmented corticotomy, n = 15) and control group (without augmented corticotomy, n = 15). Lateral cephalograms and cone-beam computed tomography images were taken before orthodontic treatment and before surgery. The measurements included the inclination and position of the mandibular incisors, labial alveolar bone area, vertical alveolar bone height, root length, and alveolar bone thickness at 3 levels surrounding the mandibular central incisors, lateral incisors, and canines. The mandibular incisors were significantly proclined in both groups (P <0.001); however, the labial movement of the incisor tip was greater in the experimental group (P <0.05). Significant vertical alveolar bone loss was observed only in the control group (P <0.001). The middle and lower alveolar thicknesses and labial alveolar bone area increased in the experimental group. In the control group, the upper and middle alveolar thicknesses and labial alveolar bone area decreased significantly. There were no significant differences in dentoalveolar changes between the 3 kinds of anterior teeth in each group, except for root length in the experimental group (P <0.05). Augmented corticotomy provided a favorable decompensation pattern of the mandibular incisors, preserving the periodontal structures surrounding the mandibular anterior teeth for skeletal Class III patients. Copyright © 2016 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

Qualitative and quantitative observations of bone tissue reactions to anodised implants.

PubMed

Sul, Young-Taeg; Johansson, Carina B; Röser, Kerstin; Albrektsson, Tomas

2002-04-01

Research projects focusing on biomaterials related factors; the bulk implant material, the macro-design of the implant and the microsurface roughness are routinely being conducted at our laboratories. In this study, we have investigated the bone tissue reactions to turned commercially pure (c.p.) titanium implants with various thicknesses of the oxide films after 6 weeks of insertion in rabbit bone. The control c.p. titanium implants had an oxide thickness of 17-200 nm while the test implants revealed an oxide thickness between 600 and 1000 nm. Routine histological investigations of the tissue reactions around the implants and enzyme histochemical detections of alkaline and acid phosphatase activities demonstrated similar findings around both the control and test implants. In general, the histomorphometrical parameters (bone to implant contact and newly formed bone) revealed significant quantitative differences between the control and test implants. The test implants demonstrated a greater bone response histomorphometrically than control implants and the osteoconductivity was more pronounced around the test implant surfaces. The parameters that differed between the implant surfaces, i.e. the oxide thickness, the pore size distribution, the porosity and the crystallinity of the surface oxides may represent factors that have an influence on the histomorphometrical results indicated by a stronger bone tissue response to the test implant surfaces, with an oxide thickness of more than 600 nm.

Internal rib structure can be predicted using mathematical models: An anatomic study comparing the chest to a shell dome with application to understanding fractures.

PubMed

Casha, Aaron R; Camilleri, Liberato; Manché, Alexander; Gatt, Ruben; Attard, Daphne; Gauci, Marilyn; Camilleri-Podesta, Marie-Therese; Mcdonald, Stuart; Grima, Joseph N

2015-11-01

The human rib cage resembles a masonry dome in shape. Masonry domes have a particular construction that mimics stress distribution. Rib cortical thickness and bone density were analyzed to determine whether the morphology of the rib cage is sufficiently similar to a shell dome for internal rib structure to be predicted mathematically. A finite element analysis (FEA) simulation was used to measure stresses on the internal and external surfaces of a chest-shaped dome. Inner and outer rib cortical thickness and bone density were measured in the mid-axillary lines of seven cadaveric rib cages using computerized tomography scanning. Paired t tests and Pearson correlation were used to relate cortical thickness and bone density to stress. FEA modeling showed that the stress was 82% higher on the internal than the external surface, with a gradual decrease in internal and external wall stresses from the base to the apex. The inner cortex was more radio-dense, P < 0.001, and thicker, P < 0.001, than the outer cortex. Inner cortical thickness was related to internal stress, r = 0.94, P < 0.001, inner cortical bone density to internal stress, r = 0.87, P = 0.003, and outer cortical thickness to external stress, r = 0.65, P = 0.035. Mathematical models were developed relating internal and external cortical thicknesses and bone densities to rib level. The internal anatomical features of ribs, including the inner and outer cortical thicknesses and bone densities, are similar to the stress distribution in dome-shaped structures modeled using FEA computer simulations of a thick-walled dome pressure vessel. Fixation of rib fractures should include the stronger internal cortex. © 2015 Wiley Periodicals, Inc.

Prostaglandin E2 Prevents Bone Loss and Adds Extra Bone to Immobilized Distal Femoral Metaphysis in Female Rats

NASA Technical Reports Server (NTRS)

Akamine, T.; Jee, W. S. S.; Ke, H. Z.; Li, X. J.; Lin, B. Y.

1992-01-01

The object of this study was to determine whether prostaglandin E2 (PGE2) can prevent disuse (underloading)-induced cancellous bone loss. Thirteen-month-old retired female Sprague-Dawley breeders served as controls or were subjected to right hindlimb immobilization by bandaging and simultaneously treated subcutaneously daily with 0, 1, 3, or 6 mg PGE2/kg/d for two and six weeks. Histomorphometric analyses were performed on the cancellous bone using double-fluorescent labeled, 20 micron thick, undecalcified distal femoral metaphysis sections. We found that PGE2 administration not only prevented disuse-induced bone loss, but also added extra bone to disuse cancellous bone in a dose-response manner. PGE2 prevented the disuse-induced osteopenia by stimulating more bone formation than and shortening the period of bone remodeling. It activated woven bone formation, stimulated lamellar bone formation, and increased the eroded bone surface above that caused by disuse alone. While underloading increased the remodeling period (sigma), PGE2 treatment of underloaded bone shortened the time for osteoclastic bone resorption and bone remodeling, and thus reduced the remodeling space. The study shows that PGE2 is a powerful anabolic agent that prevents disuse-induced osteopenia and adds extra bone to these same bones.

A digital volumetric tomography (DVT) study in the mandibular molar region for miniscrew placement during mixed dentition

PubMed Central

Bhattad, Mayur S.; Baliga, Sudhindra; Vibhute, Pavan

2015-01-01

OBJECTIVE: To assess bone thickness for miniscrew placement in the mandible during mixed dentition by using digital volumetric tomograph (DVT). MATERIAL AND METHODS: A total of 15 healthy patients aged 8-10 years old, with early exfoliated mandibular second deciduous molar, were included. DVT images of one quadrant of the mandible were obtained using Kodak extraoral imaging systems and analyzed by Kodak dental imaging software. The error of the method (EM) was calculated using Dahlberg's formula. Mean and standard deviation were calculated at 6 and 8 mm from the cementoenamel junction (CEJ).Paired t-test was used to analyze the measurements. RESULTS: Buccal cortical bone thickness, mesiodistal width and buccolingual bone depth at 6 mm were found to be 1.73 + 0.41, 2.15 + 0.49 and 13.18 + 1.22 mm, respectively; while at 8 mm measurements were 2.42 + 0.34, 2.48 + 0.33 and 13.65 + 1.25 mm, respectively. EM for buccal cortical bone thickness, mesiodistal width and buccolingual bone depth was 0.58, 0.40 and 0.48, respectively. The difference in measurement at 6 and 8 mm for buccal cortical plate thickness (P < 0.05) and buccolingual bone thickness (P < 0.05) was found to be significant, whereas for mesiodistal width it was insignificant (P > 0.05). CONCLUSION: Bone thickness measurement has shown promising evidence for safe placement of miniscrews in the mandible during mixed dentition. The use of miniscrew is the best alternative, even in younger patients. PMID:25992988

Dynamic Alterations in Microarchitecture, Mineralization and Mechanical Property of Subchondral Bone in Rat Medial Meniscal Tear Model of Osteoarthritis

PubMed Central

Yu, De-Gang; Nie, Shao-Bo; Liu, Feng-Xiang; Wu, Chuan-Long; Tian, Bo; Wang, Wen-Gang; Wang, Xiao-Qing; Zhu, Zhen-An; Mao, Yuan-Qing

2015-01-01

Background: The properties of subchondral bone influence the integrity of articular cartilage in the pathogenesis of osteoarthritis (OA). However, the characteristics of subchondral bone alterations remain unresolved. The present study aimed to observe the dynamic alterations in the microarchitecture, mineralization, and mechanical properties of subchondral bone during the progression of OA. Methods: A medial meniscal tear (MMT) operation was performed in 128 adult Sprague Dawley rats to induce OA. At 2, 4, 8, and 12 weeks following the MMT operation, cartilage degeneration was evaluated using toluidine blue O staining, whereas changes in the microarchitecture indices and tissue mineral density (TMD), mineral-to-collagen ratio, and intrinsic mechanical properties of subchondral bone plates (BPs) and trabecular bones (Tbs) were measured using micro-computed tomography scanning, confocal Raman microspectroscopy and nanoindentation testing, respectively. Results: Cartilage degeneration occurred and worsened progressively from 2 to 12 weeks after OA induction. Microarchitecture analysis revealed that the subchondral bone shifted from bone resorption early (reduced trabecular BV/TV, trabecular number, connectivity density and trabecular thickness [Tb.Th], and increased trabecular spacing (Tb.Sp) at 2 and 4 weeks) to bone accretion late (increased BV/TV, Tb.Th and thickness of subchondral bone plate, and reduced Tb.Sp at 8 and 12 weeks). The TMD of both the BP and Tb displayed no significant changes at 2 and 4 weeks but decreased at 8 and 12 weeks. The mineral-to-collagen ratio showed a significant decrease from 4 weeks for the Tb and from 8 weeks for the BP after OA induction. Both the elastic modulus and hardness of the Tb showed a significant decrease from 4 weeks after OA induction. The BP showed a significant decrease in its elastic modulus from 8 weeks and its hardness from 4 weeks. Conclusion: The microarchitecture, mineralization and mechanical properties of subchondral bone changed in a time-dependent manner as OA progressed. PMID:26521785

Nanostructured thick 3D nanofibrous scaffold can induce bone.

PubMed

Eap, Sandy; Morand, David; Clauss, François; Huck, Olivier; Stoltz, Jean-François; Lutz, Jean-Christophe; Gottenberg, Jacques-Eric; Benkirane-Jessel, Nadia; Keller, Laetitia; Fioretti, Florence

2015-01-01

Designing unique nanostructured biomimetic materials is a new challenge in modern regenerative medicine. In order to develop functional substitutes for damaged organs or tissues, several methods have been used to create implants able to regenerate robust and durable bone. Electrospinning produces nonwoven scaffolds based on polymer nanofibers mimicking the fibrillar organization of bone extracellular matrix. Here, we describe a biomimetic 3D thick nanofibrous scaffold obtained by electrospinning of the biodegradable, bioresorbable and FDA-approved polymer, poly(ε-caprolactone). Such scaffold presents a thickness reaching one centimeter. We report here the demonstration that the designed nanostructured implant is able to induce in vivo bone regeneration.

Quantitative evaluation of palatal bone thickness for the placement of orthodontic miniscrews in adults with different facial types

PubMed Central

Wang, Yunji; Qiu, Ye; Liu, Henglang; He, Jinlong; Fan, Xiaoping

2017-01-01

Objectives: To quantitatively evaluate palatal bone thickness in adults with different facial types using cone beam computed tomography (CBCT). Methods: The CBCT volumetric data of 123 adults (mean age, 26.8 years) collected between August 2014 and August 2016 was retrospectively studied. The subjects were divided into a low-angle group (39 subjects), a normal-angle group (48 subjects) and a high-angle group (36 subjects) based on facial types assigned by cephalometric radiography. The thickness of the palatal bone was assessed at designated points. A repeated-measure analysis of variance (rm-ANOVA) test was used to test the relationship between facial types and palatal bone thickness. Results: Compared to the low-angle group, the high-angle group had significantly thinner palatal bones (p<0.05), except for the anterior-midline, anterior-medial and middle-midline areas. Conclusion: The safest zone for the placement of microimplants is the anterior part of the paramedian palate. Clinicians should pay special attention to the probability of thinner bone plates and the risk of perforation in high-angle patients. PMID:28917071

Impact of oral ibandronate 150 mg once monthly on bone structure and density in post-menopausal osteoporosis or osteopenia derived from in vivo μCT.

PubMed

Bock, Oliver; Börst, Hendrikje; Beller, Gisela; Armbrecht, Gabriele; Degner, Corina; Martus, Peter; Roth, Heinz-Jürgen; Felsenberg, Dieter

2012-01-01

The effect of ibandronate 150 mg/once monthly in the treatment of post-menopausal osteopenia and osteoporosis on bone micro-structure at the distal tibia and radius has not been considered to date. Seventy post-menopausal women with osteoporosis or osteopenia were recruited. All subjects received calcium and vitamin D supplementation and were randomized to either a group which took 150 mg ibandronate oral monthly or a placebo group over a 12-month period. μCT measures of the distal tibia and radius were conducted every three months, with DXA lumbar spine and hip measurements conducted only pre and post and serum markers of bone formation and resorption measured every 6 months. After 12-months no significant impact of ibandronate on the primary outcome measures bone-volume to tissue-volume and trabecular separation at the distal tibia (p≥0.15) was found. Further multiple regression analyses of the primary end-points indicated a significant effect favoring the ibandronate intervention (p=0.045). Analysis of secondary end-points showed greater increases in distal tibia cortical thickness, cortical density and total density (p≤0.043) with ibandronate and no significant effects at the distal radius, but greater increases of hip DXA-BMD and lumbar spine DXA-BMD (p≤0.017). Ibandronate use resulted in a marked reduction in bone turnover (p<0.001). While ibandronate resulted in greater mineralization of bone, this effect differed from one body region to another. There was some impact of ibandronate on bone structure (cortical thickness) at the distal tibia, but not on bone-volume to tissue-volume or trabecular separation. Copyright © 2011 Elsevier Inc. All rights reserved.

Prophylactic pamidronate partially protects from glucocorticoid-induced bone loss in the mdx mouse model of Duchenne muscular dystrophy.

PubMed

Yoon, Sung-Hee; Chen, Jinghan; Grynpas, Marc D; Mitchell, Jane

2016-09-01

Glucocorticoids are extensively used to treat patients with Duchenne muscular dystrophy because of their ability to delay muscle damage, prolong ambulation and extend life. However, use of glucocorticoids significantly increases bone loss, fragility and fractures. To determine if antiresorptive bisphosphonates could prevent the effects of glucocorticoids on bone quality, we used dystrophic mdx mice treated with the glucocorticoid prednisone during 8weeks of rapid bone growth from 5 to 13weeks of age and treated some mice with the bisphosphonate pamidronate during the first two weeks of prednisone administration. Prednisone reduced long bone growth, decreased cortical bone thickness and area and decreased the strength of the femurs. Pamidronate treatment protected mice from cortical bone loss but did not increase bone strength. The combination of prednisone and pamidronate inhibited remodeling of metaphyseal trabecular bone with large numbers of trabeculae containing remnants of calcified cartilage. Prednisone improved muscle strength in the mdx mice and decreased serum creatine kinase with evidence of improved muscle histology and these effects were maintained in mice treated with pamidronate. Copyright © 2016. Published by Elsevier Inc.

Culture-expanded mesenchymal stem cell sheets enhance extraction-site alveolar bone growth: An animal study.

PubMed

Mu, S; Tee, B C; Emam, H; Zhou, Y; Sun, Z

2018-04-06

Impaired bone formation of the buccal alveolar plate after tooth extraction during adolescence increases the difficulty of future implant restoration. This study was undertaken to assess the feasibility and efficacy of transplanting autogenous scaffold-free culture-expanded mesenchymal stem cell (MSC) sheets to the buccal alveolar bone surface to stimulate local bone growth. Mandibular bone marrow was aspirated from 3-month-old pigs (n = 5), from which MSCs were isolated and culture expanded. Triple-layer MSC sheets were then fabricated using temperature-responsive tissue culture plates. One month after bone marrow aspirations, the same pigs underwent bilateral extraction of mandibular primary molars, immediately followed by transplantation of 3 autogenous triple-layer MSC sheets on to the subperiosteal buccal alveolar surface of 1 randomly chosen side. The contralateral side (control) underwent the same periosteal reflection surgery without receiving MSC sheet transplantation. Six weeks later, the animals were killed and specimens from both sides were immediately harvested for radiographic and histological analysis. Buccal alveolar bone thickness, tissue mineral density (TMD), mineral apposition and bone volume fraction (BV/TV) were quantified and compared between the MSC sheet and control sides using paired t-tests. Triple-layer MSC sheets were reliably fabricated and the majority of cells remained vital before transplantation. The thickness of buccal bone tended to increase with MSC sheet transplantation (P = .18), with 4 of 5 animals showing an average of 1.82 ± 0.73 mm thicker bone on the MSC sheet side than the control side. After being normalized by the TMD of intracortical bone, the TMD of surface cortical bone was 0.5-fold higher on the MSC sheet side than the control side (P < .05). Likewise, the BV/TV measurements of the buccal surface region were also 0.4-fold higher on the MSC sheet side than the control side (P < .05) after being normalized by measurements from the intracortical region. Mineral apposition measurements were not different between the 2 sides. Mandibular marrow-derived MSCs can be fabricated into cell sheets and autogenous transplantation of MSC sheets onto the subperiosteal buccal alveolar bone surface at the tooth-extraction site may increase local bone density. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A myostatin and activin decoy receptor enhances bone formation in mice.

PubMed

Bialek, P; Parkington, J; Li, X; Gavin, D; Wallace, C; Zhang, J; Root, A; Yan, G; Warner, L; Seeherman, H J; Yaworsky, P J

2014-03-01

Myostatin is a member of the bone morphogenetic protein/transforming growth factor-β (BMP/TGFβ) super-family of secreted differentiation factors. Myostatin is a negative regulator of muscle mass as shown by increased muscle mass in myostatin deficient mice. Interestingly, these mice also exhibit increased bone mass suggesting that myostatin may also play a role in regulating bone mass. To investigate the role of myostatin in bone, young adult mice were administered with either a myostatin neutralizing antibody (Mstn-mAb), a soluble myostatin decoy receptor (ActRIIB-Fc) or vehicle. While both myostatin inhibitors increased muscle mass, only ActRIIB-Fc increased bone mass. Bone volume fraction (BV/TV), as determined by microCT, was increased by 132% and 27% in the distal femur and lumbar vertebrae, respectively. Histological evaluation demonstrated that increased BV/TV in both locations was attributed to increased trabecular thickness, trabecular number and bone formation rate. Increased BV/TV resulted in enhanced vertebral maximum compressive force compared to untreated animals. The fact that ActRIIB-Fc, but not Mstn-mAb, increased bone volume suggested that this soluble decoy receptor may be binding a ligand other than myostatin, that plays a role in regulating bone mass. This was confirmed by the significant increase in BV/TV in myostatin deficient mice treated with ActRIIB-Fc. Of the other known ActRIIB-Fc ligands, BMP3 has been identified as a negative regulator of bone mass. However, BMP3 deficient mice treated with ActRIIB-Fc showed similar increases in BV/TV as wild type (WT) littermates treated with ActRIIB-Fc. This result suggests that BMP3 neutralization is not the mechanism responsible for increased bone mass. The results of this study demonstrate that ActRIIB-Fc increases both muscle and bone mass in mice. Therefore, a therapeutic that has this dual activity represents a potential approach for the treatment of frailty. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Reference ranges for foetal nasal bone length, prenasal thickness, and interocular distance at 18 to 24 weeks' gestation in low-risk pregnancies.

PubMed

Altunkeser, Ayşegül; Körez, M Kazım

2017-12-12

The aim of the present study was to establish the normal ranges for foetal nasal bone length (NBL), prenasal skin thickness (PNT), interocular distance (IOD), and ratio of prenasal thickness to- nasal bone length (PNT/ NBL) at 18-24 weeks using two-dimensional (2D) ultrasound. This study was a retrospective study of prenatal ultrasonographic records from 407 foetuses between 18 and 24 weeks gestational age (GA). The NBL, PNT, IOD, PNT/ NBL ratio, biparietal diameter (BPD), and femur length (FL) were investigated. The relationships among NBL, PNT, IOD, PNT/ NBL, and GA were evaluated. Additionally, descriptive statistics for NBL, PNT, and IOD values for each gestational week were obtained. There was a significant association between GA and NBL, PNT, and IOD between 18 and 24 weeks. NBL increased from a mean of 5.5 mm to 8.3 mm, PNT increased from a mean of 3.5 mm to 5.1 mm, and IOD increased from a mean of 11.1 mm to 14.5 mm. PNT/NBL ratio did not change with gestational age. This study showed normal ranges for NBL, PNT, IOD, and PNT/ NBL ratios for foetuses between 18 and 24 weeks in low-risk pregnancies. There was a positive linear relationship between GA and NBL, PNT, and IOD. The PNT/NBL ratio might be a more useful measurement than NBL or PNT alone.

High-Dietary Alpha-Tocopherol or Mixed Tocotrienols Have No Effect on Bone Mass, Density, or Turnover in Male Rats During Skeletal Maturation.

PubMed

Tennant, Katherine G; Leonard, Scott W; Wong, Carmen P; Iwaniec, Urszula T; Turner, Russell T; Traber, Maret G

2017-07-01

High levels of alpha-tocopherol, the usual vitamin E supplement, are reported to decrease bone mass in rodents; however, the effects of other vitamin E forms on the skeleton are unknown. To test the hypothesis that high intakes of various vitamin E forms or the vitamin E metabolite, carboxyethyl hydroxy chromanol, were detrimental to bone status, Sprague-Dawley rats (n = 6 per group, 11-week males) for 18 weeks consumed semipurified diets that contained adequate alpha-tocopherol, high alpha-tocopherol (500 mg/kg diet), or 50% Tocomin (250 mg mixed tocopherols and tocotrienols/kg diet). Vitamin E status was evaluated by measuring plasma, liver, and bone marrow vitamin E concentrations. Bone density, microarchitecture (cross-sectional volume, cortical volume, marrow volume, cortical thickness, and cancellous bone volume fraction, trabecular number, thickness, and spacing), and cancellous bone formation were assessed in the tibia using dual-energy X-ray absorptiometry, microcomputed tomography, and histomorphometry, respectively. In addition, serum osteocalcin was assessed as a global marker of bone turnover; gene expression in response to treatment was evaluated in the femur using targeted (osteogenesis related) gene profiling. No significant differences were detected between treatment groups for any of the bone endpoints measured. Vitamin E supplementation, either as alpha-tocopherol or mixed tocotrienols, while increasing vitamin E concentrations both in plasma and tissues, had no effect on the skeleton in rats.

[Expression of mRNA and protein of p38, Osx, PI3K and Akt1 in rat bone with chronic fluorosis].

PubMed

Yu, Yan-ni; Yang, Dan; Zhu, Hai-zhen; Deng, Chao-nan; Guan, Zhi-zhong

2012-09-01

To investigate the expressions of mRNA and protein of p38, Osx, PI3K, Akt1 in the rats bone with chronic fluorosis. Dental fluorosis were observed and the fluoride contents in the urine and bone were detected by fluorin-ion selective electrode. The morphologic changes and ultrastructure of rats' bone were observed by light and electronic microscopy. The expressions of protein and mRNA of p38, Osx, PI3K and Akt1 were detected by immunohistochemistry and real-time PCR, respectively. The contents of BALP and BGP in serum were detected by ELISA. The rates of dental fluorosis in the fluorosis rats were increased, and the fluoride contents in bone and urine of the fluorosis rats were increased compared to the control group, the difference was statistically significant (P < 0.05). The bone trabeculae thickness and density and the thickness of bone cortex in fluorosis rats were remarkably increased, the space of bone trabeculae was reduced, and in accordance with the matching morphometrical indices, the difference was statistically significant (P < 0.05) as compared with the control rats. The contents of BALP [(54.61 ± 2.27) U/L] and BGP [(2.38 ± 0.16) µg/L]in the fluoride groups were higher than those in the control group, the difference was statistically significant (P < 0.05). Ultrastructurally, the broadening of the osseouslacuna was observed. The reduced protuberances of the osteocytes, the unclear organelle structure, pyknosis, karyotheca increasation and edged chromatin were also observed. Compared to the control group, the expressions of protein and its mRNA of p38, Osx, PI3K and Akt1 were higher in the fluorosis rats than those in the control rats, and the difference was statistically significant (P < 0.05). There is no any expression of p38, Osx, PI3K and Akt1 in the osteocytes in fluorosis rats. The over-expression of p38, Osx, PI3K and Akt1 in bone tissue of fluorosis rats may relate to the accumulation of fluorine in the body. The bone injury mainly occur in the stage of the differentiation and proliferation. The upregulation of P38MARK signal path and PI3K/Akt1 signal path may be involved in the pathogenesis of bone injury caused by fluoride.

Influence of basis images and skull position on evaluation of cortical bone thickness in cone beam computed tomography.

PubMed

Nascimento, Monikelly do Carmo Chagas; Boscolo, Solange Maria de Almeida; Haiter-Neto, Francisco; Santos, Emanuela Carla Dos; Lambrichts, Ivo; Pauwels, Ruben; Jacobs, Reinhilde

2017-06-01

The aim of this study was to assess the influence of the number of basis images and the orientation of the skull on the evaluation of cortical alveolar bone in cone beam computed tomography (CBCT). Eleven skulls with a total of 59 anterior teeth were selected. CBCT images were acquired by using 4 protocols, by varying the rotation of the tube-detector arm and the orientation of the skull (protocol 1: 360°/0°; protocol 2: 180°/0°; protocol 3: 180°/90°; protocol 4: 180°/180°). Observers evaluated cortical bone as absent, thin, or thick. Direct observation of the skulls was used as the gold standard. Intra- and interobserver agreement, as well as agreement of scoring between the 3 bone thickness classifications, were calculated by using the κ statistic. The Wilcoxon signed-rank test was used to compare the 4 protocols. For lingual cortical bone, protocol 1 showed no statistical difference from the gold standard. Higher reliability was found in protocol 3 for absent (κ = 0.80) and thin (κ = 0.47) cortices, whereas for thick cortical bone, protocol 2 was more consistent (κ = 0.60). In buccal cortical bone, protocol 1 obtained the highest agreement for absent cortices (κ = 0.61), whereas protocol 4 was better for thin cortical plates (κ = 0.38) and protocol 2 for thick cortical plates (κ = 0.40). No consistent effect of the number of basis images or head orientation for visual detection of alveolar bone was detected, except for lingual cortical bone, for which full rotation scanning showed improved visualization. Copyright © 2017 Elsevier Inc. All rights reserved.

Automated trabecular bone histomorphometry

NASA Technical Reports Server (NTRS)

Polig, E.; Jee, W. S. S.

1985-01-01

The toxicity of alpha-emitting bone-seeking radionuclides and the relationship between bone tumor incidence and the local dosimetry of radionuclides in bone are investigated. The microdistributions of alpha-emitting radionuclides in the trabecular bone from the proximal humerus, distal humerus, proximal ulna, proximal femur, and distal femur of six young adult beagles injected with Am-241 (three with 2.8 micro-Ci/kg and three with 0.9 micro-Ci/kg) are estimated using a computer-controlled microscope photometer system; the components of the University of Utah Optical Track Scanner are described. The morphometric parameters for the beagles are calculated and analyzed. It is observed that the beagles injected with 0.9 micro-Ci of Am-241/kg showed an increase in the percentage of bone and trabecular bone thickness, and a reduction in the width of the bone marrow space and surface/volume ratio. The data reveal that radiation damage causes abnormal bone structure.

The influence of the periodontal biotype on peri-implant tissues around immediate implants with and without xenografts. Clinical and micro-computerized tomographic study in small Beagle dogs.

PubMed

Maia, Luciana P; Reino, Danilo M; Muglia, Valdir A; de Souza, Sérgio L S; Palioto, Daniela B; Novaes, Arthur B

2015-01-01

Soft tissues and buccal bone plate remodeling after immediate implantation in sockets with thin buccal bone, using the flapless approach with or without bone graft into the buccal gap, was compared between sites with thin and normal gingiva. Eight dogs had the gingiva of one side of the mandible thinned, the mandibular premolars were extracted without flaps, and 4 implants were installed in each side, positioned 1.5 mm from the buccal bone. The sites were randomly assigned into: TG (test group) = thin gingiva; TG + GM (TG with grafting material); CG (control group) = normal gingiva; and CG + GM (CG with grafting material). Buccal bone thickness (BBT), thickness of keratinized tissue (TKT), alveolar thickness (AT), gingival recession (GR), and probing depth (PD) were clinically evaluated. Within 12 weeks the dogs were sacrificed and the samples were analyzed by micro-computerized tomography. A thin BBT was observed in all the dogs. The presurgical procedures reduced TKT in the test group, with minimal changes of the AT. There were no statistically significant differences among the groups for the clinical parameters and the tomographic analysis showed similar linear and tri-dimensional bone reduction in all the groups. The thickness of the buccal bone was a fundamental factor in buccal bone plate resorption, even with flapless implantation. The decrease in gingival thickness or the addition of a biomaterial in the gap did not influence the results. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The Effects of GATA-1 and NF-E2 Deficiency on Bone Biomechanical, Biochemical, and Mineral Properties

PubMed Central

Kacena, Melissa A.; Gundberg, Caren M.; Kacena, William J.; Landis, William J.; Boskey, Adele L.; Bouxsein, Mary L.; Horowitz, Mark C.

2014-01-01

Mice deficient in GATA-1 or NF-E2, transcription factors required for normal megakaryocyte (MK) development, have increased numbers of MKs, reduced numbers of platelets, and a striking high bone mass phenotype. Here, we show the bone geometry, microarchitecture, biomechanical, biochemical, and mineral properties from these mutant mice. We found that the outer geometry of the mutant bones was similar to controls, but that both mutants had a striking increase in total bone area (up to a 35% increase) and trabecular bone area (up to a 19% increase). Interestingly, only the NF-E2 deficient mice had a significant increase in cortical bone area (21%) and cortical thickness (27%), which is consistent with the increase in bone mineral density (BMD) seen only in the NF-E2 deficient femurs. Both mutant femurs exhibited significant increases in several biomechanical properties including peak load (up to a 32% increase) and stiffness (up to a 13% increase). Importantly, the data also demonstrate differences between the two mutant mice. GATA-1 deficient femurs break in a ductile manner, whereas NF-E2 deficient femurs are brittle in nature. To better understand these differences, we examined the mineral properties of these bones. Although none of the parameters measured were different between the NF-E2 deficient and control mice, an increase in calcium (21%) and an increase in the mineral/matrix ratio (32%) was observed in GATA-1 deficient mice. These findings appear to contradict biomechanical findings, suggesting the need for further research into the mechanisms by which GATA-1 and NF-E2 deficiency alter the material properties of bone. PMID:23359245

Osteoblast-derived WNT16 represses osteoclastogenesis and prevents cortical bone fragility fractures

PubMed Central

Movérare-Skrtic, Sofia; Henning, Petra; Liu, Xianwen; Nagano, Kenichi; Saito, Hiroaki; Börjesson, Anna E; Sjögren, Klara; Windahl, Sara H; Farman, Helen; Kindlund, Bert; Engdahl, Cecilia; Koskela, Antti; Zhang, Fu-Ping; Eriksson, Emma E; Zaman, Farasat; Hammarstedt, Ann; Isaksson, Hanna; Bally, Marta; Kassem, Ali; Lindholm, Catharina; Sandberg, Olof; Aspenberg, Per; Sävendahl, Lars; Feng, Jian Q; Tuckermann, Jan; Tuukkanen, Juha; Poutanen, Matti; Baron, Roland; Lerner, Ulf H; Gori, Francesca; Ohlsson, Claes

2015-01-01

The WNT16 locus is a major determinant of cortical bone thickness and nonvertebral fracture risk in humans. The disability, mortality and costs caused by osteoporosis-induced nonvertebral fractures are enormous. We demonstrate here that Wnt16-deficient mice develop spontaneous fractures as a result of low cortical thickness and high cortical porosity. In contrast, trabecular bone volume is not altered in these mice. Mechanistic studies revealed that WNT16 is osteoblast derived and inhibits human and mouse osteoclastogenesis both directly by acting on osteoclast progenitors and indirectly by increasing expression of osteoprotegerin (Opg) in osteoblasts. The signaling pathway activated by WNT16 in osteoclast progenitors is noncanonical, whereas the pathway activated in osteoblasts is both canonical and noncanonical. Conditional Wnt16 inactivation revealed that osteoblast-lineage cells are the principal source of WNT16, and its targeted deletion in osteoblasts increases fracture susceptibility. Thus, osteoblast-derived WNT16 is a previously unreported key regulator of osteoclastogenesis and fracture susceptibility. These findings open new avenues for the specific prevention or treatment of nonvertebral fractures, a substantial unmet medical need. PMID:25306233

Subsequent somatic axis and bone tissue metabolism responses to a low-zinc diet with or without phytase inclusion in broiler chickens.

PubMed

Muszyński, Siemowit; Tomaszewska, Ewa; Kwiecień, Małgorzata; Dobrowolski, Piotr; Tomczyk-Warunek, Agnieszka

2018-01-01

Zinc is required for normal bone development and cartilage formation. The purpose of this study was to assess the effect of with adding organic Zn (alone or phytase inclusion) at the reduced dose to growing male Ross 308 chickens on somatic axis and bone tissue metabolism. 200 one-day old broilers were divided into the negative control group fed diet without Zn or phytase inclusion, positive control group receiving Zn in the 100% of daily recommended dose from ZnO, and two experimental groups fed diet introduced Zn in 25% of daily recommendation as a glycine chelate (Zn-Gly) with or without phytase inclusion (500 FTU·kg-1). Supplemental organic Zn increased bone Zn and Mg content, serum IGF-1, growth hormone and leptin concentration. Additional phytase inclusion increased body weight gain, blood plasma Ca, Fe, Zn and osteocalcin concentration and tibia ash percentage when compared to the Zn-deprived control. Bone geometry, yield and ultimate strengths were enhanced in both organic Zn supplemented groups, and the overall mechanical strength parameters of bone were better in these groups than in the positive control group supplemented with standard dose of inorganic Zn. Also marked improvements in the thickness of articular and the growth plate cartilages as well as real bone volume and thickness of metaphyseal trabeculae were achieved in all broilers fed Zn-supplemented diet irrespective of phytase inclusion, however, the highest cancellous bone mass and the best trabecular structure were noted after ZnO supplementation. In concludion, although dietary organic Zn given to growing broilers in 25% of daily recommended dose improved general bone properties and mechanical strength, the obtained results do not allow to unambiguously state that organic Zn supplementation at this level, even after phytase inclusion, is sufficient for proper bone development.

Subsequent somatic axis and bone tissue metabolism responses to a low-zinc diet with or without phytase inclusion in broiler chickens

PubMed Central

Tomaszewska, Ewa; Kwiecień, Małgorzata; Dobrowolski, Piotr; Tomczyk-Warunek, Agnieszka

2018-01-01

Zinc is required for normal bone development and cartilage formation. The purpose of this study was to assess the effect of with adding organic Zn (alone or phytase inclusion) at the reduced dose to growing male Ross 308 chickens on somatic axis and bone tissue metabolism. 200 one-day old broilers were divided into the negative control group fed diet without Zn or phytase inclusion, positive control group receiving Zn in the 100% of daily recommended dose from ZnO, and two experimental groups fed diet introduced Zn in 25% of daily recommendation as a glycine chelate (Zn-Gly) with or without phytase inclusion (500 FTU·kg-1). Supplemental organic Zn increased bone Zn and Mg content, serum IGF-1, growth hormone and leptin concentration. Additional phytase inclusion increased body weight gain, blood plasma Ca, Fe, Zn and osteocalcin concentration and tibia ash percentage when compared to the Zn-deprived control. Bone geometry, yield and ultimate strengths were enhanced in both organic Zn supplemented groups, and the overall mechanical strength parameters of bone were better in these groups than in the positive control group supplemented with standard dose of inorganic Zn. Also marked improvements in the thickness of articular and the growth plate cartilages as well as real bone volume and thickness of metaphyseal trabeculae were achieved in all broilers fed Zn-supplemented diet irrespective of phytase inclusion, however, the highest cancellous bone mass and the best trabecular structure were noted after ZnO supplementation. In concludion, although dietary organic Zn given to growing broilers in 25% of daily recommended dose improved general bone properties and mechanical strength, the obtained results do not allow to unambiguously state that organic Zn supplementation at this level, even after phytase inclusion, is sufficient for proper bone development. PMID:29373588

Chitosan porous 3D scaffolds embedded with resolvin D1 to improve in vivo bone healing.

PubMed

Vasconcelos, Daniela P; Costa, Madalena; Neves, Nuno; Teixeira, José H; Vasconcelos, Daniel M; Santos, Susana G; Águas, Artur P; Barbosa, Mário A; Barbosa, Judite N

2018-06-01

The aim of this study was to investigate the effect chitosan (Ch) porous 3D scaffolds embedded with resolvin D1 (RvD1), an endogenous pro-resolving lipid mediator, on bone tissue healing. These scaffolds previous developed by us have demonstrated to have immunomodulatory properties namely in the modulation of the macrophage inflammatory phenotypic profile in an in vivo model of inflammation. Herein, results obtained in an in vivo rat femoral defect model demonstrated that two months after Ch + RvD1 scaffolds implantation, an increase in new bone formation, in bone trabecular thickness, and in collagen type I and Coll I/Coll III ratio were observed. These results suggest that Ch scaffolds embedded with RvD1 were able to lead to the formation of new bone with improvement of trabecular thickness. This study shows that the presence of RvD1 in the acute phase of the inflammatory response to the implanted biomaterial had a positive role in the subsequent bone tissue repair, thus demonstrating the importance of innovative approaches for the control of immune responses to biomedical implants in the design of advanced strategies for regenerative medicine. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1626-1633, 2018. © 2018 Wiley Periodicals, Inc.

Crystallographic orientation of the c-axis of biological apatite as a new index of the quality of subchondral bone in knee joint osteoarthritis.

PubMed

Lee, Jee-Wook; Kobayashi, Akio; Nakano, Takayoshi

2017-05-01

The aim of the present study was to investigate the preferred orientation of biological apatite (BAp) as a new index of the quality of subchondral bone (SB) in knee joint osteoarthritis (OA). Ten OA and five normal knee joints were obtained. Thickness, quantity and bone mineral density (BMD) of SB were analyzed at the medial condyle of the femur in dry conditions by peripheral quantitative computed tomography. In addition, the preferred crystallographic orientation of the c-axis of BAp was evaluated as bone quality parameter using a microbeam X-ray diffractometer technique. BMD and thickness of SB were significantly increased in OA specimens compared to normal knee specimens (P < 0.01), and the preferred orientation of the c-axis of BAp along the normal direction of SB surface was significantly higher in OA specimens (P < 0.01), reflecting the change in stress of concentration in the pathological portion without cartilage. SB sclerosis in OA results in both proliferation of bone tissues and enhanced degree of preferential alignment of the c-axis of BAp. Our findings could have major implications for the diagnosis of clinical studies, including pathologic elucidation in OA.

Influence of physical activity on tibial bone material properties in laying hens

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rodriguez-Navarro, A. B.; McCormack, H. M.; Fleming, R. H.

Laying hens develop a type of osteoporosis that arises from a loss of structural bone, resulting in high incidence of fractures. In this study, a comparison of bone material properties was made for lines of hens created by divergent selection to have high and low bone strength and housed in either individual cages, with restricted mobility, or in an aviary system, with opportunity for increased mobility. Improvement of bone biomechanics in the high line hens and in aviary housing was mainly due to increased bone mass, thicker cortical bone and more medullary bone. However, bone material properties such as corticalmore » and medullary bone mineral composition and crystallinity as well as collagen maturity did not differ between lines. However, bone material properties of birds from the different type of housing were markedly different. The cortical bone in aviary birds had a lower degree of mineralization and bone mineral was less mature and less organized than in caged birds. Here, these differences can be explained by increased bone turnover rates due to the higher physical activity of aviary birds that stimulates bone formation and bone remodeling. Multivariate statistical analyses shows that both cortical and medullary bone contribute to breaking strengthThe cortical thickness was the single most important contributor while its degree of mineralization and porosity had a smaller contribution. Lastly, bone properties had poorer correlations with mechanical properties in cage birds than in aviary birds presumably due to the greater number of structural defects of cortical bone in cage birds.« less

Influence of physical activity on tibial bone material properties in laying hens

DOE PAGES

Rodriguez-Navarro, A. B.; McCormack, H. M.; Fleming, R. H.; ...

2017-11-03

Laying hens develop a type of osteoporosis that arises from a loss of structural bone, resulting in high incidence of fractures. In this study, a comparison of bone material properties was made for lines of hens created by divergent selection to have high and low bone strength and housed in either individual cages, with restricted mobility, or in an aviary system, with opportunity for increased mobility. Improvement of bone biomechanics in the high line hens and in aviary housing was mainly due to increased bone mass, thicker cortical bone and more medullary bone. However, bone material properties such as corticalmore » and medullary bone mineral composition and crystallinity as well as collagen maturity did not differ between lines. However, bone material properties of birds from the different type of housing were markedly different. The cortical bone in aviary birds had a lower degree of mineralization and bone mineral was less mature and less organized than in caged birds. Here, these differences can be explained by increased bone turnover rates due to the higher physical activity of aviary birds that stimulates bone formation and bone remodeling. Multivariate statistical analyses shows that both cortical and medullary bone contribute to breaking strengthThe cortical thickness was the single most important contributor while its degree of mineralization and porosity had a smaller contribution. Lastly, bone properties had poorer correlations with mechanical properties in cage birds than in aviary birds presumably due to the greater number of structural defects of cortical bone in cage birds.« less

Computational design analysis for deployment of cardiovascular stents

NASA Astrophysics Data System (ADS)

Tammareddi, Sriram; Sun, Guangyong; Li, Qing

2010-06-01

Cardiovascular disease has become a major global healthcare problem. As one of the relatively new medical devices, stents offer a minimally-invasive surgical strategy to improve the quality of life for numerous cardiovascular disease patients. One of the key associative issues has been to understand the effect of stent structures on its deployment behaviour. This paper aims to develop a computational model for exploring the biomechanical responses to the change in stent geometrical parameters, namely the strut thickness and cross-link width of the Palmaz-Schatz stent. Explicit 3D dynamic finite element analysis was carried out to explore the sensitivity of these geometrical parameters on deployment performance, such as dog-boning, fore-shortening, and stent deformation over the load cycle. It has been found that an increase in stent thickness causes a sizeable rise in the load required to deform the stent to its target diameter, whilst reducing maximum dog-boning in the stent. An increase in the cross-link width showed that no change in the load is required to deform the stent to its target diameter, and there is no apparent correlation with dog-boning but an increased fore-shortening with increasing cross-link width. The computational modelling and analysis presented herein proves an effective way to refine or optimise the design of stent structures.

MACF1 Overexpression by Transfecting the 21 kbp Large Plasmid PEGFP-C1A-ACF7 Promotes Osteoblast Differentiation and Bone Formation.

PubMed

Zhang, Yan; Yin, Chong; Hu, Lifang; Chen, Zhihao; Zhao, Fan; Li, Dijie; Ma, Jianhua; Ma, Xiaoli; Su, Peihong; Qiu, Wuxia; Yang, Chaofei; Wang, Pai; Li, Siyu; Zhang, Ge; Wang, Liping; Qian, Airong; Xian, Cory J

2018-02-01

Microtubule actin crosslinking factor 1 (MACF1) is a large spectraplakin protein known to have crucial roles in regulating cytoskeletal dynamics, cell migration, growth, and differentiation. However, its role and action mechanism in bone remain unclear. The present study investigated optimal conditions for effective transfection of the large plasmid PEGFP-C1A-ACF7 (∼21 kbp) containing full-length human MACF1 cDNA, as well as the potential role of MACF1 in bone formation. To enhance MACF1 expression, the plasmid was transfected into osteogenic cells by electroporation in vitro and into mouse calvaria with nanoparticles. Then, transfection efficiency, osteogenic marker expression, calvarial thickness, and bone formation were analyzed. Notably, MACF1 overexpression triggered a drastic increase in osteogenic gene expression, alkaline phosphatase activity, and matrix mineralization in vitro. Mouse calvarial thickness, mineral apposition rate, and osteogenic marker protein expression were significantly enhanced by local transfection. In addition, MACF1 overexpression promoted β-catenin expression and signaling. In conclusion, MACF1 overexpression by transfecting the large plasmid containing full-length MACF1 cDNA promotes osteoblast differentiation and bone formation via β-catenin signaling. Current data will provide useful experimental parameters for the transfection of large plasmids and a novel strategy based on promoting bone formation for prevention and therapy of bone disorders.

Assessing bone volume for orthodontic miniplate fixation below the maxillary frontal process.

PubMed

Präger, T M; Brochhagen, H G; Mischkowski, R; Jost-Brinkmann, P-G; Müller-Hartwich, R

2014-09-01

The maxillary bone below the frontal process is used for orthodontic anchorage; indications have included skeletally anchored protraction of the maxilla for treating Class III malocclusions or the intrusion of teeth in patients with a deep bite. This study was conducted to assess the condition of bone before cortically implanting miniplates in that area of the maxilla. A total of 51 thin-sliced computed tomography scans of 51 fully-dentate adult patients (mean age 24.0 ± 8.1 years; 27 men and 24 women) obtained prior to third-molar osteotomy were evaluated. Study parameters included total bone thickness, thickness of the facial cortical plate, and width of the nasal maxillary buttress. All these parameters were measured at different vertical levels. The bone volume adjacent to the piriform aperture was most pronounced at the basal level and decreased progressively toward more cranial levels. The basal bone structure had a mean total thickness of 7.8 mm, facial cortical plate thickness of 1.9 mm, and nasal maxillary buttress width of 9.2 mm. At 16 mm cranial to the aperture base, these values fell to 5.6 mm, 1.3 mm, and 5.8 mm, respectively. These bone measurements suggest that screws 7 mm in length can be inserted at the base level of the piriform aperture and screws 5 mm long at the cranial end of the bone.

Deterioration of Cortical Bone Microarchitecture: Critical Component of Renal Osteodystrophy Evaluation.

PubMed

Sharma, Ashish K; Toussaint, Nigel D; Masterson, Rosemary; Holt, Stephen G; Rajapakse, Chamith S; Ebeling, Peter R; Mohanty, Sindhu T; Baldock, Paul; Elder, Grahame J

2018-05-23

Cortical bone is a significant determinant of bone strength and its deterioration contributes to bone fragility. Thin cortices and increased cortical porosity have been noted in patients with chronic kidney disease (CKD), but the "Turnover Mineralization Volume" classification of renal osteodystrophy does not emphasize cortical bone as a key parameter. We aimed to assess trabecular and cortical bone microarchitecture by histomorphometry and micro-CT in patients with CKD G5 and 5D (dialysis). Transiliac bone biopsies were performed in 14 patients undergoing kidney transplantation (n = 12) and parathyroidectomy (n = 2). Structural parameters were analysed by histomorphometry and micro-CT including trabecular bone volume, thickness (TbTh), number (TbN) and separation and cortical thickness (CtTh) and porosity (CtPo). Indices of bone remodelling and mineralisation were obtained and relationships to bone biomarkers examined. Associations were determined by Spearman's or Pearson's rank correlation coefficients. By micro-CT, trabecular parameters were within normal ranges in most patients, but all patients showed very low CtTh (127 ± 44 µm) and high CtPo (60.3 ± 22.5%). CtPo was inversely related to TbN (r = -0.56; p = 0.03) by micro-CT and to TbTh (r = -0.60; p = 0.024) by histomorphometry and correlated to parathyroid hormone values (r = 0.62; p = 0.021). By histomorphometry, bone turnover was high in 50%, low in 21% and normal in 29%, while 36% showed abnormal patterns of mineralization. Significant positive associations were observed between osteoblast surface, osteoclast surface, mineralization surface and bone turnover markers. Deterioration of cortical -microarchitecture despite predominantly normal trabecular parameters reinforces the importance of comprehensive cortical evaluation in patients with CKD. © 2018 S. Karger AG, Basel.

Combination of hindlimb suspension and immobilization by casting exaggerates sarcopenia by stimulating autophagy but does not worsen osteopenia.

PubMed

Speacht, Toni L; Krause, Andrew R; Steiner, Jennifer L; Lang, Charles H; Donahue, Henry J

2018-05-01

Astronauts in space experience a unique environment that causes the concomitant loss of bone and muscle. However, the interaction between these tissues and how osteopenia and sarcopenia affect each other is unclear. We explored this relationship by exaggerating unloading-induced muscle loss using a unilateral casting model in conjunction with hindlimb suspension (HLS). Five-month-old, male C57Bl/6J mice subjected to HLS for 2 weeks displayed a significant decrease in gastrocnemius and quadriceps weight (-9-10%), with a two-fold greater decrease in muscle mass observed in the HLS + casted limb. However, muscle from casted limbs had a higher rate of protein synthesis (+16%), compared to HLS alone, with coordinated increases in S6K1 (+50%) and 4E-BP1 (+110%) phosphorylation. Increased protein content for surrogate markers of autophagy, including LC3-II (+75%), Atg7 (+10%), and Atg5-12 complex (+20%) was only detected in muscle from the casted limb. In proximal tibias, HLS resulted in significant decreases in bone volume fraction (-24% vs -8%), trabecular number (-6% vs +0.3%), trabecular thickness (-10% vs -2%), and trabecular spacing (+8.4% vs +2%) compared to ground controls. There was no further bone loss in casted limbs compared to HLS alone. In tibia midshafts, HLS resulted in decreased total area (-2% vs +1%) and increased bone mineral density (+1% vs -0.3%) compared to ground controls. Cortical bone from casted limbs showed an increase in cortical thickness (+9% vs +2%) and cortical area/total area (+1% vs -0.6%) compared to HLS alone. Our results suggest that casting exacerbates unloading-induced muscle loss via activation of autophagy. Casting did not exacerbate bone loss suggesting that the unloading-induced loss of muscle and bone can be temporally dissociated and the effect of reduced muscle activity plays a relatively minor role compared to reduced load bearing on trabecular bone structure. Copyright © 2018 Elsevier Inc. All rights reserved.

Significant bone microarchitecture impairment in premenopausal women with active celiac disease.

PubMed

Zanchetta, María Belén; Costa, Florencia; Longobardi, Vanesa; Longarini, Gabriela; Mazure, Roberto Martín; Moreno, María Laura; Vázquez, Horacio; Silveira, Fernando; Niveloni, Sonia; Smecuol, Edgardo; Temprano, María de la Paz; Hwang, Hui Jer; González, Andrea; Mauriño, Eduardo César; Bogado, Cesar; Zanchetta, Jose R; Bai, Julio César

2015-07-01

Patients with active celiac disease (CD) are more likely to have osteoporosis and increased risk of fractures. High-resolution peripheral quantitative computed tomography (HR-pQCT) permits three-dimensional exploration of bone microarchitectural characteristics measuring separately cortical and trabecular compartments, and giving a more profound insight into bone disease pathophysiology and fracture. We aimed to determine the volumetric and microarchitectural characteristics of peripheral bones-distal radius and tibia-in an adult premenopausal cohort with active CD assessed at diagnosis. We prospectively enrolled 31 consecutive premenopausal women with newly diagnosed CD (median age 29 years, range: 18-49) and 22 healthy women of similar age (median age 30 years, range 21-41) and body mass index. Compared with controls, peripheral bones of CD patients were significantly lower in terms of total volumetric density mg/cm(3) (mean ± SD: 274.7 ± 51.7 vs. 324.7 ± 45.8, p 0.0006 at the radius; 264.4 ± 48.7 vs. 307 ± 40.7, p 0.002 at the tibia), trabecular density mg/cm(3) (118.6 ± 31.5 vs. 161.9 ± 33.6, p<0.0001 at the radius; 127.9 ± 28.7 vs. 157.6 ± 15.6, p < 0.0001 at the tibia); bone volume/trabecular volume ratio % (9.9 ± 2.6 vs. 13.5 ± 2.8, p<0.0001 at the radius; 10.6 ± 2.4 vs. 13.1 ± 1.3, p < 0.0001 at the tibia); number of trabeculae 1/mm (1.69 ± 0.27 vs. 1.89 ± 0.26, p 0.009 at the radius; 1.53 ± 0.32 vs. 1.80 ± 0.26, p 0.002 at the tibia); and trabecular thickness mm (0.058 ± 0.010 vs. 0.071 ± 0.008, p < 0.0001 at the radius with no significant difference at the tibia). Cortical density was significantly lower in both regions (D comp mg/cm(3) 860 ± 57.2 vs. 893.9 ± 43, p 0.02; 902.7 ± 48.7 vs. 932.6 ± 32.6, p 0.01 in radius and tibia respectively). Although cortical thickness was lower in CD patients, it failed to show any significant inter-group difference (a-8% decay with p 0.11 in both bones). Patients with symptomatic CD (n = 22) had a greater bone microarchitectural deficit than those with subclinical CD. HR-pQCT was used to successfully identify significant deterioration in the microarchitecture of trabecular and cortical compartments of peripheral bones. Impairment was characterized by lower trabecular number and thickness-which increased trabecular network heterogeneity-and lower cortical density and thickness. In the prospective follow-up of this group of patients we expect to be able to assess whether bone microarchitecture recovers and to what extend after gluten-free diet. Copyright © 2015 Elsevier Inc. All rights reserved.

Skeletal dosimetry for external exposure to photons based on µCT images of spongiosa from different bone sites

NASA Astrophysics Data System (ADS)

Kramer, R.; Khoury, H. J.; Vieira, J. W.; Kawrakow, I.

2007-11-01

Micro computed tomography (µCT) images of human spongiosa have recently been used for skeletal dosimetry with respect to external exposure to photon radiation. In this previous investigation, the calculation of equivalent dose to the red bone marrow (RBM) and to the bone surface cells (BSC) was based on five different clusters of micro matrices derived from µCT images of vertebrae, and the BSC equivalent dose for 10 µm thickness of the BSC layer was determined using an extrapolation method. The purpose of this study is to extend the earlier investigation by using µCT images from eight different bone sites and by introducing an algorithm for the direct calculation of the BSC equivalent dose with sub-micro voxel resolution. The results show that for given trabecular bone volume fractions (TBVFs) the whole-body RBM equivalent dose does not depend on bone site-specific properties or imaging parameters. However, this study demonstrates that apart from the TBVF and the BSC layer thickness, the BSC equivalent dose additionally depends on a so-called trabecular bone structure (TBS) effect, i.e. that the contribution of photo-electrons released in trabecular bone to the BSC equivalent dose also depends on the bone site-specific structure of the trabeculae. For a given bone site, the TBS effect is also a function of the thickness of the BSC layer, and it could be shown that this effect would disappear almost completely, should the BSC layer thickness be raised from 10 to 50 µm, according to new radiobiological findings.

The effects of growth hormone treatment on bone mineral density and body composition in girls with turner syndrome.

PubMed

Ari, Mim; Bakalov, Vladimir K; Hill, Suvimol; Bondy, Carolyn A

2006-11-01

Many girls with Turner syndrome (TS) are treated with GH to increase adult height. In addition to promoting longitudinal bone growth, GH has effects on bone and body composition. The objective was to determine how GH treatment affects bone mineral density (BMD) and body composition in girls with TS. In a cross-sectional study, we compared measures of body composition and BMD by dual energy x-ray absorptiometry, and phalangeal cortical thickness by hand radiography in 28 girls with TS who had never received GH and 39 girls who were treated with GH for at least 1 yr. All girls were participants in a National Institutes of Health (NIH) Clinical Research Center (CRC) protocol between 2001 and 2006. The two groups were similar in age (12.3 yr, sd 2.9), bone age (11.5 yr, sd 2.6), and weight (42.8 kg, sd 16.6); but the GH-treated group was taller (134 vs. 137 cm, P = 0.001). The average duration of GH treatment was 4.2 (sd 3.2) yr (range 1-14 yr). After adjustment for size and bone age, there were no significant differences in BMD at L1-L4, 1/3 radius or cortical bone thickness measured at the second metacarpal. However, lean body mass percent was higher (P < 0.001), whereas body fat percent was lower (P < 0.001) in the GH-treated group. These effects were independent of estrogen exposure and were still apparent in girls that had finished GH treatment at least 1 yr previously. Although GH treatment has little effect on cortical or trabecular BMD in girls with TS, it is associated with increased lean body mass and reduced adiposity.

Bone and Soft Tissue Nasal Angles Discrepancies and Overlying Skin Thickness: A Computed Tomography Study.

PubMed

Alharethy, Sami; Alohali, Sama; Alquniabut, Ibrahim; Jang, Yong Ju

2018-04-11

The aim of this study was to derive the normal values for bone and soft tissue nasal angles as well as the overlying skin thickness and to attempt to determine the correlation between differences in bone and soft tissue angles and overlying skin thickness in Middle Eastern patients. Three-dimensional cephalometric analysis was performed for 100 patients who underwent computed tomography of the paranasal sinuses. The nasofrontal angle, pyramidal angle-nasal root, pyramidal angle-tip of the nasal bone, and overlying skin thickness were measured, and the results were analyzed according to sex, age, and body mass index (BMI). All soft tissue angles were significantly larger than the bone angles, with the mean difference being 11.62°, 30.80°, and 27.05° for the nasofrontal angle (P = 0.000), pyramidal angle-nasal root (P = 0.000), and pyramidal angle-tip of the nasal bone (P = 0.000), respectively. The mean overlying skin thickness was 3.89 ± 1.48 mm at the nasion, 1.16 ± 0.6 mm at the rhinion, and 2.93 ± .97 mm at the nasal tip. Differences in the nasofrontal angle were strongly correlated with the skin thickness at the nasion (P = 0.001). A simple clinical exam of the soft tissue nasal angles does not reflect the underlying bone angles that will be encountered during rhinoplasty. BMI does not influence nasal shape, and rhinoplasty surgery should take into account the ethnic group, age, and sex of the patient. Surgeons should leave a minor skeletal hump at the end of the nasal bone for Middle Eastern patients. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Effect of open wedge high tibial osteotomy on the lateral tibiofemoral compartment in sheep. Part III: analysis of the microstructure of the subchondral bone and correlations with the articular cartilage and meniscus.

PubMed

Ziegler, Raphaela; Goebel, Lars; Seidel, Roland; Cucchiarini, Magali; Pape, Dietrich; Madry, Henning

2015-09-01

First, to evaluate whether medial open wedge high tibial osteotomy (HTO) induces alterations of the microstructure of the lateral tibial subchondral bone plate of sheep. Second, to test the hypothesis that specific correlations exist between topographical structural alterations of the subchondral bone, the cartilage and the lateral meniscus. Three experimental groups received biplanar osteotomies of the right proximal tibiae: (a) closing wedge HTO (4.5° of tibial varus), (b) opening wedge HTO (4.5° tibial valgus; standard correction) and (c) opening wedge HTO (9.5° of valgus; overcorrection), each of which was compared to the non-osteotomised contralateral proximal tibiae. After 6 months, subchondral bone structure indices were measured by computed tomography. Correlations between the subchondral bone, the articular cartilage and the lateral meniscus were determined. Increased loading by valgus overcorrection led to an enlarged specific bone surface (BS/BV) in the subarticular spongiosa compared with unloading by varisation. The subchondral bone plate was 3.9-fold thicker in the central region of the lateral tibial plateau than in the submeniscal periphery. Its thickness in the central region significantly correlated with the thickness of the articular cartilage. In the submeniscal region, such correlation did not exist. In general, a higher degree of osteoarthritis (OA) correlated with alterations of the subchondral bone plate microstructure. OA of the submeniscal articular cartilage also correlated with worse matrix staining of the lateral meniscus. Osteoarthritis changes are associated with alterations of the subchondral bone plate microstructure. Specific topographical relationships exist in the central region between the articular cartilage and subchondral bone plate thickness, and in the submeniscal periphery between and the articular cartilage and lateral meniscus. From a clinical perspective, the combined follow-up data from this and the previous two investigations suggest that open wedge valgus HTO is a safe procedure for the lateral compartment to manage medial osteoarthritis of the knee with varus malalignment in the short term.

Morphometric assessment of periodontal tissues in relation to periodontal disease in dogs.

PubMed

Kyllar, Michal; Doskarova, Barbora; Paral, Vaclav

2013-01-01

Dimensions of periodontal tissues are thought to predispose to the development of periodontal disease in man and dogs. Several studies have suggested that thin gingiva correlates with an increased incidence of periodontal disease. In this study, we hypothesized that the dimensions of periodontal tissues will vary in different breeds of dogs and could possibly correlate with the incidence of periodontal disease. Forty-two jaws of dogs aged up to 5-years were examined post-mortem and gingival and alveolar bone thickness were measured using methods of transgingival probing and digital calipers, respectively. Dogs were divided into three groups based on their body weight. Group I (< 5.0 kg; n=21), group II (5 to 10 kg; n=11), and group III (10 to 15 kg; n=10). Thickness of gingiva ranged from 0.30-mm to 3.2-mm and was relatively thinner in group I than in group II and III based on the means of ratios comparison. Alveolar bone thickness ranged from 0.27-mm to 4.1-mm and was relatively thinner in group I compared with groups II and III. Our study showed significantly thinner gingiva and alveolar bone in toy breed dogs compared with small and medium-sized breed dogs. Both gingival and alveolar bone dimensions may be predictors for severity of periodontal disease and influence clinical outcome in certain periodontal surgical procedures.

Tailoring the excitation of fundamental flexural guide waves in coated bone by phase-delayed array: two-dimensional simulations.

PubMed

Kilappa, Vantte; Moilanen, Petro; Salmi, Ari; Haeggström, Edward; Zhao, Zuomin; Myllylä, Risto; Timonen, Jussi

2015-03-01

The fundamental flexural guided wave (FFGW) enables ultrasonic assessment of cortical bone thickness. In vivo, it is challenging to detect this mode, as its power ratio with respect to disturbing ultrasound is reduced by soft tissue covering the bone. A phase-delayed ultrasound source is proposed to tailor the FFGW excitation in order to improve its power ratio. This situation is analyzed by 2D finite-element simulations. The soft tissue coating (7-mm thick) was simulated as a fluid covering an elastic plate (bone, 2-6 mm thick). A six-element array of emitters on top of the coating was excited by 50-kHz tone bursts so that each emitter was appropriately delayed from the previous one. Response was recorded by an array of receivers on top of the coating, 20-50 mm away from the closest emitter. Simulations predicted that such tailored/phase-delayed excitations should improve the power ratio of FFGW by 23 ± 5 dB, independent of the number of emitters (N). On the other hand, the FFGW magnitude should increase by 5.8 ± 0.5 dB for each doubling of N. This suggests that mode tailoring based on phase-delayed excitation may play a key role in the development of an in vivo FFGW assessment.

Modifications in Bone Matrix of Estrogen-Deficient Rats Treated with Intermittent PTH

PubMed Central

Campos, Jenifer Freitas; Katchburian, Eduardo; de Medeiros, Valquíria Pereira; Nader, Helena Bonciani; Nonaka, Keico Okino; Plotkin, Lilian Irene; Reginato, Rejane Daniele

2015-01-01

Bone matrix dictates strength, elasticity, and stiffness to the bone. Intermittent parathyroid hormone (iPTH), a bone-forming treatment, is widely used as a therapy for osteoporosis. We investigate whether low doses of intermittent PTH (1-34) change the profile of organic components in the bone matrix after 30 days of treatment. Forty 6-month-old female Wistar rats underwent ovariectomy and after 3 months received low doses of iPTH administered for 30 days: daily at 0.3 µg/kg/day (PTH03) or 5 µg/kg/day (PTH5); or 3 times per week at 0.25 µg/kg/day (PTH025). After euthanasia, distal femora were processed for bone histomorphometry, histochemistry for collagen and glycosaminoglycans, biochemical quantification of sulfated glycosaminoglycans, and hyaluronan by ELISA and TUNEL staining. Whole tibiae were used to estimate the bone mineral density (BMD). Histomorphometric analysis showed that PTH5 increased cancellous bone volume by 6% over vehicle-treated rats. In addition, PTH5 and PTH03 increased cortical thickness by 21% and 20%, respectively. Tibial BMD increased in PTH5-treated rats and this group exhibited lower levels of chondroitin sulfate; on the other hand, hyaluronan expression was increased. Hormonal administration in the PTH5 group led to decreased collagen maturity. Further, TUNEL-positive osteocytes were decreased in the cortical compartment of PTH5 whereas administration of PTH025 increased the osteocyte death. Our findings suggest that daily injections of PTH at low doses alter the pattern of organic components from the bone matrix, favoring the increase of bone mass. PMID:25695082

Hyperthyroidism and Hypothyroidism in Male Mice and Their Effects on Bone Mass, Bone Turnover, and the Wnt Inhibitors Sclerostin and Dickkopf-1.

PubMed

Tsourdi, Elena; Rijntjes, Eddy; Köhrle, Josef; Hofbauer, Lorenz C; Rauner, Martina

2015-10-01

Thyroid hormones are key regulators of bone homeostasis, and Wnt signaling has been implicated in thyroid hormone-associated bone loss. Here we tested whether hyperthyroidism and hypothyroidism interfere with dickkopf-1 (DKK1) and sclerostin, two inhibitors of Wnt signaling. Twelve-week-old male C57BL/6 mice were rendered either hyperthyroid or hypothyroid. Hyperthyroid mice displayed decreased trabecular (-54%, P < .001) and cortical bone density (-5%, P < .05) and reduced cortical thickness (-15%, P < .001), whereas hypothyroid mice showed a higher trabecular bone density (+26%, P < .001) with unchanged cortical bone parameters. Histomorphometry and biochemical markers of bone remodeling indicated high bone turnover in hyperthyroid mice and low bone turnover in hypothyroid mice. In vivo, serum DKK1 concentrations were decreased in hyperthyroid mice (-24%, P < .001) and increased in hypothyroid mice (+18%, P < .01). The increase of the number of DKK1-positive cells in hypothyroid mice was confirmed at the tissue level. Interestingly, sclerostin was increased in both disease models, although to a higher extent in hyperthyroid mice (+50%, P < .001, and +24%, P < .05). Serum sclerostin concentrations adjusted for bone mass were increased by 3.3-fold in hyperthyroid (P < .001) but not in hypothyroid mice. Consistently, sclerostin mRNA expression and the number of sclerostin-positive cells were increased in hyperthyroid but not in hypothyroid mice. Our data show that thyroid hormone-induced changes in bone remodeling are associated with a divergent regulation of DKK1 and sclerostin. Thus, the modulation of Wnt signaling by thyroid hormones may contribute to thyroid hormone-associated bone disease and altered expression of Wnt inhibitors may emerge as potential therapeutic targets.

Crestal Sinus Augmentation in the Presence of Severe Sinus Mucosal Thickening: A Report of 3 Cases.

PubMed

Fang, Yiqin; An, Xueyin; Jeong, Seung-Mi; Choi, Byung-Ho

2018-06-01

In the presence of severe sinus mucosal thickening, the ostium can be blocked when the sinus membrane is lifted, causing drainage disturbances and sinusitis. Here, we present 3 cases in which maxillary sinus floor elevation was performed using a crestal approach in the presence of severe sinus mucosal thickening (>10 mm). The effects of maxillary sinus floor elevation using the crestal approach technique on sinus mucosal thickening and bone formation in the sinus were evaluated using cone beam computed tomography. None of the patients exhibited an increase in sinus membrane thickness. No complications were encountered during the follow-up periods, and bone formation was observed around the implants at the sinus floor. All implants were functioning successfully. Maxillary sinus floor elevation using the crestal approach technique in the presence of severe sinus mucosal thickening allows for minimally invasive sinus grafting and simultaneous implant placement and does not increase sinus membrane thickness.

Acute Exposure to High Dose γ-Radiation Results in Transient Activation of Bone Lining Cells

PubMed Central

Turner, Russell T.; Iwaniec, Urszula T.; Wong, Carmen P.; Lindenmaier, Laurence B.; Wagner, Lindsay A.; Branscum, Adam J.; Menn, Scott A.; Taylor, James; Zhang, Ye; Wu, Honglu; Sibonga, Jean D.

2014-01-01

The present studies investigated the cellular mechanisms for the detrimental effects of high dose whole body γ-irradiation on bone. In addition, radioadaptation and bone marrow transplantation were assessed as interventions to mitigate the skeletal complications of irradiation. Increased trabecular thickness and separation and reduced fractional cancellous bone volume, connectivity density, and trabecular number were detected in proximal tibia and lumbar vertebra 14 days following γ-irradiation with 6 Gy. To establish the cellular mechanism for the architectural changes, vertebrae were analyzed by histomorphometry 1, 3, and 14 days following irradiation. Marrow cell density decreased within 1 day (67% reduction, p<0.0001), reached a minimum value after 3 days (86% reduction, p<0.0001), and partially rebounded by 14 days (30% reduction, p=0.0025) following irradiation. In contrast, osteoblast-lined bone perimeter was increased by 290% (1 day, p=0.04), 1230% (3 days, p<0.0001), and 530% (14 days, p=0.003), respectively. There was a strong association between radiation-induced marrow cell death and activation of bone lining cells to express the osteoblast phenotype (Pearson correlation −0.85, p<0.0001). An increase (p=0.004) in osteoclast-lined bone perimeter was also detected with irradiation. A priming dose of γ-radiation (0.5 mGy), previously shown to reduce mortality, had minimal effect on the cellular responses to radiation and did not prevent detrimental changes in bone architecture. Bone marrow transplantation normalized marrow cell density, bone turnover, and most indices of bone architecture following irradiation. In summary, radiation-induced death of marrow cells is associated with 1) a transient increase in bone formation due, at least in part, to activation of bone lining cells, and 2) an increase in bone resorption due to increased osteoclast perimeter. Bone marrow transplantation is effective in mitigating the detrimental effects of acute exposure to high dose whole body γ-radiation on bone turnover. PMID:23954507

Mechanical strength of ceramic scaffolds reinforced with biopolymers is comparable to that of human bone.

PubMed

Henriksen, S S; Ding, M; Juhl, M Vinther; Theilgaard, N; Overgaard, S

2011-05-01

Eight groups of calcium-phosphate scaffolds for bone implantation were prepared of which seven were reinforced with biopolymers, poly lactic acid (PLA) or hyaluronic acid in different concentrations in order to increase the mechanical strength, without significantly impairing the microarchitecture. Controls were un-reinforced calcium-phosphate scaffolds. Microarchitectural properties were quantified using micro-CT scanning. Mechanical properties were evaluated by destructive compression testing. Results showed that adding 10 or 15% PLA to the scaffold significantly increased the mechanical strength. The increase in mechanical strength was seen as a result of increased scaffold thickness and changes to plate-like structure. However, the porosity was significantly lowered as a consequence of adding 15% PLA, whereas adding 10% PLA had no significant effect on porosity. Hyaluronic acid had no significant effect on mechanical strength. The novel composite scaffold is comparable to that of human bone which may be suitable for transplantation in specific weight-bearing situations, such as long bone repair.

Does cortical bone thickness in the last sacral vertebra differ among tail types in primates?

PubMed

Nishimura, Abigail C; Russo, Gabrielle A

2017-04-01

The external morphology of the sacrum is demonstrably informative regarding tail type (i.e., tail presence/absence, length, and prehensility) in living and extinct primates. However, little research has focused on the relationship between tail type and internal sacral morphology, a potentially important source of functional information when fossil sacra are incomplete. Here, we determine if cortical bone cross-sectional thickness of the last sacral vertebral body differs among tail types in extant primates and can be used to reconstruct tail types in extinct primates. Cortical bone cross-sectional thickness in the last sacral vertebral body was measured from high-resolution CT scans belonging to 20 extant primate species (N = 72) assigned to tail type categories ("tailless," "nonprehensile short-tailed," "nonprehensile long-tailed," and "prehensile-tailed"). The extant dataset was then used to reconstruct the tail types for four extinct primate species. Tailless primates had significantly thinner cortical bone than tail-bearing primates. Nonprehensile short-tailed primates had significantly thinner cortical bone than nonprehensile long-tailed primates. Cortical bone cross-sectional thickness did not distinguish between prehensile-tailed and nonprehensile long-tailed taxa. Results are strongly influenced by phylogeny. Corroborating previous studies, Epipliopithecus vindobonensis was reconstructed as tailless, Archaeolemur edwardsi as long-tailed, Megaladapis grandidieri as nonprehensile short-tailed, and Palaeopropithecus kelyus as nonprehensile short-tailed or tailless. Results indicate that, in the context of phylogenetic clade, measures of cortical bone cross-sectional thickness can be used to allocate extinct primate species to tail type categories. © 2017 Wiley Periodicals, Inc.

In vivo study of microarc oxidation coated biodegradable magnesium plate to heal bone fracture defect of 3mm width.

PubMed

Wu, Y F; Wang, Y M; Jing, Y B; Zhuang, J P; Yan, J L; Shao, Z K; Jin, M S; Wu, C J; Zhou, Y

2017-10-01

Microarc oxidation (MAO) coated magnesium (Mg) with improved corrosion resistance appeal increasing interests as a revolutionary biodegradable metal for fractured bone fixing implants application. However, the in vivo corrosion degradation of the implants and bone healing response are not well understood, which is highly required in clinic. In the present work, 10μm and 20μm thick biocompatible MAO coatings mainly composed of MgO, Mg 2 SiO 4 , CaSiO 3 and Mg 3 (PO 4 ) 2 phases were fabricated on AZ31 magnesium alloy. The electrochemical tests indicated an improved corrosion resistance of magnesium by the MAO coatings. The 10μm and 20μm coated and uncoated magnesium plates were separately implanted into the radius bone fracture site of adult New Zealand white rabbits using a 3mm width bone fracture defect model to investigate the magnesium implants degradation and uninhibited bone healing. Taking advantage of the good biocompatibility of the MAO coatings, no adverse effects were detected through the blood test and histological examination. The implantation groups of coated and uncoated magnesium plates were both observed the promoting effect of bone fracture healing compared with the simple fracture group without implant. The releasing Mg 2+ by the degradation of implants into the fracture site improved the bone fracture healing, which is attributed to the magnesium promoting CGRP-mediated osteogenic differentiation. Mg degradation and bone fracture healing promoting must be tailored by microarc oxidation coating with different thickness for potential clinic application. Copyright © 2017. Published by Elsevier B.V.

Is cortical bone hip? What determines cortical bone properties?

PubMed

Epstein, Sol

2007-07-01

Increased bone turnover may produce a disturbance in bone structure which may result in fracture. In cortical bone, both reduction in turnover and increase in hip bone mineral density (BMD) may be necessary to decrease hip fracture risk and may require relatively greater proportionate changes than for trabecular bone. It should also be noted that increased porosity produces disproportionate reduction in bone strength, and studies have shown that increased cortical porosity and decreased cortical thickness are associated with hip fracture. Continued studies for determining the causes of bone strength and deterioration show distinct promise. Osteocyte viability has been observed to be an indicator of bone strength, with viability as the result of maintaining physiological levels of loading and osteocyte apoptosis as the result of a decrease in loading. Osteocyte apoptosis and decrease are major factors in the bone loss and fracture associated with aging. Both the osteocyte and periosteal cell layer are assuming greater importance in the process of maintaining skeletal integrity as our knowledge of these cells expand, as well being a target for pharmacological agents to reduce fracture especially in cortical bone. The bisphosphonate alendronate has been seen to have a positive effect on cortical bone by allowing customary periosteal growth, while reducing the rate of endocortical bone remodeling and slowing bone loss from the endocortical surface. Risedronate treatment effects were attributed to decrease in bone resorption and thus a decrease in fracture risk. Ibandronate has been seen to increase BMD as the spine and femur as well as a reduced incidence of new vertebral fractures and non vertebral on subset post hoc analysis. And treatment with the anabolic agent PTH(1-34) documented modeling and remodelling of quiescent and active bone surfaces. Receptor activator of nuclear factor kappa B ligand (RANKL) plays a key role in bone destruction, and the human monoclonal antibody denosumab binds to RANKL, inhibiting its action and thus improving BMD significantly.

Human stem cell osteoblastogenesis mediated by novel glycogen synthase kinase 3 inhibitors induces bone formation and a unique bone turnover biomarker profile in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gilmour, Peter S., E-mail: Peter.Gilmour@astrazeneca.com; O'Shea, Patrick J.; Fagura, Malbinder

Wnt activation by inhibiting glycogen synthase kinase 3 (GSK-3) causes bone anabolism in rodents making GSK-3 a potential therapeutic target for osteoporotic and osteolytic metastatic bone disease. To understand the wnt pathway related to human disease translation, the ability of 3 potent inhibitors of GSK-3 (AZD2858, AR79, AZ13282107) to 1) drive osteoblast differentiation and mineralisation using human adipose-derived stem cells (hADSC) in vitro; and 2) stimulate rat bone formation in vivo was investigated. Bone anabolism/resorption was determined using clinically relevant serum biomarkers as indicators of bone turnover and bone formation assessed in femurs by histopathology and pQCT/μCT imaging. GSK-3 inhibitorsmore » caused β-catenin stabilisation in human and rat mesenchymal stem cells, stimulated hADSC commitment towards osteoblasts and osteogenic mineralisation in vitro. AZD2858 produced time-dependent changes in serum bone turnover biomarkers and increased bone mass over 28 days exposure in rats. After 7 days, AZD2858, AR79 or AZ13282107 exposure increased the bone formation biomarker P1NP, and reduced the resorption biomarker TRAcP-5b, indicating increased bone anabolism and reduced resorption in rats. This biomarker profile was differentiated from anabolic agent PTH{sub 1–34} or the anti-resorptive Alendronate-induced changes. Increased bone formation in cortical and cancellous bone as assessed by femur histopathology supported biomarker changes. 14 day AR79 treatment increased bone mineral density and trabecular thickness, and decreased trabecular number and connectivity assessed by pQCT/μCT. GSK-3 inhibition caused hADSC osteoblastogenesis and mineralisation in vitro. Increased femur bone mass associated with changes in bone turnover biomarkers confirmed in vivo bone formation and indicated uncoupling of bone formation and resorption. - Highlights: • Wnt modulation with 3 novel GSK-3 inhibitors alters bone growth. • Human stem cell osteoblastogenesis and mineralisation produced by GSK-3 inhibition. • In rats, 3 GSK-3 inhibitors produced a unique serum bone turnover biomarker profile. • Enhanced bone formation was seen within 7 to 14 days of compound treatment in rats.« less

[Is there a relation between weight in rats, bone density, ash weight and histomorphometric indicators of trabecular volume and thickness in the bones of extremities?].

PubMed

Zák, J; Kapitola, J; Povýsil, C

2003-01-01

Authors deal with question, if there is possibility to infer bone histological structure (described by histomorphometric parameters of trabecular bone volume and trabecular thickness) from bone density, ash weight or even from weight of animal (rat). Both tibias of each of 30 intact male rats, 90 days old, were processed. Left tibia was utilized to the determination of histomorphometric parameters of undecalcified bone tissue patterns by automatic image analysis. Right tibia was used to the determination of values of bone density, using Archimedes' principle. Values of bone density, ash weight, ash weight related to bone volume and animal weight were correlated with histomorphometric parameters (trabecular bone volume, trabecular thickness) by Pearson's correlation test. One could presume the existence of relation between data, describing bone mass at the histological level (trabecular bone of tibia) and other data, describing mass of whole bone or even animal mass (weight). But no statistically significant correlation was found. The reason of the present results could be in the deviations of trabecular density in marrow of tibia. Because of higher trabecular bone density in metaphyseal and epiphyseal regions, the histomorphometric analysis of trabecular bone is preferentially done in these areas. It is possible, that this irregularity of trabecular tibial density could be the source of the deviations, which could influence the results of correlations determined. The values of bone density, ash weight and animal weight do not influence trabecular bone volume and vice versa: static histomorphometric parameters of trabecular bone do not reflect bone density, ash weight and weight of animal.

Visfatin alters the cytokine and matrix-degrading enzyme profile during osteogenic and adipogenic MSC differentiation.

PubMed

Tsiklauri, Lali; Werner, Janina; Kampschulte, Marian; Frommer, Klaus W; Berninger, Lucija; Irrgang, Martina; Glenske, Kristina; Hose, Dirk; El Khassawna, Thaqif; Pons-Kühnemann, Jörn; Rehart, Stefan; Wenisch, Sabine; Müller-Ladner, Ulf; Neumann, Elena

2018-06-13

Age-related bone loss is associated with bone marrow adiposity. Adipokines (e.g. visfatin, resistin, leptin) are adipocyte-derived factors with immunomodulatory properties and might influence differentiation of bone marrow-derived mesenchymal stem cells (MSC) in osteoarthritis (OA) and osteoporosis. Thus, the presence of adipokines and MMPs in bone marrow and their effects on MSC differentiation were analyzed. MSC and RNA were isolated from femoral heads after hip replacement surgery of OA or osteoporotic femoral neck fracture (FF) patients. Bone structural parameters were evaluated by μCT. MSC were differentiated towards adipocytes or osteoblasts with/without adipokines. Gene expression (adipokines, bone marker genes, MMPs, TIMPs) and cytokine production was evaluated by realtime-PCR and ELISA. Matrix mineralization was quantified using Alizarin red S staining. μCT showed an osteoporotic phenotype of FF compared to OA bone (reduced trabecular thickness and increased ratio of bone surface vs. volume of solid bone). Visfatin and leptin were increased in FF vs OA. Visfatin induced the secretion of IL-6, IL-8, and MCP-1 during osteogenic and adipogenic differentiation. In contrast to resistin and leptin, visfatin increased MMP2 and MMP13 during Adipognesis. In osteogenically differentiated cells, MMPs and TIMPs were reduced by visfatin. Visfatin significantly increased matrix mineralization during osteogenesis, whereas collagen type I expression was reduced. Visfatin-mediated increase of matrix mineralization and reduced collagen type I expression could contribute to bone fragility. Visfatin is involved in impaired bone remodeling at the adipose tissue/bone interface through induction of proinflammatory factors and dysregulated MMP/TIMP balance during MSC differentiation. Copyright © 2018. Published by Elsevier Ltd.

Immediate periodontal bone plate changes induced by rapid maxillary expansion in the early mixed dentition: CT findings

PubMed Central

Garib, Daniela Gamba; Menezes, Maria Helena Ocké; da Silva Filho, Omar Gabriel; dos Santos, Patricia Bittencourt Dutra

2014-01-01

Objective This study aimed at evaluating buccal and lingual bone plate changes caused by rapid maxillary expansion (RME) in the mixed dentition by means of computed tomography (CT). Methods The sample comprised spiral CT exams taken from 22 mixed dentition patients from 6 to 9 years of age (mean age of 8.1 years) presenting constricted maxillary arch treated with Haas-type expanders. Patients were submitted to spiral CT scan before expansion and after the screw activation period with a 30-day interval between T1 and T2. Multiplanar reconstruction was used to measure buccal and lingual bone plate thickness and buccal bone crest level of maxillary posterior deciduous and permanent teeth. Changes induced by expansion were evaluated using paired t test (p < 0.05). Results Thickness of buccal and lingual bone plates of posterior teeth remained unchanged during the expansion period, except for deciduous second molars which showed a slight reduction in bone thickness at the distal region of its buccal aspect. Buccal bone dehiscences were not observed in the supporting teeth after expansion. Conclusion RME performed in mixed dentition did not produce immediate undesirable effects on periodontal bone tissues. PMID:25162564

Effects of age, vitamin D3, and fructooligosaccharides on bone growth and skeletal integrity of broiler chicks.

PubMed

Kim, W K; Bloomfield, S A; Ricke, S C

2011-11-01

A study was conducted to evaluate the effects of age, vitamin D(3), and fructooligosaccharides (FOS) on bone mineral density (BMD), bone mineral content (BMC), cortical thickness, cortical and trabecular area, and mechanical properties in broiler chicks using peripheral quantitative computed tomography and mechanical testing. A total of 54 male broiler chicks (1 d old) were placed in battery brooders and fed a corn-soybean starter diet for 7 d. After 7 d, the chicks were randomly assigned to pens of 3 birds each. Each treatment was replicated 3 times. There were 6 treatments: 1) early age control (control 1); 2) control 2; 3) 125 µg/kg of vitamin D(3); 4) 250 µg/kg of vitamin D(3); 5) 2% FOS); and 6) 4% FOS. The control 1 chicks were fed a control broiler diet and killed on d 14 to collect femurs for bone analyses. The remaining groups were killed on d 21. Femurs from 3-wk-old chicks showed greater midshaft cortical BMD, BMC, bone area, thickness, and marrow area than those from 2-wk-old chicks (P = 0.016, 0.0003, 0.0002, 0.01, and 0.0001, respectively). Total, cortical, and trabecular BMD of chick proximal femurs were not influenced by age. However, BMC and bone area were significantly affected by age. The femurs of 2-wk-old chicks exhibited significantly lower stiffness and ultimate load than those of 3-wk-old chicks (P = 0.0001), whereas ultimate stress and elastic modulus of the femurs of 2-wk-old chicks were significantly higher than that of femurs of 3-wk-old chicks (P = 0.0001). Chicks fed 250 µg/kg of vitamin D(3) exhibited significantly greater midshaft cortical BMC (P = 0.04), bone area (P = 0.04), and thickness (P = 0.03) than control 2, 2% FOS, or 4% FOS chicks. In summary, our study suggests that high levels of vitamin D(3) can increase bone growth and mineral deposition in broiler chicks. However, FOS did not have any beneficial effects on bone growth and skeletal integrity. Age is an important factor influencing skeletal integrity and mechanical properties in broiler chicks.

The skeletal structure of insulin-like growth factor I-deficient mice

NASA Technical Reports Server (NTRS)

Bikle, D.; Majumdar, S.; Laib, A.; Powell-Braxton, L.; Rosen, C.; Beamer, W.; Nauman, E.; Leary, C.; Halloran, B.

2001-01-01

The importance of insulin-like growth factor I (IGF-I) for growth is well established. However, the lack of IGF-I on the skeleton has not been examined thoroughly. Therefore, we analyzed the structural properties of bone from mice rendered IGF-I deficient by homologous recombination (knockout [k/o]) using histomorphometry, peripheral quantitative computerized tomography (pQCT), and microcomputerized tomography (muCT). The k/o mice were 24% the size of their wild-type littermates at the time of study (4 months). The k/o tibias were 28% and L1 vertebrae were 26% the size of wild-type bones. Bone formation rates (BFR) of k/o tibias were 27% that of the wild-type littermates. The k/o bones responded normally to growth hormone (GH; 1.7-fold increase) and supranormally to IGF-I (5.2-fold increase) with respect to BFR. Cortical thickness of the proximal tibia was reduced 17% in the k/o mouse. However, trabecular bone volume (bone volume/total volume [BV/TV]) was increased 23% (male mice) and 88% (female mice) in the k/o mice compared with wild-type controls as a result of increased connectivity, increased number, and decreased spacing of the trabeculae. These changes were either less or not found in L1. Thus, lack of IGF-I leads to the development of a bone structure, which, although smaller, appears more compact.

Effect of oral monthly ibandronate on bone microarchitecture in women with osteopenia-a randomized placebo-controlled trial.

PubMed

Chapurlat, R D; Laroche, M; Thomas, T; Rouanet, S; Delmas, P D; de Vernejoul, M-C

2013-01-01

We have examined the effect of oral monthly ibandronate on distal radius and tibia microarchitecture with high-resolution peripheral quantitative tomography compared with placebo, in women with osteopenia, and found that ibandronate did not significantly affect trabecular bone but improved cortical density and thickness at the tibia. We have examined the effect of ibandronate on bone microarchitecture with peripheral high-resolution quantitative computed tomography (HR-pQCT) in a randomized placebo-controlled trial among 148 women with osteopenia. Patients received either oral 150 mg monthly ibandronate or placebo over 24 months. Bone microarchitecture was assessed at baseline, 6, 12, and 24 months, using HR-pQCT at the distal radius and tibia; areal bone mineral density (aBMD) was measured with DXA at the spine, hip, and radius. At 12 months, there was no significant difference in trabecular bone volume at the radius (the primary end point) between women on ibandronate (10.8 ± 2.5%) and placebo (10.5 ± 2.9%), p = 0.25. There was no significant difference in other radius trabecular and cortical microarchitecture parameters at 12 and 24 months. In contrast, at the tibia, cortical vBMD in the ibandronate group was significantly greater than in the placebo group at 6, 12, and 24 months, with better cortical thickness at 6, 12, and 24 months. With ibandronate, aBMD was significantly increased at the hip and spine at 12 and 24 months but at the radius was significantly superior to placebo only at 24 months. Most of the adverse events related to ibandronate were expected with bisphosphonate use, and none of them were serious. We conclude that 12 months of treatment with ibandronate in women with osteopenia did not affect trabecular bone microarchitecture, but improved cortical vBMD at the tibia at 12 and 24 months, and preserved cortical thickness at the tibia.

Histomorphometric Evaluation of the Effects of Various Diode Lasers and Force Levels on Orthodontic Mini Screw Stability

PubMed Central

Isman, Eren; Taner, Lale; Kurkcu, Mehmet

2015-01-01

Abstract Objective The purpose of this study was to evaluate the effects of different laser dose and force levels on the stability of orthodontic mini screws used for anchorage, by histomorphometric analyses. Background data Low-level laser therapy speeds up blood flow, improves the mechanism of the revitalization processes, reduces the risk of infection, boosts metabolic activities, and accelerates the healing of the damaged tissue. Although there are many research studies about low-level laser therapy applications in a variety of areas, no investigations were found concerning mini screw stability using various laser dose levels with different force level applications. Methods Seventeen New Zealand white rabbits were used. A total of 68 cylindrical, self-drilling orthodontic mini screws were threaded at the fibula. Experimental subjects were divided into six groups; force application was not performed in the first three groups, whereas 150g of force was applied via nickel-titanium closed-coil springs placed between two mini screws in the other three groups. Measurements of the initial torque values (10 Ncm) were manipulated by a digital portable torque gauge. Various low-level laser doses were applied to the groups during the postoperative 10 days. After 4 weeks, bone-to-implant contact and cortical bone thickness were histomorphometrically analyzed. Results In the 150g force plus 20 J/cm2 dosage group, the highest bone-to-implant contact values were observed. (p<0.05) There were no statistically significant correlations between cortical bone thickness and bone-to-implant contact values; on the other hand, no significant difference was found among the same groups in terms of cortical bone thickness values (p>0.05). Conclusions Low-level laser therapy was noticed to induce the mini screw–bone contact area. Low-level laser therapy may be a supplementary treatment method to increase the stability of the orthodontic mini screw. PMID:25594769

Disrupted trabecular bone micro-architecture in middle-aged male HIV-infected treated patients.

PubMed

Sellier, P; Ostertag, A; Collet, C; Trout, H; Champion, K; Fernandez, S; Lopes, A; Morgand, M; Clevenbergh, P; Evans, J; Souak, S; de Vernejoul, M-C; Bergmann, J-F

2016-08-01

HIV-infected individuals are at increased risk of incident fractures. Evaluation of trabecular bone micro-architecture is an important tool to assess bone strength, but its use has not yet been reported in middle-aged HIV-infected male individuals. The aim of the study was to compare bone micro-architecture between HIV-infected and HIV-uninfected men. In this cross-sectional study, 53 HIV-infected male individuals with a mean (± standard deviation) age of 49 ± 9 years who had been receiving antiretroviral therapy including tenofovir disoproxil fumarate (DF) for at least 60 months were compared with 50 HIV-uninfected male controls, matched for age and ethnic origin. We studied the volumetric bone density and micro-architecture of the radius and tibia using high-resolution peripheral quantitative computed tomography (HR-p QCT). Volumetric trabecular bone density was 17% lower in the tibia (P < 10(-4) ) and 16% lower in the radius (P < 10(-3) ) in HIV-infected patients compared with controls. By contrast, the cortical bone density was normal at both sites. The tibial trabecular micro-architecture differed markedly between patients and controls: bone volume/total volume (BV/TV) and trabecular number were each 13% lower (P < 10(-4) for both). Trabecular separation and inhomogeneity of the network were 18% and 24% higher in HIV-infected patients than in controls, respectively. The radial BV/TV and trabecular thickness were each 13% lower (P < 10(-3) and 10(-2) , respectively). Cortical thickness was not different between the two groups. The findings of lower volumetric trabecular bone density and disrupted trabecular micro-architectural parameters in middle-aged male HIV-infected treated patients help to explain bone frailty in these patients. © 2016 British HIV Association.

In vitro comparison of the effect of different slice thicknesses on the accuracy of linear measurements on cone beam computed tomography images in implant sites.

PubMed

Shokri, Abbas; Khajeh, Samira

2015-01-01

Use of dental implants in edentulous patients has become a common treatment modality. Treatment of such implants requires radiographic evaluation, and in most cases, several different imaging techniques are necessary to evaluate the height, width, and structure of the bone at the implant site. In the current study, an attempt was made to evaluate the accuracy of measurements on cone beam computed tomography (CBCT) images with different slice thicknesses so that accurate data can be collected for proper clinical applications. In the present in vitro study, 11 human dry mandibles were used. The width and height of bone at the central, canine, and molar teeth areas were measured on the left and right sides by using digital calipers (as gold standard) and on CBCT images with 0.5-, 1-, 2-, 3-, 5-, and 10-mm slice thicknesses. Data were analyzed with SPSS 16, using paired t-test, Tukey test, and inter class correlation. Data were collected by evaluation of 11 skulls and 63 samples on the whole. There were no significant differences in bone width in any area (P > 0.05). There were significant differences in bone height in the central and molar teeth areas (P = 0.02). The measurements were not significant only at 4-mm slice thickness option and 5-mm slice thickness option for height compared with the gold standard (P = 0.513 and 0.173, respectively). The results did not show any significant differences between the observers (P = 0.329). The highest measurement accuracy of CBCT software program was observed at 4-mm slices for bone width and 5-mm slice thickness for bone height.

Osteopathia striata with cranial sclerosis: clinical, radiological, and bone histological findings in an adolescent girl.

PubMed

Ward, L M; Rauch, F; Travers, R; Roy, M; Montes, J; Chabot, G; Glorieux, F H

2004-08-15

Osteopathia striata with cranial sclerosis (OS-CS) is a rare skeletal dysplasia characterized by linear striations of the long bones, osteosclerosis of the cranium, and extra-skeletal anomalies. We provide a comprehensive description of the skeletal phenotype in a French-Canadian girl with a moderate to severe form of sporadic OS-CS. Multiple medical problems, including anal stenosis and the Pierre-Robin sequence, were evident in the first few years of life. At 14 years, she was fully mobile, with normal intellect and stature. She suffered chronic lower extremity pain in the absence of fractures, as well as severe headaches, unilateral facial paralysis, and bilateral mixed hearing loss. Biochemical indices of bone and mineral metabolism were within normal limits. Bone densitometry showed increased areal bone mineral density in the skull, trunk, and pelvis, but not in the upper and lower extremities. An iliac bone biopsy specimen revealed an increased amount of trabecular bone. Trabeculae were abnormally thick, but there was no evidence of disturbed bone remodeling. In a cranial bone specimen, multiple layers of periosteal bone were found that covered a compact cortical compartment containing tightly packed haversian canals. Bone lamellation was normal in both the iliac and skull samples. Osteoclast differentiation studies showed that peripheral blood osteoclast precursors from this patient formed functional osteoclasts in vitro. Thus, studies of bone metabolism did not explain why bone mass is increased in most skeletal areas of this patient. Cranial histology points to exuberant periosteal bone formation as a potential cause of the cranial sclerosis.

PTH prevents the adverse effects of focal radiation on bone architecture in young rats.

PubMed

Chandra, Abhishek; Lan, Shenghui; Zhu, Ji; Lin, Tiao; Zhang, Xianrong; Siclari, Valerie A; Altman, Allison R; Cengel, Keith A; Liu, X Sherry; Qin, Ling

2013-08-01

Radiation therapy is a common treatment regimen for cancer patients. However, its adverse effects on the neighboring bone could lead to fractures with a great impact on quality of life. The underlying mechanism is still elusive and there is no preventive or curative solution for this bone loss. Parathyroid hormone (PTH) is a current therapy for osteoporosis that has potent anabolic effects on bone. In this study, we found that focal radiation from frequent scans of the right tibiae in 1-month-old rats by micro-computed tomography severely decreased trabecular bone mass and deteriorated bone structure. Interestingly, PTH daily injections remarkably improved trabecular bone in the radiated tibiae with increases in trabecular number, thickness, connectivity, structure model index and stiffness, and a decrease in trabecular separation. Histomorphometric analysis revealed that radiation mainly decreased the number of osteoblasts and impaired their mineralization activity but had little effects on osteoclasts. PTH reversed these adverse effects and greatly increased bone formation to a similar level in both radiated and non-radiated bones. Furthermore, PTH protects bone marrow mesenchymal stem cells from radiation-induced damage, including a decrease in number and an increase in adipogenic differentiation. While radiation generated the same amount of free radicals in the bone marrow of vehicle-treated and PTH-treated animals, the percentage of apoptotic bone marrow cells was significantly attenuated in the PTH group. Taken together, our data demonstrate a radioprotective effect of PTH on bone structure and bone marrow and shed new light on a possible clinical application of anabolic treatment in radiotherapy. Copyright © 2013 Elsevier Inc. All rights reserved.

Cone-Beam Computed Tomography Evaluation of Horizontal and Vertical Dimensional Changes in Buccal Peri-Implant Alveolar Bone and Soft Tissue: A 1-Year Prospective Clinical Study.

PubMed

Kaminaka, Akihiro; Nakano, Tamaki; Ono, Shinji; Kato, Tokinori; Yatani, Hirofumi

2015-10-01

This study evaluated changes in the horizontal and vertical dimensions of the buccal alveolar bone and soft tissue over a 1-year period following implant prosthesis. Thirty-three participants with no history of guided bone regeneration or soft tissue augmentation underwent dental implant placement with different types of connections. The dimensions of the buccal alveolar bone and soft tissue were evaluated immediately and at 1 year after prosthesis from reconstructions of cross-sectional cone-beam computed tomography images. The vertical and horizontal loss of buccal bone and soft tissue around implants with conical connections were lower than around those with external or internal connections. Statistically significant negative correlations were observed between initial horizontal bone thickness and changes in vertical bone and soft tissue height (p < .05), and between initial horizontal soft tissue thickness and the change in vertical soft tissue height (p < .05). Implants with a conical connection preserve peri-implant alveolar bone and soft tissue more effectively than other connection types. Furthermore, the initial buccal alveolar bone and soft tissue thickness around the implant platform may influence their vertical dimensional changes at 1 year after implant prosthesis. © 2014 Wiley Periodicals, Inc.

CORRELATION OF ARTICULAR CARTILAGE THICKNESS MEASUREMENTS MADE WITH MAGNETIC RESONANCE IMAGING, MAGNETIC RESONANCE ARTHROGRAPHY, AND COMPUTED TOMOGRAPHIC ARTHROGRAPHY WITH GROSS ARTICULAR CARTILAGE THICKNESS IN THE EQUINE METACARPOPHALANGEAL JOINT.

PubMed

Porter, Erin G; Winter, Matthew D; Sheppard, Barbara J; Berry, Clifford R; Hernandez, Jorge A

2016-09-01

Osteoarthritis of the metacarpophalangeal joint is common cause of lameness in equine athletes, and is hallmarked by articular cartilage damage. An accurate, noninvasive method for measuring cartilage thickness would be beneficial to screen for cartilage injury and allow for prompt initiation of interventional therapy. The objective of this methods comparison study was to compare computed tomographic arthrography (CTA), magnetic resonance imaging (MRI), and magnetic resonance arthrography (MRA) measurements of articular cartilage thickness with gross measurements in the metacarpophalangeal joint of Thoroughbred horses. Fourteen cadaveric, equine thoracic limbs were included. Limbs were excluded from the study if pathology of the metacarpophalangeal articular cartilage was observed with any imaging modality. Articular cartilage thickness was measured in nine regions of the third metacarpal bone and proximal phalanx on sagittal plane MRI sequences. After intra-articular contrast administration, the measurements were repeated on sagittal plane MRA and sagittal CTA reformations. In an effort to increase cartilage conspicuity, the volume of intra-articular contrast was increased from 14.5 ml, to maximal distention for the second set of seven limbs. Mean and standard deviation values were calculated, and linear regression analysis was used to determine correlations between gross and imaging measurements of cartilage thickness. This study failed to identify one imaging test that consistently yielded measurements correlating with gross cartilage thickness. Even with the use of intra-articular contrast, cartilage surfaces were difficult to differentiate in regions where the cartilage surfaces of the proximal phalanx and third metacarpal bone were in close contact with each other. © 2016 American College of Veterinary Radiology.

Prefabricated scalping forehead flap with skeletal support.

PubMed

Fujiwara, Masao; Suzuki, Ayano; Mizukami, Takahide; Terai, Tsutomu; Fukamizu, Hidekazu

2009-07-01

It is difficult to reconstruct a nose with adequate shape, color, and texture in patients who have full-thickness nasal defects with extensive loss of skeletal support. The scalping forehead flap is a reliable technique for nasal reconstruction. To our knowledge, however, there have been no reports about a prefabricated scalping forehead flap with a bone graft as skeletal support. In the case reported here, a prefabricated scalping forehead flap combined with an iliac bone graft as skeletal support was used to successfully reconstruct a full-thickness defect of the nose associated with partial frontal bone loss and complete loss of the nasal bones. Acceptable functional and aesthetic results were achieved. This method may be a good alternative for reconstruction of full-thickness nasal defects with extensive loss of skeletal support.

Bone density and anisotropy affect periprosthetic cement and bone stresses after anatomical glenoid replacement: A micro finite element analysis.

PubMed

Chevalier, Yan; Santos, Inês; Müller, Peter E; Pietschmann, Matthias F

2016-06-14

Glenoid loosening is still a main complication for shoulder arthroplasty. We hypothesize that cement and bone stresses potentially leading to fixation failure are related not only to glenohumeral conformity, fixation design or eccentric loading, but also to bone volume fraction, cortical thickness and degree of anisotropy in the glenoid. In this study, periprosthetic bone and cement stresses were computed with micro finite element models of the replaced glenoid depicting realistic bone microstructure. These models were used to quantify potential effects of bone microstructural parameters under loading conditions simulating different levels of glenohumeral conformity and eccentric loading simulating glenohumeral instability. Results show that peak cement stresses were achieved near the cement-bone interface in all loading schemes. Higher stresses within trabecular bone tissue and cement mantle were obtained within specimens of lower bone volume fraction and in regions of low anisotropy, increasing with decreasing glenohumeral conformity and reaching their maxima below the keeled design when the load is shifted superiorly. Our analyses confirm the combined influences of eccentric load shifts with reduced bone volume fraction and anisotropy on increasing periprosthetic stresses. They finally suggest that improving fixation of glenoid replacements must reduce internal cement and bone tissue stresses, in particular in glenoids of low bone density and heterogeneity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Programmed administration of parathyroid hormone increases bone formation and reduces bone loss in hindlimb-unloaded ovariectomized rats

NASA Technical Reports Server (NTRS)

Turner, R. T.; Evans, G. L.; Cavolina, J. M.; Halloran, B.; Morey-Holton, E.

1998-01-01

Gonadal insufficiency and reduced mechanical usage are two important risk factors for osteoporosis. The beneficial effects of PTH therapy to reverse the estrogen deficiency-induced bone loss in the laboratory rat are well known, but the influence of mechanical usage in this response has not been established. In this study, the effects of programed administration of PTH on cancellous bone volume and turnover at the proximal tibial metaphysis were determined in hindlimb-unloaded, ovariectomized (OVX), 3-month-old Sprague-Dawley rats. PTH was administered to weight-bearing and hindlimb-unloaded OVX rats with osmotic pumps programed to deliver 20 microg human PTH (approximately 80 microg/kg x day) during a daily 1-h infusion for 7 days. Compared with sham-operated rats, OVX increased longitudinal and radial bone growth, increased indexes of cancellous bone turnover, and resulted in net resorption of cancellous bone. Hindlimb unloading of OVX rats decreased longitudinal and radial bone growth, decreased osteoblast number, increased osteoclast number, and resulted in a further decrease in cancellous bone volume compared with those in weight-bearing OVX rats. Programed administration of PTH had no effect on either radial or longitudinal bone growth in weight-bearing and hindlimb-unloaded OVX rats. PTH treatment had dramatic effects on selected cancellous bone measurements; PTH maintained cancellous bone volume in OVX weight-bearing rats and greatly reduced cancellous bone loss in OVX hindlimb-unloaded rats. In the latter animals, PTH treatment prevented the hindlimb unloading-induced reduction in trabecular thickness, but the hormone was ineffective in preventing either the increase in osteoclast number or the loss of trabecular plates. Importantly, PTH treatment increased the retention of a baseline flurochrome label, osteoblast number, and bone formation in the proximal tibial metaphysis regardless of the level of mechanical usage. These findings demonstrate that programed administration of PTH is effective in increasing osteoblast number and bone formation and has beneficial effects on bone volume in the absence of weight-bearing and gonadal hormones. We conclude that the actions of PTH on cancellous bone are independent of the level of mechanical usage.

Trabecular architecture in the sciuromorph femoral head: allometry and functional adaptation.

PubMed

Mielke, Maja; Wölfer, Jan; Arnold, Patrick; van Heteren, Anneke H; Amson, Eli; Nyakatura, John A

2018-01-01

Sciuromorpha (squirrels and close relatives) are diverse in terms of body size and locomotor behavior. Individual species are specialized to perform climbing, gliding or digging behavior, the latter being the result of multiple independent evolutionary acquisitions. Each lifestyle involves characteristic loading patterns acting on the bones of sciuromorphs. Trabecular bone, as part of the bone inner structure, adapts to such loading patterns. This network of thin bony struts is subject to bone modeling, and therefore reflects habitual loading throughout lifetime. The present study investigates the effect of body size and lifestyle on trabecular structure in Sciuromorpha. Based upon high-resolution computed tomography scans, the femoral head 3D inner microstructure of 69 sciuromorph species was analyzed. Species were assigned to one of the following lifestyle categories: arboreal, aerial, fossorial and semifossorial. A cubic volume of interest was selected in the center of each femoral head and analyzed by extraction of various parameters that characterize trabecular architecture (degree of anisotropy, bone volume fraction, connectivity density, trabecular thickness, trabecular separation, bone surface density and main trabecular orientation). Our analysis included evaluation of the allometric signals and lifestyle-related adaptation in the trabecular parameters. We show that bone surface density, bone volume fraction, and connectivity density are subject to positive allometry, and degree of anisotropy, trabecular thickness, and trabecular separation to negative allometry. The parameters connectivity density, bone surface density, trabecular thickness, and trabecular separation show functional signals which are related to locomotor behavior. Aerial species are distinguished from fossorial ones by a higher trabecular thickness, lower connectivity density and lower bone surface density. Arboreal species are distinguished from semifossorial ones by a higher trabecular separation. This study on sciuromorph trabeculae supplements the few non-primate studies on lifestyle-related functional adaptation of trabecular bone. We show that the architecture of the femoral head trabeculae in Sciuromorpha correlates with body mass and locomotor habits. Our findings provide a new basis for experimental research focused on functional significance of bone inner microstructure.

Randomized clinical study assessing two membranes for guided bone regeneration of peri-implant bone defects: clinical and histological outcomes at 6 months.

PubMed

Naenni, Nadja; Schneider, David; Jung, Ronald E; Hüsler, Jürg; Hämmerle, Christoph H F; Thoma, Daniel S

2017-10-01

To test whether or not one of two membranes is superior for peri-implant-guided bone regeneration in terms of clinical and histologic outcomes. In 27 patients, 27 two-piece dental implants were placed in single-tooth gaps in the esthetic area. Buccal dehiscence and/or fenestration-type defects were regenerated using demineralized bovine bone mineral and randomly covered with either a resorbable membrane (RES) or a titanium-reinforced non-resorbable membrane (N-RES). Clinical measurements included vertical defect resolution and the horizontal thickness of regenerated bone at implant placement and at 6 months. Statistics were performed by means of nonparametric testing. The remaining mean vertical defect measured 4 mm (±2.07) (RES) and 2.36 mm (±2.09) (N-RES) (P = 0.044) at baseline and 0.77 mm (±0.85) (RES) and 0.21 mm (±0.80) (N-RES) (P = 0.021) at re-entry. This translated into a defect resolution of 85% (RES) and 90.7% (N-RES) (P = 0.10). The horizontal thickness after augmentation measured 3.46 mm (±0.52) (RES) and 2.82 mm (±0.50) (N-RES) (P = 0.004). The mean loss in horizontal thickness from baseline to re-entry measured 2.23 mm (SD ±1.21) (RES) and 0.14 mm (±0.79) (N-RES) (P = 0.017). The horizontal changes in thickness at the implant shoulder level were statistically significant between the groups (P = 0.0001). Both treatment modalities were clinically effective in regenerating bone as demonstrated by a similar horizontal thickness and vertical defect fill at 6 months. The N-RES group exhibited significantly less horizontal bone thickness reduction from baseline to follow-up. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The Soy Isoflavones for Reducing Bone Loss (SIRBL) Study: Three year effects on pQCT bone mineral density and strength measures in postmenopausal women

PubMed Central

SHEDD-WISE, KRISTINE M.; ALEKEL, D. LEE; HOFMANN, HEIKE; HANSON, KATHY B.; SCHIFERL, DAN J.; HANSON, LAURA N.; VAN LOAN, MARTA D.

2011-01-01

Soy isoflavones exert inconsistent bone density-preserving effects, but the bone strength-preserving effects in humans are unknown. Our double-blind randomized controlled trial examined two soy isoflavone doses (80 or 120 mg/d) vs placebo tablets on volumetric bone mineral density (vBMD) and strength (via peripheral quantitative computed tomography) in healthy postmenopausal women (46–63 y). We measured 3 y change in cortical (Ct) BMD, cortical thickness (CtThk), periosteal circumference (PC), endosteal circumference (EC), and strength-strain index (SSI) at 1/3 midshaft femur (N=171) and trabecular (Tb) BMD, PC, and SSI at 4% distal tibia (N=162). We found no treatment effect on femur CtThk, PC, or EC, or tibia TbBMD or PC. Strongest predictors (negative) of tibia TbBMD and SSI and femur CtBMD were timepoint and bone resorption; whole body fat mass was protective of SSI. As time since last menstrual period (TLMP) increased (p=0.012), 120 mg/d was protective of CtBMD. Strongest predictors of femur SSI were timepoint, bone resorption, and TLMP (protective). Isoflavone tablets were negative predictors of SSI, but 80 mg/d became protective as bone turnover increased (p=0.011). Soy isoflavone treatment for 3 y was modestly beneficial for midshaft femur vBMD as TLMP increased, and for midshaft femur SSI as bone turnover increased. PMID:21295742

Accelerated Growth Plate Mineralization and Foreshortened Proximal Limb Bones in Fetuin-A Knockout Mice

PubMed Central

Gupta, Himadri S.; Schäfer, Cora; Krauss, Stefanie; Dunlop, John W. C.; Masic, Admir; Kerschnitzki, Michael; Zaslansky, Paul; Boesecke, Peter; Catalá-Lehnen, Philip; Schinke, Thorsten; Fratzl, Peter; Jahnen-Dechent, Willi

2012-01-01

The plasma protein fetuin-A/alpha2-HS-glycoprotein (genetic symbol Ahsg) is a systemic inhibitor of extraskeletal mineralization, which is best underscored by the excessive mineral deposition found in various tissues of fetuin-A deficient mice on the calcification-prone genetic background DBA/2. Fetuin-A is known to accumulate in the bone matrix thus an effect of fetuin-A on skeletal mineralization is expected. We examined the bones of fetuin-A deficient mice maintained on a C57BL/6 genetic background to avoid bone disease secondary to renal calcification. Here, we show that fetuin-A deficient mice display normal trabecular bone mass in the spine, but increased cortical thickness in the femur. Bone material properties, as well as mineral and collagen characteristics of cortical bone were unaffected by the absence of fetuin-A. In contrast, the long bones especially proximal limb bones were severely stunted in fetuin-A deficient mice compared to wildtype littermates, resulting in increased biomechanical stability of fetuin-A deficient femora in three-point-bending tests. Elevated backscattered electron signal intensities reflected an increased mineral content in the growth plates of fetuin-A deficient long bones, corroborating its physiological role as an inhibitor of excessive mineralization in the growth plate cartilage matrix - a site of vigorous physiological mineralization. We show that in the case of fetuin-A deficiency, active mineralization inhibition is a necessity for proper long bone growth. PMID:23091616

Protective Effects of Vildagliptin against Pioglitazone-Induced Bone Loss in Type 2 Diabetic Rats

PubMed Central

Kwak, Kyung Min; Kim, Ju-Young; Yu, Seung Hee; Lee, Sihoon; Kim, Yeun Sun; Park, Ie Byung; Kim, Kwang-Won; Lee, Kiyoung

2016-01-01

Long-term use of thiazolidinediones (TZDs) is associated with bone loss and an increased risk of fracture in patients with type 2 diabetes (T2DM). Incretin-based drugs (glucagon-like peptide-1 (GLP-1) agonists and dipeptidylpeptidase-4 (DPP-4) inhibitors) have several benefits in many systems in addition to glycemic control. In a previous study, we reported that exendin-4 might increase bone mineral density (BMD) by decreasing the expression of SOST/sclerostin in osteocytes in a T2DM animal model. In this study, we investigated the effects of a DPP-4 inhibitor on TZD-induced bone loss in a T2DM animal model. We randomly divided 12-week-old male Zucker Diabetic Fatty (ZDF) rats into four groups; control, vildagliptin, pioglitazone, and vildagliptin and pioglitazone combination. Animals in each group received the respective treatments for 5 weeks. We performed an intraperitoneal glucose tolerance test (IPGTT) before and after treatment. BMD and the trabecular micro-architecture were measured by DEXA and micro CT, respectively, at the end of the treatment. The circulating levels of active GLP-1, bone turnover markers, and sclerostin were assayed. Vildagliptin treatment significantly increased BMD and trabecular bone volume. The combination therapy restored BMD, trabecular bone volume, and trabecular bone thickness that were decreased by pioglitazone. The levels of the bone formation marker, osteocalcin, decreased and that of the bone resorption marker, tartrate-resistant acid phosphatase (TRAP) 5b increased in the pioglitazone group. These biomarkers were ameliorated and the pioglitazone-induced increase in sclerostin level was lowered to control values by the addition of vildagliptin. In conclusion, our results indicate that orally administered vildagliptin demonstrated a protective effect on pioglitazone-induced bone loss in a type 2 diabetic rat model. PMID:27997588

Protective Effects of Vildagliptin against Pioglitazone-Induced Bone Loss in Type 2 Diabetic Rats.

PubMed

Eom, Young Sil; Gwon, A-Ryeong; Kwak, Kyung Min; Kim, Ju-Young; Yu, Seung Hee; Lee, Sihoon; Kim, Yeun Sun; Park, Ie Byung; Kim, Kwang-Won; Lee, Kiyoung; Kim, Byung-Joon

2016-01-01

Long-term use of thiazolidinediones (TZDs) is associated with bone loss and an increased risk of fracture in patients with type 2 diabetes (T2DM). Incretin-based drugs (glucagon-like peptide-1 (GLP-1) agonists and dipeptidylpeptidase-4 (DPP-4) inhibitors) have several benefits in many systems in addition to glycemic control. In a previous study, we reported that exendin-4 might increase bone mineral density (BMD) by decreasing the expression of SOST/sclerostin in osteocytes in a T2DM animal model. In this study, we investigated the effects of a DPP-4 inhibitor on TZD-induced bone loss in a T2DM animal model. We randomly divided 12-week-old male Zucker Diabetic Fatty (ZDF) rats into four groups; control, vildagliptin, pioglitazone, and vildagliptin and pioglitazone combination. Animals in each group received the respective treatments for 5 weeks. We performed an intraperitoneal glucose tolerance test (IPGTT) before and after treatment. BMD and the trabecular micro-architecture were measured by DEXA and micro CT, respectively, at the end of the treatment. The circulating levels of active GLP-1, bone turnover markers, and sclerostin were assayed. Vildagliptin treatment significantly increased BMD and trabecular bone volume. The combination therapy restored BMD, trabecular bone volume, and trabecular bone thickness that were decreased by pioglitazone. The levels of the bone formation marker, osteocalcin, decreased and that of the bone resorption marker, tartrate-resistant acid phosphatase (TRAP) 5b increased in the pioglitazone group. These biomarkers were ameliorated and the pioglitazone-induced increase in sclerostin level was lowered to control values by the addition of vildagliptin. In conclusion, our results indicate that orally administered vildagliptin demonstrated a protective effect on pioglitazone-induced bone loss in a type 2 diabetic rat model.

[Surgical Techniques for Patella Replacement in Cases of Deficient Bone Stock in Revision TKA].

PubMed

Ritschl, P; Machacek, F; Strehn, L; Kloiber, J

2015-06-01

The patella replacement in revision surgery is a challenge especially in cases of unsufficient bone stock. Depending on the extent of the bone defect, the following videos demonstrate different approaches: Video 1: bone sparing removal of the patella implant: onlay-type patella implants. Video 2: complete cortical bone rim of the patella, residual thickness between 6 to 10 mm: biconvex patella implant. Video 3 and 4: small defects of the cortical bone rim of the patella, residual thickness 1 to 5 mm (patella shell): gull-wing osteotomy, patella bone grafting techniques. Video 5: partial necrosis/defect of the patella shell with incomplete cortical bone rim: porous tantalum patella prosthesis. On account of the various surgical options for different bone defects of the patella, patellectomy and pure patelloplasty should be avoided to prevent functional shortcomings. Georg Thieme Verlag KG Stuttgart · New York.

Prostaglandin E2 Adds Bone to a Cancellous Bone Site with a Closed Growth Plate and Low Bone Turnover in Ovariectomized Rats

NASA Technical Reports Server (NTRS)

Ma, Y. F.; Ke, H. Z.; Jee, W. S. S.

1994-01-01

The objects of this study were to determine the responses of a cancellous bone site with a closed growth plate, (the distal tibial metaphysis (DTM), to ovariectomy (OVX) and OVX plus a prostaglandin E(2) treatment, and compare the site's response to previous findings reported for another site, the proximal tibial metaphysis (PTM). Thirty five 3-month old female Sprague-Dawley rats were divided into five groups; basal, sham OVX, and OVX+0, +1, or +6 mg PGE(2)/kg/d injected subcutaneously for 3 months and given double fluorescent labels before sacrifice. Cancellous bone histomorphometric analyses were performed on 20 micrometer thick undecalcified DTM sections. Similar to the PTM, the DTM showed age-related decreases in bone formation and increases in bone resorption, but it differed in that at 3 months POST OVX there was neither bone loss nor changes in formation endpoints. Giving 1 mg PGE(2)/kg/d to OVX rats prevented most age-related changes and maintained the bone formation histomorphometry near basal levels. Treating OVX rats with 6 mg PGE(2)/kd/d prevented age-related bone changes, added extra bone, and improved microanatomical structure by stimulating bone formation, without altering bone resportion. Futhermore, After PGE(2) admimnistration, the DTM, a cancellous bone site with a closed growth plate, increased bone formation more than did the cancellous bone in the PTM.

Vps35 loss promotes hyperresorptive osteoclastogenesis and osteoporosis via sustained RANKL signaling

PubMed Central

Xia, Wen-Fang; Tang, Fu-Lei; Xiong, Lei; Xiong, Shan; Jung, Ji-Ung; Lee, Dae-Hoon; Li, Xing-Sheng; Feng, Xu; Mei, Lin

2013-01-01

Receptor activator of NF-κB (RANK) plays a critical role in osteoclastogenesis, an essential process for the initiation of bone remodeling to maintain healthy bone mass and structure. Although the signaling and function of RANK have been investigated extensively, much less is known about the negative regulatory mechanisms of its signaling. We demonstrate in this paper that RANK trafficking, signaling, and function are regulated by VPS35, a major component of the retromer essential for selective endosome to Golgi retrieval of membrane proteins. VPS35 loss of function altered RANK ligand (RANKL)–induced RANK distribution, enhanced RANKL sensitivity, sustained RANKL signaling, and increased hyperresorptive osteoclast (OC) formation. Hemizygous deletion of the Vps35 gene in mice promoted hyperresorptive osteoclastogenesis, decreased bone formation, and caused a subsequent osteoporotic deficit, including decreased trabecular bone volumes and reduced trabecular thickness and density in long bones. These results indicate that VPS35 critically deregulates RANK signaling, thus restraining increased formation of hyperresorptive OCs and preventing osteoporotic deficits. PMID:23509071

Impaired rib bone mass and quality in end-stage cystic fibrosis patients.

PubMed

Mailhot, Geneviève; Dion, Natalie; Farlay, Delphine; Rizzo, Sébastien; Bureau, Nathalie J; Jomphe, Valérie; Sankhe, Safiétou; Boivin, Georges; Lands, Larry C; Ferraro, Pasquale; Ste-Marie, Louis-Georges

2017-05-01

Advancements in research and clinical care have considerably extended the life expectancy of cystic fibrosis (CF) patients. However, with this extended survival come comorbidities. One of the leading co-morbidities is CF-related bone disease (CFBD), which progresses with disease severity and places patients at high risk for fractures, particularly of the ribs and vertebrae. Evidence that CF patients with vertebral fractures had higher bone mineral density (BMD) than the nonfracture group led us to postulate that bone quality is impaired in these patients. We therefore examined rib specimens resected at the time of lung transplant in CF patients to measure parameters of bone quantity and quality. In this exploratory study, we analysed 19 end-stage CF and 13 control rib specimens resected from otherwise healthy lung donors. BMD, bone microarchitecture, static parameters of bone formation and resorption and microcrack density of rib specimens were quantified by imaging, histomorphometric and histological methods. Variables reflecting the mineralization of ribs were assessed by digitized microradiography. The degree of bone mineralization (g/cm 3 ) and the heterogeneity index of the mineralization (g/cm 3 ) were calculated for trabecular and cortical bone. Compared to controls, CF ribs exhibited lower areal and trabecular volumetric BMD, decreased trabecular thickness and osteoid parameters, and increased microcrack density, that was particularly pronounced in specimens from patients with CF-related diabetes. Static parameters of bone resorption were similar in both groups. Degree of mineralization of total bone, but not heterogeneity index, was increased in CF specimens. The combination of reduced bone mass, altered microarchitecture, imbalanced bone remodeling (maintained bone resorption but decreased formation), increased microdamage and a small increase of the degree of mineralization, may lead to decreased bone strength, which, when coupled with chronic coughing and chest physical therapy, may provide an explanation for the increased incidence of rib fractures previously reported in this population. Copyright © 2017 Elsevier Inc. All rights reserved.

Cranial vault thickness in primates: Homo erectus does not have uniquely thick vault bones.

PubMed

Copes, Lynn E; Kimbel, William H

2016-01-01

Extremely thick cranial vaults have been noted as a diagnostic characteristic of Homo erectus since the first fossil of the species was identified, but relatively little work has been done on elucidating its etiology or variation across fossils, living humans, or extant non-human primates. Cranial vault thickness (CVT) is not a monolithic trait, and the responsiveness of its layers to environmental stimuli is unknown. We obtained measurements of cranial vault thickness in fossil hominins from the literature and supplemented those data with additional measurements taken on African fossil specimens. Total CVT and the thickness of the cortical and diploë layers individually were compared to measures of CVT in extant species measured from more than 500 CT scans of human and non-human primates. Frontal and parietal CVT in fossil primates was compared to a regression of CVT on cranial capacity calculated for extant species. Even after controlling for cranial capacity, African and Asian H. erectus do not have uniquely high frontal or parietal thickness residuals, either among hominins or extant primates. Extant primates with residual CVT thickness similar to or exceeding H. erectus (depending on the sex and bone analyzed) include Nycticebus coucang, Perodicticus potto, Alouatta caraya, Lophocebus albigena, Galago alleni, Mandrillus sphinx, and Propithecus diadema. However, the especially thick vaults of extant non-human primates that overlap with H. erectus values are composed primarily of cortical bone, while H. erectus and other hominins have diploë-dominated vault bones. Thus, the combination of thick vaults comprised of a thickened diploë layer may be a reliable autapomorphy for members of the genus Homo. Copyright © 2015 Elsevier Ltd. All rights reserved.

Genistein supplementation increases bone turnover but does not prevent alcohol-induced bone loss in male mice.

PubMed

Yang, Carrie S; Mercer, Kelly E; Alund, Alexander W; Suva, Larry J; Badger, Thomas M; Ronis, Martin J J

2014-10-01

Chronic alcohol consumption results in bone loss through increased bone resorption and decreased bone formation. These effects can be reversed by estradiol (E2) supplementation. Soy diets are suggested to have protective effects on bone loss in men and women, as a result of the presence of soy protein-associated phytoestrogens such as genistein (GEN). In this study, male mice were pair-fed (PF), a control diet, an ethanol (EtOH) diet, or EtOH diet supplemented with 250 mg/kg of GEN for 8 weeks to test if GEN protects against bone loss associated with chronic drinking. Interestingly, alcohol consumption reduced cortical area and thickness and trabecular bone volume in both EtOH and EtOH/GEN groups when compared to the corresponding PF and PF/GEN controls, P < 0.05. However, in the trabecular bone compartment, we observed a significant increase in overall trabecular bone density in the PF/GEN group compared to the PF controls. Bone loss in the EtOH-treated mice was associated with the inhibition of osteoblastogenesis as indicated by decreased alkaline phosphatase staining in ex vivo bone marrow cultures, P < 0.05. GEN supplementation improved osteoblastogenesis in the EtOH/GEN cultures compared to the EtOH group, P < 0.05. Vertebral expression of bone-formation markers, osteocalcin, and runt-related transcription factor 2 (Runx2) was also significantly up-regulated in the PF/GEN and EtOH/GEN groups compared to the PF and EtOH-treated groups. GEN supplementation also increased the expression of receptor activator of nuclear factor κ-B ligand (RANKL) in the PF/GEN, an increase that persisted in the EtOH/GEN-treated animals (P < 0.05), and increased basal hydrogen peroxide production and RANKL mRNA expression in primary bone marrow cultures in vitro, P < 0.05. These findings suggest that GEN supplementation increases the overall bone remodeling and, in the context of chronic alcohol consumption, does not protect against the oxidative stress-associated EtOH-mediated bone resorption. © 2014 by the Society for Experimental Biology and Medicine.

Thirty days of spaceflight does not alter murine calvariae structure despite increased Sost expression.

PubMed

Macaulay, Timothy R; Siamwala, Jamila H; Hargens, Alan R; Macias, Brandon R

2017-12-01

Previously our laboratory documented increases in calvaria bone volume and thickness in mice exposed to 15 days of spaceflight aboard the NASA Shuttle mission STS-131. However, the tissues were not processed for gene expression studies to determine what bone formation pathways might contribute to these structural adaptations. Therefore, this study was designed to investigate both the structural and molecular changes in mice calvariae after a longer duration of spaceflight. The primary purpose was to determine the calvaria bone volume and thickness of mice exposed to 30 days of spaceflight using micro-computed tomography for comparison with our previous findings. Because sclerostin, the secreted glycoprotein of the Sost gene, is a potent inhibitor of bone formation, our second aim was to quantify Sost mRNA expression using quantitative PCR. Calvariae were obtained from six mice aboard the Russian 30-day Bion-M1 biosatellite and seven ground controls. In mice exposed to 30 days of spaceflight, calvaria bone structure was not significantly different from that of their controls (bone volume was about 5% lower in spaceflight mice, p = 0.534). However, Sost mRNA expression was 16-fold (16.4 ± 0.4, p < 0.001) greater in the spaceflight group than that in the ground control group. Therefore, bone formation may have been suppressed in mice exposed to 30 days of spaceflight. Genetic responsiveness (e.g. sex or strain of animals) or in-flight environmental conditions other than microgravity (e.g. pCO 2 levels) may have elicited different bone adaptations in STS-131 and Bion-M1 mice. Although structural results were not significant, this study provides biochemical evidence that calvaria mechanotransduction pathways may be altered during spaceflight, which could reflect vascular and interstitial fluid adaptations in non-weight bearing bones. Future studies are warranted to elucidate the processes that mediate these effects and the factors responsible for discordant calvaria bone adaptations between STS-131 and Bion-M1 mice.

Correlations between the MR Diffusion-weighted Image (DWI) and the bone mineral density (BMD) as a function of the soft tissue thickness-focus on phantom and patient

NASA Astrophysics Data System (ADS)

Kim, Myung-Sam; Cho, Jae-Hwan; Lee, Hae-Kag; Lee, Sang-Jeong; Park, Cheol-Soo; Dong, Kyung-Rae; Park, Yong-Soon; Chung, Woon-Kwan; Lee, Jong-Woong; Kim, Ho-Sung; Kim, Eun-Hye; Kweon, Dae Cheol; Yeo, Hwa-Yeon

2013-02-01

In this study we used lumbar phantoms to determine if the BMD (bone mineral density) changes when only the thickness of soft tissue is increased. Second, we targeted osteoporosis patients to analyze the dependences of the changes in the SNR (signal-to-noise ratio) and the ADC (apparent diffusion coefficient) on changes in T-score. We used a bone mineral densitometer, phantoms such as an aluminum spine phantom (ASP), a Hologic spine phantom (HSP), and a European spine phantom (ESP), five sheets of acrylic panel, and a water bath to study the effects of changes in the thickness of soft tissue. First, we measured the ASP, the HSP and the ESP. For the measurement of the ASP, we filled it with water to increase the height by 0.5 cm starting from the baseline height. We then did three measurements for each height. For the measurements of the HSP and the ESP, we placed an acrylic panel on the phantom and then did three measurements at each height. We used the ASP to calculate the degree of precision of the standard mode and the thick mode at the maximum height of the water bath. To assess the degree of precision in the measurements of the three types of phantoms, we calculated precision errors and analyzed the correlation between the change in the thickness of soft tissue and the variables of the BMD. Using DWIs (diffusion weighted images), we targeted 30 healthy persons without osteoporosis and 30 patients with a finding of osteoporosis and measured the T-scores for the L1 — L4 (lumbar spine) segments of by the spine using the dual-energy X-ray absorptiometry (DXA) before classifying the measurement at each part of the spine as osteopenia or osteoporosis. We measured the signal intensity on all four parts of L1-L4 in the DWIs obtained using a 1.5T MR scanner and measured the ADC in the ADC map image. We compared changes in the SNR and the ADC for each group. The study results confirmed that an increase in the thickness of the soft tissue had a significant correlation with the BMD and that the SNR and the ADC decreased as the T-score in the DWI went down.

Attainment of peak bone mass at the lumbar spine, femoral neck and radius in men and women: relative contributions of bone size and volumetric bone mineral density.

PubMed

Henry, Yvette M; Fatayerji, Diana; Eastell, Richard

2004-04-01

The age at which peak bone mineral content (peak BMC) is reached remains controversial and the mechanism underlying bone mass "consolidation" is still undefined. The aims of this study were to investigate; (1) the timing of peak BMC by studying bone size and volumetric BMD (vBMD) as separate entities and (2) to determine the relative contributions of bone size and vBMD to bone mass "consolidation". A total of 132 healthy Caucasian children (63 boys and 69 girls, ages 11-19 years) and 134 healthy Caucasian adults (66 men and 68 women, ages 20-50 years) were studied. BMC was measured by DXA at the AP and lateral lumbar spine (LS) femoral neck (FN) and ultradistal radius (UDR). vBMD and bone volume (size) were estimated. Bone mass "consolidation" was examined between age 16 years to the age peak bone values were attained. During growth, BMC and bone size increased steeply with age and approximately 80-90% of peak values were achieved by late adolescence. vBMD at the spine and UDR (in women) increased gradually, but vBMD at the FN and UDR in men remained almost constant. During "consolidation", bone size continued to increase with little change in vBMD. Peak vBMD at the lumbar spine was reached at 22 and 29 years in men and women, respectively, but earlier at the FN at 12 years. At the UDR peak vBMD was achieved at age 19 years in women, with little change in men. In conclusion, peak vBMD and bone size are almost fully attained during late adolescence. Although speculative, the lack of change in vBMD during consolidation implies that the continued increase in bone mass may primarily be due to increases in bone size rather than increases in either trabecular volume, cortical thickness or the degree of mineralisation of existing bone matrix (vBMD). Skeletal growth and maturation is heterogeneous, but crucial in understanding how the origins of osteoporosis may begin during childhood and young adulthood.

Different configuration of socket shield technique in peri-implant bone preservation: An experimental study in dog mandible.

PubMed

Calvo-Guirado, José Luis; Troiano, Miguel; López-López, P J; Ramírez-Fernandez, María Piedad; de Val, José Eduardo Maté Sánchez; Marin, Jose Manuel Granero; Gehrke, Sergio Alexandre

2016-11-01

The aim of this study was to evaluate the influence of the residual root and peri implant bone dimensions on the clinical success of the socket shield technique. Thirty-six dental implants were installed in 6 dogs. The clinical crowns of teeth P3, P4 and M1 were beheaded. Afterwards, the roots were worn down 2-3mm in apical direction until they were located at crestal level. Posterior implant beds were prepared in the center of the roots passing by 3mm apically forming 6 groups in accordance to the remaining root thickness. Radiography of the crestal bone level was performed on day 0 and after 12 weeks. Histomorphometric analyses of the specimens were carried out to measure the crestal bone level, the bone to implant contact and the buccal and lingual bone thickness at the implant shoulder portion. Correlations between groups were analyzed through nonparametric Friedman test, statistical significance was set as p<0.05. All 36 implants were osseointegrated, but 3 samples showed a clinical inflammatory reaction and some radicular fragments presented a small resorption process. On the buccal and lingual side, the radicular fragment was attached to the buccal bone plate by a physiologic periodontal ligament. In the areas where there was space between the implant and the fragment, newly formed bone was demonstrated directly on the implant surface. Within the limitations of an animal pilot study, root-T belt technique may be beneficial in preserving and protecting the bundle bone and preservation of soft tissues. If the thickness of the buccal bone is 3mm, and the thickness of the remaining root fragment is 2mm, the socket shield technique is more predictable and the bone contours can be maintained. Copyright © 2016 Elsevier GmbH. All rights reserved.

Prefabricated bone flap: an experimental study comparing deep-frozen and lyophilized-demineralized allogenic bones and tissue expression of transforming growth factor β.

PubMed

Rodrigues, Leandro; dos Reis, Luciene Machado; Denadai, Rafael; Raposo-Amaral, Cassio Eduardo; Alonso, Nivaldo; Ferreira, Marcus Castro; Jorgetti, Vanda

2013-11-01

Extensive bone defects are still a challenge for reconstructive surgery. Allogenic bones can be an alternative with no donor area morbidity and unlimited amount of tissue. Better results can be achieved after allogenic bone preparation and adding a vascular supply, which can be done along with flap prefabrication. The purpose of this study was to evaluate demineralized/lyophilized and deep-frozen allogenic bones used for flap prefabrication and the tissue expression of transforming growth factor β (TGF-β) in these bone fragments. Fifty-six Wistar rat bone diaphyses were prepared and distributed in 4 groups: demineralized/lyophilized (experimental group 1 and control group 2) and deep freezing (experimental group 3 and control group 4). Two bone segments (one of each group) were implanted in rats to prefabricate flaps using superficial epigastric vessels (experimental groups) or only transferred as grafts (control groups). These fragments remained in their respective inguinal regions until the death that occurred at 2, 4, and 6 weeks after the operation. Semiquantitative histologic (tetracycline marking, cortical resorption, number of giant cells, and vascularization) and histomorphometrical quantitative (osteoid thickness, cortical thickness, and fibrosis thickness) analyses were performed. Transforming growth factor β immunohistochemistry staining was also performed. Group 1 fragments presented an osteoid matrix on their external surface in all periods. Cartilage formation and mineralization areas were also noticed. These findings were not observed in group 3 fragments. Group 1 had more mineralization and double tetracycline marks, which were almost not seen in group 3. Cortical resorption and the number of giant cells were greater in group 3 in all periods. Vascularization and fibrosis thickness were similar in both experimental groups. Group 1 had more intense TGF-β staining within 2 weeks of study. Nevertheless, from 4 weeks onward, group 3 presented statistically significant stronger staining. Although there are some differences between the preparation methods of allogenic bone, it is possible to prefabricate flaps with demineralized/lyophilized and deep-frozen bones.

[Prophylactic osteotomy of pelvis in dysplastic acetabulum.].

PubMed

Richtr, M; Sosna, A

1998-01-01

Acetabular dysplasia and anatomical changes of pelvis accompanied with gracility of iliac bone pose a problem for a reliable fixation of acetabular component. In extreme cases the bone stock is not sufficient to accommodate the smallest size of the cup. Sometimes even reaming of the bed down to lamina interna is not sufficient for an adequate covering of the implant. Consequently, weakening of the bottom of acetabulum may be not only one of the causes of the failure of the implant but it makes difficult also the following revision surgeries. Therefore in acetabular dysplasia the authors recommend acetabuloplasty of the bottom of acetabulum preserving its original thickness including inner cortex. They recommend to perform osteotomy of the full thickness of the medial wall of acetabulum and move the massive bone graft created in this way farther into pelvis. At the same time they take care to preserve blood supply of the bone graft by retaining corticoperiostal bridge by means of osteoclasia. The suggested procedure allows full coverage of the implant by iliac bone and at the same time preserves a firm support of acetabular fossa. The original thickness of the medial wall of acetabulum is considered by authors as a significant antimigration barrier. In the period 1991 -1994 the authors used this method at Ist Orthopaedic Clinic of 1st Medical Faculty, Charles University in Prague in total in 16 patients. In all of them after 6 months the bone graft was fully absorbed. Remodelling of the bone graft occurred 1 to 2 years after the surgery and after that the thickness of the graft remained the same. Neither any change of the structure nor reduction of the thickness of the graft was found between 3rd and 4th year after the surgery. The nature of trabecular remodelling of the bone graft corresponds to the transfer of forces in loading the graft by acetabular cup. Key words: acetabuloplasty, osteotomy of the medial wall of acetabulum, osteotomy of pelvis, THR, acetabular dysplasia.

Archeological Data Recovery at Darrow (16AN54), Ascension Parish, Louisiana.

DTIC Science & Technology

1998-02-01

bones with cut marks are tabulated into steak (long bone segment ə inch thick), chop (vertebra segment ə inch thick), roast (segment >1 inch thick...clean as this wall." Many families raised chickens that picked at any grass that appeared. The Moxley family collected drinking water from the roof...retrieving them. Meals often consisted of gumbo and sweet potato pie. No recipes were used, but ingredients were combined 50 Archeological Data

Magnitude and regional distribution of cartilage loss associated with grades of joint space narrowing in radiographic osteoarthritis--data from the Osteoarthritis Initiative (OAI).

PubMed

Eckstein, F; Wirth, W; Hunter, D J; Guermazi, A; Kwoh, C K; Nelson, D R; Benichou, O

2010-06-01

Clinically, radiographic joint space narrowing (JSN) is regarded a surrogate of cartilage loss in osteoarthritis (OA). Using magnetic resonance imaging (MRI), we explored the magnitude and regional distribution of differences in cartilage thickness and subchondral bone area associated with specific Osteoarthritis Research Society International (OARSI) JSN grades. Seventy-three participants with unilateral medial JSN were selected from the first half (2678 cases) of the OA Initiative cohort (45, 21, and 7 with OARSI JSN grades 1, 2, and 3, respectively, no medial JSN in the contra-lateral knee). Bilateral sagittal baseline DESSwe MRIs were segmented by experienced operators. Intra-person between-knee differences in cartilage thickness and subchondral bone areas were determined in medial femorotibial subregions. Knees with medial OARSI JSN grades 1, 2, and 3 displayed a 190 microm (5.2%), 630 microm (18%), and 1560 microm (44%) smaller cartilage thickness in weight-bearing medial femorotibial compartments compared to knees without JSN, respectively. The weight-bearing femoral condyle displayed relatively greater differences than the posterior femoral condyle or the medial tibia (MT). The central subregion within the weight-bearing medial femur (cMF) of the femoral condyle (30-75 degrees ), and the external and central subregions within the tibia displayed relatively greater JSN-associated differences compared to other medial femorotibial subregions. Knees with higher JSN grades also displayed larger than contra-lateral femorotibial subchondral bone areas. This study provides quantitative estimates of JSN-related cartilage loss, with the central part of the weight-bearing femoral condyle being most strongly affected. Knees with higher JSN grades displayed larger subchondral bone areas, suggesting that an increase in subchondral bone area occurs in advanced OA. Copyright 2010 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Metal-backed versus all-polyethylene unicompartmental knee arthroplasty

PubMed Central

Eaton, M. J.; Nutton, R. W.; Wade, F. A.; Evans, S. L.; Pankaj, P.

2017-01-01

Objectives Up to 40% of unicompartmental knee arthroplasty (UKA) revisions are performed for unexplained pain which may be caused by elevated proximal tibial bone strain. This study investigates the effect of tibial component metal backing and polyethylene thickness on bone strain in a cemented fixed-bearing medial UKA using a finite element model (FEM) validated experimentally by digital image correlation (DIC) and acoustic emission (AE). Materials and Methods A total of ten composite tibias implanted with all-polyethylene (AP) and metal-backed (MB) tibial components were loaded to 2500 N. Cortical strain was measured using DIC and cancellous microdamage using AE. FEMs were created and validated and polyethylene thickness varied from 6 mm to 10 mm. The volume of cancellous bone exposed to < -3000 µε (pathological loading) and < -7000 µε (yield point) minimum principal (compressive) microstrain and > 3000 µε and > 7000 µε maximum principal (tensile) microstrain was computed. Results Experimental AE data and the FEM volume of cancellous bone with compressive strain < -3000 µε correlated strongly: R = 0.947, R2 = 0.847, percentage error 12.5% (p < 0.001). DIC and FEM data correlated: R = 0.838, R2 = 0.702, percentage error 4.5% (p < 0.001). FEM strain patterns included MB lateral edge concentrations; AP concentrations at keel, peg and at the region of load application. Cancellous strains were higher in AP implants at all loads: 2.2- (10 mm) to 3.2-times (6 mm) the volume of cancellous bone compressively strained < -7000 µε. Conclusion AP tibial components display greater volumes of pathologically overstrained cancellous bone than MB implants of the same geometry. Increasing AP thickness does not overcome these pathological forces and comes at the cost of greater bone resection. Cite this article: C. E. H. Scott, M. J. Eaton, R. W. Nutton, F. A. Wade, S. L. Evans, P. Pankaj. Metal-backed versus all-polyethylene unicompartmental knee arthroplasty: Proximal tibial strain in an experimentally validated finite element model. Bone Joint Res 2017;6:22–30. DOI:10.1302/2046-3758.61.BJR-2016-0142.R1 PMID:28077394

Metal-backed versus all-polyethylene unicompartmental knee arthroplasty: Proximal tibial strain in an experimentally validated finite element model.

PubMed

Scott, C E H; Eaton, M J; Nutton, R W; Wade, F A; Evans, S L; Pankaj, P

2017-01-01

Up to 40% of unicompartmental knee arthroplasty (UKA) revisions are performed for unexplained pain which may be caused by elevated proximal tibial bone strain. This study investigates the effect of tibial component metal backing and polyethylene thickness on bone strain in a cemented fixed-bearing medial UKA using a finite element model (FEM) validated experimentally by digital image correlation (DIC) and acoustic emission (AE). A total of ten composite tibias implanted with all-polyethylene (AP) and metal-backed (MB) tibial components were loaded to 2500 N. Cortical strain was measured using DIC and cancellous microdamage using AE. FEMs were created and validated and polyethylene thickness varied from 6 mm to 10 mm. The volume of cancellous bone exposed to < -3000 µε (pathological loading) and < -7000 µε (yield point) minimum principal (compressive) microstrain and > 3000 µε and > 7000 µε maximum principal (tensile) microstrain was computed. Experimental AE data and the FEM volume of cancellous bone with compressive strain < -3000 µε correlated strongly: R = 0.947, R 2 = 0.847, percentage error 12.5% (p < 0.001). DIC and FEM data correlated: R = 0.838, R 2 = 0.702, percentage error 4.5% (p < 0.001). FEM strain patterns included MB lateral edge concentrations; AP concentrations at keel, peg and at the region of load application. Cancellous strains were higher in AP implants at all loads: 2.2- (10 mm) to 3.2-times (6 mm) the volume of cancellous bone compressively strained < -7000 µε. AP tibial components display greater volumes of pathologically overstrained cancellous bone than MB implants of the same geometry. Increasing AP thickness does not overcome these pathological forces and comes at the cost of greater bone resection.Cite this article: C. E. H. Scott, M. J. Eaton, R. W. Nutton, F. A. Wade, S. L. Evans, P. Pankaj. Metal-backed versus all-polyethylene unicompartmental knee arthroplasty: Proximal tibial strain in an experimentally validated finite element model. Bone Joint Res 2017;6:22-30. DOI:10.1302/2046-3758.61.BJR-2016-0142.R1. © 2017 Scott et al.

Subcutaneous administration of insulin-like growth factor (IGF)-II/IGF binding protein-2 complex stimulates bone formation and prevents loss of bone mineral density in a rat model of disuse osteoporosis

NASA Technical Reports Server (NTRS)

Conover, Cheryl A.; Johnstone, Edward W.; Turner, Russell T.; Evans, Glenda L.; John Ballard, F. John; Doran, Patrick M.; Khosla, Sundeep

2002-01-01

Elevated serum levels of insulin-like growth factor binding protein-2 (IGFBP-2) and a precursor form of IGF-II are associated with marked increases in bone formation and skeletal mass in patients with hepatitis C-associated osteosclerosis. In vitro studies indicate that IGF-II in complex with IGFBP-2 has high affinity for bone matrix and is able to stimulate osteoblast proliferation. The purpose of this study was to determine the ability of the IGF-II/IGFBP-2 complex to increase bone mass in vivo. Osteopenia of the femur was induced by unilateral sciatic neurectomy in rats. At the time of surgery, 14-day osmotic minipumps containing vehicle or 2 microg IGF-II+9 microg IGFBP-2/100g body weight/day were implanted subcutaneously in the neck. Bone mineral density (BMD) measurements were taken the day of surgery and 14 days later using a PIXImus small animal densitometer. Neurectomy of the right hindlimb resulted in a 9% decrease in right femur BMD (P<0.05 vs. baseline). This loss in BMD was completely prevented by treatment with IGF-II/IGFBP-2. On the control limb, there was no loss of BMD over the 14 days and IGF-II/IGFBP-2 treatment resulted in a 9% increase in left femur BMD (P<0.05). Bone histomorphometry indicated increases in endocortical and cancellous bone formation rates and in trabecular thickness. These results demonstrate that short-term administration of the IGF-II/IGFBP-2 complex can prevent loss of BMD associated with disuse osteoporosis and stimulate bone formation in adult rats. Furthermore, they provide proof of concept for a novel anabolic approach to increasing bone mass in humans with osteoporosis.

Maternal Dietary Supplementation with Oligofructose-Enriched Inulin in Gestating/Lactating Rats Preserves Maternal Bone and Improves Bone Microarchitecture in Their Offspring

PubMed Central

Diaz-Castro, Javier; López-Aliaga, Inmaculada; Rueda, Ricardo

2016-01-01

Nutrition during pregnancy and lactation could exert a key role not only on maternal bone, but also could influence the skeletal development of the offspring. This study was performed in rats to assess the relationship between maternal dietary intake of prebiotic oligofructose-enriched inulin and its role in bone turnover during gestation and lactation, as well as its effect on offspring peak bone mass/architecture during early adulthood. Rat dams were fed either with standard rodent diet (CC group), calcium-fortified diet (Ca group), or prebiotic oligofructose-enriched inulin supplemented diet (Pre group), during the second half of gestation and lactation. Bone mineral density (BMD) and content (BMC), as well as micro-structure of dams and offspring at different stages were analysed. Dams in the Pre group had significantly higher trabecular thickness (Tb.Th), trabecular bone volume fraction (BV/TV) and smaller specific bone surface (BS/BV) of the tibia in comparison with CC dams. The Pre group offspring during early adulthood had an increase of the lumbar vertebra BMD when compared with offspring of CC and Ca groups. The Pre group offspring also showed significant increase versus CC in cancellous and cortical structural parameters of the lumbar vertebra 4 such as Tb.Th, cortical BMD and decreased BS/BV. The results indicate that oligofructose-enriched inulin supplementation can be considered as a plausible nutritional option for protecting against maternal bone loss during gestation and lactation preventing bone fragility and for optimizing peak bone mass and architecture of the offspring in order to increase bone strength. PMID:27115490

Thiazide-sensitive Na+ -Cl- cotransporter (NCC) gene inactivation results in increased duodenal Ca2+ absorption, enhanced osteoblast differentiation and elevated bone mineral density.

PubMed

Hsu, Yu-Juei; Yang, Sung-Sen; Cheng, Chih-Jen; Liu, Shu-Ting; Huang, Shih-Ming; Chau, Tom; Chu, Pauling; Salter, Donald M; Lee, Herng-Sheng; Lin, Shih-Hua

2015-01-01

Inactivation of the thiazide-sensitive sodium chloride cotransporter (NCC) due to genetic mutations in Gitelman's syndrome (GS) or pharmacological inhibition with thiazide diuretics causes hypocalciuria and increased bone mineral density (BMD) with unclear extrarenal calcium (Ca(2+) ) regulation. We investigated intestinal Ca(2+) absorption and bone Ca(2+) metabolism in nonsense Ncc Ser707X (S707X) homozygous knockin mice (Ncc(S707X/S707X) mice). Compared to wild-type and heterozygous knockin littermates, Ncc(S707X/S707X) mice had increased intestinal absorption of (45) Ca(2+) and expression of the active Ca(2+) transport machinery (transient receptor potential vanilloid 6, calbindin-D9K , and plasma membrane Ca(2+) ATPase isoform 1b). Ncc(S707X/S707X) mice had also significantly increased Ca(2+) content accompanied by greater mineral apposition rate (MAR) in their femurs and higher trabecular bone volume, cortical bone thickness, and BMD determined by μCT. Their osteoblast differentiation markers, such as bone alkaline phosphatase, procollagen I, osteocalcin, and osterix, were also significantly increased while osteoclast activity was unaffected. Analysis of marrow-derived bone cells, either treated with thiazide or directly cultured from Ncc S707X knockin mice, showed that the differentiation of osteoblasts was associated with increased phosphorylation of mechanical stress-induced focal adhesion kinase (FAK) and extracellular signal-regulated kinase (ERK). In conclusion, NCC inhibition stimulates duodenal Ca(2+) absorption as well as osteoblast differentiation and bone Ca(2+) storage, possibly through a FAK/ERK dependent mechanism. © 2014 American Society for Bone and Mineral Research.

Alpha-linolenic acid supplementation and resistance training in older adults.

PubMed

Cornish, Stephen M; Chilibeck, Philip D

2009-02-01

Increased inflammation with aging has been linked to sarcopenia. The purpose of this study was to evaluate the effects of supplementing older adults with alpha-linolenic acid (ALA) during a resistance training program, based on the hypothesis that ALA decreases the plasma concentration of the inflammatory cytokine tumor necrosis factor (TNF)-alpha and interleukin (IL)-6, which in turn would improve muscle size and strength. Fifty-one older adults (65.4 +/- 0.8 years) were randomized to receive ALA in flax oil (~14 g.day-1) or placebo for 12 weeks while completing a resistance training program (3 days a week). Subjects were evaluated at baseline and after 12 weeks for muscle thickness of knee and elbow flexors and extensors (B-mode ultrasound), muscle strength (1 repetition maximum), body composition (dual energy X-ray absorptiometry), and concentrations of TNF-alpha and IL-6. Males supplementing with ALA decreased IL-6 concentration over the 12 weeks (62 +/- 36% decrease; p = 0.003), with no other changes in inflammatory cytokines. Chest and leg press strength, lean tissue mass, muscle thickness, hip bone mineral content and density, and total bone mineral content significantly increased, and percent fat and total body mass decreased with training (p < 0.05), with the only benefit of ALA being a significantly greater increase in knee flexor muscle thickness in males (p < 0.05). Total-body bone mineral density improved in the placebo group, with no change in the ALA group (p = 0.05). ALA supplementation lowers the IL-6 concentration in older men but not women, but had minimal effect on muscle mass and strength during resistance training.

Does Cu supplementation affect the mechanical and structural properties and mineral content of red deer antler bone tissue?

PubMed

Gambín, P; Serrano, M P; Gallego, L; García, A; Cappelli, J; Ceacero, F; Landete-Castillejos, T

2017-08-01

The main factors affecting the mechanical (and other) properties of bone, including antler, are the proportions of ash (especially Ca and P) and collagen content. However, some trace minerals may also play more important roles than would be expected, given their low levels in bone and antler. One such trace mineral is Cu. Here, we studied the effects of Cu supplementation on the mechanical and structural characteristics, and mineral content of antlers from yearling and adult (4 years of age) red deer fed a balanced diet. Deer (n=35) of different ages (21 yearlings and 14 adults) were studied. A total of 18 stags (11 yearlings and 7 adults) were injected with Cu (0.83 mg Cu/kg BW) every 42 days, whereas the remaining 17 (10 yearlings and 7 adults) were injected with physiological saline solution (control group). The Cu content of serum was analysed at the beginning of the trial and 84 days after the first injection to assess whether the injected Cu was mobilized in blood. Also, the mechanical and structural properties of antlers and the mineral content in their cortical walls were examined at three (yearlings) or four (adults) points along the antler beam. The effect of Cu supplementation was different in yearlings and adults. In yearlings, supplementation increased the Cu content of serum by 28%, but did not affect antler properties. However, in adults, Cu supplementation increased the Cu content of serum by 38% and tended to increase the cortical thickness of antlers (P=0.06). Therefore, we conclude that, even in animals receiving balanced diets, supplementation with Cu could increase antler cortical thickness in adult deer, although not in yearlings. This may improve the trophy value of antlers, as well as having potential implications for bones in elderly humans, should Cu supplementation have similar effects on bones as those observed in antlers.

Application of in vivo micro-computed tomography in the temporal characterisation of subchondral bone architecture in a rat model of low-dose monosodium iodoacetate-induced osteoarthritis

PubMed Central

2011-01-01

Introduction Osteoarthritis (OA) is a complex, multifactorial joint disease affecting both the cartilage and the subchondral bone. Animal models of OA aid in the understanding of the pathogenesis of OA and testing suitable drugs for OA treatment. In this study we characterized the temporal changes in the tibial subchondral bone architecture in a rat model of low-dose monosodium iodoacetate (MIA)-induced OA using in vivo micro-computed tomography (CT). Methods Male Wistar rats received a single intra-articular injection of low-dose MIA (0.2 mg) in the right knee joint and sterile saline in the left knee joint. The animals were scanned in vivo by micro-CT at two, six, and ten weeks post-injection, analogous to early, intermediate, and advanced stages of OA, to assess architectural changes in the tibial subchondral bone. The articular cartilage changes in the tibiae were assessed macroscopically and histologically at ten weeks post-injection. Results Interestingly, tibiae of the MIA-injected knees showed significant bone loss at two weeks, followed by increased trabecular thickness and separation at six and ten weeks. The trabecular number was decreased at all time points compared to control tibiae. The tibial subchondral plate thickness of the MIA-injected knee was increased at two and six weeks and the plate porosity was increased at all time points compared to control. At ten weeks, histology revealed loss of proteoglycans, chondrocyte necrosis, chondrocyte clusters, cartilage fibrillation, and delamination in the MIA-injected tibiae, whereas the control tibiae showed no changes. Micro-CT images and histology showed the presence of subchondral bone sclerosis, cysts, and osteophytes. Conclusions These findings demonstrate that the low-dose MIA rat model closely mimics the pathological features of progressive human OA. The low-dose MIA rat model is therefore suitable to study the effect of therapeutic drugs on cartilage and bone in a non-trauma model of OA. In vivo micro-CT is a non-destructive imaging technique that can track structural changes in the tibial subchondral bone in this animal model, and could also be used to track changes in bone in preclinical drug intervention studies for OA treatments. PMID:22185204

Age-related changes in vertebral and iliac crest 3D bone microstructure--differences and similarities.

PubMed

Thomsen, J S; Jensen, M V; Niklassen, A S; Ebbesen, E N; Brüel, A

2015-01-01

Age-related changes of vertebra and iliac crest 3D microstructure were investigated, and we showed that they were in general similar. The 95th percentile of vertebral trabecular thickness distribution increased with age for women. Surprisingly, vertebral and iliac crest bone microstructure was only weakly correlated (r = 0.38 to 0.75), despite the overall similar age-related changes. The purposes of the study were to determine the age-related changes in iliac and vertebral bone microstructure for women and men over a large age range and to investigate the relationship between the bone microstructure at these skeletal sites. Matched sets of transiliac crest bone biopsies and lumbar vertebral body (L2) specimens from 41 women (19-96 years) and 39 men (23-95 years) were micro-computed tomography (μCT) scanned, and the 3D microstructure was quantified. For both women and men, bone volume per total volume (BV/TV), connectivity density (CD), and trabecular number (Tb.N) decreased significantly, while structure model index (SMI) and trabecular separation (Tb.Sp) increased significantly with age at either skeletal site. Vertebral trabecular thickness (Tb.Th) was independent of age for both women and men, while iliac Tb.Th decreased significantly with age for men, but not for women. In general, the vertebral and iliac age-related changes were similar. The 95th percentile of the Tb.Th distribution increased significantly with age for women but was independent of age for men at the vertebral body, while it was independent of age for either sex at the iliac crest. The Tb.Th probability density functions at the two skeletal sites became significantly more similar with age for women, but not for men. The microstructural parameters at the iliac crest and the vertebral bodies were only moderately correlated from r = 0.38 for SMI in women to r = 0.75 for Tb.Sp in men. Age-related changes in vertebral and iliac bone microstructure were in general similar. The iliac and vertebral Tb.Th distributions became more similar with age for women. Despite the overall similar age-related changes in trabecular bone microstructure, the vertebral and iliac bone microstructural measures were only weakly correlated (r = 0.38 to 0.75).

Dietary magnesium reduction to 25% of nutrient requirement disrupts bone and mineral metabolism in the rat.

PubMed

Rude, Robert K; Gruber, Helen E; Norton, H James; Wei, Livia Y; Frausto, Angelica; Kilburn, Jeremy

2005-08-01

Low dietary magnesium (Mg) may be a risk factor for osteoporosis. In animals, severe Mg deficiency (0.04% of nutrient requirement [NR]) results in bone loss. We have also found that a more moderate dietary Mg restriction (10% of NR) also resulted in loss of bone. We now report the effect of Mg intake of 25% NR on bone and mineral metabolism in the rat. Serum Mg, Ca, PTH, 1,25(OH)2-vitamin D, alkaline phosphatase, osteocalcin, and pyridinoline were measured at 2, 4, and 6 months in control and Mg-deficient animals. Femurs and tibias were collected for mineral content, micro-computerized tomography, histomorphometry, and immunocytochemical localization. Profound Mg deficiency developed as assessed by marked hypomagnesemia and 27% reduction in bone Mg content. Serum calcium was not significantly different between groups. Mg depletion resulted in a significantly lower serum PTH concentrations. Serum 1,25(OH)2-vitamin D was also significantly lower. No difference was noted in markers of bone turnover. Histomorphometry and micro-computerized tomography demonstrated decreased bone volume and trabecular thickness. No difference was observed for osteoclast or osteoblast number. Inflammatory cytokines may contribute to bone loss. We found that immunocytochemical localization of TNFalpha in osteoclasts was increased 138-150%. This increase in TNFalpha may be due to increased substance P as it was found to be elevated from 179% to 432%. These data demonstrate that Mg intake of 25% NR in the rat causes lower bone mass which may be related to increased release of substance P and TNFalpha.

The soy isoflavones for reducing bone loss study: 3-yr effects on pQCT bone mineral density and strength measures in postmenopausal women.

PubMed

Shedd-Wise, Kristine M; Alekel, D Lee; Hofmann, Heike; Hanson, Kathy B; Schiferl, Dan J; Hanson, Laura N; Van Loan, Marta D

2011-01-01

Soy isoflavones exert inconsistent bone density-preserving effects, but the bone strength-preserving effects in humans are unknown. Our double-blind randomized controlled trial examined 2 soy isoflavone doses (80 or 120mg/d) vs placebo tablets on volumetric bone mineral density (vBMD) and strength (by means of peripheral quantitative computed tomography) in healthy postmenopausal women (46-63yr). We measured 3-yr changes in cortical BMD (CtBMD), cortical thickness (CtThk), periosteal circumference (PC), endosteal circumference (EC), and strength-strain index (SSI) at 1/3 midshaft femur (N=171), and trabecular BMD (TbBMD), PC, and SSI at 4% distal tibia (N=162). We found no treatment effect on femur CtThk, PC, or EC, or tibia TbBMD or PC. The strongest predictors (negative) of tibia TbBMD and SSI and femur CtBMD were timepoint and bone resorption; whole-body fat mass was protective of SSI. As time since last menstrual period (TLMP) increased (p=0.012), 120-mg/d dose was protective of CtBMD. The strongest predictors of femur SSI were timepoint, bone resorption, and TLMP (protective). Isoflavone tablets were negative predictors of SSI, but 80-mg/d dose became protective as bone turnover increased (p=0.011). Soy isoflavone treatment for 3yr was modestly beneficial for midshaft femur vBMD as TLMP increased and for midshaft femur SSI as bone turnover increased. Copyright © 2011 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.

Total-body irradiation of postpubertal mice with (137)Cs acutely compromises the microarchitecture of cancellous bone and increases osteoclasts.

PubMed

Kondo, Hisataka; Searby, Nancy D; Mojarrab, Rose; Phillips, Jonathan; Alwood, Joshua; Yumoto, Kenji; Almeida, Eduardo A C; Limoli, Charles L; Globus, Ruth K

2009-03-01

Ionizing radiation can cause substantial tissue degeneration, which may threaten the long-term health of astronauts and radiotherapy patients. To determine whether a single dose of radiation acutely compromises structural integrity in the postpubertal skeleton, 18-week-old male mice were exposed to (137)Cs gamma radiation (1 or 2 Gy). The structure of high-turnover, cancellous bone was analyzed by microcomputed tomography (microCT) 3 or 10 days after irradiation and in basal controls (tissues harvested at the time of irradiation) and age-matched controls. Irradiation (2 Gy) caused a 20% decline in tibial cancellous bone volume fraction (BV/TV) within 3 days and a 43% decline within 10 days, while 1 Gy caused a 28% reduction 10 days later. The BV/TV decrement was due to increased spacing and decreased thickness of trabeculae. Radiation also increased ( approximately 150%) cancellous surfaces lined with tartrate-resistant, acid phosphatase-positive osteoclasts, an index of increased bone resorption. Radiation decreased lumbar vertebral BV/TV 1 month after irradiation, showing the persistence of cancellous bone loss, although mechanical properties in compression were unaffected. In sum, a single dose of gamma radiation rapidly increased osteoclast surface in cancellous tissue and compromised cancellous microarchitecture in the remodeling appendicular and axial skeleton of postpubertal mice.

A micro-architectural evaluation of osteoporotic human femoral heads to guide implant placement in proximal femoral fractures.

PubMed

Jenkins, Paul J; Ramaesh, Rishikesan; Pankaj, Pankaj; Patton, James T; Howie, Colin R; Goffin, Jérôme M; Merwe, Andrew van der; Wallace, Robert J; Porter, Daniel E; Simpson, A Hamish

2013-10-01

The micro-architecture of bone has been increasingly recognized as an important determinant of bone strength. Successful operative stabilization of fractures depends on bone strength. We evaluated the osseous micro-architecture and strength of the osteoporotic human femoral head. 6 femoral heads, obtained during arthroplasty surgery for femoral neck fracture, underwent micro-computed tomography (microCT) scanning at 30 μm, and bone volume ratio (BV/TV), trabecular thickness, structural model index, connection density, and degree of anisotropy for volumes of interest throughout the head were derived. A further 15 femoral heads underwent mechanical testing of compressive failure stress of cubes of trabecular bone from different regions of the head. The greatest density and trabecular thickness was found in the central core that extended from the medial calcar to the physeal scar. This region also correlated with the greatest degree of anisotropy and proportion of plate-like trabeculae. In the epiphyseal region, the trabeculae were organized radially from the physeal scar. The weakest area was found at the apex and peripheral areas of the head. The strongest region was at the center of the head. The center of the femoral head contained the strongest trabecular bone, with the thickest, most dense trabeculae. The apical region was weaker. From an anatomical and mechanical point of view, implants that achieve fixation in or below this central core may achieve the most stable fixation during fracture healing.

Role of TGF-β in a mouse model of high turnover renal osteodystrophy.

PubMed

Liu, Shiguang; Song, Wenping; Boulanger, Joseph H; Tang, Wen; Sabbagh, Yves; Kelley, Brian; Gotschall, Russell; Ryan, Susan; Phillips, Lucy; Malley, Katie; Cao, Xiaohong; Xia, Tai-He; Zhen, Gehua; Cao, Xu; Ling, Hong; Dechow, Paul C; Bellido, Teresita M; Ledbetter, Steven R; Schiavi, Susan C

2014-01-01

Altered bone turnover is a key pathologic feature of chronic kidney disease-mineral and bone disorder (CKD-MBD). Expression of TGF-β1, a known regulator of bone turnover, is increased in bone biopsies from individuals with CKD. Similarly, TGF-β1 mRNA and downstream signaling is increased in bones from jck mice, a model of high-turnover renal osteodystrophy. A neutralizing anti-TGF-β antibody (1D11) was used to explore TGF-β's role in renal osteodystrophy. 1D11 administration to jck significantly attenuated elevated serum osteocalcin and type I collagen C-telopeptides. Histomorphometric analysis indicated that 1D11 administration increased bone volume and suppressed the elevated bone turnover in a dose-dependent manner. These effects were associated with reductions in osteoblast and osteoclast surface areas. Micro-computed tomography (µCT) confirmed the observed increase in trabecular bone volume and demonstrated improvements in trabecular architecture and increased cortical thickness. 1D11 administration was associated with significant reductions in expression of osteoblast marker genes (Runx2, alkaline phosphatase, osteocalcin) and the osteoclast marker gene, Trap5. Importantly, in this model, 1D11 did not improve kidney function or reduce serum parathyroid hormone (PTH) levels, indicating that 1D11 effects on bone are independent of changes in renal or parathyroid function. 1D11 also significantly attenuated high-turnover bone disease in the adenine-induced uremic rat model. Antibody administration was associated with a reduction in pSMAD2/SMAD2 in bone but not bone marrow as assessed by quantitative immunoblot analysis. Immunostaining revealed pSMAD staining in osteoblasts and osteocytes but not osteoclasts, suggesting 1D11 effects on osteoclasts may be indirect. Immunoblot and whole genome mRNA expression analysis confirmed our previous observation that repression of Wnt/β-catenin expression in bone is correlated with increased osteoclast activity in jck mice and bone biopsies from CKD patients. Furthermore, our data suggest that elevated TGF-β may contribute to the pathogenesis of high-turnover disease partially through inhibition of β-catenin signaling. © 2014 American Society for Bone and Mineral Research.

Electron absorbed fractions of energy and S-values in an adult human skeleton based on µCT images of trabecular bone

NASA Astrophysics Data System (ADS)

Kramer, R.; Richardson, R. B.; Cassola, V. F.; Vieira, J. W.; Khoury, H. J.; Lira, C. A. B. de O.; Robson Brown, K.

2011-03-01

When the human body is exposed to ionizing radiation, among the soft tissues at risk are the active marrow (AM) and the bone endosteum (BE) located in tiny, irregular cavities of trabecular bone. Determination of absorbed fractions (AFs) of energy or absorbed dose in the AM and the BE represent one of the major challenges of dosimetry. Recently, at the Department of Nuclear Energy at the Federal University of Pernambuco, a skeletal dosimetry method based on µCT images of trabecular bone introduced into the spongiosa voxels of human phantoms has been developed and applied mainly to external exposure to photons. This study uses the same method to calculate AFs of energy and S-values (absorbed dose per unit activity) for electron-emitting radionuclides known to concentrate in skeletal tissues. The modelling of the skeletal tissue regions follows ICRP110, which defines the BE as a 50 µm thick sub-region of marrow next to the bone surfaces. The paper presents mono-energetic AFs for the AM and the BE for eight different skeletal regions for electron source energies between 1 keV and 10 MeV. The S-values are given for the beta emitters 14C, 59Fe, 131I, 89Sr, 32P and 90Y. Comparisons with results from other investigations showed good agreement provided that differences between methodologies and trabecular bone volume fractions were properly taken into account. Additionally, a comparison was made between specific AFs of energy in the BE calculated for the actual 50 µm endosteum and the previously recommended 10 µm endosteum. The increase in endosteum thickness leads to a decrease of the endosteum absorbed dose by up to 3.7 fold when bone is the source region, while absorbed dose increases by ~20% when the beta emitters are in marrow.

Effect of antipronation foot orthosis geometry on compression of heel and arch soft tissues.

PubMed

Sweeney, Declan; Nester, Christopher; Preece, Stephen; Mickle, Karen

2015-01-01

This study aimed to understand how systematic changes in arch height and two designs of heel wedging affect soft tissues under the foot. Soft tissue thickness under the heel and navicular was measured using ultrasound. Heel pad thickness was measured when subjects were standing on a flat surface and standing on an orthosis with 4 and 8 degree extrinsic wedges and 4 mm and 8 mm intrinsic wedges (n = 27). Arch soft tissue thickness was measured when subjects were standing and when standing on an orthosis with -6 mm, standard, and +6 mm increments in arch height (n = 25). Extrinsic and intrinsic heel wedges significantly increased soft tissue thickness under the heel compared with no orthosis. The 4 and 8 degree extrinsic wedges increased tissue thickness by 28% and 27.6%, respectively, while the 4 mm and 8 mm intrinsic wedges increased thickness by 23% and 14.6%, respectively. Orthotic arch height significantly affected arch soft tissue thickness. Compared with the no orthosis condition, the -6 mm, standard, and +6 mm arch heights decreased arch tissue thickness by 9%, 10%, and 11.8%, respectively. This study demonstrates that change in orthotic geometry creates different plantar soft tissue responses that we expect to affect transmission of force to underlying foot bones.

Effect of risedronate on bone in renal transplant recipients.

PubMed

Coco, Maria; Pullman, James; Cohen, Hillel W; Lee, Sally; Shapiro, Craig; Solorzano, Clemencia; Greenstein, Stuart; Glicklich, Daniel

2012-08-01

Bisphosphonates may prevent or treat the bone loss promoted by the immunosuppressive regimens used in renal transplantation. Risedronate is a commonly used third-generation amino-bisphosphonate, but little is known about its effects on the bone health of renal transplant recipients. We randomly assigned 42 new living-donor kidney recipients to either 35 mg of risedronate weekly or placebo for 12 months. We obtained bone biopsies at the time of renal transplant and after 12 months of protocol treatment. Treatment with risedronate did not affect bone mineral density (BMD) in the overall cohort. In subgroup analyses, it tended to preserve BMD in female participants but did not significantly affect the BMD of male participants. Risedronate did associate with increased osteoid volume and trabecular thickness in male participants, however. There was no evidence for the development of adynamic bone disease. In summary, further study is needed before the use of prophylactic bisphosphonates to attenuate bone loss can be recommended in renal transplant recipients.

Genetic randomization reveals functional relationships among morphologic and tissue-quality traits that contribute to bone strength and fragility

PubMed Central

Hu, Bin; Tommasini, Steven M.; Courtland, Hayden-William; Price, Christopher; Terranova, Carl J.; Nadeau, Joseph H.

2007-01-01

We examined femora from adult AXB/BXA recombinant inbred (RI) mouse strains to identify skeletal traits that are functionally related and to determine how functional interactions among these traits contribute to genetic variability in whole-bone stiffness, strength, and toughness. Randomization of A/J and C57BL/6J genomic regions resulted in each adult male and female RI strain building mechanically functional femora by assembling unique sets of morphologic and tissue-quality traits. A correlation analysis was conducted using the mean trait values for each RI strain. A third of the 66 correlations examined were significant, indicating that many bone traits covaried or were functionally related. Path analysis revealed important functional interactions among bone slenderness, cortical thickness, and tissue mineral density. The path coefficients describing these functional relations were similar for both sexes. The causal relationship among these three traits suggested that cellular processes during growth simultaneously regulate bone slenderness, cortical thickness, and tissue mineral density so that the combination of traits is sufficiently stiff and strong to satisfy daily loading demands. A disadvantage of these functional interactions was that increases in tissue mineral density also deleteriously affected tissue ductility. Consequently, slender bones with high mineral density may be stiff and strong but they are also brittle. Thus, genetically randomized mouse strains revealed a basic biological paradigm that allows for flexibility in building bones that are functional for daily activities but that creates preferred sets of traits under extreme loading conditions. Genetic or environmental perturbations that alter these functional interactions during growth would be expected to lead to loss of function and suboptimal adult bone quality. PMID:17557179

Suppression of Autophagy in Osteocytes Mimics Skeletal Aging*

PubMed Central

Onal, Melda; Piemontese, Marilina; Xiong, Jinhu; Wang, Yiying; Han, Li; Ye, Shiqiao; Komatsu, Masaaki; Selig, Martin; Weinstein, Robert S.; Zhao, Haibo; Jilka, Robert L.; Almeida, Maria; Manolagas, Stavros C.; O'Brien, Charles A.

2013-01-01

Bone mass declines with age but the mechanisms responsible remain unclear. Here we demonstrate that deletion of a conditional allele for Atg7, a gene essential for autophagy, from osteocytes caused low bone mass in 6-month-old male and female mice. Cancellous bone volume and cortical thickness were decreased, and cortical porosity increased, in conditional knock-out mice compared with control littermates. These changes were associated with low osteoclast number, osteoblast number, bone formation rate, and wall width in the cancellous bone of conditional knock-out mice. In addition, oxidative stress was higher in the bones of conditional knock-out mice as measured by reactive oxygen species levels in the bone marrow and by p66shc phosphorylation in L6 vertebra. Each of these changes has been previously demonstrated in the bones of old versus young adult mice. Thus, these results demonstrate that suppression of autophagy in osteocytes mimics, in many aspects, the impact of aging on the skeleton and suggest that a decline in autophagy with age may contribute to the low bone mass associated with aging. PMID:23645674

Accurate 3-D Profile Extraction of Skull Bone Using an Ultrasound Matrix Array.

PubMed

Hajian, Mehdi; Gaspar, Robert; Maev, Roman Gr

2017-12-01

The present study investigates the feasibility, accuracy, and precision of 3-D profile extraction of the human skull bone using a custom-designed ultrasound matrix transducer in Pulse-Echo. Due to the attenuative scattering properties of the skull, the backscattered echoes from the inner surface of the skull are severely degraded, attenuated, and at some points overlapped. Furthermore, the speed of sound (SOS) in the skull varies significantly in different zones and also from case to case; if considered constant, it introduces significant error to the profile measurement. A new method for simultaneous estimation of the skull profiles and the sound speed value is presented. The proposed method is a two-folded procedure: first, the arrival times of the backscattered echoes from the skull bone are estimated using multi-lag phase delay (MLPD) and modified space alternating generalized expectation maximization (SAGE) algorithms. Next, these arrival times are fed into an adaptive sound speed estimation algorithm to compute the optimal SOS value and subsequently, the skull bone thickness. For quantitative evaluation, the estimated bone phantom thicknesses were compared with the mechanical measurements. The accuracies of the bone thickness measurements using MLPD and modified SAGE algorithms combined with the adaptive SOS estimation were 7.93% and 4.21%, respectively. These values were 14.44% and 10.75% for the autocorrelation and cross-correlation methods. Additionally, the Bland-Altman plots showed the modified SAGE outperformed the other methods with -0.35 and 0.44 mm limits of agreement. No systematic error that could be related to the skull bone thickness was observed for this method.

High phosphate feeding promotes mineral and bone abnormalities in mice with chronic kidney disease.

PubMed

Lau, Wei Ling; Linnes, Michael; Chu, Emily Y; Foster, Brian L; Bartley, Bryan A; Somerman, Martha J; Giachelli, Cecilia M

2013-01-01

Chronic kidney disease-mineral bone disorder (CKD-MBD) is a systemic syndrome characterized by imbalances in mineral homeostasis, renal osteodystrophy (ROD) and ectopic calcification. The mechanisms underlying this syndrome in individuals with chronic kidney disease (CKD) are not yet clear. We examined the effect of normal phosphate (NP) or high phosphate (HP) feeding in the setting of CKD on bone pathology, serum biochemistry and vascular calcification in calcification-prone dilute brown non-agouti (DBA/2) mice. In both NP and HP-fed CKD mice, elevated serum parathyroid hormone and alkaline phosphatase (ALP) levels were observed, but serum phosphorus levels were equivalent compared with sham controls. CKD mice on NP diet showed trabecular alterations in the long bone consistent with high-turnover ROD, including increased trabecular number with abundant osteoblasts and osteoclasts. Despite trabecular bone and serum biochemical changes, CKD/NP mice did not develop vascular calcification. In contrast, CKD/HP mice developed arterial medial calcification (AMC), more severe trabecular bone alterations and cortical bone abnormalities that included decreased cortical thickness and density, and increased cortical porosity. Cortical bone porosity and trabecular number strongly correlated with the degree of aortic calcification. HP feeding was required to induce the full spectrum of CKD-MBD symptoms in CKD mice.

The Effects of Combined Treatment with Naringin and Treadmill Exercise on Osteoporosis in Ovariectomized Rats

PubMed Central

SUN, Xiaolei; Fengbo, LI; Xinlong, MA; Jianxiong, MA; ZHAO, Bin; ZHANG, Yang; Yanjun, LI; Jianwei, LV; MENG, Xinmin

2015-01-01

Osteoporosis is a disease characterized by low bone mass and progressive destruction of bone microstructure, resulting in increased the risk of fracture. Previous studies have demonstrated the effect of naringin (NG) or treadmill exercise (EX) on osteoporosis, however, reports about effects of NG plus EX on osteoporosis are limited. This study was designed to investigate the impact of combined treatment with naringin and treadmill exercise on osteoporosis in ovariectomized (OVX) rats. Three months after bilateral ovariectomy, Seventy-five rats were randomly assigned to the following treatment groups: OVX, sham-operated (SHAM), NG, EX, or NG plus EX treatment. Treatments were administered for 60 days. Bone metabolism, bone mineral density, trabecular bone parameters, immunohistochemistry, and the bone strength were evaluated. Compared to the OVX groups, all treatments increased bone volume (BV/TV), trabecula number (Tb.N), trabecula thickness (Tb.Th), bone mineral density (BMD), and mechanical strength. NG + EX showed the strongest effects on BV/TV, Tb.Th, and biomechanical strength. Additionally, decreased C-terminal telopeptides of type I collagen (CTX-1) and enhanced osteocalcin (OCN) expression were observed in the NG + EX group. The present study demonstrates that the NG + EX may have a therapeutic advantage over each monotherapy for the treatment of osteoporosis. PMID:26260240

Excessive dietary intake of vitamin A reduces skull bone thickness in mice

PubMed Central

Öhman, Caroline; Calounova, Gabriela; Rasmusson, Annica; Andersson, Göran; Pejler, Gunnar; Melhus, Håkan

2017-01-01

Calvarial thinning and skull bone defects have been reported in infants with hypervitaminosis A. These findings have also been described in humans, mice and zebrafish with loss-of-function mutations in the enzyme CYP26B1 that degrades retinoic acid (RA), the active metabolite of vitamin A, indicating that these effects are indeed caused by too high levels of vitamin A and that evolutionary conserved mechanisms are involved. To explore these mechanisms, we have fed young mice excessive doses of vitamin A for one week and then analyzed the skull bones using micro computed tomography, histomorphometry, histology and immunohistochemistry. In addition, we have examined the effect of RA on gene expression in osteoblasts in vitro. Compared to a standard diet, a high dietary intake of vitamin A resulted in a rapid and significant reduction in calvarial bone density and suture diastasis. The bone formation rate was almost halved. There was also increased staining of tartrate resistant acid phosphatase in osteocytes and an increased perilacunar matrix area, indicating osteocytic osteolysis. Consistent with this, RA induced genes associated with bone degradation in osteoblasts in vitro. Moreover, and in contrast to other known bone resorption stimulators, vitamin A induced osteoclastic bone resorption on the endocranial surfaces. PMID:28426756

Evaluation of Cameroonian plants towards experimental bone regeneration.

PubMed

Ngueguim, Florence Tsofack; Khan, Mohd Parvez; Donfack, Jean Hubert; Siddiqui, Jawed Akhtar; Tewari, Deepshikha; Nagar, Geet K; Tiwari, Satish C; Theophile, Dimo; Maurya, Rakesh; Chattopadhyay, Naibedya

2012-05-07

Elephantopus mollis, Spilanthes africana, Urena lobata, Momordica multiflora, Asystasia gangetica and Brillantaisia ovariensis are used in Cameroonian traditional medicine for the treatment of bone diseases and fracture repair. The aim of this study was to evaluate the effect of ethanolic extracts of six Cameroonian medicinal plants on bone regeneration following bone and marrow injury. Ethanol extract of Cameroonian medicinal plants were administered (each extract at 250, 500 and 750mg/kg doses) orally to adult female Sprague-Dawley rats having a drill hole injury (0.8mm) in the femur diaphysis. Vehicle (gum-acacia in distilled water) was given to the control group. After 12 days of treatment, animals were euthanized and femur bones collected. Confocal microscopy of fractured bone was performed to evaluate bone regeneration (calcein labeling). Only active plant extracts were used for further experiments. Thus, callus was analyzed by microcomputed tomography. Osteogenic effects of the extracts were evaluated by assessing mineralized nodules formation of bone marrow stromal cells and osteoblast recruitment at drill hole site by immunohistochemistry. Ethanolic extract of the leaves and twigs of Elephantopus mollis (EM) and whole plant of Spilanthes africana (SA) dose-dependently stimulated bone regeneration at the drill hole site. EM at 250 and 750mg/kg doses and SA at 750mg/kg dose significantly increased mineral deposition compared to controls. Both extracts at 500 and 750mg/kg doses improved microarchitecture of the regenerating bone evident from increased bone volume fraction, trabecular thickness, trabecular number, and decreased trabecular separation and structure model index. EM and SA extracts increased the formation of mineralized nodules from the bone marrow stromal cells. In addition, EM and SA extracts increased osteoblast recruitment at the drill hole site evident from increased Runx-2 positive cells following their treatments compared to control. Ethanolic extracts of EM and SA accelerate fracture repair in rats via stimulatory effects on osteoblast differentiation and mineralization, thereby justifying their traditional use. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Kinetic examination of femoral bone modeling in broilers.

PubMed

Prisby, R; Menezes, T; Campbell, J; Benson, T; Samraj, E; Pevzner, I; Wideman, R F

2014-05-01

Lameness in broilers can be associated with progressive degeneration of the femoral head leading to femoral head necrosis and osteomyelitis. Femora from clinically healthy broilers were dissected at 7 (n = 35, 2), 14 (n = 32), 21 (n = 33), 28 (n = 34), and 42 (n = 28) d of age, and were processed for bone histomorphometry to examine bone microarchitecture and bone static and dynamic properties in the secondary spongiosa (IISP) of the proximal femoral metaphysis. Body mass increased rapidly with age, whereas the bone volume to tissue volume ratio remained relatively consistent. The bone volume to tissue volume ratio values generally reflected corresponding values for both mean trabecular thickness and mean trabecular number. Bone metabolism was highest on d 7 when significant osteoblast activity was reflected by increased osteoid surface to bone surface and mineralizing surface per bone surface ratios. However, significant declines in osteoblast activity and bone formative processes occurred during the second week of development, such that newly formed but unmineralized bone tissue (osteoid) and the percentages of mineralizing surfaces both were diminished. Osteoclast activity was elevated to the extent that measurement was impossible. Intense osteoclast activity presumably reflects marked bone resorption throughout the experiment. The overall mature trabecular bone volume remained relatively low, which may arise from extensive persistence of chondrocyte columns in the metaphysis, large areas in the metaphysis composed of immature bone, destruction of bone tissue in the primary spongiosa, and potentially reduced bone blood vessel penetration that normally would be necessary for robust development. Delayed bone development in the IISP was attributable to an uncoupling of osteoblast and osteoclast activity, whereby bone resorption (osteoclast activity) outpaced bone formation (osteoblast activity). Insufficient maturation and mineralization of the IISP may contribute to subsequent pathology of the femoral head in fast-growing broilers.

Protective effect of egg yolk peptide on bone metabolism.

PubMed

Kim, Hye Kyung; Lee, Sena; Leem, Kang-Hyun

2011-03-01

Osteoporosis is a major health problem worldwide, and most current therapy used in osteoporosis treatment acts by either increasing bone formation or decreasing bone resorption. However, the adverse effects of these therapies may preclude their long-term use. We examined the effects of egg yolk water-soluble peptide (YPEP) on bone metabolism as an alternative to current therapeutic agents in ovariectomized (OVX) rats. In the first step, the in vitro effects of YPEP on bone loss were determined. The proliferation, collagen content, and alkaline phosphatase activity of preosteoblastic MC3T3-E1 cells and osteoclastogenesis from bone marrow-derived precursor cells were measured. The in vivo experiment confirmed the positive effect of YPEP on bone tissue. Three-month-old female Sprague-Dawley rats were either sham operated or ovariectomized and fed commercial chow diet or 0.1% YPEP-supplemented diet for 3 month. YPEP increased preosteoblastic MC3T3-E1 cell proliferation and alkaline phosphatase activity in a dose-dependent manner. Collagen content was also increased by YPEP treatment. Furthermore, YPEP potently suppressed osteoclastogenesis from bone marrow-derived precursor cells. YPEP (100 μg/mL) abolished the formation of osteoclasts positive for tartrate-resistant acid phosphatase. OVX rats supplemented with YPEP showed an osteoprotective effect, as the bone mineral density and cortical thickness in the tibia were increased compared with the OVX controls. Moreover, histological data indicate that YPEP prevented the cancellous bone loss induced by ovariectomy. None of these protective effects were observed in casein-treated rats. The present study suggests that YPEP is a promising alternative to current therapeutic agents for the management of osteoporosis.

Losartan increases bone mass and accelerates chondrocyte hypertrophy in developing skeleton

PubMed Central

Rianon, Nahid; Rajagopal, Abbhirami; Munivez, Elda; Bertin, Terry; Dawson, Brian; Chen, Yuqing; Jiang, Ming-Ming; Lee, Brendan; Yang, Tao; Bae, Yangjin

2015-01-01

Angiotensin receptor blockers (ARBs) are a group of anti-hypertensive drugs that are widely used to treat pediatric hypertension. Recent application of ARBs to treat diseases such as Marfan syndrome or Alport syndrome has shown positive outcomes in animal and human studies, suggesting a broader therapeutic potential for this class of drugs. Multiple studies have reported a benefit of ARBs on adult bone homeostasis; however, its effect on the growing skeleton in children is unknown. We investigated the effect of Losartan, an ARB, in regulating bone mass and cartilage during development in mice. Wild type mice were treated with Losartan from birth until 6 weeks of age, after which bones were collected for microCT and histomorphometric analyses. Losartan increased trabecular bone volume vs. tissue volume (a 98% increase) and cortical thickness (a 9% increase) in 6-weeks old wild type mice. The bone changes were attributed to decreased osteoclastogenesis as demonstrated by reduced osteoclast number per bone surface in vivo and suppressed osteoclast differentiation in vitro. At the molecular level, Angiotensin II-induced ERK1/2 phosphorylation in RAW cells was attenuated by Losartan. Similarly, RANKL-induced ERK1/2 phosphorylation was suppressed by Losartan, suggesting a convergence of RANKL and angiotensin signaling at the level of ERK1/2 regulation. To assess the effect of Losartan on cartilage development, we examined the cartilage phenotype of wild type mice treated with Losartan in utero from conception to 1 day of age. Growth plates of these mice showed an elongated hypertrophic chondrocyte zone and increased Col10a1 expression level, with minimal changes in chondrocyte proliferation. Altogether, inhibition of the angiotensin pathway by Losartan increases bone mass and accelerates chondrocyte hypertrophy in growth plate during skeletal development. PMID:25779879

Losartan increases bone mass and accelerates chondrocyte hypertrophy in developing skeleton.

PubMed

Chen, Shan; Grover, Monica; Sibai, Tarek; Black, Jennifer; Rianon, Nahid; Rajagopal, Abbhirami; Munivez, Elda; Bertin, Terry; Dawson, Brian; Chen, Yuqing; Jiang, Ming-Ming; Lee, Brendan; Yang, Tao; Bae, Yangjin

2015-05-01

Angiotensin receptor blockers (ARBs) are a group of anti-hypertensive drugs that are widely used to treat pediatric hypertension. Recent application of ARBs to treat diseases such as Marfan syndrome or Alport syndrome has shown positive outcomes in animal and human studies, suggesting a broader therapeutic potential for this class of drugs. Multiple studies have reported a benefit of ARBs on adult bone homeostasis; however, its effect on the growing skeleton in children is unknown. We investigated the effect of Losartan, an ARB, in regulating bone mass and cartilage during development in mice. Wild type mice were treated with Losartan from birth until 6 weeks of age, after which bones were collected for microCT and histomorphometric analyses. Losartan increased trabecular bone volume vs. tissue volume (a 98% increase) and cortical thickness (a 9% increase) in 6-weeks old wild type mice. The bone changes were attributed to decreased osteoclastogenesis as demonstrated by reduced osteoclast number per bone surface in vivo and suppressed osteoclast differentiation in vitro. At the molecular level, Angiotensin II-induced ERK1/2 phosphorylation in RAW cells was attenuated by Losartan. Similarly, RANKL-induced ERK1/2 phosphorylation was suppressed by Losartan, suggesting a convergence of RANKL and angiotensin signaling at the level of ERK1/2 regulation. To assess the effect of Losartan on cartilage development, we examined the cartilage phenotype of wild type mice treated with Losartan in utero from conception to 1 day of age. Growth plates of these mice showed an elongated hypertrophic chondrocyte zone and increased Col10a1 expression level, with minimal changes in chondrocyte proliferation. Altogether, inhibition of the angiotensin pathway by Losartan increases bone mass and accelerates chondrocyte hypertrophy in growth plate during skeletal development. Copyright © 2015 Elsevier Inc. All rights reserved.

Anabolic Responses of an Adult Cancellous Bone Site to Prostaglandin E2 in the Rat

NASA Technical Reports Server (NTRS)

Ito, Hiroshi; Ke, Hua Zhu; Jee, Webster S. S.; Sakou, Takashi

1993-01-01

The objects of this study were to determine: (1) the response of a non-growing cancellous bone site to daily prostaglandin E2 (PGE2) administration; and (2) the differences in the effects of daily PGE2, administration in growing (proximal tibial metaphysis, PTM) and non-growing cancellous bone sites (distal tibial metaphysis, DTM). Seven-month-old male Sprague-Dawley rats were given daily subcutaneous injections of 0, 1, 3 and 6 mg PGE2/kg per day for 60, 120 and 180 days. The static and dynamic histomorphometric analyses were performed on double-fluorescent labeled undecalcified distal tibial metaphyses (DTM). No age-related changes were found in static and dynamic histomorphometry of DTM cancellous bone between 7 and 13 months of age. The DTM of 7-month-old (basal controls) rats consisted of a 24.5 +/- 7.61%-metaphyseal cancellous bone mass, and a thick trabeculae (92 +/- 12 micro-m). It also had a very low tissue-base bone formation rate (3.0 +/- 7.31%/year). Exogenous PGE2 administration produced the following transient changes in a dose-response manner between zero and 60 days: (1) increased trabecular bone mass and improved architecture (increased trabecular bone area, width and number, and decreased trabecular separation); (2) increased trabecular interconnections: (3) increased bone formation parameters; and (4) decreased eroded perimeter. A new steady state with more cancellous bone mass and higher bone turnover was observed from day 60 onward, The elevated bone mass induced by the first 60 days of PGE2 treatment was maintained by another 60 and 120 days with continuous daily PGE2 treatment. When these findings were compared to those previously reported for the PTM, we found that the DTM was much more responsive to PGE2 treatment than the PTM. Percent trabecular bone area and tissue based bone formation rate increased significantly more in DTM as compared to PTM after the 60 days of 6 mg PGE2 treatment. These observations indicate that a non-growing cancellous bone site is more responsive than growing bone site to long-term daily administration of PGE2.

Role of TGF-β in a Mouse Model of High Turnover Renal Osteodystrophy†

PubMed Central

Liu, Shiguang; Song, Wenping; Boulanger, Joseph H; Tang, Wen; Sabbagh, Yves; Kelley, Brian; Gotschall, Russell; Ryan, Susan; Phillips, Lucy; Malley, Katie; Cao, Xiaohong; Xia, Tai-He; Zhen, Gehua; Cao, Xu; Ling, Hong; Dechow, Paul C; Bellido, Teresita M; Ledbetter, Steven R; Schiavi, Susan C

2014-01-01

Altered bone turnover is a key pathologic feature of chronic kidney disease-mineral and bone disorder (CKD-MBD). Expression of TGF-β1, a known regulator of bone turnover, is increased in bone biopsies from individuals with CKD. Similarly, TGF-β1 mRNA and downstream signaling is increased in bones from jck mice, a model of high-turnover renal osteodystropy. A neutralizing anti-TGF-β antibody (1D11) was used to explore TGF-βs role in renal osteodystrophy. 1D11 administration to jck significantly attenuated elevated serum osteocalcin and type I collagen C-telopeptides. Histomorphometric analysis indicated that 1D11 administration increased bone volume and suppressed the elevated bone turnover in a dose-dependent manner. These effects were associated with reductions in osteoblast and osteoclast surface areas. μCT confirmed the observed increase in trabecular bone volume and demonstrated improvements in trabecular architecture and increased cortical thickness. 1D11 administration was associated with significant reductions in expression of osteoblast marker genes (Runx2, alkaline phosphatase, osteocalcin) and the osteoclast marker gene, Trap5. Importantly, in this model, 1D11 did not improve kidney function or reduce serum PTH levels indicating that 1D11 effects on bone are independent of changes in renal or parathyroid function. 1D11 also significantly attenuated high turnover bone disease in the adenine-induced uremic rat model. Antibody administration was associated with a reduction in pSMAD2/SMAD2 in bone but not bone marrow as assessed by quantitative immunoblot analysis. Immunostaining revealed pSMAD staining in osteoblasts and osteocytes but not osteoclasts, suggesting 1D11 effects on osteoclasts may be indirect. Immunoblot and whole genome mRNA expression analysis confirmed our previous observation that repression of Wnt/β catenin expression in bone is correlated with increased osteoclast activity in jck mice and bone biopsies from CKD patients. Furthermore, our data suggests that elevated TGF-β may contribute to the pathogenesis of high turnover disease partially through inhibition of β-catenin signaling. PMID:24166835

Predictive role of prenasal thickness and nasal bone for Down syndrome in the second trimester.

PubMed

Ozcan, Tulin; Özlü, Tülay; Allen, Julie; Peterson, Jeanne; Pressman, Eva K

2013-12-01

To assess the efficacy of prenasal thickness (PNT) and nasal bone (NB) for prediction of Down syndrome (DS) fetuses in the second trimester ultrasound examination. PNT was measured from stored two-dimensional fetal profile images taken at 15-23 weeks in 242 fetuses with normal karyotype (Group 1) and 24 fetuses with DS (Group 2). It was measured as the shortest distance from the anterior edge of the lowest part of the frontal bone to the skin. The efficacy of PNT, NB, PNT/NB and biparietal diameter (BPD)/NB was evaluated for prediction of DS. PNT values increased with gestational age in normal fetuses. PNT measurement was ≥95th percentile in 54.2% (13/24) of the DS cases and 2.9% of the normal cases. Receiver operator curve analysis showed that PNT/NB ratio had the best area under the curve with a detection rate of 80% for a false positive rate of 5% at a cut-off value of 0.76. PNT is increased in fetuses with DS as compared to normal fetuses. PNT/NB≥0.76 in the second trimester is a better predictor of DS than the use of PNT or NB alone. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Nasal bone length: prenasal thickness ratio: a strong 2D ultrasound marker for Down syndrome.

PubMed

Szabó, Andrea; Szili, Károly; Szabó, János Tamás; Sikovanyecz, János; Isaszegi, Dóra; Horváth, Emese; Szabó, János

2014-12-01

To evaluate the feasibility of incorporating two-dimensional ultrasound measurements of nasal bone length (NBL) and prenasal thickness (PT) into the second-trimester anomaly scan and to determine whether the NBL : PT ratio could help in differentiating euploid and Down syndrome fetuses. Two-dimensional measurements of NBL and PT were obtained from the midsagittal plane of the fetal head at 14-28 weeks of gestation in a Caucasian population at risk for aneuploidy. The screening performances of NBL, PT, and the ratios NBL : PT and PT : NBL were analyzed in euploid (n = 1330) and Down syndrome (n = 33) fetuses. Nasal bone length and PT alone showed strong correlations with Down syndrome (sensitivity: 76% at 1.88% and 2.35% false positive rate, respectively). However, the NBL : PT ratio showed an even stronger correlation with Down syndrome (false positive rate: 0.9%, sensitivity: 97%). The mean NBL : PT ratio showed a gradual increase from 1.48 to 1.79 (a 21.2% increase) between 14 and 28 weeks of gestation. Two-dimensional ultrasound measurements of NBL and PT, particularly the NBL : PT ratio, are highly sensitive markers for Down syndrome fetuses. © 2014 John Wiley & Sons, Ltd.

Effects of Vitamin K2 on the Development of Osteopenia in Rats as the Models of Osteoporosis

PubMed Central

Takeda, Tsuyoshi; Sato, Yoshihiro

2006-01-01

Vitamin K2 is widely used for the treatment of osteoporosis in Japan. To understand the effects of vitamin K2 on bone mass and bone metabolism, we reviewed its effects on the development of osteopenia in rats, which characterizes models of osteoporosis. Vitamin K2 was found to attenuate the increase in bone resorption and/or maintain bone formation, reduce bone loss, protect against the loss of trabecular bone mass and its connectivity, and prevent the decrease in strength of the long bone in ovariectomized rats. However, combined treatment of bisphosphonates and vitamin K2 had an additive effect in preventing the deterioration of the trabecular bone architecture in ovariectomized rats, while the combined treatment of raloxifene and vitamin K2 improved the bone strength of the femoral neck. The use of vitamin K2 alone suppressed the increase in trabecular bone turnover and endocortical bone resorption, which attenuated the development of cancellous and cortical osteopenia in orchidectomized rats. In addition, vitamin K2 inhibited the decrease in bone formation in prednisolone-treated rats, thereby preventing cancellous and cortical osteopenia. In sciatic neurectomized rats, vitamin K2 suppressed endocortical bone resorption and stimulated bone formation, delaying the reduction of the trabecular thickness and retarding the development of cortical osteopenia. Vitamin K2 also prevented the acceleration of bone resorption and the reduction in bone formation in tail-suspended rats, which counteracted cancellous bone loss. Concomitant use of vitamin K2 with a bisphosphonate ameliorated the suppression of bone formation and more effectively prevented cancellous bone loss in tail-suspended rats. Vitamin K2 stimulated renal calcium reabsorption, retarded the increase in serum parathyroid hormone levels, and attenuated cortical bone loss primarily by suppressing bone resorption in calcium-deficient rats while maintaining the strength of the long bone in rats with magnesium deficiency. These findings suggest that vitamin K2 may not only stimulate bone formation, but may also suppress bone resorption. Thus, vitamin K2 could regulate bone metabolism in rats, which represented the various models of osteoporosis. However, the effects of vitamin K2 on bone mass and bone metabolism seem to be modest. PMID:16642543

Osteoblast-Specific Overexpression of Human WNT16 Increases Both Cortical and Trabecular Bone Mass and Structure in Mice

PubMed Central

Alkhouli, Mohammed; Gerard-O'Riley, Rita L.; Wright, Weston B.; Acton, Dena; Gray, Amie K.; Patel, Bhavmik; Reilly, Austin M.; Lim, Kyung-Eun; Robling, Alexander G.; Econs, Michael J.

2016-01-01

Previous genome-wide association studies have identified common variants in genes associated with bone mineral density (BMD) and risk of fracture. Recently, we identified single nucleotide polymorphisms (SNPs) in Wingless-type mouse mammary tumor virus integration site (WNT)16 that were associated with peak BMD in premenopausal women. To further identify the role of Wnt16 in bone mass regulation, we created transgenic (TG) mice overexpressing human WNT16 in osteoblasts. We compared bone phenotypes, serum biochemistry, gene expression, and dynamic bone histomorphometry between TG and wild-type (WT) mice. Compared with WT mice, WNT16-TG mice exhibited significantly higher whole-body areal BMD and bone mineral content (BMC) at 6 and 12 weeks of age in both male and female. Microcomputer tomography analysis of trabecular bone at distal femur revealed 3-fold (male) and 14-fold (female) higher bone volume/tissue volume (BV/TV), and significantly higher trabecular number and trabecular thickness but lower trabecular separation in TG mice compared with WT littermates in both sexes. The cortical bone at femur midshaft also displayed significantly greater bone area/total area and cortical thickness in the TG mice in both sexes. Serum biochemistry analysis showed that male TG mice had higher serum alkaline phosphatase, osteocalcin, osteoprotegerin (OPG), OPG to receptor activator of NF-kB ligand (tumor necrosis family ligand superfamily, number 11; RANKL) ratio as compared with WT mice. Also, lower carboxy-terminal collagen cross-link (CTX) to tartrate-resistant acid phosphatase 5, isoform b (TRAPc5b) ratio was observed in TG mice compared with WT littermates in both male and female. Histomorphometry data demonstrated that both male and female TG mice had significantly higher cortical and trabecular mineralizing surface/bone surface and bone formation rate compared with sex-matched WT mice. Gene expression analysis demonstrated higher expression of Alp, OC, Opg, and Opg to Rankl ratio in bone tissue in the TG mice compared with WT littermates. Our data indicate that WNT16 is critical for positive regulation of both cortical and trabecular bone mass and structure and that this molecule might be targeted for therapeutic interventions to treat osteoporosis. PMID:26584014

Multiscale, Converging Defects of Macro-Porosity, Microstructure and Matrix Mineralization Impact Long Bone Fragility in NF1

PubMed Central

Kühnisch, Jirko; Seto, Jong; Lange, Claudia; Schrof, Susanne; Stumpp, Sabine; Kobus, Karolina; Grohmann, Julia; Kossler, Nadine; Varga, Peter; Osswald, Monika; Emmerich, Denise; Tinschert, Sigrid; Thielemann, Falk; Duda, Georg; Seifert, Wenke; el Khassawna, Thaqif; Stevenson, David A.; Elefteriou, Florent; Kornak, Uwe; Raum, Kay; Fratzl, Peter; Mundlos, Stefan; Kolanczyk, Mateusz

2014-01-01

Bone fragility due to osteopenia, osteoporosis or debilitating focal skeletal dysplasias is a frequent observation in the Mendelian disease Neurofibromatosis type 1 (NF1). To determine the mechanisms underlying bone fragility in NF1 we analyzed two conditional mouse models, Nf1Prx1 (limb knock-out) and Nf1Col1 (osteoblast specific knock-out), as well as cortical bone samples from individuals with NF1. We examined mouse bone tissue with micro-computed tomography, qualitative and quantitative histology, mechanical tensile analysis, small-angle X-ray scattering (SAXS), energy dispersive X-ray spectroscopy (EDX), and scanning acoustic microscopy (SAM). In cortical bone of Nf1Prx1 mice we detected ectopic blood vessels that were associated with diaphyseal mineralization defects. Defective mineral binding in the proximity of blood vessels was most likely due to impaired bone collagen formation, as these areas were completely devoid of acidic matrix proteins and contained thin collagen fibers. Additionally, we found significantly reduced mechanical strength of the bone material, which was partially caused by increased osteocyte volume. Consistent with these observations, bone samples from individuals with NF1 and tibial dysplasia showed increased osteocyte lacuna volume. Reduced mechanical properties were associated with diminished matrix stiffness, as determined by SAM. In line with these observations, bone tissue from individuals with NF1 and tibial dysplasia showed heterogeneous mineralization and reduced collagen fiber thickness and packaging. Collectively, the data indicate that bone fragility in NF1 tibial dysplasia is partly due to an increased osteocyte-related micro-porosity, hypomineralization, a generalized defect of organic matrix formation, exacerbated in the regions of tensional and bending force integration, and finally persistence of ectopic blood vessels associated with localized macro-porotic bone lesions. PMID:24465906

Makings of a brittle bone: Unexpected lessons from a low protein diet study of a mouse OI model

PubMed Central

Mertz, E.L.; Makareeva, E.; Mirigian, L.S.; Koon, K.Y.; Perosky, J.E.; Kozloff, K.M.; Leikin, S.

2016-01-01

Glycine substitutions in type I collagen appear to cause osteogenesis imperfecta (OI) by disrupting folding of the triple helix, the structure of which requires Gly in every third position. It is less clear, however, whether the resulting bone malformations and fragility are caused by effects of intracellular accumulation of misfolded collagen on differentiation and function of osteoblasts, effects of secreted misfolded collagen on the function of bone matrix, or both. Here we describe a study originally conceived for testing how reducing intracellular accumulation of misfolded collagen would affect mice with a Gly610 to Cys substitution in the triple helical region of the α2(I) chain. To stimulate degradation of misfolded collagen by autophagy, we utilized a low protein diet. The diet had beneficial effects on osteoblast differentiation and bone matrix mineralization, but it also affected bone modeling and suppressed overall animal growth. Our more important observations, however, were not related to the diet. They revealed how altered osteoblast function and deficient bone formation by each cell caused by the G610C mutation combined with increased osteoblastogenesis might make the bone more brittle, all of which are common OI features. In G610C mice, increased bone formation surface compensated for reduced mineral apposition rate, resulting in normal cortical area and thickness at the cost of altering cortical modeling process, retaining woven bone, and reducing the ability of bone to absorb energy through plastic deformation. Reduced collagen and increased mineral density in extracellular matrix of lamellar bone compounded the problem, further reducing bone toughness. The latter observations might have particularly important implications for understanding OI pathophysiology and designing more effective therapeutic interventions. PMID:27039252

A living thick nanofibrous implant bifunctionalized with active growth factor and stem cells for bone regeneration.

PubMed

Eap, Sandy; Keller, Laetitia; Schiavi, Jessica; Huck, Olivier; Jacomine, Leandro; Fioretti, Florence; Gauthier, Christian; Sebastian, Victor; Schwinté, Pascale; Benkirane-Jessel, Nadia

2015-01-01

New-generation implants focus on robust, durable, and rapid tissue regeneration to shorten recovery times and decrease risks of postoperative complications for patients. Herein, we describe a new-generation thick nanofibrous implant functionalized with active containers of growth factors and stem cells for regenerative nanomedicine. A thick electrospun poly(ε-caprolactone) nanofibrous implant (from 700 μm to 1 cm thick) was functionalized with chitosan and bone morphogenetic protein BMP-7 as growth factor using layer-by-layer technology, producing fish scale-like chitosan/BMP-7 nanoreservoirs. This extracellular matrix-mimicking scaffold enabled in vitro colonization and bone regeneration by human primary osteoblasts, as shown by expression of osteocalcin, osteopontin, and bone sialoprotein (BSPII), 21 days after seeding. In vivo implantation in mouse calvaria defects showed significantly more newly mineralized extracellular matrix in the functionalized implant compared to a bare scaffold after 30 days' implantation, as shown by histological scanning electron microscopy/energy dispersive X-ray microscopy study and calcein injection. We have as well bifunctionalized our BMP-7 therapeutic implant by adding human mesenchymal stem cells (hMSCs). The activity of this BMP-7-functionalized implant was again further enhanced by the addition of hMSCs to the implant (living materials), in vivo, as demonstrated by the analysis of new bone formation and calcification after 30 days' implantation in mice with calvaria defects. Therefore, implants functionalized with BMP-7 nanocontainers associated with hMSCs can act as an accelerator of in vivo bone mineralization and regeneration.

Chronic Hyperglycemia Modulates Rat Osteoporotic Cortical Bone Microarchitecture into Less Fragile Structures

PubMed Central

de Mello-Sampayo, Cristina; Agripino, Alaíde Alves; Stilwell, Duarte; Vidal, Bruno; Fernando, Ana Luisa; Silva-Lima, Beatriz; Vaz, Maria Fátima; Canhão, Helena

2017-01-01

There is controversy concerning the diabetes impact on bone quality, notorious in type 2 diabetic postmenopausal women. One pointed cause might be uncontrolled glycemia. In this study, the effect of chronic hyperglycemia in bone turnover, morphology, and biomechanics was evaluated in female Wistar rats in the presence/absence of estrogens (ovariectomy). Animals (n = 28) were divided into sham, ovariectomized (OVX), hyperglycemic (streptozotocin 40 mg/kg, single-dose i.p.-STZ), and hyperglycemic-ovariectomized (STZ + OVX) animals. Blood biomarkers were estimated 60 days postovariectomy. Body weight, vertebral microarchitecture (L4-histomorphometry), femur biomechanical properties (bending tests), tibia ultrastructure (scanning electron microscopy), and femur and urinary calcium (atomic absorption) were also evaluated. The increased PINP/CTX ratio of hyperglycemic animals and the similar ratio between STZ + OVX and healthy animals contrasting with the lower ratio of OVX (in line with its histomorphometric data) suggest a tendency for improved bone formation in hyperglycemic-ovariectomized animals. The increased tibia medullar canal, which contrasts with the unaffected cortical thickness of both hyperglycemic groups while that of OVX decreased, was associated to the increased stiffness and strength of STZ + OVX bones compared to those of OVX, in line with the observed ultrastructure. Concluding, chronic hyperglycemia in ovariectomized female rats causes bone morphological changes that translate positively in the ultrastructure and mechanical properties of cortical bones. PMID:29081798

Treatment of Labial Soft Tissue Recession Around Dental Implants in the Esthetic Zone Using Guided Bone Regeneration With Mineralized Allograft: A Retrospective Clinical Case Series.

PubMed

Le, Bach; Borzabadi-Farahani, Ali; Nielsen, Brady

2016-08-01

Soft tissue augmentation procedures are often performed to correct gingival recession on the facial aspects of implants in the esthetic zone. This retrospective clinical case series reports on the use of guided bone regeneration (GBR) and a coronal advancement flap with a resorbable membrane and allograft. We analyzed the records of 14 patients (7 men and 7 women) with a mean age of 36.78 years (SD, 13.9 years) who were treated for soft tissue recessions around implant-supported restorations in the maxillary central or lateral incisor location. Implant diameters ranged from 3.3 to 4.7 mm. All patients had bone loss confined to the labial surface of the implant. A solvent-dehydrated particulate mineralized allograft (Puros Cancellous Bone Allograft; Zimmer Biomet Dental, Palm Beach Gardens, FL) and a resorbable membrane (CopiOs Pericardium; Zimmer Biomet Dental) were used in a GBR surgical procedure in combination with a roughened titanium tenting screw placed 3 to 4 mm below the implant platform to restore unesthetic defects in the anterior maxilla. All postoperative tissue changes from their preoperative states were statistically significant (P < .05, Wilcoxon signed rank test). Mean preoperative crestal bone thickness (measured 2 mm from crest) and mid-implant buccal bone thickness increased by 1.84 mm (SD, 0.89 mm; 95% confidence interval [CI], 1.32 to 2.35 mm) and 2.07 mm (SD, 0.81 mm; 95% CI, 1.60 to 2.53 mm), respectively, approximately 1 year after treatment (P < .001). Significant mean increases of 1.28 mm (SD, 0.53 mm; 95% CI, 0.97 to 1.58 mm), 1.29 mm (SD, 0.81 mm; 95% CI, 0.82 to 1.75 mm) and 1.23 mm (SD, 0.53 mm; 95% CI, 0.92 to 1.53 mm) also were noted in soft tissue thickness, keratinized tissue width, and gingival height, respectively (P < .001). Use of the allograft and xenogeneic membrane effectively increased alveolar hard and soft tissue dimensions in the esthetic zone of the anterior maxilla. Future prospective clinical trials with a control group are needed to compare this technique with conventional methods such as connective tissue graft. Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Impact of implant size on cement filling in hip resurfacing arthroplasty.

PubMed

de Haan, Roel; Buls, Nico; Scheerlinck, Thierry

2014-01-01

Larger proportions of cement within femoral resurfacing implants might result in thermal bone necrosis. We postulate that smaller components are filled with proportionally more cement, causing an elevated failure rate. A total of 19 femoral heads were fitted with polymeric replicas of ReCap (Biomet) resurfacing components fixed with low-viscosity cement. Two specimens were used for each even size between 40 and 56 mm and one for size 58 mm. All specimens were imaged with computed tomography, and the cement thickness and bone density were analyzed. The average cement mantle thickness was 2.63 mm and was not correlated with the implant size. However, specimen with low bone density had thicker cement mantles regardless of size. The average filling index was 36.65% and was correlated to both implant size and bone density. Smaller implants and specimens with lower bone density contained proportionally more cement than larger implants. According to a linear regression model, bone density but not implant size influenced cement thickness. However, both implant size and bone density had a significant impact on the filling index. Large proportions of cement within the resurfacing head have the potential to generate thermal bone necrosis and implant failure. When considering hip resurfacing in patients with a small femoral head and/or osteoporotic bone, extra care should be taken to avoid thermal bone necrosis, and alternative cementing techniques or even cementless implants should be considered. This study should help delimiting the indications for hip resurfacing and to choose an optimal cementing technique taking implant size into account.

IGFBP-4 regulates adult skeletal growth in a sex-specific manner.

PubMed

Maridas, David E; DeMambro, Victoria E; Le, Phuong T; Nagano, Kenichi; Baron, Roland; Mohan, Subburaman; Rosen, Clifford J

2017-04-01

Insulin-like growth factor-1 (IGF-1) and its binding proteins are critical mediators of skeletal growth. Insulin-like growth factor-binding protein 4 (IGFBP-4) is highly expressed in osteoblasts and inhibits IGF-1 actions in vitro Yet, in vivo studies suggest that it could potentiate IGF-1 and IGF-2 actions. In this study, we hypothesized that IGFBP-4 might potentiate the actions of IGF-1 on the skeleton. To test this, we comprehensively studied 8- and 16-week-old Igfbp4 -/- mice. Both male and female adult Igfbp4 -/- mice had marked growth retardation with reductions in body weight, body and femur lengths, fat proportion and lean mass at 8 and 16 weeks. Marked reductions in aBMD and aBMC were observed in 16-week-old Igfbp4 -/- females, but not in males. Femoral trabecular BV/TV and thickness, cortical fraction and thickness in 16-week-old Igfbp4 -/- females were significantly reduced. However, surprisingly, males had significantly more trabeculae with higher connectivity density than controls. Concordantly, histomorphometry revealed higher bone resorption and lower bone formation in Igfbp4 -/- females. In contrast, Igfbp4 -/- males had lower mineralized surface/bone surface. Femoral expression of Sost and circulating levels of sclerostin were reduced but only in Igfbp4 -/- males. Bone marrow stromal cultures from mutants showed increased osteogenesis, whereas osteoclastogenesis was markedly increased in cells from Igfbp4 -/- females but decreased in males. In sum, our results indicate that loss of Igfbp4 affects mesenchymal stromal cell differentiation, regulates osteoclastogenesis and influences both skeletal development and adult bone maintenance. Thus, IGFBP-4 modulates the skeleton in a gender-specific manner, acting as both a cell autonomous and cell non-autonomous factor. © 2017 The authors.

Targeted Disruption of NF1 in Osteocytes Increases FGF23 and Osteoid With Osteomalacia-like Bone Phenotype.

PubMed

Kamiya, Nobuhiro; Yamaguchi, Ryosuke; Aruwajoye, Olumide; Kim, Audrey J; Kuroyanagi, Gen; Phipps, Matthew; Adapala, Naga Suresh; Feng, Jian Q; Kim, Harry Kw

2017-08-01

Neurofibromatosis type 1 (NF1, OMIM 162200), caused by NF1 gene mutations, exhibits multi-system abnormalities, including skeletal deformities in humans. Osteocytes play critical roles in controlling bone modeling and remodeling. However, the role of neurofibromin, the protein product of the NF1 gene, in osteocytes is largely unknown. This study investigated the role of neurofibromin in osteocytes by disrupting Nf1 under the Dmp1-promoter. The conditional knockout (Nf1 cKO) mice displayed serum profile of a metabolic bone disorder with an osteomalacia-like bone phenotype. Serum FGF23 levels were 4 times increased in cKO mice compared with age-matched controls. In addition, calcium-phosphorus metabolism was significantly altered (calcium reduced; phosphorus reduced; parathyroid hormone [PTH] increased; 1,25(OH) 2 D decreased). Bone histomorphometry showed dramatically increased osteoid parameters, including osteoid volume, surface, and thickness. Dynamic bone histomorphometry revealed reduced bone formation rate and mineral apposition rate in the cKO mice. TRAP staining showed a reduced osteoclast number. Micro-CT demonstrated thinner and porous cortical bones in the cKO mice, in which osteocyte dendrites were disorganized as assessed by electron microscopy. Interestingly, the cKO mice exhibited spontaneous fractures in long bones, as found in NF1 patients. Mechanical testing of femora revealed significantly reduced maximum force and stiffness. Immunohistochemistry showed significantly increased FGF23 protein in the cKO bones. Moreover, primary osteocytes from cKO femora showed about eightfold increase in FGF23 mRNA levels compared with control cells. The upregulation of FGF23 was specifically and significantly inhibited by PI3K inhibitor Ly294002, indicating upregulation of FGF23 through PI3K in Nf1-deficient osteocytes. Taken together, these results indicate that Nf1 deficiency in osteocytes dramatically increases FGF23 production and causes a mineralization defect (ie, hyperosteoidosis) via the alteration of calcium-phosphorus metabolism. This study demonstrates critical roles of neurofibromin in osteocytes for osteoid mineralization. © 2017 American Society for Bone and Mineral Research. © 2017 American Society for Bone and Mineral Research.

An investigation of heat transfer to the implant-bone interface when drilling through a zirconia crown attached to a titanium or zirconia abutment.

PubMed

Mason, Amy G; Sutton, Alan; Turkyilmaz, Ilser

2014-11-01

Thermal injury to the implant-bone interface may lead to bone necrosis and loss of osseointegration. This is a concern during manipulation of the implant throughout the restorative phase of treatment. The risk of heat transfer to the implant-bone interface during abutment preparation or prosthesis removal should be considered. The purpose of the study was to examine the amount of heat transferred to the implant-bone interface when a zirconia crown is drilled to access the screw channel or section a crown with a high-speed dental handpiece. Of the 64 ceramic-veneered zirconia crowns fabricated, 32 had a coping thickness of 0.5 mm and 32 had a coping thickness of 1.0 mm. The crowns were cemented on either titanium stock abutments or zirconia stock abutments. Each group was further subdivided to evaluate heat transfer when the screw channel was accessed or the crown was sectioned with a high-speed handpiece with or without irrigation. Temperature change was recorded for each specimen at the cervical and apical aspect of the implant with thermocouples and a logging thermometer. ANOVA was used to assess the statistical significance in temperature change between the test combinations, and nonparametric Mann-Whitney U tests were used to evaluate the findings. The use of irrigation during both crown removal processes yielded an average temperature increase of 3.59 ±0.35°C. Crown removal in the absence of irrigation yielded an average temperature increase of 18.76 ±3.09°C. When all parameter combinations in the presence of irrigation were evaluated, the maximum temperature change was below the threshold of thermal injury to bone. The maximum temperature change was above the threshold for thermal injury at the coronal aspect of the implant and below the threshold at the apical aspect in the absence of irrigation. Within the limitations of this investigation, the use of irrigation with a high-speed dental handpiece to remove a ceramic-veneered zirconia crown results in a temperature increase at the implant-bone interface insufficient to cause irreversible damage. Conversely, a lack of irrigation may yield a temperature increase capable of producing irreversible damage at the coronal aspect of the implant. Copyright © 2014 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Altered Osteocyte-Specific Protein Expression in Bone after Childhood Solid Organ Transplantation

PubMed Central

Pereira, Renata C.; Valta, Helena; Tumber, Navdeep; Salusky, Isidro B.; Jalanko, Hannu

2015-01-01

Background Bone fragility is common post solid organ transplantation but little is known about bone pathology on a tissue level. Abnormal osteocytic protein expression has been linked to compromised bone health in chronic kidney disease (CKD) and immunosuppressant medications may impact osteocyte function. Methods Transiliac bone biopsies were obtained from 22 pediatric solid organ allograft recipients (average age 15.6 years) an average of 6.3 ± 1.2 years after transplantation and from 12 pediatric pre-dialysis CKD patients (average age 13.2 years). Histomorphometry and immunohistochemistry for FGF23, DMP1, sclerostin, and osteopontin were performed on all biopsies. Results FGF23 and sclerostin were increased in transplant recipients relative to non-transplant CKD, regardless of the type of allograft received and despite, in the case of liver and heart recipients, a higher GFR. Bone DMP1 expression was higher in liver or heart than in kidney recipients, concomitant with higher serum phosphate values. Osteopontin expression was higher in CKD than in transplant recipients (p<0.01). Bone FGF23 and sclerostin correlated directly (r = 0.38, p<0.05); bone FGF23 expression and osteoid thickness correlated inversely (r = - 0.46, p<0.01). Conclusions Solid-organ transplantation is associated with increased FGF23 and sclerostin expression. The contribution of these findings to compromised bone health post transplantation warrants further evaluation. PMID:26390291

Altered Osteocyte-Specific Protein Expression in Bone after Childhood Solid Organ Transplantation.

PubMed

Pereira, Renata C; Valta, Helena; Tumber, Navdeep; Salusky, Isidro B; Jalanko, Hannu; Mäkitie, Outi; Wesseling Perry, Katherine

2015-01-01

Bone fragility is common post solid organ transplantation but little is known about bone pathology on a tissue level. Abnormal osteocytic protein expression has been linked to compromised bone health in chronic kidney disease (CKD) and immunosuppressant medications may impact osteocyte function. Transiliac bone biopsies were obtained from 22 pediatric solid organ allograft recipients (average age 15.6 years) an average of 6.3 ± 1.2 years after transplantation and from 12 pediatric pre-dialysis CKD patients (average age 13.2 years). Histomorphometry and immunohistochemistry for FGF23, DMP1, sclerostin, and osteopontin were performed on all biopsies. FGF23 and sclerostin were increased in transplant recipients relative to non-transplant CKD, regardless of the type of allograft received and despite, in the case of liver and heart recipients, a higher GFR. Bone DMP1 expression was higher in liver or heart than in kidney recipients, concomitant with higher serum phosphate values. Osteopontin expression was higher in CKD than in transplant recipients (p<0.01). Bone FGF23 and sclerostin correlated directly (r = 0.38, p<0.05); bone FGF23 expression and osteoid thickness correlated inversely (r = - 0.46, p<0.01). Solid-organ transplantation is associated with increased FGF23 and sclerostin expression. The contribution of these findings to compromised bone health post transplantation warrants further evaluation.

Low-level laser therapy stimulates bone metabolism and inhibits root resorption during tooth movement in a rodent model.

PubMed

Suzuki, Selly Sayuri; Garcez, Aguinaldo Silva; Suzuki, Hideo; Ervolino, Edilson; Moon, Won; Ribeiro, Martha Simões

2016-12-01

This study evaluated the biological effects of low-level laser therapy (LLLT) on bone remodeling, tooth displacement and root resorption, occurred during the orthodontic tooth movement. Upper first molars of a total of sixty-eight male rats were subjected to orthodontic tooth movement and euthanized on days 3, 6, 9, 14 and 21 days and divided as negative control, control and LLLT group. Tooth displacement and histomorphometric analysis were performed in all animals; scanning electron microscopy analysis was done on days 3, 6 and 9, as well as the immunohistochemistry analysis of RANKL/OPG and TRAP markers. Volumetric changes in alveolar bone were analyzed using MicroCT images on days 14 and 21. LLLT influenced bone resorption by increasing the number of TRAP-positive osteoclasts and the RANKL expression at the compression side. This resulted in less alveolar bone and hyalinization areas on days 6, 9 and 14. LLLT also induced less bone volume and density, facilitating significant acceleration of tooth movement and potential reduction in root resorption besides stimulating bone formation at the tension side by enhancing OPG expression, increasing trabecular thickness and bone volume on day 21. Taken together, our results indicate that LLLT can stimulate bone remodeling reducing root resorption in a rat model. LLLT improves tooth movement via bone formation and bone resorption in a rat model. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Conditional mouse models support the role of SLC39A14 (ZIP14) in Hyperostosis Cranialis Interna and in bone homeostasis

PubMed Central

Steenackers, Ellen; Yorgan, Timur A.; Hermans, Christophe; Boudin, Eveline; Waterval, Jérôme J.; Jansen, Ineke D. C.; Aydemir, Tolunay Beker; Kamerling, Niels; Plumeyer, Christine; D’Haese, Patrick C.; Everts, Vincent; Lammens, Martin; Mortier, Geert; Cousins, Robert J.; Schinke, Thorsten; Stokroos, Robert J.; Manni, Johannes J.; Van Hul, Wim

2018-01-01

Hyperostosis Cranialis Interna (HCI) is a rare bone disorder characterized by progressive intracranial bone overgrowth at the skull. Here we identified by whole-exome sequencing a dominant mutation (L441R) in SLC39A14 (ZIP14). We show that L441R ZIP14 is no longer trafficked towards the plasma membrane and excessively accumulates intracellular zinc, resulting in hyper-activation of cAMP-CREB and NFAT signaling. Conditional knock-in mice overexpressing L438R Zip14 in osteoblasts have a severe skeletal phenotype marked by a drastic increase in cortical thickness due to an enhanced endosteal bone formation, resembling the underlying pathology in HCI patients. Remarkably, L438R Zip14 also generates an osteoporotic trabecular bone phenotype. The effects of osteoblastic overexpression of L438R Zip14 therefore mimic the disparate actions of estrogen on cortical and trabecular bone through osteoblasts. Collectively, we reveal ZIP14 as a novel regulator of bone homeostasis, and that manipulating ZIP14 might be a therapeutic strategy for bone diseases. PMID:29621230

Subprimal purchasing and merchandising decisions for pork: relationship to retail value.

PubMed

Lorenzen, C L; Walter, J P; Dockerty, T R; Griffin, D B; Johnson, H K; Savell, J W

1996-01-01

To assess retail value and profitability, cutting test data were obtained in a simulated retail cutting room for boxed pork subprimals, bone-in loins (n = 180), boneless loins (n = 94), Boston butts (n = 148), fresh hams (n = 28), and boneless hams (n = 23). Processing times (seconds) and retail weights (kilograms) were used to determine relative value. Cutting style affected (P < .05) value differential (US$/subprimal) for bone-in and boneless loins. When cutting styles within subprimals were pooled, value differential was affected (P < .05) by purchasing specification for bone-in loins, boneless loins, Boston butts, and inside fresh hams. Processing bone-in loins to a boneless end point produced a greater (P < .05) value differential and percentage of gross margin than a bone-in retail end point. Bone-in loins fabricated to a boneless retail end point produced a greater (P < .05) value differential and percentage of gross margin than boneless loins fabricated to the same end point. The increase in retail value can be attributed to the increased number and weight of retail cuts produced from bone-in loins. The thick, boneless loin cutting style produced a greater (P < .05) value differential and percentage of gross margin as a result of a lower (P < .05) cost of fabrication and increased value of retail cuts than the thin, boneless cutting style. In general, boneless pork cutting methods were more profitable than bone-in cutting methods regardless of subprimal.

Effects of the 1, 4-dihydropyridine L-type calcium channel blocker benidipine on bone marrow stromal cells.

PubMed

Ma, Zhong-ping; Liao, Jia-cheng; Zhao, Chang; Cai, Dao-zhang

2015-08-01

Osteoporosis (OP) often increases the risk of bone fracture and other complications and is a major clinical problem. Previous studies have found that high blood pressure is associated with bone formation abnormalities, resulting in increased calcium loss. We have investigated the effect of the antihypertensive drug benidipine on bone marrow stromal cell (BMSC) differentiation into osteoblasts and bone formation under osteoporotic conditions. We used a combination of in vitro and in vivo approaches to test the hypothesis that benidipine promotes murine BMSC differentiation into osteoblasts. Alkaline phosphatase (ALP), osteocalcin (OCN), runt-related transcription factor 2 (RUNX2), β-catenin, and low-density lipoprotein receptor-related protein 5 (LRP5) protein expression was evaluated in primary femoral BMSCs from C57/BL6 mice cultured under osteogenic conditions for 2 weeks to examine the effects of benidipine. An ovariectomized (OVX) mouse model was used to investigate the effect of benidipine treatment for 3 months in vivo. We found that ALP, OCN, and RUNX2 expression was up-regulated and WNT/β-catenin signaling was enhanced in vitro and in vivo. In OVX mice that were intragastrically administered benidipine, bone parameters (trabecular thickness, bone mineral density, and trabecular number) in the distal femoral metaphysis were significantly increased compared with control OVX mice. Consistently, benidipine promoted BMSC differentiation into osteoblasts and protected against bone loss in OVX mice. Therefore, benidipine might be a suitable candidate for the treatment of patients with postmenopausal osteoporosis and hypertension.

Influence of microarchitecture alterations on ultrasonic backscattering in an experimental simulation of bovine cancellous bone aging.

PubMed

Apostolopoulos, K N; Deligianni, D D

2008-02-01

An experimental model which can simulate physical changes that occur during aging was developed in order to evaluate the effects of change of mineral content and microstructure on ultrasonic properties of bovine cancellous bone. Timed immersion in hydrochloric acid was used to selectively alter the mineral content. Scanning electron microscopy and histological staining of the acid-treated trabeculae demonstrated a heterogeneous structure consisting of a mineralized core and a demineralized layer. The presence of organic matrix contributed very little to normalized broadband ultrasound attenuation (nBUA) and speed of sound. All three ultrasonic parameters, speed of sound, nBUA and backscatter coefficient, were sensitive to changes in apparent density of bovine cancellous bone. A two-component model utilizing a combination of two autocorrelation functions (a densely populated model and a spherical distribution) was used to approximate the backscatter coefficient. The predicted attenuation due to scattering constituted a significant part of the measured total attenuation (due to both scattering and absorption mechanisms) for bovine cancellous bone. Linear regression, performed between trabecular thickness values and estimated from the model correlation lengths, showed significant linear correlation, with R(2)=0.81 before and R(2)=0.80 after demineralization. The accuracy of estimation was found to increase with trabecular thickness.

Targeted disruption of BMP signaling through type IA receptor (BMPR1A) in osteocyte suppresses SOST and RANKL, leading to dramatic increase in bone mass, bone mineral density and mechanical strength.

PubMed

Kamiya, Nobuhiro; Shuxian, Lin; Yamaguchi, Ryosuke; Phipps, Matthew; Aruwajoye, Olumide; Adapala, Naga Suresh; Yuan, Hui; Kim, Harry K W; Feng, Jian Q

2016-10-01

Recent studies suggest a critical role of osteocytes in controlling skeletal development and bone remodeling although the molecular mechanism is largely unknown. This study investigated BMP signaling in osteocytes by disrupting Bmpr1a under the Dmp1-promoter. The conditional knockout (cKO) mice displayed a striking osteosclerotic phenotype with increased trabecular bone volume, thickness, number, and mineral density as assessed by X-ray and micro-CT. The bone histomorphometry, H&E, and TRAP staining revealed a dramatic increase in trabecular and cortical bone masses but a sharp reduction in osteoclast number. Moreover, there was an increase in BrdU positive osteocytes (2-5-fold) and osteoid volume (~4-fold) but a decrease in the bone formation rate (~85%) in the cKO bones, indicating a defective mineralization. The SEM analysis revealed poorly formed osteocytes: a sharp increase in cell numbers, a great reduction in cell dendrites, and a remarkable change in the cell distribution pattern. Molecular studies demonstrated a significant decrease in the Sost mRNA levels in bone (>95%), and the SOST protein levels in serum (~85%) and bone matrices. There was a significant increase in the β-catenin (>3-fold) mRNA levels as well as its target genes Tcf1 (>6-fold) and Tcf3 (~2-fold) in the cKO bones. We also showed a significant decrease in the RANKL levels of serum proteins (~65%) and bone mRNA (~57%), and a significant increase in the Opg mRNA levels (>20-fold) together with a significant reduction in the Rankl/Opg ratio (>95%), which are responsible for a sharp reduction in the cKO osteoclasts. The values of mechanical strength were higher in cKO femora (i.e. max force, displacement, and work failure). These results suggest that loss of BMP signaling specifically in osteocytes dramatically increases bone mass presumably through simultaneous inhibition of RANKL and SOST, leading to osteoclast inhibition and Wnt activation together. Finally, a working hypothesis is proposed to explain how BMPR1A controls bone remodeling by inhibiting cell proliferation and stimulating differentiation. It is reported that RANKL and SOST are abundantly expressed by osteocytes. Thus, BMP signaling through BMPR1A plays important roles in osteocytes. Copyright © 2016 Elsevier Inc. All rights reserved.

Synthetic Parathyroid Hormone May Augment Bone Volume in Autogenous Grafts: A Study in Rats.

PubMed

dos Santos, Rodrigo A B; Ferreira, Marcelo S; Mafra, Carlos Eduardo S; Holzhausen, Marinella; de Lima, Luiz Antônio Pugliesi Alves; Mendes Pannuti, Cláudio; César Neto, João Batista

2016-01-01

Synthetic parathyroid hormone [PTH(1-34)] has been investigated for its benefits on bone healing and osteoporosis treatment; however, there is little information regarding bone grafts. This study therefore investigates the effect of PTH(1-34) on autogenous bone graft healing. Bone grafts were harvested from the calvarium of rats with a trephine bur (3-mm internal diameter) and placed on the cortex near the mandible angle with a titanium screw. Animals were randomly assigned to group 1 (control): subcutaneous injections of saline solution, three times a week (n = 15); group 2: 2 μg/kg PTH(1-34), three times a week (n = 15); and group 3: 40 μg/kg PTH(1-34), three times a week (n = 15). Thirty days postoperatively, the animals were killed, and specimens (implant + bed + graft) were removed and used for undecalcified sections. The following histometric parameters were evaluated: total bone thickness (TT) (bed + gap + graft), graft thickness (GT) (adjacent to the implant), bone-to-implant contact (BIC), and bone area (BA) (within the limits of the threads). Five additional animals were sacrificed immediately after surgery (zero hour) to register bed and graft sizes before healing. Group 3 showed significantly greater bone gain compared with groups 1 and 2 (TT and GT, P <0.05). In relation to initial thickness (zero hour), groups 1 and 2 showed a total decrease in volume of 15.91% and 20.83%, respectively, whereas group 3 showed a slight bone gain (1.21%). Data analysis revealed a significant difference for group 3 compared with groups 1 and 2 (P <0.01). No differences were observed for BIC and BA (P >0.05). Systemic administration of PTH(1-34) augmented bone volume in autogenous grafts.

Impact of beta thalassemia on maxillary sinuses and sino-nasal passages: A case control study.

PubMed

Ragab, Ahmed; Ragab, Seham Mohammed; Shawki, Mohammed

2015-12-01

Skeletal changes among beta (β) thalassemia children are well documented, but without available data regarding sino-nasal passages alterations. The authors investigated the maxillary sinuses and sino-nasal passages changes in β-thalassemia children and correlated such changes with the amount of transfused red cells and the erythroid marrow activity. Clinical analyses including otorhinolaryngical examination (ORL) were obtained in twenty β-thalassemia children and 20 matched healthy controls. Hemoglobin (Hb), serum ferritin, soluble transferrin receptor (sTfR) levels and bone mineral density of the lumbar spine (BMD ls) were assayed. The two groups were analyzed for the CT image parameters: bone thickness, anterior and posterior choanae diameters, extramedullary hematopoiesis and chronic rhinosinusitis (CRS) RESULTS: Nasal congestion/obstruction was identified in 14 (70%) children. Eight patients (40%) had criteria of chronic rhinosinusitis. In comparison with the normal controls, the increase in the roof, floor, medial, anterior, lateral and posterior maxillary bony walls thickness was significantly higher (1.26, 2.46, 2.6, 2.9, 3.23 and 5.34-folds, respectively). The mean posterior choanae horizontal, vertical diameters and their surface area were significantly reduced in the patients compared to the controls. The mean anterior maxillary wall bone thickness directly correlated with sTfR (P=0.047) while that of the posterior wall correlated inversely with Hb level (P=0.013). The mean vertical posterior choanae diameter had positive correlation with the amount of transfused red cells (P=0.001) and negative correlation with sTfR (P=0.001). The Hounsfield unit of maxillary sinus wall had direct relation with BMDls (P=0.003) CONCLUSIONS: Thalassemia children are at risk of different folds increase of maxillary sinuses walls thicknesses utmost at posterior and lateral walls. Other sino-nasal morbidities include diminished posterior choanal diameter, nasal obstruction and CRS. Certain morbidities had relations to the erythroid marrow activity and the transfusion adequacy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Wideband Single-Crystal Transducer for Bone Characterization

NASA Technical Reports Server (NTRS)

Liang, Yu; Snook, Kevin

2012-01-01

The microgravity conditions of space travel result in unique physiological demands on the human body. In particular, the absence of the continual mechanical stresses on the skeletal system that are present on Earth cause the bones to decalcify. Trabecular structure decreases in thickness and increases in spacing, resulting in decreased bone strength and increased risk of injury. Thus, monitoring bone health is a high priority for long-term space travel. A single probe covering all frequency bands of interest would be ideal for such measurements, and this would also minimize storage space and eliminate the complexity of integrating multiple probes. This invention is an ultrasound transducer for the structural characterization of bone. Such characterization measures features of reflected and transmitted ultrasound signals, and correlates these signals with bone structure metrics such as bone mineral density, trabecular spacing, and thickness, etc. The techniques used to determine these various metrics require measurements over a broad range of ultrasound frequencies, and therefore, complete characterization requires the use of several narrowband transducers. This is a single transducer capable of making these measurements in all the required frequency bands. The device achieves this capability through a unique combination of a broadband piezoelectric material; a design incorporating multiple resonator sizes with distinct, overlapping frequency spectra; and a micromachining process for producing the multiple-resonator pattern with common electrode surfaces between the resonators. This device consists of a pattern of resonator bars with common electrodes that is wrapped around a central mandrel such that the radiating faces of the resonators are coplanar and can be simultaneously applied to the sample to be measured. The device operates as both a source and receiver of acoustic energy. It is operated by connection to an electronic system capable of both providing an excitation signal to the transducer and amplifying the signal received from the transducer. The excitation signal may be either a wide-bandwidth signal to excite the transducer across its entire operational spectrum, or a narrow-bandwidth signal optimized for a particular measurement technique. The transducer face is applied to the skin covering the bone to be characterized, and may be operated in through transmission mode using two transducers, or in pulse-echo mode.

Local delivery of parathyroid hormone-related protein-derived peptides coated onto a hydroxyapatite-based implant enhances bone regeneration in old and diabetic rats.

PubMed

Ardura, Juan A; Portal-Núñez, Sergio; Lozano, Daniel; Gutiérrez-Rojas, Irene; Sánchez-Salcedo, Sandra; López-Herradón, Ana; Mulero, Francisca; Villanueva-Peñacarrillo, María L; Vallet-Regí, María; Esbrit, Pedro

2016-08-01

Diabetes mellitus (DM) and aging are associated with bone fragility and increased fracture risk. Both (1-37) N- and (107-111) C-terminal parathyroid hormone-related protein (PTHrP) exhibit osteogenic properties. We here aimed to evaluate and compare the efficacy of either PTHrP (1-37) or PTHrP (107-111) loaded into gelatin-glutaraldehyde-coated hydroxyapatite (HA-Gel) foams to improve bone repair of a transcortical tibial defect in aging rats with or without DM, induced by streptozotocin injection at birth. Diabetic old rats showed bone structural deterioration compared to their age-matched controls. Histological and μ-computerized tomography studies showed incomplete bone repair at 4 weeks after implantation of unloaded Ha-Gel foams in the transcortical tibial defects, mainly in old rats with DM. However, enhanced defect healing, as shown by an increase of bone volume/tissue volume and trabecular and cortical thickness and decreased trabecular separation, occurred in the presence of either PTHrP peptide in the implants in old rats with or without DM. This was accompanied by newly formed bone tissue around the osteointegrated HA-Gel implant and increased gene expression of osteocalcin and vascular endothelial growth factor (bone formation and angiogenic markers, respectively), and decreased expression of Sost gene, a negative regulator of bone formation, in the healing bone area. Our findings suggest that local delivery of PTHrP (1-37) or PTHrP (107-111) from a degradable implant is an attractive strategy to improve bone regeneration in aged and diabetic subjects. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2060-2070, 2016. © 2016 Wiley Periodicals, Inc.

Influence of high-altitude grazing on bone metabolism of growing sheep.

PubMed

Liesegang, A; Hüttenmoser, D; Risteli, J; Leiber, F; Kreuzer, M; Wanner, M

2013-02-01

The objective of this study was to identify the effect of high alpine grazing, associated with varying pasture grass qualities and more pronounced exercise on typically steep slopes, on bone metabolism by improving bone density and enhancing bone turnover in growing sheep. Twenty-four 5-month-old sheep were randomly assigned to two groups. One group was kept at high altitude (HA; 2000-2200 m a.s.l.) for 3 months, and the other group (C; control) remained in the lowlands (400 m a.s.l.). Both groups were kept in grazing pastures with access to good-quality swards. Before the start of the experiment, blood samples were taken, the sheep were weighed, and the left metatarsus of each animal was analysed by quantitative computer tomography. After 1 month, blood samples were taken and body weight was measured, followed by biweekly sampling. Finally, the animals were slaughtered, and the bones were collected for analysis of various bone parameters. Body weight development did not differ between the groups. Concentrations of 25-OH-Vitamin D, carboxy-terminal telopeptide of type I collagen and activities of bone-specific alkaline phosphatase were always higher in the HA group than in the C group, except on the last two sampling dates. Bone mineral content and density increased in both groups during the experiment, but more intensively in the HA group. In addition, the cortical thickness of the HA group increased. The present study demonstrates an increase in bone turnover and mineral content of the bones of the growing sheep grazing in high alpine pastures. The factors associated with HA grazing, therefore, clearly seem to improve bone composition. © 2011 Blackwell Verlag GmbH.

Central Depletion of Brain-Derived Neurotrophic Factor in Mice Results in High Bone Mass and Metabolic Phenotype

PubMed Central

Zayzafoon, M.; Rymaszewski, M.; Heiny, J.; Rios, M.; Hauschka, P. V.

2012-01-01

Brain-derived neurotrophic factor (BDNF) plays important roles in neuronal differentiation/survival, the regulation of food intake, and the pathobiology of obesity and type 2 diabetes mellitus. BDNF and its receptor are expressed in osteoblasts and chondrocyte. BDNF in vitro has a positive effect on bone; whether central BDNF affects bone mass in vivo is not known. We therefore examined bone mass and energy use in brain-targeted BDNF conditional knockout mice (Bdnf2lox/2lox/93). The deletion of BDNF in the brain led to a metabolic phenotype characterized by hyperphagia, obesity, and increased abdominal white adipose tissue. Central BDNF deletion produces a marked skeletal phenotype characterized by increased femur length, elevated whole bone mineral density, and bone mineral content. The skeletal changes are developmentally regulated and appear concurrently with the metabolic phenotype, suggesting that the metabolic and skeletal actions of BDNF are linked. The increased bone development is evident in both the cortical and trabecular regions. Compared with control, Bdnf2lox/2lox/93 mice show greater trabecular bone volume (+50% for distal femur, P < 0.001; +35% for vertebral body, P < 0.001) and midfemoral cortical thickness (+11 to 17%, P < 0.05), measured at 3 and 6 months of age. The skeletal and metabolic phenotypes were gender dependent, with female being more affected than male mice. However, uncoupling protein-1 expression in brown fat, a marker of sympathetic tone, was not different between genotypes. We show that deletion of central BDNF expression in mice results in increased bone mass and white adipose tissue, with no significant changes in sympathetic signaling or peripheral serotonin, associated with hyperphagia, obesity, and leptin resistance. PMID:23011922

A histomorphometric study of adaptive responses of cancellous bone in different regions in the sheep mandibular condyle following experimental forward mandibular displacement.

PubMed

Ma, Bingkui; Sampson, Wayne; Wilson, David; Wiebkin, Ole; Fazzalari, Nicola

2002-07-01

Forward mandibular displacement in animal models is associated with faster and/or redirected condylar growth. Here the effect of forward displacement induced with an intraoral appliance on modelling/remodelling of the mandibular condyle was investigated in eight, 4-month-old, castrated male Merino sheep, randomly allocated to experimental and control groups (n=4 in each group). The study period was 15 weeks, during that time, (1). calcein, (2). tetracycline, and (3). alizarin red S fluorochromes were given to all animals from day 1. Midsagittal sections of the temporomandibular joints were selected for analysis. Dynamic variables of bone formation, static indices of bone-forming and -resorbing activity, and structural indices of trabecular bone were estimated histomorphometrically. The sampling site was divided into two regions for analysis: (a). a 'subchondral region' (2 and 3 labels only), believed to be the bone newly formed during the experimental period; (b). a 'central region' (labelled by all three fluorochromes), believed to be the bone that existed before the experiment. Regional differences in adaptive response were found. In the experimental group, the bone-volume fraction (BV/TV) of the subchondral regions had decreased, although the specific bone-surface and bone-formation rates had increased. This low BV/TV was associated with decreased trabecular thickness and increased trabecular separation. In the central condylar region of the experimental group, BV/TV was unchanged, but an increased osteoid surface was apparent when the eroded surface was taken into consideration. These adaptive condylar responses to forward mandibular displacement appeared to be the result of increased osteoblastic activity. Further studies are recommended to examine why the subchondral and central regions responded differently.

Radiological and clinical difficulties in the management of chronic maxillary sinusitis in β Thalassemic paediatric patients.

PubMed

Di Mauro, R; Greco, L; Melis, M; Manenti, G; Floris, R; Giacomini, P G; Di Girolamo, M; Di Girolamo, S

2016-05-01

Beta thalassemia is a blood dyscrasia that caused a marked expansion of active marrow spaces and extramedullary haematopoiesis results. In these patients various alterations and abnormalities affects different body areas, including increased risk of sinusitis. The marrow expansion in the facial bones results in delay in pneumatisation of the sinuses, overgrowth of the maxillae, and forward displacement of the upper incisors with skeletal deformities. In current literature, maxillary sinuses are not deeply evaluated by CT scan studies in these kind of patients. The aim of our study was to investigate the presence of maxillary sinuses abnormalities by the use of CT in patients with beta-thalassemia major and to compare these findings with a control group free from this disease. A retrospective analysis of 22 paediatric patients with beta-thalassemia major and 22 control subjects without sinonasal diseases was performed. CT was done using a 64-multidetector-row CT scanner without contrast injection, obtained in axial plane using thin-slice technique. Evaluated parameters were: bone thickness of the lateral and anterior wall, density and volume of the maxillary sinuses. Significant difference was found between the study group and control group in the evaluation of all the parameters examined. The maxillary sinus of β thalassemic patients was smaller respect of controls, the bone was more dense and thick in the side and anterior wall. Beta-thalassemic patients have a relative risk of 2.87 to develop a maxillary sinusitis. In these patients there is an increased incidence of sinonasal infections due to the abnormal development of cranio facial skeleton. These bone alterations might confuse the physicians and lead to an increased rate of sinusitis diagnoses. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Monte Carlo investigation of backscatter point spread function for x-ray imaging examinations

NASA Astrophysics Data System (ADS)

Xiong, Zhenyu; Vijayan, Sarath; Rudin, Stephen; Bednarek, Daniel R.

2017-03-01

X-ray imaging examinations, especially complex interventions, may result in relatively high doses to the patient's skin inducing skin injuries. A method was developed to determine the skin-dose distribution for non-uniform x-ray beams by convolving the backscatter point-spread-function (PSF) with the primary-dose distribution to generate the backscatter distribution that, when added to the primary dose, gives the total-dose distribution. This technique was incorporated in the dose-tracking system (DTS), which provides a real-time color-coded 3D-mapping of skin dose during fluoroscopic procedures. The aim of this work is to investigate the variation of the backscatter PSF with different parameters. A backscatter PSF of a 1-mm x-ray beam was generated by EGSnrc Monte-Carlo code for different x-ray beam energies, different soft-tissue thickness above bone, different bone thickness and different entrance-beam angles, as well as for different locations on the SK-150 anthropomorphic head phantom. The results show a reduction of the peak scatter to primary dose ratio of 48% when X-ray beam voltage is increased from 40 keV to 120 keV. The backscatter dose was reduced when bone was beneath the soft tissue layer and this reduction increased with thinner soft tissue and thicker bone layers. The backscatter factor increased about 21% as the angle of incidence of the beam with the entrance surface decreased from 90° (perpendicular) to 30°. The backscatter PSF differed for different locations on the SK-150 phantom by up to 15%. The results of this study can be used to improve the accuracy of dose calculation when using PSF convolution in the DTS.

Augmented corticotomy-assisted surgical orthodontics decompensates lower incisors in Class III malocclusion patients.

PubMed

Wang, Bo; Shen, Guofang; Fang, Bing; Yu, Hongbo; Wu, Yong; Sun, Liangyan

2014-03-01

To quantitatively evaluate lower incisor decompensation and the surrounding periodontal region after augmented corticotomy-assisted surgical orthodontics in patients with Class III malocclusion. This prospective study enrolled patients with severe Class III malocclusion who underwent augmented corticotomy in the lower anterior region before orthodontic surgery. Cone-beam computed tomograms and lateral cephalograms were obtained before treatment (T0), after presurgical orthodontic treatment (T1), and at removal of the orthodontic surgical appliances (T2). Repeated measures analysis of variance was used to compare variables at each time point: root length (RL), anterior vertical alveolar bone level at the labial side (AVBL), posterior vertical alveolar bone level at the lingual side (PVBL), labial alveolar bone thickness at the apex (LA), lingual alveolar bone thickness at the apex (LP), and angle of the incisor to the mandibular plane (L1-MP). In the 8 subjects studied, RL was maintained from T0 to T2 (P > .05), whereas AVBL and PVBL increased from T0 to T1 (P < .05) and then decreased from T1 to T2 (P < .05). LA and L1-MP increased from T0 to T1 (P < .001) but remained steady from T1 to T2 (P > .05). LP decreased from T0 to T1 (P < .05) but increased from T1 to T2 (P < .05) with no further change. Augmented corticotomy-assisted surgical orthodontics can achieve adequate tooth decompensation with minimal periodontal side-effects in the lower anterior region in patients with Class III malocclusion. Copyright © 2014 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

[New methods for the evaluation of bone quality. Bone anabolic agents and bone quality.

PubMed

Yamamoto, Norio; Tsuchiya, Hiroyuki

Teriparatide(TPTD)products that can be used clinically in Japan include a daily subcutaneous injection form produced by genetic engineering and a weekly subcutaneous injectable TPTD acetate form produced by chemical synthesis. Published reports indicate that both forms exhibit excellent antifracture efficacy, and as the only anabolic agents that promote osteogenesis, TPTD products now occupy a prominent position. However, the two forms differ considerably, not only in frequency of administration, but also in mechanism of action. The daily form stimulates osteogenesis and accompanying resorption through more radical high bone turnover, and early in the course of treatment, intracortical porosity and apatite crystallization decrease, while immature collagen crosslinking increases. However, because daily formulations also produce an increase in cortical surface area or cortical thickness, the effects are counterbalanced, and bone strength is maintained. In contrast, the weekly form prioritizes osteogenesis, and by concurrently lowering turnover below pretreatment levels, improves trabecular bone mass and structure, and enhances strength without leading to cortical porosity and other undesirable phenomena. Abaloparatide, a PTHrP(1-34)analog that is homologous with the biologically active site of PTH drugs, is currently under development, and we eagerly anticipate further clarification of the mechanism of action of each formulation on bone.

Photo-acoustic excitation and optical detection of fundamental flexural guided wave in coated bone phantoms.

PubMed

Moilanen, Petro; Zhao, Zuomin; Karppinen, Pasi; Karppinen, Timo; Kilappa, Vantte; Pirhonen, Jalmari; Myllylä, Risto; Haeggström, Edward; Timonen, Jussi

2014-03-01

Photo-acoustic (PA) imaging was combined with skeletal quantitative ultrasound (QUS) for assessment of human long bones. This approach permitted low-frequency excitation and detection of ultrasound so as to efficiently receive the thickness-sensitive fundamental flexural guided wave (FFGW) through a coating of soft tissue. The method was tested on seven axisymmetric bone phantoms, whose 1- to 5-mm wall thickness and 16-mm diameter mimicked those of the human radius. Phantoms were made of a composite material and coated with a 2.5- to 7.5-mm layer of soft material that mimicked soft tissue. Ultrasound was excited with a pulsed Nd:YAG laser at 1064-nm wavelength and received on the same side of the coated phantom with a heterodyne interferometer. The FFGW was detected at 30-kHz frequency. Fitting the FFGW phase velocity by the FLC(1,1) tube mode provided an accurate (9.5 ± 4.0%) wall thickness estimate. Ultrasonic in vivo characterization of cortical bone thickness may thus become possible. Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

[A study of linearity and reciprocity during shock applied with a hammer to human dry skull].

PubMed

Kumazawa, Y; Sekiguchi, J; Saito, M; Honma, K; Toyoda, M; Matsuo, E

1990-09-01

The authors used a human dry skull on which the cranial bone mandible had been joined with an artificial articulator disk to form a single unit. Impact acceleration corresponding to weak and strong tapping was considered a dynamic load in examining the vibration transfer characteristics of the facial cranial bone when impact was applied from the mentum section in a situation designed to be closer to reality. Flexion injection type (resonance frequency f0 = 100 to 150 Hz, produced by GC Corp.) was applied to the human dry skull as an artificial periodontal membrane at thickness of 0.3 mm. In addition, Exaflex heavy body type (f0 = 400 Hz, produced by GC Corp.) was applied as an artificial disk. This was then placed on a damper produced by spreading a rubber dam sheet with a thickness of 35 microns on a tire tube with a diameter of 35 cm and an air pressure of 35 kg/cm2. Investigations were then made concerning linearity and reciprocity to determine whether an experimental system could be achieved or not. This was then followed by modal analysis. As a result, the following matters were ascertained: (1) The resonating area differed according to the extent of the force. (2) An increase in the viscoelastic elements of the silicon was accompanied by attenuation of force. (3) Directionality of force attenuation was caused by the complexity of bone structure. (4) A tapping force of 0.3G or 1G was sufficiently attenuated by the facial cranial bone. (5) The transfer function at the bone seams and thinner areas of the bones was insufficient for modal analysis of the facial region and total cranial bone of the human dry skull.

Longitudinal change in patellofemoral cartilage thickness, cartilage T2 relaxation times, and subchondral bone plate area in adolescent vs mature athletes.

PubMed

Culvenor, Adam G; Wirth, Wolfgang; Maschek, Susanne; Boeth, Heide; Diederichs, Gerd; Duda, Georg; Eckstein, Felix

2017-07-01

Patellofemoral cartilage changes have been evaluated in knee trauma and osteoarthritis; however, little is known about changes in patellar and trochlear cartilage thickness, T2 relaxation-time and subchondral bone plate area (tAB) during growth. Our prospective study aimed to explore longitudinal change in patellofemoral cartilage thickness, T2 and tAB in adolescent athletes, and to compare these data with those of mature (i.e., adult) athletes. 20 adolescent (age 16±1years) and 20 mature (46±5years) volleyball players were studied over 2-years (10 men and 10 women each group). 1.5T MRI 3D-VIBE and multi-echo spin-echo sequences were acquired at baseline and 2-year follow-up. Using manual segmentation and 3D reconstruction, longitudinal changes in patellar and trochlear cartilage thickness, patellar cartilage T2 (mono-exponential decay curve with five echoes [9.7-67.9ms]), and patellar and trochlear tAB were determined. The annual increase in both patellar and trochlear cartilage thickness was 0.8% (95% confidence interval [CI] 0.6, 1.0) and 0.6% (0.3, 0.9), for adolescent males and females respectively; the longitudinal gain in patellar and trochlear tAB was 1.3% (1.1, 1.5) and 0.5% (0.2, 0.8), and 1.6% (1.1, 2.2) and 0.8% (0.3, 0.7) for adolescent males and females, respectively (no significant between-sex differences). Mature athletes showed smaller gains in tAB, and loss of <1% of cartilage thickness annually. While no significant sex-differences existed in adolescent patellar T2 changes, mature males gained significantly greater T2 than mature females (p=0.002-0.013). Patellar and trochlear cartilage thickness and tAB were observed to increase in young athletes in late adolescence, without significant differences between sexes. Mature athletes displayed patellar cartilage loss (and T2 increases in mature males), potentially reflecting degenerative changes. Copyright © 2017 Elsevier B.V. All rights reserved.

Insulin-like growth factor I is required for the anabolic actions of parathyroid hormone on mouse bone

NASA Technical Reports Server (NTRS)

Bikle, Daniel D.; Sakata, Takeshi; Leary, Colin; Elalieh, Hashem; Ginzinger, David; Rosen, Clifford J.; Beamer, Wesley; Majumdar, Sharmila; Halloran, Bernard P.

2002-01-01

Parathyroid hormone (PTH) is a potent anabolic agent for bone, but the mechanism(s) by which it works remains imperfectly understood. Previous studies have indicated that PTH stimulates insulin-like growth factor (IGF) I production, but it remains uncertain whether IGF-I mediates some or all of the skeletal actions of PTH. To address this question, we examined the skeletal response to PTH in IGF-I-deficient (knockout [k/o]) mice. These mice and their normal littermates (NLMs) were given daily injections of PTH (80 microg/kg) or vehicle for 2 weeks after which their tibias were examined for fat-free weight (FFW), bone mineral content, bone structure, and bone formation rate (BFR), and their femurs were assessed for mRNA levels of osteoblast differentiation markers. In wild-type mice, PTH increased FFW, periosteal BFR, and cortical thickness (C.Th) of the proximal tibia while reducing trabecular bone volume (BV); these responses were not seen in the k/o mice. The k/o mice had normal mRNA levels of the PTH receptor and increased mRNA levels of the IGF-I receptor but markedly reduced basal mRNA levels of the osteoblast markers. Surprisingly, these mRNAs in the k/o bones increased several-fold more in response to PTH than the mRNAs in the bones from their wild-type littermates. These results indicate that IGF-I is required for the anabolic actions of PTH on bone formation, but the defect lies distal to the initial response of the osteoblast to PTH.

Daily intermittent decreases in serum levels of parathyroid hormone have an anabolic-like action on the bones of uremic rats with low-turnover bone and osteomalacia.

PubMed

Ishii, H; Wada, M; Furuya, Y; Nagano, N; Nemeth, E F; Fox, J

2000-02-01

The calcium receptor agonist (calcimimetic) compound NPS R-568 causes rapid decreases in circulating levels of parathyroid hormone (PTH) in rats and humans. We hypothesized that daily intermittent decreases in serum PTH levels may have different effects on bone than do chronically sustained decreases. To test this hypothesis, we compared two NPS R-568 dosing regimens in rats with chronic renal insufficiency induced by two intravenous injections of adriamycin. Fourteen weeks after the second adriamycin injection, creatinine clearance was reduced by 52%, PTH levels were elevated approximately 2.5-fold, and serum 25(OH)D3 and 1,25(OH)2D3 levels were reduced substantially. Treatment by daily per os gavage, which decreased PTH levels intermittently, or continuous subcutaneous infusion, which resulted in a sustained suppression of serum PTH levels, then began for 8 weeks. Despite the hyperparathyroidism, the adriamycin-injected rats developed a low-turnover bone lesion with osteomalacia (fourfold increase in osteoid volume in the proximal tibial metaphysis) and osteopenia (67% decrease in cancellous bone volume and an 18% reduction in bone mineral density at the distal femur). Daily administered (but not infused) NPS R-568 significantly increased cancellous bone volume solely by normalizing trabecular thickness, and increased femoral bone mineral density by 14%. These results indicate that daily intermittent, but not sustained, decreases in PTH levels have an "anabolic-like" effect on bones with a low-turnover lesion in this animal model of chronic renal insufficiency.

Increased cortical area and thickness in the distal radius in subjects with SHOX-gene mutation.

PubMed

Frederiksen, A L; Hansen, S; Brixen, K; Frost, M

2014-12-01

Short-stature homeobox (SHOX) gene haploinsufficiency may cause skeletal dysplasia including Léri-Weill Dyschondrosteosis (LWD), a clinical entity characterised by the triad of low height, mesomelic disproportion and Madelung's deformity of the wrist. Bone microarchitecture and estimated strength in adult SHOX mutation carriers have not been examined. Twenty-two subjects with a SHOX mutation including 7 males and 15 females with a median age of 38.8 [21.1-52.2] years were recruited from five unrelated families. The control group consisted of 22 healthy subjects matched on age and sex. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry. Bone geometry, volumetric density, microarchitecture and finite element estimated (FEA) bone strength were measured using high-resolution peripheral quantitative computed tomography (HR-pQCT). A full region of interest (ROI) image analysis and height-matched ROI analyses adjusting for differences in body height between the two groups were performed. Areal BMD and T-scores showed no significant differences between cases and controls. Total radius area was smaller in cases than controls (207 [176-263] vs. 273 [226-298] mm, p<0.01). Radius cortical bone area (74 ± 20 vs. 58 ± 17 mm(2), p=0.01) and thickness (1.16 ± 0.30 vs. 0.84 ± 0.26 mm, p<0.01) as well as total density (428 ± 99 vs. 328 ± 72 mg/cm(3), p<0.01) were higher in SHOX mutation carriers compared to controls. Radius trabecular bone area (119 [103-192] vs. 202 [168-247] mm(2), p<0.01) and trabecular number (1.61 [1.46-2.07] vs. 1.89 [1.73-2.08] mm(-1), p=0.01) were smaller in SHOX mutation carriers. Tibia trabecular thickness was lower in cases (0.067 ± 0.012 vs. 0.076 ± 0.012 mm, p=0.01). These results remained significant after adjustment for differences in body height and when restricting analyses to females. There were no differences in BMD, radius and tibia cortical porosity or FEA failure load between groups. A segment of cortical bone defect was identified in the distal radius adjacent to ulna in five unrelated SHOX mutation carriers. Subjects with a SHOX mutation presented with a different bone geometry in radius and tibia while there were no differences in BMD or failure load compared to controls, suggesting that mutations in SHOX gene may have an impact on bone microarchitecture albeit not bone strength. Copyright © 2014 Elsevier Inc. All rights reserved.

Effects of soft tissue augmentation procedures on peri-implant health or disease: A systematic review and meta-analysis.

PubMed

Thoma, Daniel S; Naenni, Nadja; Figuero, Elena; Hämmerle, Christoph H F; Schwarz, Frank; Jung, Ronald E; Sanz-Sánchez, Ignacio

2018-03-01

To review the dental literature in terms of soft tissue augmentation procedures and their influence on peri-implant health or disease in partially and fully edentulous patients. A MEDLINE search from 1966 to 2016 was performed to identify controlled clinical studies comparing soft tissue grafting versus no soft tissue grafting (maintenance) or two types of soft tissue grafting procedures at implant sites. The soft tissue grafting procedures included either an increase of keratinized tissue or an increase of the thickness of the peri-implant mucosa. Studies reporting on the peri-implant tissue health, as assessed by bleeding or gingival indices, were included in the review. The search was complemented by an additional hand search of all selected full-text articles and reviews published between 2011 and 2016. The initial search yielded a total number of 2,823 studies. Eligible studies were selected based on the inclusion criteria (finally included: four studies on gain of keratinized tissue; six studies on gain of mucosal thickness) and quality assessments conducted. Meta-analyses were applied whenever possible. Soft tissue grafting procedures for gain of keratinized tissue resulted in a significantly greater improvement of gingival index values compared to maintenance groups (with or without keratinized tissue) [n = 2; WMD = 0.863; 95% CI (0.658; 1.067); p < .001]. For final marginal bone levels, statistically significant differences were calculated in favor of an apically positioned flap (APF) plus autogenous grafts versus all control treatments (APF alone; APF plus a collagen matrix; maintenance without intervention [with or without residual keratinized tissue]) [n = 4; WMD = -0.175 mm; 95% CI: (-0.313; -0.037); p = .013]. Soft tissue grafting procedures for gain of mucosal thickness did not result in significant improvements in bleeding indices over time, but in significantly less marginal bone loss over time [WMD = 0.110; 95% CI: 0.067; 0.154; p < .001] and a borderline significance for marginal bone levels at the study endpoints compared to sites without grafting. Within the limitations of this review, it was concluded that soft tissue grafting procedures result in more favorable peri-implant health: (i) for gain of keratinized mucosa using autogenous grafts with a greater improvement of bleeding indices and higher marginal bone levels; (ii) for gain of mucosal thickness using autogenous grafts with significantly less marginal bone loss. © 2018 The Authors. Clinical Oral Implants Research Published by John Wiley & Sons Ltd.

Effect of socket grafting with deproteinized bone mineral: An RCT on dimensional alterations after 6 months.

PubMed

Tomasi, Cristiano; Donati, Mauro; Cecchinato, Denis; Szathvary, Isacco; Corrà, Enrico; Lindhe, Jan

2018-05-01

To examine if (i) characteristics of the fresh extraction socket site influenced subsequent dimensional alterations and (ii) placement of deproteinized bovine mineral in the socket affected volumetric change during healing. Twenty seven subjects and 28 extraction sites were included. Immediately after the removal of the tooth and after 6 months of healing, stone and virtual models of the jaw were produced. A cone beam computerized tomography scan was obtained immediately after extraction and the thickness of the buccal bone wall at the extraction site was measured. Extraction sites were randomly assigned to test or control group. In the test group, extraction sockets were filled with deproteinized bone mineral and covered with a collagen membrane. In the control group, only a collagen membrane was placed. The thickness of the buccal bone wall at the extraction site influenced the amount of volume reduction that occurred. Socket grafting influenced the degree of ridge diminution only at sites where the buccal bone wall was thin (≤ 1 mm). A graft comprised of collagen-enriched deproteinized bovine bone mineral, placed to fill extraction sockets failed to influence the overall diminution of the ridge that occurred during healing. The thickness of the buccal bone wall apparently had a significant influence on volumetric alterations of the edentulous ridge following tooth extraction. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Evaluation of the effects of implant materials and designs on thermal necrosis of bone in cemented hip arthroplasty.

PubMed

Li, Chaodi; Kotha, Shiva; Mason, James

2003-01-01

The exothermic polymerization of bone cement may induce thermal necrosis of bone in cemented hip arthroplasty. A finite element formulation was developed to predict the evolution of the temperature with time in the cemented hip replacement system. The developed method is capable of taking into account both the chemical reaction that generates heat during bone cement polymerization (through a kinetic model) and the physical process of heat conduction (with an energy balance equation). The possibility of thermal necrosis of bone was then evaluated based on the temperature history in the bone and an appropriate damage criterion. Specifically, we evaluate the role of implant materials and designs on the thermal response of the system. Results indicated that the peak temperature at the bone/cement interface with a metal prosthesis was lower than that with a polymer or a composite prosthesis in hip replacement systems. Necrosis of bone was predicted to occur with a polymer or a composite prosthesis while no necrosis was predicted with a metal prosthesis in the simulated conditions. When reinforcing osteoporotic hips with injected bone cement in the cancellous core of the femur, the volume of bone cement implanted is increased which may increase the risk of thermal necrosis of bone. We evaluate whether this risk can be decreased through the use of an insulator to contain the bone cement. No thermal necrosis of bone was predicted with a 3 mm thick polyurethane insulator while more damage is predicted for the use of bone cement without the insulator. This method provides a numerical tool for the quantitative simulation of the thermal behavior of bone-cement-prosthesis designs and for examining and refining new designs computationally.

Differences in Femoral Geometry and Structure Due to Immobilization

NASA Technical Reports Server (NTRS)

Kiratli, Beatrice Jenny; Yamada, M.; Smith, A.; Marcus, R. M.; Arnaud, S.; vanderMeulen, M. C. H.; Hargens, Alan R. (Technical Monitor)

1996-01-01

Reduction in bone mass of the lower extremity is well documented in individuals with paralysis resulting from spinal cord injury (SCI). The consequent osteopenia leads to elevated fracture risk with fractures occurring more commonly in the femoral shaft and supracondylar regions than the hip. A model has recently been described to estimate geometry and structure of the femoral midshaft from whole body scans by dual X-ray absorptiometry (DXA). Increases in femoral geometric and structural properties during growth were primarily related to mechanical loading as reflected by body mass. In this study, we investigate the relationship between body mass and femoral geometry and structure in adults with normal habitual mechanical loading patterns and those with severely reduced loading. The subjects were 78 ambulatory men (aged 20-72 yrs) and 113 men with complete paralysis from SCI of more than 4 years duration (aged 21 73 yrs). Subregional analysis was performed on DXA whole body scans to obtain bone mineral content (BMC, g), cortical thickness (cm), crosssectional moment of inertia (CSMI, cm4), and section modulus (cm3) of the femoral midshaft. All measured bone variables were significantly lower in SCI compared with ambulatory subjects: -29% (BMC), -33% (cortical thickness), -23% (CSMI), and -22% (section modulus) while body mass was not significantly different. However, the associations between body mass and bone properties were notably different; r2 values were higher for ambulatory than SCI subjects in regressions of body mass on BMC (0.48 vs 0.20), CSMI (0.59 vs 0.32), and section modulus (0.59 vs 0.31). No association was seen between body mass and cortical thickness for either group. The greatest difference between groups is in the femoral cortex, consistent with reduced bone mass via endosteal expansion. The relatively lesser difference in geometric and structural properties implies that there is less effect on mechanical integrity than would be expected from bone mass results alone. The reduced association in SCI subjects between body mass and bone properties is not unexpected. Although mean body mass differs little between ambulatory and SCI individuals, the association between body mass and in vivo skeletal loading is no longer present, as mechanical influences are removed except for transfer activities. The residual association is probably attributable to the strength of this influence during growth. These results highlight the importance of examining geometry and structure in conjunction with bone mass.

Dispersion characteristics of the flexural wave assessed using low frequency (50-150kHz) point-contact transducers: A feasibility study on bone-mimicking phantoms.

PubMed

Kassou, Koussila; Remram, Youcef; Laugier, Pascal; Minonzio, Jean-Gabriel

2017-11-01

Guided waves-based techniques are currently under development for quantitative cortical bone assessment. However, the signal interpretation is challenging due to multiple mode overlapping. To overcome this limitation, dry point-contact transducers have been used at low frequencies for a selective excitation of the zeroth order anti-symmetric Lamb A0 mode, a mode whose dispersion characteristics can be used to infer the thickness of the waveguide. In this paper, our purpose was to extend the technique by combining a dry point-contact transducers approach to the SVD-enhanced 2-D Fourier transform in order to measure the dispersion characteristics of the flexural mode. The robustness of our approach is assessed on bone-mimicking phantoms covered or not with soft tissue-mimicking layer. Experiments were also performed on a bovine bone. Dispersion characteristics of measured modes were extracted using a SVD-based signal processing technique. The thickness was obtained by fitting a free plate model to experimental data. The results show that, in all studied cases, the estimated thickness values are in good agreement with the actual thickness values. From the results, we speculate that in vivo cortical thickness assessment by measuring the flexural wave using point-contact transducers is feasible. However, this assumption has to be confirmed by further in vivo studies. Copyright © 2017 Elsevier B.V. All rights reserved.

Multi-layer imager design for mega-voltage spectral imaging

NASA Astrophysics Data System (ADS)

Myronakis, Marios; Hu, Yue-Houng; Fueglistaller, Rony; Wang, Adam; Baturin, Paul; Huber, Pascal; Morf, Daniel; Star-Lack, Josh; Berbeco, Ross

2018-05-01

The architecture of multi-layer imagers (MLIs) can be exploited to provide megavoltage spectral imaging (MVSPI) for specific imaging tasks. In the current work, we investigated bone suppression and gold fiducial contrast enhancement as two clinical tasks which could be improved with spectral imaging. A method based on analytical calculations that enables rapid investigation of MLI component materials and thicknesses was developed and validated against Monte Carlo computations. The figure of merit for task-specific imaging performance was the contrast-to-noise ratio (CNR) of the gold fiducial when the CNR of bone was equal to zero after a weighted subtraction of the signals obtained from each MLI layer. Results demonstrated a sharp increase in the CNR of gold when the build-up component or scintillation materials and thicknesses were modified. The potential for low-cost, prompt implementation of specific modifications (e.g. composition of the build-up component) could accelerate clinical translation of MVSPI.

Increased density and periosteal expansion of the tibia in young adult men following short-term arduous training.

PubMed

Izard, Rachel M; Fraser, William D; Negus, Charles; Sale, Craig; Greeves, Julie P

2016-07-01

Few human studies have reported early structural adaptations of bone to weight-bearing exercise, which provide a greater contribution to improved bone strength than increased density. This prospective study examined site- and regional-specific adaptations of the tibia during arduous training in a cohort of male military (infantry) recruits to better understand how bone responds in vivo to mechanical loading. Tibial bone density and geometry were measured in 90 British Army male recruits (ages 21±3years, height: 1.78±0.06m, body mass: 73.9±9.8kg) in weeks 1 (Baseline) and 10 of initial military training. Scans were performed at the 4%, 14%, 38% and 66% sites, measured from the distal end plate, using pQCT (XCT2000L, Stratec Pforzheim, Germany). Customised software (BAMPack, L-3 ATI) was used to examine whole bone cross-section and regional sectors. T-tests determined significant differences between time points (P<0.05). Bone density of trabecular and cortical compartments increased significantly at all measured sites. Bone geometry (cortical area and thickness) and bone strength (i, MMi and BSI) at the diaphyseal sites (38 and 66%) were also significantly higher in week 10. Regional changes in density and geometry were largely observed in the anterior, medial-anterior and anterior-posterior sectors. Calf muscle density and area (66% site) increased significantly at week 10 (P<0.01). In vivo mechanical loading improves bone strength of the human tibia by increased density and periosteal expansion, which varies by site and region of the bone. These changes may occur in response to the nature and distribution of forces originating from bending, torsional and shear stresses of military training. These improvements are observed early in training when the osteogenic stimulus is sufficient, which may be close to the fracture threshold in some individuals. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

Geometrical and material parameters to assess the macroscopic mechanical behaviour of fresh cranial bone samples.

PubMed

Auperrin, Audrey; Delille, Rémi; Lesueur, Denis; Bruyère, Karine; Masson, Catherine; Drazétic, Pascal

2014-03-21

The present study aims at providing quantitative data for the personalisation of geometrical and mechanical characteristics of the adult cranial bone to be applied to head FE models. A set of 351 cranial bone samples, harvested from 21 human skulls, were submitted to three-point bending tests at 10 mm/min. For each of them, an apparent elastic modulus was calculated using the beam's theory and a density-dependant beam inertia. Thicknesses, apparent densities and percentage of ash weight were also measured. Distributions of characteristics among the different skull bones show their symmetry and their significant differences between skull areas. A data analysis was performed to analyse potential relationship between thicknesses, densities and the apparent elastic modulus. A specific regression was pointed out to estimate apparent elastic modulus from the product of thickness by apparent density. These results offer quantitative tools in view of personalising head FE models and thus improve definition of local injury criteria for this body part. Copyright © 2014 Elsevier Ltd. All rights reserved.

A living thick nanofibrous implant bifunctionalized with active growth factor and stem cells for bone regeneration

PubMed Central

Eap, Sandy; Keller, Laetitia; Schiavi, Jessica; Huck, Olivier; Jacomine, Leandro; Fioretti, Florence; Gauthier, Christian; Sebastian, Victor; Schwinté, Pascale; Benkirane-Jessel, Nadia

2015-01-01

New-generation implants focus on robust, durable, and rapid tissue regeneration to shorten recovery times and decrease risks of postoperative complications for patients. Herein, we describe a new-generation thick nanofibrous implant functionalized with active containers of growth factors and stem cells for regenerative nanomedicine. A thick electrospun poly(ε-caprolactone) nanofibrous implant (from 700 μm to 1 cm thick) was functionalized with chitosan and bone morphogenetic protein BMP-7 as growth factor using layer-by-layer technology, producing fish scale-like chitosan/BMP-7 nanoreservoirs. This extracellular matrix-mimicking scaffold enabled in vitro colonization and bone regeneration by human primary osteoblasts, as shown by expression of osteocalcin, osteopontin, and bone sialoprotein (BSPII), 21 days after seeding. In vivo implantation in mouse calvaria defects showed significantly more newly mineralized extracellular matrix in the functionalized implant compared to a bare scaffold after 30 days’ implantation, as shown by histological scanning electron microscopy/energy dispersive X-ray microscopy study and calcein injection. We have as well bifunctionalized our BMP-7 therapeutic implant by adding human mesenchymal stem cells (hMSCs). The activity of this BMP-7-functionalized implant was again further enhanced by the addition of hMSCs to the implant (living materials), in vivo, as demonstrated by the analysis of new bone formation and calcification after 30 days’ implantation in mice with calvaria defects. Therefore, implants functionalized with BMP-7 nanocontainers associated with hMSCs can act as an accelerator of in vivo bone mineralization and regeneration. PMID:25709432

Photo-acoustic excitation and detection of guided ultrasonic waves in bone samples covered by a soft coating layer

NASA Astrophysics Data System (ADS)

Zhao, Zuomin; Moilanen, Petro; Karppinen, Pasi; Määttä, Mikko; Karppinen, Timo; Hæggström, Edward; Timonen, Jussi; Myllylä, Risto

2012-12-01

Photo-acoustic (PA) excitation was combined with skeletal quantitative ultrasound (QUS) for multi-mode ultrasonic assessment of human long bones. This approach permits tailoring of the ultrasonic excitation and detection so as to efficiently detect the fundamental flexural guided wave (FFGW) through a coating of soft tissue. FFGW is a clinically relevant indicator of cortical thickness. An OPO laser with tunable optical wavelength, was used to excite a photo-acoustic source in the shaft of a porcine femur. Ultrasonic signals were detected by a piezoelectric transducer, scanning along the long axis of the bone, 20-50 mm away from the source. Five femurs were measured without and with a soft coating. The coating was made of an aqueous gelatin-intralipid suspension that optically and acoustically mimicked real soft tissue. An even coating thickness was ensured by using a specific mold. The optical wave length of the source (1250 nm) was tuned to maximize the amplitude of FFGW excitation at 50 kHz frequency. The experimentally determined FFGW phase velocity in the uncoated samples was consistent with that of the fundamental antisymmetric Lamb mode (A0). Using appropriate signal processing, FFGW was also identified in the coated bone samples, this time with a phase velocity consistent with that theoretically predicted for the first mode of a fluid-solid bilayer waveguide (BL1). Our results suggest that photo-acoustic quantitative ultrasound enables assessment of the thickness-sensitive FFGW in bone through a layer of soft tissue. Photo-acoustic characterization of the cortical bone thickness may thus become possible.

Temperature evaluation during PMMA screw augmentation in osteoporotic bone--an in vitro study about the risk of thermal necrosis in human femoral heads.

PubMed

Boner, Vanessa; Kuhn, Philipp; Mendel, Thomas; Gisep, Armando

2009-08-01

The use of polymethylmethacrylate (PMMA) bone cement to augment hip screws reduces cut-out risk but is associated with an exothermic reaction. This in vitro investigation evaluated the risk of thermal necrosis when augmenting the implant purchase with PMMA. A pilot study analyzed the effects of different PMMA layer thicknesses on temperatures around an implant. The main study used either 3.0 or 6.0 cc PMMA for hip screw augmentation in human femoral heads. The risk of thermal necrosis was estimated according to critical values reported in literature. Highest temperatures were measured inside the PMMA with a significant drop of average maximum temperatures from the center of the PMMA to the PMMA/bone interface. Risk of thermal necrosis exists with PMMA layer thicknesses greater than 5.0 mm. In the main study, we found no risk of thermal necrosis at the PMMA/bone interface or in the surrounding bone, neither with 3.0 nor 6.0 cc PMMA. The results of the two studies were consistent regarding average peak temperatures related to associated cement layer thicknesses. The results of this in vitro study reduce objections concerning the risk of thermal necrosis when augmenting cancellous bone around hip screws with up to 6.0 cc PMMA.

Fast decomposition of two ultrasound longitudinal waves in cancellous bone using a phase rotation parameter for bone quality assessment: Simulation study.

PubMed

Taki, Hirofumi; Nagatani, Yoshiki; Matsukawa, Mami; Kanai, Hiroshi; Izumi, Shin-Ichi

2017-10-01

Ultrasound signals that pass through cancellous bone may be considered to consist of two longitudinal waves, which are called fast and slow waves. Accurate decomposition of these fast and slow waves is considered to be highly beneficial in determination of the characteristics of cancellous bone. In the present study, a fast decomposition method using a wave transfer function with a phase rotation parameter was applied to received signals that have passed through bovine bone specimens with various bone volume to total volume (BV/TV) ratios in a simulation study, where the elastic finite-difference time-domain method is used and the ultrasound wave propagated parallel to the bone axes. The proposed method succeeded to decompose both fast and slow waves accurately; the normalized residual intensity was less than -19.5 dB when the specimen thickness ranged from 4 to 7 mm and the BV/TV value ranged from 0.144 to 0.226. There was a strong relationship between the phase rotation value and the BV/TV value. The ratio of the peak envelope amplitude of the decomposed fast wave to that of the slow wave increased monotonically with increasing BV/TV ratio, indicating the high performance of the proposed method in estimation of the BV/TV value in cancellous bone.

Defective Bone Repair in C57Bl6 Mice With Acute Systemic Inflammation.

PubMed

Behrends, D A; Hui, D; Gao, C; Awlia, A; Al-Saran, Y; Li, A; Henderson, J E; Martineau, P A

2017-03-01

Bone repair is initiated with a local inflammatory response to injury. The presence of systemic inflammation impairs bone healing and often leads to malunion, although the underlying mechanisms remain poorly defined. Our research objective was to use a mouse model of cortical bone repair to determine the effect of systemic inflammation on cells in the bone healing microenvironment. QUESTION/PURPOSES: (1) Does systemic inflammation, induced by lipopolysaccharide (LPS) administration affect the quantity and quality of regenerating bone in primary bone healing? (2) Does systemic inflammation alter vascularization and the number or activity of inflammatory cells, osteoblasts, and osteoclasts in the bone healing microenvironment? Cortical defects were drilled in the femoral diaphysis of female and male C57BL/6 mice aged 5 to 9 months that were treated with daily systemic injections of LPS or physiologic saline as control for 7 days. Mice were euthanized at 1 week (Control, n = 7; LPS, n = 8), 2 weeks (Control, n = 7; LPS, n = 8), and 6 weeks (Control, n = 9; LPS, n = 8) after surgery. The quantity (bone volume per tissue volume [BV/TV]) and microarchitecture (trabecular separation and thickness, porosity) of bone in the defect were quantified with time using microCT. The presence or activity of vascular endothelial cells (CD34), macrophages (F4/80), osteoblasts (alkaline phosphatase [ALP]), and osteoclasts (tartrate-resistant acid phosphatase [TRAP]) were evaluated using histochemical analyses. Only one of eight defects was bridged completely 6 weeks after surgery in LPS-injected mouse bones compared with seven of nine defects in the control mouse bones (odds ratio [OR], 0.04; 95% CI, 0.003-0.560; p = 0.007). The decrease in cortical bone in LPS-treated mice was reflected in reduced BV/TV (21% ± 4% vs 39% ± 10%; p < 0.01), increased trabecular separation (240 ± 36 μm vs 171 ± 29 μm; p < 0.01), decreased trabecular thickness (81 ± 18 μm vs 110 ± 22 μm; p = 0.02), and porosity (79% ± 4% vs 60% ± 10%; p < 0.01) at 6 weeks postoperative. Defective healing was accompanied by decreased CD34 (1.1 ± 0.6 vs 3.4 ± 0.9; p < 0.01), ALP (1.9 ± 0.9 vs 6.1 ± 3.2; p = 0.03), and TRAP (3.3 ± 4.7 vs 7.2 ± 4.0; p = 0.01) activity, and increased F4/80 (13 ± 2.6 vs 6.8 ± 1.7; p < 0.01) activity at 2 weeks postoperative. The results indicate that LPS-induced systemic inflammation reduced the amount and impaired the quality of bone regenerated in mouse femurs. The effects were associated with impaired revascularization, decreased bone turnover by osteoblasts and osteoclasts, and by increased catabolic activity by macrophages. Results from this preclinical study support clinical observations of impaired primary bone healing in patients with systemic inflammation. Based on our data, local administration of VEGF in the callus to stimulate revascularization, or transplantation of stem cells to enhance bone turnover represent potentially feasible approaches to improve outcomes in clinical practice.

Finite element analysis of functionally graded bone plate at femur bone fracture site

NASA Astrophysics Data System (ADS)

Satapathy, Pravat Kumar; Sahoo, Bamadev; Panda, L. N.; Das, S.

2018-03-01

This paper focuses on the analysis of fractured Femur bone with functionally graded bone plate. The Femur bone is modeled by using the data from the CT (Computerized Tomography) scan and the material properties are assigned using Mimics software. The fracture fixation plate used here is composed of Functionally Graded Material (FGM). The functionally graded bone plate is considered to be composed of different layers of homogeneous materials. Finite element method approach is adopted for analysis. The volume fraction of the material is calculated by considering its variation along the thickness direction (z) according to a power law and the effective properties of the homogeneous layers are estimated. The model developed is validated by comparing numerical results available in the literature. Static analysis has been performed for the bone plate system by considering both axial compressive load and torsional load. The investigation shows that by introducing FG bone plate instead of titanium, the stress at the fracture site increases by 63 percentage and the deformation decreases by 15 percentage, especially when torsional load is taken into consideration. The present model yields better results in comparison with the commercially available bone plates.

Does maximum torque mean optimal pullout strength of screws?

PubMed

Tankard, Sara E; Mears, Simon C; Marsland, Daniel; Langdale, Evan R; Belkoff, Stephen M

2013-04-01

To determine the relationship between insertion torque and pullout strength of 3.5-mm-diameter cortical screws in cadaveric humeri with different bone mineral densities (BMDs). Five pairs of human humeri from each of 3 BMD groups (normal, osteopenic, and osteoporotic) were used. Holes were drilled in each humerus, and maximum insertion torque (T(max)) was measured by tightening a screw until stripping occurred. In the remaining holes, screws were tightened to 50%, 70%, or 90% of the T(max). A servohydraulic testing machine pulled each screw out at 1 mm/s while resulting force and axial displacement were recorded at 10 Hz. The authors checked for an effect of insertion torque (percent T(max)) on pullout strength using a general linearized and latent mixed model (Stata10), controlling for cortical thickness and BMD (T-score). Pullout strength for normal and osteoporotic bone was greatest for screws inserted to 50% T(max) and was significantly greater than that at T(max) but not significantly different from that at 70% or 90% T(max). For osteopenic bone, pullout strength was greatest at 70% peak torque, but it was not significantly different from the pullout strength at the 50% or 90% T(max) levels. Tightening screws beyond 50% T(max) does not increase pullout strength of the screw and may place bone at risk for damage that might result in loss of fixation. Even after adjusting for bone thickness and density, there is no clear relationship between pullout strength and screw torque.

Preventing painful age-related bone fractures: Anti-sclerostin therapy builds cortical bone and increases the proliferation of osteogenic cells in the periosteum of the geriatric mouse femur.

PubMed

Thompson, Michelle L; Chartier, Stephane R; Mitchell, Stefanie A; Mantyh, Patrick W

2016-01-01

Age-related bone fractures are usually painful and have highly negative effects on a geriatric patient's functional status, quality of life, and survival. Currently, there are few analgesic therapies that fully control bone fracture pain in the elderly without significant unwanted side effects. However, another way of controlling age-related fracture pain would be to preemptively administer an osteo-anabolic agent to geriatric patients with high risk of fracture, so as to build new cortical bone and prevent the fracture from occurring. A major question, however, is whether an osteo-anabolic agent can stimulate the proliferation of osteogenic cells and build significant amounts of new cortical bone in light of the decreased number and responsiveness of osteogenic cells in aging bone. To explore this question, geriatric and young mice, 20 and 4 months old, respectively, received either vehicle or a monoclonal antibody that sequesters sclerostin (anti-sclerostin) for 28 days. From days 21 to 28, animals also received sustained administration of the thymidine analog, bromodeoxyuridine (BrdU), which labels the DNA of dividing cells. Animals were then euthanized at day 28 and the femurs were examined for cortical bone formation, bone mineral density, and newly borne BrdU+ cells in the periosteum which is a tissue that is pivotally involved in the formation of new cortical bone. In both the geriatric and young mice, anti-sclerostin induced a significant increase in the thickness of the cortical bone, bone mineral density, and the proliferation of newly borne BrdU+ cells in the periosteum. These results suggest that even in geriatric animals, anti-sclerostin therapy can build new cortical bone and increase the proliferation of osteogenic cells and thus reduce the likelihood of painful age-related bone fractures. © The Author(s) 2016.

Estimation of the stapes-bone thickness in the stapedotomy surgical procedure using a machine-learning technique.

PubMed

Kaburlasos, V G; Petridis, V; Brett, P N; Baker, D A

1999-12-01

Stapedotomy is a surgical procedure aimed at the treatment of hearing impairment due to otosclerosis. The treatment consists of drilling a hole through the stapes bone in the inner ear in order to insert a prosthesis. Safety precautions require knowledge of the nonmeasurable stapes thickness. The technical goal herein has been the design of high-level controls for an intelligent mechatronics drilling tool in order to enable the estimation of stapes thickness from measurable drilling data. The goal has been met by learning a map between drilling features, hence no model of the physical system has been necessary. Learning has been achieved as explained in this paper by a scheme, namely the d-sigma Fuzzy Lattice Neurocomputing (d sigma-FLN) scheme for classification, within the framework of fuzzy lattices. The successful application of the d sigma-FLN scheme is demonstrated in estimating the thickness of a stapes bone "on-line" using drilling data obtained experimentally in the laboratory.

Detection of changes in bone quality of osteoporotic model induced by sciatic nerve resection by using Raman spectroscopy

NASA Astrophysics Data System (ADS)

Ishimaru, Yasumitsu; Oshima, Yusuke; Imai, Yuuki; Iimura, Tadahiro; Takanezawa, Sota; Hino, Kazunori; Miura, Hiromasa

2018-02-01

To detect the bone quality loss in osteoporosis, we performed Raman spectroscopic analysis of sciatic nerve resection (NX) mice. Eight months after surgery, lower limbs were collected from the mice and fixed with 70% ethanol. Raman spectra of anterior cortical surface of the proximal tibia at 5 points in each bone were measured by RENISHAW inVia Raman Microscope. Excitation wave length was 785 nm. We also performed DXA and micro CT measurement to confirm the bone mineral density and bone microstructure in the osteoporotic model induced by sciatic nerve resection. In the result of Raman spectroscopy, we detected changes of Raman peak intensity ratio in carbonate/phosphate, mineral/combined proline and hydroxyproline and mineral/phenylalanine. In addition, in the result of micro CT, we found significant changes in VOX BV/TV, Trabecular number, thickness, cancellous bone mineral density, cortical thickness and cortical bone mineral density. The results suggest that not only the bone mineral density but also bone quality reduced in the NX mice. We conclude that Raman spectroscopy is a useful for bone quality assessment as a complementary technique for conventional diagnostics.

Genistein treatment increases bone mass in obese, hyperglycemic mice.

PubMed

Michelin, Richard M; Al-Nakkash, Layla; Broderick, Tom L; Plochocki, Jeffrey H

2016-01-01

Obesity and type 2 diabetes mellitus are associated with elevated risk of limb bone fracture. Incidences of these conditions are on the rise worldwide. Genistein, a phytoestrogen, has been shown by several studies to demonstrate bone-protective properties and may improve bone health in obese type 2 diabetics. In this study, we test the effects of genistein treatment on limb bone and growth plate cartilage histomorphometry in obese, hyperglycemic ob/ob mice. Six-week-old ob/ob mice were divided into control and genistein-treated groups. Genistein-treated mice were fed a diet containing 600 mg genistein/kg for a period of 4 weeks. Cross-sectional geometric and histomorphometric analyses were conducted on tibias. Genistein-treated mice remained obese and hyperglycemic. However, histomorphometric comparisons show that genistein-treated mice have greater tibial midshaft diameters and ratios of cortical bone to total tissue area than the controls. Genistein-treated mice also exhibit decreased growth plate thickness of the proximal tibia. Our results indicate that genistein treatment affects bone of the tibial midshaft in the ob/ob mouse, independent of improvements in the hyperglycemic state and body weight.

Biorhythms, deciduous enamel thickness, and primary bone growth: a test of the Havers-Halberg Oscillation hypothesis.

PubMed

Mahoney, Patrick; Miszkiewicz, Justyna J; Pitfield, Rosie; Schlecht, Stephen H; Deter, Chris; Guatelli-Steinberg, Debbie

2016-06-01

Across mammalian species, the periodicity with which enamel layers form (Retzius periodicity) in permanent teeth corresponds with average body mass and the pace of life history. According to the Havers-Halberg Oscillation hypothesis (HHO), Retzius periodicity (RP) is a manifestation of a biorhythm that is also expressed in lamellar bone. Potentially, these links provide a basis for investigating aspects of a species' biology from fossilized teeth. Here, we tested intra-specific predictions of this hypothesis on skeletal samples of human juveniles. We measured daily enamel growth increments to calculate RP in deciduous molars (n = 25). Correlations were sought between RP, molar average and relative enamel thickness (AET, RET), and the average amount of primary bone growth (n = 7) in humeri of age-matched juveniles. Results show a previously undescribed relationship between RP and enamel thickness. Reduced major axis regression reveals RP is significantly and positively correlated with AET and RET, and scales isometrically. The direction of the correlation was opposite to HHO predictions as currently understood for human adults. Juveniles with higher RPs and thicker enamel had increased primary bone formation, which suggests a coordinating biorhythm. However, the direction of the correspondence was, again, opposite to predictions. Next, we compared RP from deciduous molars with new data for permanent molars, and with previously published values. The lowermost RP of 4 and 5 days in deciduous enamel extends below the lowermost RP of 6 days in permanent enamel. A lowered range of RP values in deciduous enamel implies that the underlying biorhythm might change with age. Our results develop the intra-specific HHO hypothesis. © 2016 Anatomical Society.

Electrospun nanofibrous 3D scaffold for bone tissue engineering.

PubMed

Eap, Sandy; Ferrand, Alice; Palomares, Carlos Mendoza; Hébraud, Anne; Stoltz, Jean-François; Mainard, Didier; Schlatter, Guy; Benkirane-Jessel, Nadia

2012-01-01

Tissue engineering aims at developing functional substitutes for damaged tissues by mimicking natural tissues. In particular, tissue engineering for bone regeneration enables healing of some bone diseases. Thus, several methods have been developed in order to produce implantable biomaterial structures that imitate the constitution of bone. Electrospinning is one of these methods. This technique produces nonwoven scaffolds made of nanofibers which size and organization match those of the extracellular matrix. Until now, seldom electrospun scaffolds were produced with thickness exceeding one millimeter. This article introduces a new kind of electrospun membrane called 3D scaffold of thickness easily exceeding one centimeter. The manufacturing involves a solution of poly(ε-caprolactone) in DMF/DCM system. The aim is to establish parameters for electrospinning in order to characterize these 3D scaffolds and, establish whether such scaffolds are potentially interesting for bone regeneration.

Platelet Dysfunction and a High Bone Mass Phenotype in a Murine Model of Platelet-Type von Willebrand Disease

PubMed Central

Suva, Larry J.; Hartman, Eric; Dilley, Joshua D.; Russell, Susan; Akel, Nisreen S.; Skinner, Robert A.; Hogue, William R.; Budde, Ulrich; Varughese, Kottayil I.; Kanaji, Taisuke; Ware, Jerry

2008-01-01

The platelet glycoprotein Ib-IX receptor binds surface-bound von Willebrand factor and supports platelet adhesion to damaged vascular surfaces. A limited number of mutations within the glycoprotein Ib-IX complex have been described that permit a structurally altered receptor to interact with soluble von Willebrand factor, and this is the molecular basis of platelet-type von Willebrand disease. We have developed and characterized a mouse model of platelet-type von Willebrand disease (G233V) and have confirmed a platelet phenotype mimicking the human disorder. The mice have a dramatic increase in splenic megakaryocytes and splenomegaly. Recent studies have demonstrated that hematopoetic cells can influence the differentiation of osteogenic cells. Thus, we examined the skeletal phenotype of mice expressing the G233V variant complex. At 6 months of age, G233V mice exhibit a high bone mass phenotype with an approximate doubling of trabecular bone volume in both the tibia and femur. Serum measures of bone resorption were significantly decreased in G233V animals. With decreased bone resorption, cortical thickness was increased, medullary area decreased, and consequently, the mechanical strength of the femur was significantly increased. Using ex vivo bone marrow cultures, osteoclast-specific staining in the G233V mutant marrow was diminished, whereas osteoblastogenesis was unaffected. These studies provide new insights into the relationship between the regulation of megakaryocytopoiesis and bone mass. PMID:18187573

Structural and biomechanical basis of sexual dimorphism in femoral neck fragility has its origins in growth and aging.

PubMed

Duan, Yunbo; Beck, Thomas J; Wang, Xiao-Fang; Seeman, Ego

2003-10-01

The structural basis for sex differences in femoral neck (FN) fragility was studied in 1196 subjects and 307 patients with hip fracture. The absolute and relative patterns of modeling and remodeling on the periosteal and endocortical envelopes during growth and aging produce changes in FN geometry and structure that results in FN fragility in both sexes and sexual dimorphism in hip fracture risk in old age. Femoral neck (FN) fragility in old age is usually attributed to age-related bone loss, while the sex differences in hip fracture rate are attributed to less bone loss in men than in women. The purpose of this study was to define the structural and biomechanical basis underlying the increase in FN fragility in elderly men and women and the structural basis of sex differences in hip fracture incidence in old age. We measured FN dimensions and areal bone mineral density in 1196 healthy subjects (801 females) 18-92 years of age and 307 patients (180 females) with hip fracture using DXA. We then used the DXA-derived FN areal bone mineral density (BMD) and measured periosteal diameter to estimate endocortical diameter, cortical thickness, section modulus (a measure of bending strength), and buckling ratio (indices for structural stability). Neither FN cortical thickness nor volumetric density differed in young adult women and men after height and weight adjustment. The sex differences in geometry were confined to the further displacement of the cortex from the FN neutral axis in young men, which produced 13.4% greater bending strength than in young women. Aging amplified this geometric difference; widening of the periosteal and endocortical diameters continued in both sexes but was greater in men, shifting the cortex even further from the neutral axis maintaining bending strength in men, not in women. In both sexes, less age-related periosteal than endocortical widening produced cortical thinning increasing the risk for structural failure by local buckling of the enlarged thin walled FN. Relative to age-matched controls, women and men with hip fractures had reduced cortical thickness, but FN periosteal diameter was increased in women and reduced in men, differences are likely to be originated in growth. The absolute and relative patterns of modeling and remodeling on the periosteal and endocortical envelopes during growth and aging produce changes in FN diameters, cortical thickness, and geometry that results in FN fragility in both sexes and sexual dimorphism in hip fracture risk in old age.

Early loss of subchondral bone following microfracture is counteracted by bone marrow aspirate in a translational model of osteochondral repair

PubMed Central

Gao, Liang; Orth, Patrick; Müller-Brandt, Kathrin; Goebel, Lars K. H.; Cucchiarini, Magali; Madry, Henning

2017-01-01

Microfracture of cartilage defects may induce alterations of the subchondral bone in the mid- and long-term, yet very little is known about their onset. Possibly, these changes may be avoided by an enhanced microfracture technique with additional application of bone marrow aspirate. In this study, full-thickness chondral defects in the knee joints of minipigs were either treated with (1) debridement down to the subchondral bone plate alone, (2) debridement with microfracture, or (3) microfracture with additional application of bone marrow aspirate. At 4 weeks after microfracture, the loss of subchondral bone below the defects largely exceeded the original microfracture holes. Of note, a significant increase of osteoclast density was identified in defects treated with microfracture alone compared with debridement only. Both changes were significantly counteracted by the adjunct treatment with bone marrow. Debridement and microfracture without or with bone marrow were equivalent regarding the early cartilage repair. These data suggest that microfracture induced a substantial early resorption of the subchondral bone and also highlight the potential value of bone marrow aspirate as an adjunct to counteract these alterations. Clinical studies are warranted to further elucidate early events of osteochondral repair and the effect of enhanced microfracture techniques. PMID:28345610

Curcumin reduces trabecular and cortical bone in naive and lewis lung carcinoma-bearing mice.

PubMed

Yan, Lin; Yee, John A; Cao, Jay

2013-08-01

The present study investigated the effects of curcumin on bone microstructure in non-tumor-bearing and Lewis lung carcinoma-(LLC)-bearing female C57BL/6 mice. Morphometric analysis showed that dietary supplementation with curcumin (2% or 4%) significantly reduced the bone volume to total volume ratio, connectivity density and trabecular number, and significantly increased the structure model index (an indicator of the plate- and rod-like geometry of trabecular structure) and trabecular separation in vertebral bodies compared to controls in both non-tumor-bearing and LLC-bearing mice. Similar changes in trabecular bone were observed in the femoral bone in curcumin-fed mice. Curcumin significantly reduced the cortical bone area to total area ratio and cortical thickness in femoral mid-shaft, but not in vertebral bodies, in both non-tumor-bearing and LLC-bearing mice. Curcumin feeding reduced plasma concentrations of osteocalcin and increased tartrate-resistant acid phosphate 5b in mice regardless of the presence of LLC, indicating that curcumin disrupts the balance of bone remodeling. Our results demonstrated that curcumin reduced the trabecular bone volume and cortical bone density. The skeleton is a favored site of metastasis for many types of cancers, and curcumin has been investigated in clinical trials in patients with cancer for its chemopreventive effects. Our results suggest the possibility of a combined effect of cancer-induced osteolysis and curcumin-stimulated bone loss in patients using curcumin. The assessment of bone structural changes should be considered for those who participate in curcumin clinical trials to determine its effects on skeleton health, particularly for those with advanced malignancies.

Accelerated craniofacial bone regeneration through dense collagen gel scaffolds seeded with dental pulp stem cells

NASA Astrophysics Data System (ADS)

Chamieh, Frédéric; Collignon, Anne-Margaux; Coyac, Benjamin R.; Lesieur, Julie; Ribes, Sandy; Sadoine, Jérémy; Llorens, Annie; Nicoletti, Antonino; Letourneur, Didier; Colombier, Marie-Laure; Nazhat, Showan N.; Bouchard, Philippe; Chaussain, Catherine; Rochefort, Gael Y.

2016-12-01

Therapies using mesenchymal stem cell (MSC) seeded scaffolds may be applicable to various fields of regenerative medicine, including craniomaxillofacial surgery. Plastic compression of collagen scaffolds seeded with MSC has been shown to enhance the osteogenic differentiation of MSC as it increases the collagen fibrillary density. The aim of the present study was to evaluate the osteogenic effects of dense collagen gel scaffolds seeded with mesenchymal dental pulp stem cells (DPSC) on bone regeneration in a rat critical-size calvarial defect model. Two symmetrical full-thickness defects were created (5 mm diameter) and filled with either a rat DPSC-containing dense collagen gel scaffold (n = 15), or an acellular scaffold (n = 15). Animals were imaged in vivo by microcomputer tomography (Micro-CT) once a week during 5 weeks, whereas some animals were sacrificed each week for histology and histomorphometry analysis. Bone mineral density and bone micro-architectural parameters were significantly increased when DPSC-seeded scaffolds were used. Histological and histomorphometrical data also revealed significant increases in fibrous connective and mineralized tissue volume when DPSC-seeded scaffolds were used, associated with expression of type I collagen, osteoblast-associated alkaline phosphatase and osteoclastic-related tartrate-resistant acid phosphatase. Results demonstrate the potential of DPSC-loaded-dense collagen gel scaffolds to benefit of bone healing process.

Skin thickness effects on in vivo LXRF

DOE Office of Scientific and Technical Information (OSTI.GOV)

Preiss, I.L.; Washington, W. II

The analysis of lead concentration in bone utilizing LXRF can be adversely effected by overlying issue. A quantitative measure of the attenuation of the 10.5 keV Pb L a x-ray signal by skin and skin equivalent plastic has been conducted. Concentration ranges in plaster of Paris and goat bone from 7 to 90 ppm with attenuators of Lucite{reg_sign} and pig skin were examined. It is concluded that no quantitative or semi quantitative analysis can be achieved if overlying sue thickness exceeds 3 mm for Ph concentrations of less than 30 porn Ph in bone.

Alveolar Bone Morphology Following Periodontally Accelerated Osteogenic Orthodontics: A Clinical and Radiographic Analysis.

PubMed

Chackartchi, Tali; Barkana, Idit; Klinger, Avigdor

The aim of this study was to analyze alveolar bone morphology following periodontally accelerated osteogenic orthodontics. Treated patients were called for a full periodontal examination and a cone beam computed tomography scan. Mean treatment time was 6.08 months. Mean probing pocket depth was 2.7 mm. No gingival recessions were noted. In the maxilla, buccal plate thickness was 0.48 to 2.14 mm. In the mandible, bone thickness was 0.2 to 1.82 mm. Root fenestrations and dehiscences were present in up to 40% of the anterior teeth. Although clinical outcomes were favorable, due to the presence of multiple posttreatment bone fenestrations and dehiscences, a revision of the treatment protocol might be considered.

* Composite Biomaterial as a Carrier for Bone-Active Substances for Metaphyseal Tibial Bone Defect Reconstruction in Rats.

PubMed

Horstmann, Peter Frederik; Raina, Deepak Bushan; Isaksson, Hanna; Hettwer, Werner; Lidgren, Lars; Petersen, Michael Mørk; Tägil, Magnus

2017-12-01

Restoring lost bone is a major challenge in orthopedic surgery. Currently available treatment strategies have shortcomings, such as risk of infection, nonunion, and excessive resorption. Our primary aim was to study if a commercially available gentamicin-containing composite calcium sulfate/hydroxyapatite biomaterial (GBM) could serve as a carrier for local delivery of bone morphogenic protein-2 (BMP-2) and zoledronic acid (ZA) in a tibia defect model in rats. Empty and allograft-filled defects were used as controls. A 3 × 4-mm metaphyseal bone defect was created in the proximal tibia, and the rats were grouped according to defect filling: (1) Empty, (2) Allograft, (3) GBM, (4) GBM + ZA, and (5) GBM + ZA + BMP-2. In vivo microcomputed tomography (micro-CT) images at 4 weeks showed significantly higher mineralized tissue volume (MV) in the intramedullary defect region and the neocortical/callus region in all GBM-treated groups. After euthanization at 8 weeks, ex vivo micro-CT showed that addition of ZA (GBM + ZA) and BMP-2 (GBM + ZA + BMP-2) mainly increased the neocortical and callus formation, with the highest MV in the combined ZA and BMP-2-treated group. Qualitative histological analysis, verifying the increased neocortical/callus thickness and finding of trabecular bone in all GBM-treated groups, supported that the differences in MV measured with micro-CT in fact represented bone tissue. In conclusion, GBM can serve as a carrier for ZA and BMP-2 leading to increased MV in the neocortex and callus of a metaphyseal bone defect in rats.

Osteoblast Menin Regulates Bone Mass in Vivo*

PubMed Central

Kanazawa, Ippei; Canaff, Lucie; Abi Rafeh, Jad; Angrula, Aarti; Li, Jingjing; Riddle, Ryan C.; Boraschi-Diaz, Iris; Komarova, Svetlana V.; Clemens, Thomas L.; Murshed, Monzur; Hendy, Geoffrey N.

2015-01-01

Menin, the product of the multiple endocrine neoplasia type 1 (Men1) tumor suppressor gene, mediates the cell proliferation and differentiation actions of transforming growth factor-β (TGF-β) ligand family members. In vitro, menin modulates osteoblastogenesis and osteoblast differentiation promoted and sustained by bone morphogenetic protein-2 (BMP-2) and TGF-β, respectively. To examine the in vivo function of menin in bone, we conditionally inactivated Men1 in mature osteoblasts by crossing osteocalcin (OC)-Cre mice with floxed Men1 (Men1f/f) mice to generate mice lacking menin in differentiating osteoblasts (OC-Cre;Men1f/f mice). These mice displayed significant reduction in bone mineral density, trabecular bone volume, and cortical bone thickness compared with control littermates. Osteoblast and osteoclast number as well as mineral apposition rate were significantly reduced, whereas osteocyte number was increased. Primary calvarial osteoblasts proliferated more quickly but had deficient mineral apposition and alkaline phosphatase activity. Although the mRNA expression of osteoblast marker and cyclin-dependent kinase inhibitor genes were all reduced, that of cyclin-dependent kinase, osteocyte marker, and pro-apoptotic genes were increased in isolated Men1 knock-out osteoblasts compared with controls. In contrast to the knock-out mice, transgenic mice overexpressing a human menin cDNA in osteoblasts driven by the 2.3-kb Col1a1 promoter, showed a gain of bone mass relative to control littermates. Osteoblast number and mineral apposition rate were significantly increased in the Col1a1-Menin-Tg mice. Therefore, osteoblast menin plays a key role in bone development, remodeling, and maintenance. PMID:25538250

Monte Carlo investigation of backscatter factors for skin dose determination in interventional neuroradiology procedures

NASA Astrophysics Data System (ADS)

Omar, Artur; Benmakhlouf, Hamza; Marteinsdottir, Maria; Bujila, Robert; Nowik, Patrik; Andreo, Pedro

2014-03-01

Complex interventional and diagnostic x-ray angiographic (XA) procedures may yield patient skin doses exceeding the threshold for radiation induced skin injuries. Skin dose is conventionally determined by converting the incident air kerma free-in-air into entrance surface air kerma, a process that requires the use of backscatter factors. Subsequently, the entrance surface air kerma is converted into skin kerma using mass energy-absorption coefficient ratios tissue-to-air, which for the photon energies used in XA is identical to the skin dose. The purpose of this work was to investigate how the cranial bone affects backscatter factors for the dosimetry of interventional neuroradiology procedures. The PENELOPE Monte Carlo system was used to calculate backscatter factors at the entrance surface of a spherical and a cubic water phantom that includes a cranial bone layer. The simulations were performed for different clinical x-ray spectra, field sizes, and thicknesses of the bone layer. The results show a reduction of up to 15% when a cranial bone layer is included in the simulations, compared with conventional backscatter factors calculated for a homogeneous water phantom. The reduction increases for thicker bone layers, softer incident beam qualities, and larger field sizes, indicating that, due to the increased photoelectric crosssection of cranial bone compared to water, the bone layer acts primarily as an absorber of low-energy photons. For neurointerventional radiology procedures, backscatter factors calculated at the entrance surface of a water phantom containing a cranial bone layer increase the accuracy of the skin dose determination.

Nasal bone length: prenasal thickness ratio: a strong 2D ultrasound marker for Down syndrome

PubMed Central

Szabó, Andrea; Szili, Károly; Szabó, János Tamás; Sikovanyecz, János; Isaszegi, Dóra; Horváth, Emese; Szabó, János

2014-01-01

Objectives To evaluate the feasibility of incorporating two-dimensional ultrasound measurements of nasal bone length (NBL) and prenasal thickness (PT) into the second-trimester anomaly scan and to determine whether the NBL : PT ratio could help in differentiating euploid and Down syndrome fetuses. Method Two-dimensional measurements of NBL and PT were obtained from the midsagittal plane of the fetal head at 14–28 weeks of gestation in a Caucasian population at risk for aneuploidy. The screening performances of NBL, PT, and the ratios NBL : PT and PT : NBL were analyzed in euploid (n = 1330) and Down syndrome (n = 33) fetuses. Results Nasal bone length and PT alone showed strong correlations with Down syndrome (sensitivity: 76% at 1.88% and 2.35% false positive rate, respectively). However, the NBL : PT ratio showed an even stronger correlation with Down syndrome (false positive rate: 0.9%, sensitivity: 97%). The mean NBL : PT ratio showed a gradual increase from 1.48 to 1.79 (a 21.2% increase) between 14 and 28 weeks of gestation. Conclusion Two-dimensional ultrasound measurements of NBL and PT, particularly the NBL : PT ratio, are highly sensitive markers for Down syndrome fetuses. © 2014 The Authors. Prenatal Diagnosis published by John Wiley & Sons, Ltd. PMID:24966049

Defective cancellous bone structure and abnormal response to PTH in cortical bone of mice lacking Cx43 cytoplasmic C-terminus domain

PubMed Central

Pacheco-Costa, Rafael; Davis, Hannah M.; Sorenson, Chad; Hon, Mary C.; Hassan, Iraj; Reginato, Rejane D.; Allen, Matthew R.; Bellido, Teresita; Plotkin, Lilian I.

2015-01-01

Connexin43 (Cx43) forms gap junction channels and hemichannels that allow the communication among osteocytes, osteoblasts, and osteoclasts. Cx43 carboxy-terminal (CT) domain regulates channel opening and intracellular signaling by acting as a scaffold for structural and signaling proteins. To determine the role of Cx43 CT domain in bone, mice in which one allele of full length Cx43 was replaced by a mutant lacking the CT domain (Cx43ΔCT/fl) were studied. Cx43ΔCT/fl mice exhibit lower cancellous bone volume but higher cortical thickness than Cx43fl/fl controls, indicating that the CT domain is involved in normal cancellous bone gain but opposes cortical bone acquisition. Further, Cx43ΔCT is able to exert the functions of full length osteocytic Cx43 on cortical bone geometry and mechanical properties, demonstrating that domains other than the CT are responsible for Cx43 function in cortical bone. In addition, parathyroid hormone (PTH) failed to increase endocortical bone formation or energy to failure, a mechanical property that indicates resistance to fracture, in cortical bone in Cx43ΔCT mice with or without osteocytic full length Cx43. On the other hand, bone mass and bone formation markers were increased by the hormone in all mouse models, regardless of whether full length or Cx43ΔCT were or not expressed. We conclude that Cx43 CT domain is involved in proper bone acquisition; and that Cx43 expression in osteocytes is dispensable for some but not all PTH anabolic actions. PMID:26409319

Defective cancellous bone structure and abnormal response to PTH in cortical bone of mice lacking Cx43 cytoplasmic C-terminus domain.

PubMed

Pacheco-Costa, Rafael; Davis, Hannah M; Sorenson, Chad; Hon, Mary C; Hassan, Iraj; Reginato, Rejane D; Allen, Matthew R; Bellido, Teresita; Plotkin, Lilian I

2015-12-01

Connexin 43 (Cx43) forms gap junction channels and hemichannels that allow the communication among osteocytes, osteoblasts, and osteoclasts. Cx43 carboxy-terminal (CT) domain regulates channel opening and intracellular signaling by acting as a scaffold for structural and signaling proteins. To determine the role of Cx43 CT domain in bone, mice in which one allele of full length Cx43 was replaced by a mutant lacking the CT domain (Cx43(ΔCT/fl)) were studied. Cx43(ΔCT/fl) mice exhibit lower cancellous bone volume but higher cortical thickness than Cx43(fl/fl) controls, indicating that the CT domain is involved in normal cancellous bone gain but opposes cortical bone acquisition. Further, Cx43(ΔCT) is able to exert the functions of full length osteocytic Cx43 on cortical bone geometry and mechanical properties, demonstrating that domains other than the CT are responsible for Cx43 function in cortical bone. In addition, parathyroid hormone (PTH) failed to increase endocortical bone formation or energy to failure, a mechanical property that indicates resistance to fracture, in cortical bone in Cx43(ΔCT) mice with or without osteocytic full length Cx43. On the other hand, bone mass and bone formation markers were increased by the hormone in all mouse models, regardless of whether full length or Cx43(ΔCT) were or not expressed. We conclude that Cx43 CT domain is involved in proper bone acquisition; and that Cx43 expression in osteocytes is dispensable for some but not all PTH anabolic actions. Copyright © 2015 Elsevier Inc. All rights reserved.

Bone turnover in wild type and pleiotrophin-transgenic mice housed for three months in the International Space Station (ISS).

PubMed

Tavella, Sara; Ruggiu, Alessandra; Giuliani, Alessandra; Brun, Francesco; Canciani, Barbara; Manescu, Adrian; Marozzi, Katia; Cilli, Michele; Costa, Delfina; Liu, Yi; Piccardi, Federica; Tasso, Roberta; Tromba, Giuliana; Rustichelli, Franco; Cancedda, Ranieri

2012-01-01

Bone is a complex dynamic tissue undergoing a continuous remodeling process. Gravity is a physical force playing a role in the remodeling and contributing to the maintenance of bone integrity. This article reports an investigation on the alterations of the bone microarchitecture that occurred in wild type (Wt) and pleiotrophin-transgenic (PTN-Tg) mice exposed to a near-zero gravity on the International Space Station (ISS) during the Mice Drawer System (MDS) mission, to date, the longest mice permanence (91 days) in space. The transgenic mouse strain over-expressing pleiotrophin (PTN) in bone was selected because of the PTN positive effects on bone turnover. Wt and PTN-Tg control animals were maintained on Earth either in a MDS payload or in a standard vivarium cage. This study revealed a bone loss during spaceflight in the weight-bearing bones of both strains. For both Tg and Wt a decrease of the trabecular number as well as an increase of the mean trabecular separation was observed after flight, whereas trabecular thickness did not show any significant change. Non weight-bearing bones were not affected. The PTN-Tg mice exposed to normal gravity presented a poorer trabecular organization than Wt mice, but interestingly, the expression of the PTN transgene during the flight resulted in some protection against microgravity's negative effects. Moreover, osteocytes of the Wt mice, but not of Tg mice, acquired a round shape, thus showing for the first time osteocyte space-related morphological alterations in vivo. The analysis of specific bone formation and resorption marker expression suggested that the microgravity-induced bone loss was due to both an increased bone resorption and a decreased bone deposition. Apparently, the PTN transgene protection was the result of a higher osteoblast activity in the flight mice.

Bone mass, microarchitecture and strength are influenced by race/ethnicity in young adult men and women.

PubMed

Popp, Kristin L; Hughes, Julie M; Martinez-Betancourt, Adriana; Scott, Matthew; Turkington, Victoria; Caksa, Signe; Guerriere, Katelyn I; Ackerman, Kathryn E; Xu, Chun; Unnikrishnan, Ginu; Reifman, Jaques; Bouxsein, Mary L

2017-10-01

Lower rates of fracture in both Blacks compared to Whites, and men compared to women are not completely explained by differences in bone mineral density (BMD). Prior evidence suggests that more favorable cortical bone microarchitecture may contribute to reduced fracture rates in older Black compared to White women, however it is not known whether these differences are established in young adulthood or develop during aging. Moreover, prior studies using high-resolution pQCT (HR-pQCT) have reported outcomes from a fixed-scan location, which may confound sex- and race/ethnicity-related differences in bone structure. We determined differences in bone mass, microarchitecture and strength between young adult Black and White men and women. We enrolled 185 young adult (24.2±3.4yrs) women (n=51 Black, n=50 White) and men (n=34 Black, n=50 White) in this cross-sectional study. We used dual-energy X-ray absorptiometry (DXA) to determine areal BMD (aBMD) at the femoral neck (FN), total hip (TH) and lumbar spine (LS), as well as HR-pQCT to assess bone microarchitecture and failure load by micro-finite element analysis (μFEA) at the distal tibia (4% of tibial length). We used two-way ANOVA to compare bone outcomes, adjusted for age, height, weight and physical activity. The effect of race/ethnicity on bone outcomes did not differ by sex, and the effect of sex on bone outcomes did not differ by race/ethnicty. After adjusting for covariates, Blacks had significantly greater FN, TH and LS aBMD compared to Whites (p<0.05 for all). Blacks also had greater cortical area, vBMD, and thickness, and lower cortical porosity, with greater trabecular thickness and total vBMD compared to Whites. μFEA-estimated FL was significantly higher among Blacks compared to Whites. Men had significantly greater total vBMD, trabecular thickness and cortical area and thickness, but greater cortical porosity than women, the net effects being a higher failure load in men than women. These findings demonstrate that more favorable bone microarchitecture in Blacks compared to Whites and in men compared to women is established by young adulthood. Advantageous bone strength among Blacks and men likely contributes to their lower risk of fractures throughout life compared to their White and women counterparts. Copyright © 2017 Elsevier Inc. All rights reserved.

Impaired bone formation in ovariectomized mice reduces implant integration as indicated by longitudinal in vivo micro-computed tomography.

PubMed

Li, Zihui; Kuhn, Gisela; Schirmer, Michael; Müller, Ralph; Ruffoni, Davide

2017-01-01

Although osteoporotic bone, with low bone mass and deteriorated bone architecture, provides a less favorable mechanical environment than healthy bone for implant fixation, there is no general agreement on the impact of osteoporosis on peri-implant bone (re)modeling, which is ultimately responsible for the long term stability of the bone-implant system. Here, we inserted an implant in a mouse model mimicking estrogen deficiency-induced bone loss and we monitored with longitudinal in vivo micro-computed tomography the spatio-temporal changes in bone (re)modeling and architecture, considering the separate contributions of trabecular, endocortical and periosteal surfaces. Specifically, 12 week-old C57BL/6J mice underwent OVX/SHM surgery; 9 weeks after we inserted special metal-ceramics implants into the 6th caudal vertebra and we measured bone response with in vivo micro-CT weekly for the following 6 weeks. Our results indicated that ovariectomized mice showed a reduced ability to increase the thickness of the cortical shell close to the implant because of impaired peri-implant bone formation, especially at the periosteal surface. Moreover, we observed that healthy mice had a significantly higher loss of trabecular bone far from the implant than estrogen depleted animals. Such behavior suggests that, in healthy mice, the substantial increase in peri-implant bone formation which rapidly thickened the cortex to secure the implant may raise bone resorption elsewhere and, specifically, in the trabecular network of the same bone but far from the implant. Considering the already deteriorated bone structure of estrogen depleted mice, further bone loss seemed to be hindered. The obtained knowledge on the dynamic response of diseased bone following implant insertion should provide useful guidelines to develop advanced treatments for osteoporotic fracture fixation based on local and selective manipulation of bone turnover in the peri-implant region.

Impaired bone formation in ovariectomized mice reduces implant integration as indicated by longitudinal in vivo micro-computed tomography

PubMed Central

Li, Zihui; Kuhn, Gisela; Schirmer, Michael; Müller, Ralph

2017-01-01

Although osteoporotic bone, with low bone mass and deteriorated bone architecture, provides a less favorable mechanical environment than healthy bone for implant fixation, there is no general agreement on the impact of osteoporosis on peri-implant bone (re)modeling, which is ultimately responsible for the long term stability of the bone-implant system. Here, we inserted an implant in a mouse model mimicking estrogen deficiency-induced bone loss and we monitored with longitudinal in vivo micro-computed tomography the spatio-temporal changes in bone (re)modeling and architecture, considering the separate contributions of trabecular, endocortical and periosteal surfaces. Specifically, 12 week-old C57BL/6J mice underwent OVX/SHM surgery; 9 weeks after we inserted special metal-ceramics implants into the 6th caudal vertebra and we measured bone response with in vivo micro-CT weekly for the following 6 weeks. Our results indicated that ovariectomized mice showed a reduced ability to increase the thickness of the cortical shell close to the implant because of impaired peri-implant bone formation, especially at the periosteal surface. Moreover, we observed that healthy mice had a significantly higher loss of trabecular bone far from the implant than estrogen depleted animals. Such behavior suggests that, in healthy mice, the substantial increase in peri-implant bone formation which rapidly thickened the cortex to secure the implant may raise bone resorption elsewhere and, specifically, in the trabecular network of the same bone but far from the implant. Considering the already deteriorated bone structure of estrogen depleted mice, further bone loss seemed to be hindered. The obtained knowledge on the dynamic response of diseased bone following implant insertion should provide useful guidelines to develop advanced treatments for osteoporotic fracture fixation based on local and selective manipulation of bone turnover in the peri-implant region. PMID:28910363

Thickened cranial vault and parasagittal keeling: correlated traits and autapomorphies of Homo erectus?

PubMed

Balzeau, Antoine

2013-06-01

Homo erectus sensu lato (s.l.) is a key species in the hominin fossil record for the study of human evolution, being one of the first species discovered and perhaps the most documented, but also because of its long temporal range and having dispersed out of Africa earlier than any other human species. Here I test two proposed autapomorphic traits of H. erectus, namely the increased thickness of the upper cranial vault and parasagittal keeling. The definition of these two anatomical features and their expression and variation among hominids are discussed. The results of this study indicate that the upper vault in Asian H. erectus is not absolutely thicker compared with fossil anatomically modern Homo sapiens, whereas Broken Hill and Petralona have values above the range of variation of H. erectus. Moreover, this anatomical region in Asian H. erectus is not significantly thicker compared with Pan paniscus. In addition, these results demonstrate that cranial vault thickness should not be used to make hypotheses regarding sexual attribution of fossil hominin specimens. I also show that the relation between relief on the external surface of the upper vault, parasagittal keeling and bregmatic eminence, and bone thickness is complex. In this context, the autapomorphic status of the two analysed traits in H. erectus may be rejected. Nevertheless, different patterns in the distribution of bone thickness on the upper vault were identified. Some individual variations are visible, but specificities are observable in samples of different species. The pattern of bone thickness distribution observed in Asian H. erectus, P. paniscus, possibly australopiths, and early Homo or Homo ergaster/erectus appears to be shared by these different species and would be a plesiomorphic trait among hominids. In contrast, two apomorphic states for this feature were identified for Neandertals and H. sapiens. Copyright © 2013 Elsevier Ltd. All rights reserved.

Bone strength in pure bending: bearing of geometric and material properties.

PubMed

Winter, Werner

2008-01-01

Osteoporosis is characterized by decreasing of bone mass and bone strength with advanced age. For characterization of material properties of dense and cellular bone the volumetric bone mineral density (vBMD) is one of the most important contributing factors to bone strength. Often bending tests of whole bone are used to get information about the state of osteoporosis. In a first step, different types of cellular structures are considered to characterize vBMD and its influence to elastic and plastic material properties. Afterwards, the classical theory of plastic bending is used to describe the non-linear moment-curvature relation of a whole bone. For bending of whole bone with sandwich structure an effective second moment of area can be defined. The shape factor as a pure geometrical value is considered to define bone strength. This factor is discussed for a bone with circular cross section and different thickness of cortical bone. The deduced relations and the decrease of material properties are used to demonstrate the influence of osteoporosis to bone bending strength. It can be shown that the elastic and plastic material properties of bone are related to a relative bone mineral density. Starting from an elastic-plastic bone behavior with an constant yield stress the non-linear moment-curvature relation in bending is related to yielding of the fibres in the cross section. The ultimate moment is characterized by a shape factor depending on the geometry of the cross section and on the change of cortical thickness.

A Spontaneous 3D Bone-On-a-Chip for Bone Metastasis Study of Breast Cancer Cells.

PubMed

Hao, Sijie; Ha, Laura; Cheng, Gong; Wan, Yuan; Xia, Yiqiu; Sosnoski, Donna M; Mastro, Andrea M; Zheng, Si-Yang

2018-03-01

Bone metastasis occurs at ≈70% frequency in metastatic breast cancer. The mechanisms used by tumors to hijack the skeleton, promote bone metastases, and confer therapeutic resistance are poorly understood. This has led to the development of various bone models to investigate the interactions between cancer cells and host bone marrow cells and related physiological changes. However, it is challenging to perform bone studies due to the difficulty in periodic sampling. Herein, a bone-on-a-chip (BC) is reported for spontaneous growth of a 3D, mineralized, collagenous bone tissue. Mature osteoblastic tissue of up to 85 µm thickness containing heavily mineralized collagen fibers naturally formed in 720 h without the aid of differentiation agents. Moreover, co-culture of metastatic breast cancer cells is examined with osteoblastic tissues. The new bone-on-a-chip design not only increases experimental throughput by miniaturization, but also maximizes the chances of cancer cell interaction with bone matrix of a concentrated surface area and facilitates easy, frequent observation. As a result, unique hallmarks of breast cancer bone colonization, previously confirmed only in vivo, are observed. The spontaneous 3D BC keeps the promise as a physiologically relevant model for the in vitro study of breast cancer bone metastasis. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Visual detection of particulates in x-ray images of processed meat products

NASA Astrophysics Data System (ADS)

Schatzki, Thomas F.; Young, Richard; Haff, Ron P.; Eye, J.; Wright, G.

1996-08-01

A study was conducted to test the efficacy of detecting particulate contaminants in processed meat samples by visual observation of line-scanned x-ray images. Six hundred field- collected processed-product samples were scanned at 230 cm2/s using 0.5 X 0.5-mm resolution and 50 kV, 13 mA excitation. The x-ray images were image corrected, digitally stored, and inspected off-line, using interactive image enhancement. Forty percent of the samples were spiked with added contaminants to establish the visual recognition of contaminants as a function of sample thickness (1 to 10 cm), texture of the x-ray image (smooth/textured), spike composition (wood/bone/glass), size (0.1 to 0.4 cm), and shape (splinter/round). The results were analyzed using a maximum likelihood logistic regression method. In packages less than 6 cm thick, 0.2-cm-thick bone chips were easily recognized, 0.1-cm glass splinters were recognized with some difficulty, while 0.4-cm-thick wood was generally missed. Operational feasibility in a time-constrained setting was confirmed. One half percent of the samples arriving from the field contained bone slivers > 1 cm long, 1/2% contained metallic material, while 4% contained particulates exceeding 0.3 cm in size. All of the latter appeared to be bone fragments.

Rate of occurrence, gross appearance, and age relation of hyperostosis frontalis interna in females: a prospective autopsy study.

PubMed

Nikolić, Slobodan; Djonić, Danijela; Zivković, Vladimir; Babić, Dragan; Juković, Fehim; Djurić, Marija

2010-09-01

The aim of our study was to determine rate of occurrence and appearance of hyperostosis frontalis interna (HFI) in females and correlation of this phenomenon with ageing. The sample included 248 deceased females: 45 of them with different types of HFI, and 203 without HFI, average age 68.3 +/- 15.4 years (range, 19-93), and 58.2 +/- 20.2 years (range, 10-101), respectively. According to our results, the rate of HFI was 18.14%. The older the woman was, the higher the possibility of HFI occurring (Pearson correlation 0.211, N=248, P=0.001), but the type of HFI did not correlate with age (Pearson correlation 0.229, N=45, P=0.131). Frontal and temporal bone were significantly thicker in women with than in women without HFI (t= -10.490, DF=246, P=0.000, and t= -5.658, DF=246, P=0.000, respectively). These bones became thicker with ageing (Pearson correlation 0.178, N=248, P=0.005, and 0.303, N=248, P=0.000, respectively). The best predictors of HFI occurrence were respectively, frontal bone thickness, temporal bone thickness, and age(Wald. coeff.=35.487, P=0.000; Wald. coeff.=3.288, P=0.070, and Wald.coeff. =2.727, P =0.099). Diagnosis of HFI depends not only on frontal bone thickness, but also on waviness of internal plate of the frontal bone, as well as-the involvement of the inner bone surface.

Adaptations in the Microarchitecture and Load Distribution of Maternal Cortical and Trabecular Bone in Response to Multiple Reproductive Cycles in Rats

PubMed Central

de Bakker, Chantal M. J.; Altman-Singles, Allison R.; Li, Yihan; Tseng, Wei-Ju; Li, Connie; Liu, X. Sherry

2017-01-01

Pregnancy, lactation, and weaning result in dramatic changes in maternal calcium metabolism. In particular, the increased calcium demand during lactation causes a substantial degree of maternal bone loss. This reproductive bone loss has been suggested to be largely reversible, as multiple clinical studies have found that parity and lactation history have no adverse effect on post-menopausal fracture risk. However, the precise effects of pregnancy, lactation, and post-weaning recovery on maternal bone structure are not well understood. Our study aimed to address this question by longitudinally tracking changes in trabecular and cortical bone microarchitecture at the proximal tibia in rats throughout three cycles of pregnancy, lactation, and post-weaning using in vivo μCT. We found that the trabecular thickness underwent a reversible deterioration during pregnancy and lactation, which was fully recovered after weaning, while other parameters of trabecular microarchitecture (including trabecular number, spacing, connectivity density, and structure model index) underwent a more permanent deterioration which recovered minimally. Thus, pregnancy and lactation resulted in both transient and long-lasting alterations in trabecular microstructure. In the meantime, multiple reproductive cycles appeared to improve the robustness of cortical bone (resulting in an elevated cortical area and polar moment of inertia), as well as increase the proportion of the total load carried by the cortical bone at the proximal tibia. Taken together, changes in the cortical and trabecular compartments suggest that while rat tibial trabecular bone appears to be highly involved in maintaining calcium homeostasis during female reproduction, cortical bone adapts to increase its load-bearing capacity, allowing the overall mechanical function of the tibia to be maintained. PMID:28109138

Skeletal Response of Male Mice to Anabolic Hormone Therapy in the Absence of the Igfals Gene

PubMed Central

Kennedy, Oran D.; Sun, Hui; Wu, YingJie; Courtland, Hayden-William; Williams, Garry A.; Cardoso, Luis; Basta-Pljakic, Jelena; Schaffler, Mitchell B.

2014-01-01

IGF-I is a critical regulator of skeletal acquisition, which acts in endocrine and autocrine/paracrine modes. In serum, IGF-I is carried by the IGF-binding proteins in binary complexes. Further stabilization of these complexes is achieved by binding to the acid labile subunit (ALS) in a ternary complex (of IGF-I-IGF-binding protein 3/5-ALS). Ablation of the Igfals gene in humans (ALS deficiency) and mice (ALS knockout [ALSKO]) leads to markedly decreased serum IGF-I levels, growth retardation, and impaired skeletal acquisition. To investigate whether hormonal replacement therapy would improve the skeletal phenotype in cases of Igfals gene ablation, we treated male ALSKO mice with GH, IGF-I, or a combination of both. Treatments were administered to animals between 4 and 16 weeks of age or from 8 to 16 weeks of age. Although all treatment groups showed an increase (20%) in serum IGF-I levels, there was no increase in body weight, weight gain, or bone length in either age group. Despite the blunted linear growth in response to hormone therapy, ALSKO mice treated with GH showed radial bone growth, which contributed to bone strength tested by 4-point bending. We found that ALSKO mice treated with GH showed increased total cross-sectional area, cortical bone area, and cortical thickness by microtomography. Dynamic histomorphometry showed that although GH and double treatment groups resulted in trends towards increased bone formation parameters, these did not reach significance. However, bone resorption parameters were significantly increased in all treatment groups. ALSKO mice treated between 4 and 16 weeks of age showed minor differences in bone traits compared with vehicle-treated mice. In conclusion, treatment with GH and IGF-I do not work synergistically to rescue the stunted growth found in mice lacking the Igfals gene. Although GH alone appears to increase bone parameters slightly, it does not affect body weight or linear growth. PMID:24424061

Skeletal response of male mice to anabolic hormone therapy in the absence of the Igfals gene.

PubMed

Kennedy, Oran D; Sun, Hui; Wu, Yingjie; Courtland, Hayden-William; Williams, Garry A; Cardoso, Luis; Basta-Pljakic, Jelena; Schaffler, Mitchell B; Yakar, Shoshana

2014-03-01

IGF-I is a critical regulator of skeletal acquisition, which acts in endocrine and autocrine/paracrine modes. In serum, IGF-I is carried by the IGF-binding proteins in binary complexes. Further stabilization of these complexes is achieved by binding to the acid labile subunit (ALS) in a ternary complex (of IGF-I-IGF-binding protein 3/5-ALS). Ablation of the Igfals gene in humans (ALS deficiency) and mice (ALS knockout [ALSKO]) leads to markedly decreased serum IGF-I levels, growth retardation, and impaired skeletal acquisition. To investigate whether hormonal replacement therapy would improve the skeletal phenotype in cases of Igfals gene ablation, we treated male ALSKO mice with GH, IGF-I, or a combination of both. Treatments were administered to animals between 4 and 16 weeks of age or from 8 to 16 weeks of age. Although all treatment groups showed an increase (20%) in serum IGF-I levels, there was no increase in body weight, weight gain, or bone length in either age group. Despite the blunted linear growth in response to hormone therapy, ALSKO mice treated with GH showed radial bone growth, which contributed to bone strength tested by 4-point bending. We found that ALSKO mice treated with GH showed increased total cross-sectional area, cortical bone area, and cortical thickness by microtomography. Dynamic histomorphometry showed that although GH and double treatment groups resulted in trends towards increased bone formation parameters, these did not reach significance. However, bone resorption parameters were significantly increased in all treatment groups. ALSKO mice treated between 4 and 16 weeks of age showed minor differences in bone traits compared with vehicle-treated mice. In conclusion, treatment with GH and IGF-I do not work synergistically to rescue the stunted growth found in mice lacking the Igfals gene. Although GH alone appears to increase bone parameters slightly, it does not affect body weight or linear growth.

MRI based knee cartilage assessment

NASA Astrophysics Data System (ADS)

Kroon, Dirk-Jan; Kowalski, Przemyslaw; Tekieli, Wojciech; Reeuwijk, Els; Saris, Daniel; Slump, Cornelis H.

2012-03-01

Osteoarthritis is one of the leading causes of pain and disability worldwide and a major health problem in developed countries due to the gradually aging population. Though the symptoms are easily recognized and described by a patient, it is difficult to assess the level of damage or loss of articular cartilage quantitatively. We present a novel method for fully automated knee cartilage thickness measurement and subsequent assessment of the knee joint. First, the point correspondence between a pre-segmented training bone model is obtained with use of Shape Context based non-rigid surface registration. Then, a single Active Shape Model (ASM) is used to segment both Femur and Tibia bone. The surfaces obtained are processed to extract the Bone-Cartilage Interface (BCI) points, where the proper segmentation of cartilage begins. For this purpose, the cartilage ASM is trained with cartilage edge positions expressed in 1D coordinates at the normals in the BCI points. The whole cartilage model is then constructed from the segmentations obtained in the previous step. An absolute thickness of the segmented cartilage is measured and compared to the mean of all training datasets, giving as a result the relative thickness value. The resulting cartilage structure is visualized and related to the segmented bone. In this way the condition of the cartilage is assessed over the surface. The quality of bone and cartilage segmentation is validated and the Dice's coefficients 0.92 and 0.86 for Femur and Tibia bones and 0.45 and 0.34 for respective cartilages are obtained. The clinical diagnostic relevance of the obtained thickness mapping is being evaluated retrospectively. We hope to validate it prospectively for prediction of clinical outcome the methods require improvements in accuracy and robustness.

Evidence for reduced cancellous bone mass in the spontaneously hypertensive rat

NASA Technical Reports Server (NTRS)

Wang, T. M.; Hsu, J. F.; Jee, W. S.; Matthews, J. L.

1993-01-01

The histomorphometric changes in the proximal tibial metaphysis and epiphyseal growth plate and midtibial shaft of 26-week-old spontaneously hypertensive rats (SHR) compared with those of the corresponding normotensive Wistar-Kyoto (WKY) rats were studied. A decrease in body weight, growth plate thickness, and longitudinal growth rate of the proximal tibial epiphysis, trabecular bone volume, trabecular thickness and number, the number of osteoblasts and osteoprogenitor cells per millimeter square surface of the proximal tibial metaphysis, periosteal and endocortical apposition rate and bone formation rate of the tibial diaphysis were observed in the SHR. Additionally, systolic blood pressure, the number of osteoclasts per millimeter square surface and average number of nuclei per osteoclast of the proximal tibial metaphysis were significantly increased. Thus, osteoclastic activity is dominant over osteoblastic and chondroblastic activity in the SHR that results in a cancellous bone deficit in the skeleton. It will require additional work to ascertain the underlying cause for this condition as several factors in the SHR with a potential for causing this change are present, including elevated parathyroid hormone (PTH), depressed 1,25-(OH)2D3, low calcium absorption, reduced body weight (reduced loading) elevated blood pressure and possibly other direct cell differences in the mutant strain. At present elevated PTH and adaptation to underloading from reduced weight are postulated to be a likely cause, but additional studies are required to test this interpretation.

Immediate implant placement: the fate of the buccal crest. A retrospective cone beam computed tomography study.

PubMed

Groenendijk, E; Staas, T A; Graauwmans, F E J; Bronkhorst, E; Verhamme, L; Maal, T; Meijer, G J

2017-12-01

This retrospective study aimed to analyse the fate of the buccal crest after immediate implant placement (IIP) through the use of cone beam computed tomography (CBCT). In 16 consecutive patients, an implant was placed in a more palatal position after extraction, thereby creating a gap of at least 2mm between the implant and the buccal crest. Subsequently, this gap was filled with a bone substitute. Preoperatively, immediate postoperatively, and late postoperatively, a CBCT was made to measure the thickness of the buccal crest. After application of the bone substitute, the buccal crest increased in thickness from 0.9mm to 2.4mm (mean). At a mean of 103 weeks after IIP, late postoperative CBCT scans showed that the thickness of the buccal crest was compacted to 1.8mm. In the same period, the height of the buccal crest increased by 1.6mm (mean) to, on average, 1.2mm above the implant shoulder. The aesthetic outcome was analysed using the White and Pink Esthetic Score (WES and PES). Both scored high: 8.4 and 11.8, respectively. Within the limitations of this study, the results of this IIP protocol are promising. Long-term prospective research on this topic on a large number of patients is necessary. Copyright © 2017 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

A comparative study of the bone metabolic response to dried plum supplementation and PTH treatment in adult, osteopenic ovariectomized rat.

PubMed

Smith, Brenda J; Bu, So Young; Wang, Yan; Rendina, Elizabeth; Lim, Yin F; Marlow, Denver; Clarke, Stephen L; Cullen, Diane M; Lucas, Edralin A

2014-01-01

Dried plum has been reported to have potent effects on bone in osteopenic animal models, but the mechanisms through which bone metabolism is altered in vivo remain unclear. To address this issue, a study comparing the metabolic response of dried plum to the anabolic agent, parathyroid hormone (PTH), was undertaken. Six month-old female Sprague Dawley rats (n=84) were sham-operated (SHAM) or ovariectomized (OVX) and maintained on a control diet for 6wks until osteopenia was confirmed. Treatments were initiated consisting of a control diet (AIN-93M) supplemented with dried plum (0, 5, 15 or 25%; w/w) or a positive control group receiving PTH. At the end of 6wks of treatment, whole body and femoral bone mineral density (BMD) were restored by the two higher doses of dried plum to the level of the SHAM group. Trabecular bone volume and cortical thickness were also improved with these two doses of dried plum. Dried plum suppressed the OVX-induced increase in bone turnover as indicated by systemic biomarkers of bone metabolism, N-terminal procollagen type 1 (P1NP) and deoxypyridinoline (DPD). Dynamic bone histomorphometric analysis of the tibial metaphysis revealed that dried plum restored the OVX-induced increase in cancellous bone formation rate (BFR) and mineralizing surface (MS/BS) to the SHAM group, but some doses of dried plum increased endocortical mineral apposition rate (MAR). As expected, PTH significantly increased endocortical MAR and BFR, periosteal BFR, and trabecular MAR and BFR beyond that of the OVX and maintained the accelerated rate of bone resorption associated with OVX. Dried plum up-regulated bone morphogenetic protein 4 (Bmp4) and insulin-like growth factor 1 (Igf1) while down-regulating nuclear factor T cell activator 1 (Nfatc1). These findings demonstrate that in the adult osteopenic OVX animal, the effects of dried plum differ from that of PTH in that dried plum primarily suppressed bone turnover with the exception of the indices of bone formation at the endocortical surface. © 2013.

Prostaglandin E2 Adds Bone to a Cancellous Bone Site with a Closed Growth Plate and Low Bone Turnover in Ovariectomized Rats

NASA Technical Reports Server (NTRS)

Ma, Y. F.; Ke, H. Z.; Jee, W. S. S.

1994-01-01

The objects of this study were to determine the responses of a cancellous bone site with a closed growth plate (the distal tibial metaphysis, DTM) to ovariectomy (OVX) and OVX plus a prostaglandin E2 (PGE2) treatment, and compare the site's response to previous findings reported for another site (the proximal tibial metaphysis, PTM). Thirty-five 3-month old female Sprague-Dawley rats were divided into five groups: basal, sham-OVX, and OVX+0, +1, or +6 mg PGE2/kg/d injected subcutaneously for 3 months and given double fluorescent labels before sacrifice. Cancellous bone histomorphometric analyses were performed on 20-micron-thick undecalcified DTM sections. Similar to the PTM, the DTM showed age-related decreases in bone formation and increases in bone resorption, but it differed in that at 3 months post-OVX; there was neither bone loss nor changes in formation endpoints. Giving 1 mg PGE2/kg/d to OVX rats prevented most age-related changes and maintained the bone formation histomorphometry near basal levels. Treating OVX rats with 6 mg PGE2/kg/d prevented age-related bone changes, added extra bone, and improved microanatomical structure by stimulating bone formation without altering bone resorption. Furthermore, after PGE2 administration, the DTM, a cancellous bone site with a closed growth plate, inereased bone formation more than did the cancellous bone in the PTM.

Combined effects of chronic alcohol consumption and physical activity on bone health: study in a rat model.

PubMed

Maurel, Delphine B; Boisseau, Nathalie; Ingrand, Isabelle; Dolleans, Eric; Benhamou, Claude-Laurent; Jaffre, Christelle

2011-12-01

Chronic alcohol consumption may be deleterious for bone tissue depending on the amount of ethanol consumed, whereas physical activity has positive effects on bone. This study was designed to analyze the effects of moderate alcohol consumption on bone in trained rats. 48 male Wistar rats were divided into four groups: control (C), alcohol (A), exercise (E) and alcohol + exercise (AE). A and AE groups drank a solution composed of water and ethanol. E and AE groups were trained for 2 months (treadmill: 40 min/day, 5 times/week). Body composition and bone mineral density (BMD) were assessed by dual X-ray absorptiometry and microarchitectural parameters using micro-computed tomography. Serum osteocalcin and CTx were determined by ELISA assays. The body weight and lean mass gain were lower in group A, while the fat mass gain was lower in exercised groups. BMD and BMC were higher with alcohol after body weight adjustment. Trabecular thickness was significantly higher in AE and A groups compared to C and E; cross-sectional area was larger in A and C groups compared to AE and E. CTx levels were higher in A compared to C and in AE and E versus C and A. Osteocalcin levels were significantly greater in AE and E groups versus C and A. In conclusion, the light to moderate alcohol consumption over a short period increased the trabecular thickness, BMC and BMD in A and AE groups. However, we observed alterations in bone remodeling and body composition with alcohol, at the end of the protocol, which did not appear when alcohol was combined to exercise.

Dynamic acoustic radiation force retains bone structural and mechanical integrity in a functional disuse osteopenia model.

PubMed

Uddin, Sardar M Z; Qin, Yi-Xian

2015-06-01

Disuse osteopenia and bone loss have been extensively reported in long duration space mission and long term bed rest. The pathology of the bone loss is similar to osteoporosis but highly confined to weight bearing bones. The current anabolic and/or anti-resorptive drugs have systemic effects and are costly over extended time, with concerns of long term fracture risk. This study use Low Intensity Pulsed Ultrasound (LIPUS) as a non-invasive acoustic force and anabolic stimulus to countermeasure disuse induced bone loss. Four-month old C57BL/6 mice were randomized into five groups, 1) age-matched (AM), 2) non-suspended sham (NS), 3) non-suspended-LIPUS (NU), 4) suspended sham (SS), and 5) suspended-LIPUS (SU) groups. After four weeks of suspension, μCT analyses showed significant decreases in trabecular bone volume fraction (BV/TV) (-36%, p<0.005), bone tissue mineral density (TMD) (-3%, p<0.05), trabecular thickness (Tb.Th) (-12.5%, p<0.005), and increase in bone surface/bone volume (+BS/BV) (+16%, p<0.005), relative to age-matched (AM). The application of LIPUS for 20 min/day for 5 days/week, significantly increased TMD (+3%, p<0.05), Tb.Th (+6%, p<0.05), and decreased BS/BV (-10%, p<0.005), relative to suspension alone (SS) mice. Histomorphometry analyses showed a breakdown of bone microstructure under disuse conditions consist with μCT results. In comparison to SS mice, LIPUS treated bone showed increased structural integrity with increased bone formation rates at metaphysical endosteal and trabecular surfaces (+0.104±0.07 vs 0.031±0.30 μm(3)/μm(2)/day) relative to SS. Four-point bending mechanical tests of disused SS femurs showed reduced elastic modulus (-53%, p<0.05), yield (-33%, p<0.05) and ultimate strength (-45%, p<0.05) at the femoral diaphysis relative to AM bone. LIPUS stimulation mitigated the adverse effects of disuse on bone elastic modulus (+42%, p<0.05), yield strength (+29%, p<0.05), and ultimate strength (+39%, p<0.05) relative to SS femurs. LIPUS provides the essential mechanical stimulus to retain bone morphological and mechanical integrity in disuse conditions. This study demonstrates LIPUS potential as regional therapeutic agent to countermeasure disuse induced bone loss while maintaining bone's integrity. Copyright © 2015 Elsevier Inc. All rights reserved.

Histomorphometric reference data of transiliac bone biopsy in children from 8 to 17 years old.

PubMed

Velásquez-Forero, Francisco H; Jiménez-Brau, Daniel A; Esparza-García, Mariela

2018-01-01

Histomorphometric analysis of bone samples is a key tool for studying bone metabolism; however, only a few pediatric reference data exist. The aim of the present study is to report more reference data and to investigate if histomorphometric differences exist between age and gender. We obtained 19 transiliac bone samples previously marked with tetracycline, from children between 8 and 17 years (13 were male), with normal blood test results and urine biochemical bone markers. We evaluated bone histomorphometric parameters using a digitalizing table with osteomeasure to obtain normative data of means and standard deviations, as well as median and range. Due to the small sample, a Monte Carlo simulation was applied. Structural, static, dynamic, and resorptic histomorphometric parameters were evaluated by age and gender following the American Society for Bone and Mineral Research recommendations. Bone volume (in the older children) and mineral apposition rate (in the younger children), the eroded surface (in boys), and the new bone wall thickness (in girls) were significantly increased. On the trabecular area of mineralization front, the modeling and the remodeling bone formation were similar (16 and 18%). The rest of the histomorphometric bone parameters by age and gender showed no significant difference. In healthy children, these bone histomorphometric findings, with these techniques and for this ages could be used as reference values. Copyright: © 2018 Permanyer.

Histomorphometric study of tibia of rats exposed aboard American Spacelab Life Sciences 2 Shuttle Mission

NASA Technical Reports Server (NTRS)

Durnova, G.; Kaplansky, A.; Morey-Holton, E.

1996-01-01

Tibial bones of rats flown onboard the SLS-2 shuttle mission were studied. Trabecular bone parameters were investigated, including growth plate height, trabecular bone volume, thickness and number, and trabecular separation in the primary and secondary spongiosa. Several histomorphometric changes were noted, allowing researchers to conclude that exposure to microgravity resulted in osteopenia of spongy bone of tibial metaphysis. The roles of bone formation and bone resorption are discussed.

Chitosan nanofiber scaffold improves bone healing via stimulating trabecular bone production due to upregulation of the Runx2/osteocalcin/alkaline phosphatase signaling pathway

PubMed Central

Ho, Ming-Hua; Yao, Chih-Jung; Liao, Mei-Hsiu; Lin, Pei-I; Liu, Shing-Hwa; Chen, Ruei-Ming

2015-01-01

Osteoblasts play critical roles in bone formation. Our previous study showed that chitosan nanofibers can stimulate osteoblast proliferation and maturation. This translational study used an animal model of bone defects to evaluate the effects of chitosan nanofiber scaffolds on bone healing and the possible mechanisms. In this study, we produced uniform chitosan nanofibers with fiber diameters of approximately 200 nm. A bone defect was surgically created in the proximal femurs of male C57LB/6 mice, and then the left femur was implanted with chitosan nanofiber scaffolds for 21 days and compared with the right femur, which served as a control. Histological analyses revealed that implantation of chitosan nanofiber scaffolds did not lead to hepatotoxicity or nephrotoxicity. Instead, imaging analyses by X-ray transmission and microcomputed tomography showed that implantation of chitosan nanofiber scaffolds improved bone healing compared with the control group. In parallel, microcomputed tomography and bone histomorphometric assays further demonstrated augmentation of the production of new trabecular bone in the chitosan nanofiber-treated group. Furthermore, implantation of chitosan nanofiber scaffolds led to a significant increase in the trabecular bone thickness but a reduction in the trabecular parameter factor. As to the mechanisms, analysis by confocal microscopy showed that implantation of chitosan nanofiber scaffolds increased levels of Runt-related transcription factor 2 (Runx2), a key transcription factor that regulates osteogenesis, in the bone defect sites. Successively, amounts of alkaline phosphatase and osteocalcin, two typical biomarkers that can simulate bone maturation, were augmented following implantation of chitosan nanofiber scaffolds. Taken together, this translational study showed a beneficial effect of chitosan nanofiber scaffolds on bone healing through stimulating trabecular bone production due to upregulation of Runx2-mediated alkaline phosphatase and osteocalcin gene expressions. Our results suggest the potential of chitosan nanofiber scaffolds for therapy of bone diseases, including bone defects and bone fractures. PMID:26451104

Transgenic Expression of Dspp Partially Rescued the Long Bone Defects of Dmp1-null Mice

PubMed Central

Jani, Priyam H.; Gibson, Monica P.; Liu, Chao; Zhang, Hua; Wang, Xiaofang; Lu, Yongbo; Qin, Chunlin

2016-01-01

Dentin matrix protein 1 (DMP1) and dentin sialophosphoprotein (DSPP) belong to the Small Integrin-Binding Ligand N-linked Glycoprotein (SIBLING) family. In addition to the features common to all SIBLING members, DMP1 and DSPP share several unique similarities in chemical structure, proteolytic activation and tissue localization. Mutations in, or deletion of DMP1, cause autosomal recessive hypophosphatemic rickets along with dental defects; DSPP mutations or its ablation are associated with dentinogenesis imperfecta. While the roles and functional mechanisms of DMP1 in osteogenesis have been extensively studied, those of DSPP in long bones have been studied only to a limited extent. Previous studies by our group revealed that transgenic expression of Dspp completely rescued the dentin defects of Dmp1-null (Dmp1−/−) mice. In this investigation, we assessed the effects of transgenic Dspp on osteogenesis by analyzing the formation and mineralization of the long bones in Dmp1−/− mice that expresses a transgene encoding full-length DSPP driven by a 3.6-kb rat Col1a1 promoter (referred as “Dmp1−/−;Dspp-Tg mice”). We characterized the long bones of the Dmp1−/−;Dspp-Tg mice at different ages and compared them with those from Dmp1−/− and Dmp1+/− (normal control) mice. Our analyses showed that the long bones of Dmp1−/−;Dspp-Tg mice had a significant increase in cortical bone thickness, bone volume and mineral density along with a remarkable restoration of trabecular thickness compared to those of the Dmp1−/− mice. The long bones of Dmp1−/−;Dspp-Tg mice underwent a dramatic reduction in the amount of osteoid, significant improvement of the collagen fibrillar network, and better organization of the lacunocanalicular system, compared to the Dmp1−/− mice. The elevated levels of biglycan, bone sialoprotein and osteopontin in Dmp1−/− mice were also noticeably corrected by the transgenic expression of Dspp. These findings suggest that DSPP and DMP1 may function synergistically within the complex milieus of bone matrices. PMID:26686820

Thermal isotherms in PMMA and cell necrosis during total hip arthroplasty.

PubMed

Gundapaneni, Dinesh; Goswami, Tarun

2014-12-30

Polymethylmethacrylate (PMMA), also known as bone cement, is a commonly used adhesive material to fix implants in Total Hip Arthroplasty (THA). During implantation, bone cement undergoes a polymerization reaction which is an exothermic reaction and results in the release of heat to the surrounding bone tissue, which ultimately leads to thermal necrosis. Necrosis in the bony tissue results in early loosening of the implant, which causes pain and reduces the life of the implant. The main objective of the present study was to understand the thermal isotherms in PMMA and to determine the optimal cement mantle thickness to prevent cell necrosis during THA. In this study, the environment in the bony tissue during implantation was simulated by constructing 3D solid models to observe the temperature distribution in the bony tissue at different cement mantle thicknesses (1 mm, 3 mm and 5 mm), by applying the temperature conditions that exist during the surgery. Stems made with Co-Cr-Mo, 316L stainless steel and Ti6Al4V were used, which acted as heat sinks, and a thermal damage equation was used to measure the bone damage. FEA was conducted based on temperature conditions and thermal isotherms at different cement mantle thicknesses were obtained. Thermal isotherms derived with respect to distance in the bony tissue from the center of the cement mantle, and cell necrosis was determined at different mantle thicknesses. Based on the deduced results, cement mantle thickness of 1-5 mm does not cause thermal damage in the bony tissue. Considering the long term stability of the implant, cement mantle thickness range from 3 mm-5 mm was found to be optimal in THA to prevent cell necrosis.

Bone characteristics of late-term embryonic and hatchling broilers: bone development under extreme growth rate.

PubMed

Yair, R; Uni, Z; Shahar, R

2012-10-01

The development of broilers is an extreme example of rapid growth, increasing in weight from 40 g at hatch to 2,000 g 5 to 6 wk later. Such rapid growth requires a correspondingly fast development of the skeleton. Bone development is a genetically programmed process that is modified by epigenetic factors, mainly muscle-induced stresses and strains. In this study, we describe the temporal changes in bone morphology and material properties during the prehatch period [embryonic day (E) 14, E17, E19, E21] and posthatch d 3 and 7. The bones were examined for their weight, length, ash content, mechanical properties, and cortical structure. We show that the cross-sectional shape of the tibia and femur changes during the examination period from circular to elliptical. Additionally, the changes in bone properties are time-dependent and nonuniform: from E14 to E17 and from d 3 to 7, fast bone growth was noted, with major increases in both mechanical properties (stiffness, ultimate load, and energy to fracture) and geometric properties (cross-sectional area and thickness, medullary area, and moment of inertia). On the other hand, during the last days of incubation, most mechanical and geometric properties remain unchanged or even decrease. The reasons for this finding may relate to the hatching process but also to mineral shortage during the last days of incubation. This study leads to better understanding of bone development in ovo and posthatch in fast-growing broilers.

Micro-finite element analysis applied to high-resolution MRI reveals improved bone mechanical competence in the distal femur of female pre-professional dancers

PubMed Central

Rajapakse, C. S.; Diamond, M.; Honig, S.; Recht, M. P.; Weiss, D. S.; Regatte, R. R.

2013-01-01

Summary Micro-finite element analysis applied to high-resolution (0.234-mm length scale) MRI reveals greater whole and cancellous bone stiffness, but not greater cortical bone stiffness, in the distal femur of female dancers compared to controls. Greater whole bone stiffness appears to be mediated by cancellous, rather than cortical bone adaptation. Introduction The purpose of this study was to compare bone mechanical competence (stiffness) in the distal femur of female dancers compared to healthy, relatively inactive female controls. Methods This study had institutional review board approval. We recruited nine female modern dancers (25.7± 5.8 years, 1.63±0.06 m, 57.1±4.6 kg) and ten relatively inactive, healthy female controls matched for age, height, and weight (32.1±4.8 years, 1.6±0.04 m, 55.8±5.9 kg). We scanned the distal femur using a 7-T MRI scanner and a three-dimensional fast low-angle shot sequence (TR/TE= 31 ms/5.1 ms, 0.234 mm×0.234 mm×1 mm, 80 slices). We applied micro-finite element analysis to 10-mm-thick volumes of interest at the distal femoral diaphysis, metaphysis, and epiphysis to compute stiffness and cross-sectional area of whole, cortical, and cancellous bone, as well as cortical thickness. We applied two-tailed t-tests and ANCOVA to compare groups. Results Dancers demonstrated greater whole and cancellous bone stiffness and cross-sectional area at all locations (p< 0.05). Cortical bone stiffness, cross-sectional area, and thickness did not differ between groups (>0.08). At all locations, the percent of intact whole bone stiffness for cortical bone alone was lower in dancers (p<0.05). Adjustment for cancellous bone cross-sectional area eliminated significant differences in whole bone stiffness between groups (p>0.07), but adjustment for cortical bone cross-sectional area did not (p<0.03). Conclusions Modern dancers have greater whole and cancellous bone stiffness in the distal femur compared to controls. Elevated whole bone stiffness in dancers may be mediated via cancellous, rather than cortical bone adaptation. PMID:22893356

Fabrication of polycaprolactone-silanated β-tricalcium phosphate-heparan sulfate scaffolds for spinal fusion applications.

PubMed

Bhakta, Gajadhar; Ekaputra, Andrew K; Rai, Bina; Abbah, Sunny A; Tan, Tuan Chun; Le, Bach Quang; Chatterjea, Anindita; Hu, Tao; Lin, Tingxuan; Arafat, M Tarik; van Wijnen, Andre J; Goh, James; Nurcombe, Victor; Bhakoo, Kishore; Birch, William; Xu, Li; Gibson, Ian; Wong, Hee-Kit; Cool, Simon M

2018-05-01

Interbody spinal fusion relies on the use of external fixation and the placement of a fusion cage filled with graft materials (scaffolds) without regard for their mechanical performance. Stability at the fusion site is instead reliant on fixation hardware combined with a selected cage. Ideally, scaffolds placed into the cage should both support the formation of new bone and contribute to the mechanical stability at the fusion site. We recently developed a scaffold consisting of silane-modified PCL-TCP (PCL-siTCP) with mechanical properties that can withstand the higher loads generated in the spine. To ensure the scaffold more closely mimicked the bone matrix, we incorporated collagen (Col) and a heparan sulfate glycosaminoglycan sugar (HS3) with increased affinity for heparin-binding proteins such as bone morphogenetic protein-2 (BMP-2). The osteostimulatory characteristic of this novel device delivering exogenous BMP2 was assessed in vitro and in vivo as a prelude to future spinal fusion studies with this device. A combination of cell-free assays (BMP2 release), progenitor cell-based assays (BMP2 bioactivity, cell proliferation and differentiation), and rodent ectopic bone formation assays was used to assess the osteostimulatory characteristics of the PCL-siTCP-based scaffolds. Freshly prepared rat mesenchymal stem cells were used to determine reparative cell proliferation and differentiation on the PCL-siTCP-based scaffolds over a 28-day period in vitro. The bioactivity of BMP2 released from the scaffolds was assessed on progenitor cells over a 28-day period using ALP activity assays and release kinetics as determined by enzyme-linked immunosorbent assay. For ectopic bone formation, intramuscular placement of scaffolds into Sprague Dawley rats (female, 4 weeks old, 120-150 g) was achieved in five animals, each receiving four treatments randomized for location along the limb. The four groups tested were (1) PCL-siTCP/Col (5-mm diameter×1-mm thickness), PCL-siTCP/Col/BMP2 (5 µg), (3) PCL-siTCP/Col/HS3 (25 µg), and (4) PCL-siTCP/Col/HS3/BMP2 (25 and 5 µg, respectively). Bone formation was evaluated at 8 weeks post implantation by microcomputed tomography (µCT) and histology. Progenitor cell-based assays (proliferation, mRNA transcripts, and ALP activity) confirmed that BMP2 released from PCL-siTCP/Col/HS3 scaffolds increased ALP expression and mRNA levels of the osteogenic biomarkers Runx2, Col1a2, ALP, and bone gla protein-osteocalcin compared with devices without HS3. When the PCL-siTCP/Col/HS3/BMP2 scaffolds were implanted into rat hamstring muscle, increased bone formation (as determined by two-dimensional and three-dimensional µCTs and histologic analyses) was observed compared with scaffolds lacking BMP2. More consistent increases in the amount of ectopic bone were observed for the PCL-siTCP/Col/HS3/BMP2 implants compared with PCL-siTCP/Col/BMP2. Also, increased mineralizing tissue within the pores of the scaffold was seen with modified-tetrachrome histology, a result confirmed by µCT, and a modest but detectable increase in both the number and the thickness of ectopic bone structures were observed with the PCL-siTCP/Col/HS3/BMP2 implants. The combination of PCL-siTCP/Col/HS3/BMP2 thus represents a promising avenue for further development as a bone graft alternative for spinal fusion surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

Estrogens and women's health: interrelation of coronary heart disease, breast cancer and osteoporosis.

PubMed

Kuller, L H; Matthews, K A; Meilahn, E N

2000-11-30

The determinants of blood levels of estrogen, estrogen metabolites, and relation to receptors and post-transitional effects are the likely primary cause of breast cancer. Very high risk women for breast cancer can now be identified by measuring bone mineral density and hormone levels. These high risk women have rates of breast cancer similar to risk of myocardial infarction. They are candidates for SERM therapies to reduce risk of breast cancer. The completion of the Women's Health Initiative and other such trials will likely provide a definite association of risk and benefit of both estrogen alone and estrogen-progesterone therapy, coronary heart disease, osteoporotic fracture, and breast cancer. The potential intervention of hormone replacement therapy, obesity, or weight gain and increased atherogenic lipoproteinemia may be of concern and confound the results of clinical trials. Estrogens, clearly, are important in the risk of bone loss and osteoporotic fracture. Obesity is the primary determinant of postmenopausal estrogen levels and reduced risk of fracture. Weight reduction may increase rates of bone loss and fracture. Clinical trials that evaluate weight loss should monitor effects on bone. The beneficial addition of increased physical activity, higher dose of calcium or vitamin D, or use of bone reabsorption drugs in coordination with weight loss should be evaluated. Any therapy that raises blood estrogen or metabolite activity and decreases bone loss may increase risk of breast cancer. Future clinical trials must evaluate multiple endpoints such as CHD, osteoporosis, and breast cancer within the study. The use of surrogate markers such as bone mineral density, coronary calcium, carotid intimal medial thickness and plaque, endothelial function, breast density, hormone levels and metabolites could enhance the evaluation of risk factors, genetic-environmental intervention, and new therapies.

Quantifying the degradation of degradable implants and bone formation in the femoral condyle using micro-CT 3D reconstruction

PubMed Central

Xu, Yichi; Meng, Haoye; Yin, Heyong; Sun, Zhen; Peng, Jiang; Xu, Xiaolong; Guo, Quanyi; Xu, Wenjing; Yu, Xiaoming; Yuan, Zhiguo; Xiao, Bo; Wang, Cheng; Wang, Yu; Liu, Shuyun; Lu, Shibi; Wang, Zhaoxu; Wang, Aiyuan

2018-01-01

Degradation limits the application of magnesium alloys, and evaluation methods for non-traumatic in vivo quantification of implant degradation and bone formation are imperfect. In the present study, a micro-arc-oxidized AZ31 magnesium alloy was used to evaluate the degradation of implants and new bone formation in 60 male New Zealand white rabbits. Degradation was monitored by weighing the implants prior to and following implantation, and by performing micro-computed tomography (CT) scans and histological analysis after 1, 4, 12, 24, 36, and 48 weeks of implantation. The results indicated that the implants underwent slow degradation in the first 4 weeks, with negligible degradation in the first week, followed by significantly increased degradation during weeks 12–24 (P<0.05), and continued degradation until the end of the 48-week experimental period. The magnesium content decreased as the implant degraded (P<0.05); however, the density of the material exhibited almost no change. Micro-CT results also demonstrated that pin volume, pin mineral density, mean ‘pin thickness’, bone surface/bone volume and trabecular separation decreased over time (P<0.05), and that the pin surface area/pin volume, bone volume fraction, trabecular thickness, trabecular number and tissue mineral density increased over time (P<0.05), indicating that the number of bones and density of new bone increased as magnesium degraded. These results support the positive effect of magnesium on osteogenesis. However, from the maximum inner diameter of the new bone loop and diameter of the pin in the same position, the magnesium alloy was not capable of creating sufficient bridges between the bones and biomaterials when there were preexisting gaps. Histological analyses indicated that there were no inflammatory responses around the implants. The results of the present study indicate that a micro-arc-oxidized AZ31 magnesium alloy is safe in vivo and efficiently degraded. Furthermore, the novel bone formation increased as the implant degraded. The findings concluded that micro-CT, which is useful for providing non-traumatic, in vivo, quantitative and precise data, has great value for exploring the degradation of implants and novel bone formation. PMID:29375677

Effects of Artemisia Princeps Supplementation on Bone Metabolism in Ovariectomized Rats.

PubMed

Cho, H-J; Kim, J-W; Ju, S-Y; Park, Y-K

2016-01-01

The aim of this study was to investigate the effects of Artemisia princeps (AP) extract on bone metabolism and its potential role in the prevention of osteoporosis in ovariectomized rats. Twenty-six female Sprague-Dawley rats were divided into five groups and treated as follows: sham-operated control group (SHAM); ovariectomized control group (OVX), ovariectomized group treated by gavage with 10 mg/kg/day alendronate (ALEN); ovariectomized group treated by gavage with 100 mg/kg/day Artemisia princeps (AP100); ovariectomized group treated by gavage with 300 mg/kg/day Artemisia princeps (AP300). Treatment of ovariectomized rats with AP extracts for 15 weeks prevented the reduction in bone thickness and trabecular bone mineral density caused by urinary Ca and Cr excretion, and also prevented the increase in bone turnover by maintaining the serum Ca/P ratio. As a result, the microarchitecture of the trabecular bone and cortical bone after ovariectomy was markedly improved by administration of AP extracts. In conclusion, AP prevented bone loss and osteoclast activity associated with high bone turnover in ovariectomized rats by controlling the serum Ca/P ratio and through anti-inflammatory and anti-oxidant properties. Our data implicate AP as a promising therapeutic option for the improvement of postmenopausal osteoporosis.

Bisphosphonate effects in rat unloaded hindlimb bone loss model: three-dimensional microcomputed tomographic, histomorphometric, and densitometric analyses.

PubMed

Barou, O; Lafage-Proust, M H; Martel, C; Thomas, T; Tirode, F; Laroche, N; Barbier, A; Alexandre, C; Vico, L

1999-10-01

The effects of antiresorptive drugs on bone loss remain unclear. Using three-dimensional microtomography, dual X-ray/densitometry, and histomorphometry, we evaluated tiludronate effects in the bone loss model of immobilization in tail-suspended rats after 7, 13, and 23 days. Seventy-eight 12-week-old Wistar male rats were assigned to 13 groups: 1 baseline group, and for each time point, 1 control group treated with vehicle and three tail-suspended groups treated with either tiludronate (0.5 or 5 mg/kg) or vehicle, administered s. c. every other day, during the last week before sacrifice. In primary spongiosa (ISP), immobilization-induced bone loss plateaued after day 7 and was prevented by tiludronate. In secondary spongiosa (IISP), bone loss appeared at day 13 with a decrease in trabecular thickness and trabecular number (Tb.N) as assessed by three-dimensional microtomography. Osteoclastic parameters did not differ in tail-suspended rats versus control rats, whereas bone formation showed a biphasic pattern: after a marked decrease at day 7, osteoblastic activity and recruitment normalized at days 13 and 23, respectively. At day 23, the 80% decrease in bone mass was fully prevented by high-dose tiludronate with an increase in Tb.N without preventing trabecular thinning. In summary, at day 7, tiludronate prevented bone loss in ISP. After day 13, tiludronate prevented bone loss in ISP and IISP despite a further decrease in bone formation. Thus, the preventive effects of tiludronate in this model may be related to the alteration in bone modeling with an increase in Tb.N in ISP and subsequently in IISP.

Fructose Consumption Does Not Worsen Bone Deficits Resulting From High-Fat Feeding in Young Male Rats

PubMed Central

Yarrow, Joshua F.; Toklu, Hale Z.; Balaez, Alex; Phillips, Ean G.; Otzel, Dana M.; Chen, Cong; Wronski, Thomas J.; Aguirre, J. Ignacio; Sakarya, Yasemin; Tümer, Nihal; Scarpace, Philip J.

2016-01-01

Dietary-induced obesity (DIO) resulting from high-fat (HF) or high-sugar diets produces a host of deleterious metabolic consequences including adverse bone development. We compared the effects of feeding standard rodent chow (Control), a 30% moderately HF (starch-based/sugar-free) diet, or a combined 30%/40% HF/high-fructose (HF/F) diet for 12 weeks on cancellous/cortical bone development in male Sprague-Dawley rats aged 8 weeks. Both HF feeding regimens reduced the lean/fat mass ratio, elevated circulating leptin, and reduced serum total antioxidant capacity (tAOC) when compared with Controls. Distal femur cancellous bone mineral density (BMD) was 23–34% lower in both HF groups (p<0.001) and was characterized by lower cancellous bone volume (BV/TV, p<0.01), lower trabecular number (Tb.N, p<0.001), and increased trabecular separation versus Controls (p<0.001). Cancellous BMD, BV/TV, and Tb.N were negatively associated with leptin and positively associated with tAOC at the distal femur. Similar cancellous bone deficits were observed at the proximal tibia, along with increased bone marrow adipocyte density (p<0.05), which was negatively associated with BV/TV and Tb.N. HF/F animals also exhibited lower osteoblast surface and reduced circulating osteocalcin (p<0.05). Cortical thickness (p<0.01) and tissue mineral density (p<0.05) were higher in both HF-fed groups versus Controls, while whole bone biomechanical characteristics were not different among groups. These results demonstrate that “westernized” HF diets worsen cancellous, but not cortical, bone parameters in skeletally-immature male rats and that fructose incorporation into HF diets does not exacerbate bone loss. In addition, they suggest that leptin and/or oxidative stress may influence DIO-induced alterations in adolescent bone development. PMID:26855373

Fructose consumption does not worsen bone deficits resulting from high-fat feeding in young male rats.

PubMed

Yarrow, Joshua F; Toklu, Hale Z; Balaez, Alex; Phillips, Ean G; Otzel, Dana M; Chen, Cong; Wronski, Thomas J; Aguirre, J Ignacio; Sakarya, Yasemin; Tümer, Nihal; Scarpace, Philip J

2016-04-01

Dietary-induced obesity (DIO) resulting from high-fat (HF) or high-sugar diets produces a host of deleterious metabolic consequences including adverse bone development. We compared the effects of feeding standard rodent chow (Control), a 30% moderately HF (starch-based/sugar-free) diet, or a combined 30%/40% HF/high-fructose (HF/F) diet for 12weeks on cancellous/cortical bone development in male Sprague-Dawley rats aged 8weeks. Both HF feeding regimens reduced the lean/fat mass ratio, elevated circulating leptin, and reduced serum total antioxidant capacity (tAOC) when compared with Controls. Distal femur cancellous bone mineral density (BMD) was 23-34% lower in both HF groups (p<0.001) and was characterized by lower cancellous bone volume (BV/TV, p<0.01), lower trabecular number (Tb.N, p<0.001), and increased trabecular separation versus Controls (p<0.001). Cancellous BMD, BV/TV, and Tb.N were negatively associated with leptin and positively associated with tAOC at the distal femur. Similar cancellous bone deficits were observed at the proximal tibia, along with increased bone marrow adipocyte density (p<0.05), which was negatively associated with BV/TV and Tb.N. HF/F animals also exhibited lower osteoblast surface and reduced circulating osteocalcin (p<0.05). Cortical thickness (p<0.01) and tissue mineral density (p<0.05) were higher in both HF-fed groups versus Controls, while whole bone biomechanical characteristics were not different among groups. These results demonstrate that "westernized" HF diets worsen cancellous, but not cortical, bone parameters in skeletally-immature male rats and that fructose incorporation into HF diets does not exacerbate bone loss. In addition, they suggest that leptin and/or oxidative stress may influence DIO-induced alterations in adolescent bone development. Published by Elsevier Inc.

Peripubertal female athletes in high-impact sports show improved bone mass acquisition and bone geometry.

PubMed

Maïmoun, Laurent; Coste, Olivier; Philibert, Pascal; Briot, Karine; Mura, Thibault; Galtier, Florence; Mariano-Goulart, Denis; Paris, Françoise; Sultan, Charles

2013-08-01

Intensive physical training may have a sport-dependent effect on bone mass acquisition. This cross-sectional study evaluated bone mass acquisition in girls practicing sports that put different mechanical loads on bone. Eighty girls from 10.7 to 18.0 years old (mean 13.83 ± 1.97) were recruited: 20 artistic gymnasts (AG; high-impact activity), 20 rhythmic gymnasts (RG; medium-impact activity), 20 swimmers (SW, no-impact activity), and 20 age-matched controls (CON; leisure physical activity <3h/wk). Areal bone mineral density (aBMD) was determined using DEXA. Hip structural analysis applied at the femur evaluated cross-sectional area (CSA, cm(2)), section modulus (Z, cm(3)), and buckling ratio. Bone turnover markers and OPG/RANKL levels were analyzed. AG had higher aBMD than SW and CON at all bone sites and higher values than RG in the lumbar spine and radius. RG had higher aBMD than SW and CON only in the femoral region. CSA and mean cortical thickness were significantly higher and the buckling ratio was significantly lower in both gymnast groups compared with SW and CON. In RG only, endocortical diameter and width were reduced, while Z was only increased in AG compared with SW and CON. Reduced bone remodeling was observed in RG compared with AG only when groups were subdivided according to menarcheal status. All groups showed similar OPG concentrations, while RANKL concentrations increased with age and were decreased in SW. High-impact activity clearly had a favorable effect on aBMD and bone geometry during the growth period, although the bone health benefits seem to be more marked after menarche. Copyright © 2013 Elsevier Inc. All rights reserved.

Halofuginone attenuates osteoarthritis by inhibition of TGF-β activity and H-type vessel formation in subchondral bone

PubMed Central

Cui, Zhuang; Crane, Janet; Xie, Hui; Jin, Xin; Zhen, Gehua; Li, Changjun; Xie, Liang; Wang, Long; Bian, Qin; Qiu, Tao; Wan, Mei; Xie, Min; Ding, Sheng; Yu, Bin; Cao, Xu

2016-01-01

Objectives Examine whether osteoarthritis (OA) progression can be delayed by halofuginone in anterior cruciate ligament transection (ACLT) rodent models. Methods 3-month-old male C57BL/6J (wild type; WT) mice and Lewis rats were randomised to sham-operated, ACLT-operated, treated with vehicle, or ACLT-operated, treated with halofuginone. Articular cartilage degeneration was graded using the Osteoarthritis Research Society International (OARSI)-modified Mankin criteria. Immunostaining, flow cytometry, RT-PCR and western blot analyses were conducted to detect relative protein and RNA expression. Bone micro CT (μCT) and CT-based microangiography were quantitated to detect alterations of microarchitecture and vasculature in tibial subchondral bone. Results Halofuginone attenuated articular cartilage degeneration and subchondral bone deterioration, resulting in substantially lower OARSI scores. Specifically, we found that proteoglycan loss and calcification of articular cartilage were significantly decreased in halofuginone-treated ACLT rodents compared with vehicle-treated ACLT controls. Halofuginone reduced collagen X (Col X), matrix metalloproteinase-13 and A disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS 5) and increased lubricin, collagen II and aggrecan. In parallel, halofuginone-attenuated uncoupled subchondral bone remodelling as defined by reduced subchondral bone tissue volume, lower trabecular pattern factor (Tb.pf) and increased thickness of subchondral bone plate compared with vehicle-treated ACLT controls. We found that halofuginone exerted protective effects in part by suppressing Th17-induced osteoclastic bone resorption, inhibiting Smad2/3-dependent TGF-β signalling to restore coupled bone remodelling and attenuating excessive angiogenesis in subchondral bone. Conclusions Halofuginone attenuates OA progression by inhibition of subchondral bone TGF-β activity and aberrant angiogenesis as a potential preventive therapy for OA. PMID:26470720

SEM corrosion-casts study of the microcirculation of the flat bones in the rat.

PubMed

Pannarale, L; Morini, S; D'Ubaldo, E; Gaudio, E; Marinozzi, G

1997-04-01

Little is known about the organization of microcirculation in flat bones in comparison with long bones. This study, therefore, helps us to determine the design of this vascular system in flat bones in relation to their structure and function. The organization of microvasculature in parietal, scapula, and ileum bones of 15 young sexually mature rats, aged 6-7 weeks, was studied by light and scanning electron microscopy (SEM) from vascular corrosion cast (vcc), a resin-cast obtained material. Our observations show that the pattern of the microcirculation in flat bones is different in the thick and thin parts of such bones. Where the bone is thinner than 0.4 mm, only periosteal and dural network exist. Larger vessels which do not form a real network connect the two tables of the bones in these regions. In thicker areas, the organization of the microvasculature is similar to that in long bones, with distinct periosteal, cortical and bone marrow networks. Moreover, in different bones, outer networks show slightly different characteristics according to the different adjacent structures (dura mater, muscles etc.). Different types of vessels were recognized by comparing their different diameter, course and endothelial imprints. The microvascular patterns of the flat bones are strongly influenced by the bone thickness. The different microvascular systems can interact both with the bone modelling and remodeling and with the variable metabolic needs, modifying the microvascular pattern and the blood flow. This is even more important in view of the reciprocal influence of the different networks within the same bone.

The effect of operative fit and hydroxyapatite coating on the mechanical and biological response to porous implants.

PubMed

Dalton, J E; Cook, S D; Thomas, K A; Kay, J F

1995-01-01

Femoral intramedullary implants were constructed by threading 4.0-millimeter-thick disks with a titanium-alloy (Ti-6Al-4V) porous bead coating onto a two-millimeter-diameter threaded rod. Each porous-coated disk, which was 6.0, 8.0, 9.0, or 10.0 millimeters in diameter, was separated by a two-millimeter-thick acrylic disk with a diameter of ten millimeters. Implants with and without a hydroxyapatite coating of twenty-five micrometers were inserted into fifteen skeletally mature adult mongrel dogs. The femoral canal was sequentially reamed bilaterally to a ten-millimeter diameter, resulting in uniform initial implant-bone interface gaps of 0.0, 0.5, 1.0, and 2.0 millimeters. Each animal received paired hydroxyapatite-coated and uncoated implants. Three animals each were killed at four, eight, twelve, twenty-four, and fifty-two weeks after the implantation. The harvested femora were sectioned through the acrylic spacers, transverse to the long axis, to produce individual push-out test specimens for mechanical testing. Characteristics of interface attachment were determined with test fixtures that supported the surrounding bone to within 150 micrometers of the interface. Histological sections were prepared, and the amount of bone within the porous structure and the amount of the original gap that was filled with new bone were quantified with a computerized video image-analysis system. Mechanical attachment strength and bone ingrowth were found to increase with the time after implantation and with a decrease in the size of the gap. Placement of the implant in proximal (cancellous) compared with distal (cortical) locations had no significant effect on the strength of attachment, bone ingrowth, or gap-filling. However, implants with a large initial gap (1.0 or 2.0 millimeters) demonstrated greater attachment strength in cancellous bone than in cortical bone. With a few exceptions, hydroxyapatite-coated implants with an initial gap of 1.0 millimeter or less demonstrated significantly increased mechanical attachment strength and bone ingrowth at all time-periods. Interface attachment strengths were positively correlated with bone ingrowth, the time after implantation, the use of a hydroxyapatite coating, and decreasing initial gap size. Initial implant-bone apposition is thought to be a prerequisite for good biological fixation. This apposition is often not achieved because of the design of the implant or instruments and the operative technique. Poor initial fit during the operation may decrease the longevity of the implant. The results of the present study indicate that attachment strength and bone ingrowth are significantly affected by gaps in the interface, particularly those of more than 1.0 millimeter.(ABSTRACT TRUNCATED AT 400 WORDS)

Design and validation of a dynamic cell-culture system for bone biology research and exogenous tissue-engineering applications.

PubMed

Allori, Alexander C; Davidson, Edward H; Reformat, Derek D; Sailon, Alexander M; Freeman, James; Vaughan, Adam; Wootton, David; Clark, Elizabeth; Ricci, John L; Warren, Stephen M

2016-10-01

Bone lacunocanalicular fluid flow ensures chemotransportation and provides a mechanical stimulus to cells. Traditional static cell-culture methods are ill-suited to study the intricacies of bone biology because they ignore the three-dimensionality of meaningful cellular networks and the lacunocanalicular system; furthermore, reliance on diffusion alone for nutrient supply and waste product removal effectively limits scaffolds to 2-3 mm thickness. In this project, a flow-perfusion system was custom-designed to overcome these limitations: eight adaptable chambers housed cylindrical cell-seeded scaffolds measuring 12 or 24 mm in diameter and 1-10 mm in thickness. The porous scaffolds were manufactured using a three-dimensional (3D) periodic microprinting process and were composed of hydroxyapatite/tricalcium phosphate with variable thicknesses, strut sizes, pore sizes and structural configurations. A multi-channel peristaltic pump drew medium from parallel reservoirs and perfused it through each scaffold at a programmable rate. Hermetically sealed valves permitted sampling or replacement of medium. A gas-permeable membrane allowed for gas exchange. Tubing was selected to withstand continuous perfusion for > 2 months without leakage. Computational modelling was performed to assess the adequacy of oxygen supply and the range of fluid shear stress in the bioreactor-scaffold system, using 12 × 6 mm scaffolds, and these models suggested scaffold design modifications that improved oxygen delivery while enhancing physiological shear stress. This system may prove useful in studying complex 3D bone biology and in developing strategies for engineering thick 3D bone constructs. Copyright © 2013 John Wiley & Sons, Ltd. Copyright © 2013 John Wiley & Sons, Ltd.

Suppression of autophagy in osteocytes does not modify the adverse effects of glucocorticoids on cortical bone.

PubMed

Piemontese, Marilina; Onal, Melda; Xiong, Jinhu; Wang, Yiying; Almeida, Maria; Thostenson, Jeff D; Weinstein, Robert S; Manolagas, Stavros C; O'Brien, Charles A

2015-06-01

Glucocorticoid excess decreases bone mass and strength in part by acting directly on osteoblasts and osteocytes, but the mechanisms remain unclear. Macroautophagy (herein referred to as autophagy) is a lysosome-based recycling pathway that promotes the turnover of intracellular components and can promote cell function and survival under stressful conditions. Recent studies have shown that glucocorticoids stimulate autophagy in osteocytes, suggesting that autophagy may oppose the negative actions of glucocorticoids on this cell type. To address this possibility, we compared the impact of prednisolone administration on the skeletons of adult mice in which autophagy was suppressed in osteocytes, via deletion of Atg7 with a Dmp1-Cre transgene, to their control littermates. In control mice, prednisolone increased autophagic flux in osteocyte-enriched bone as measured by LC3 conversion, but this change did not occur in the mice lacking Atg7 in osteocytes. Nonetheless, prednisolone reduced femoral cortical thickness, increased cortical porosity, and reduced bone strength to similar extents in mice with and without autophagy in osteocytes. Prednisolone also suppressed osteoblast number and bone formation in the cancellous bone of control mice. As shown previously, Atg7 deletion in osteocytes reduced osteoblast number and bone formation in cancellous bone, but these parameters were not further reduced by prednisolone administration. In cortical bone, prednisolone elevated osteoclast number to a similar extent in both genotypes. Taken together, these results demonstrate that although glucocorticoids stimulate autophagy in osteocytes, suppression of autophagy in this cell type does not worsen the negative impact of glucocorticoids on the skeleton. Published by Elsevier Inc.

Suppression of Autophagy in Osteocytes Does Not Modify the Adverse Effects of Glucocorticoids on Cortical Bone

PubMed Central

Piemontese, Marilina; Onal, Melda; Xiong, Jinhu; Wang, Yiying; Almeida, Maria; Thostenson, Jeff D.; Weinstein, Robert S.; Manolagas, Stavros C.; O’Brien, Charles A.

2015-01-01

Glucocorticoid excess decreases bone mass and strength in part by acting directly on osteoblasts and osteocytes, but the mechanisms remain unclear. Macroautophagy (herein referred to as autophagy) is a lysosome-based recycling pathway that promotes the turnover of intracellular components and can promote cell function and survival under stressful conditions. Recent studies have shown that glucocorticoids stimulate autophagy in osteocytes, suggesting that autophagy may oppose the negative actions of glucocorticoids on this cell type. To address this possibility, we compared the impact of prednisolone administration on the skeletons of adult mice in which autophagy was suppressed in osteocytes, via deletion of Atg7 with a Dmp1-Cre transgene, to their control littermates. In control mice, prednisolone increased autophagic flux in osteocyte-enriched bone as measured by LC3 conversion, but this change did not occur in the mice lacking Atg7 in osteocytes. Nonetheless, prednisolone reduced femoral cortical thickness, increased cortical porosity, and reduced bone strength to similar extents in mice with and without autophagy in osteocytes. Prednisolone also suppressed osteoblast number and bone formation in the cancellous bone of control mice. As shown previously, Atg7 deletion in osteocytes reduced osteoblast number and bone formation in cancellous bone, but these parameters were not further reduced by prednisolone administration. In cortical bone, prednisolone elevated osteoclast number to a similar extent in both genotypes. Taken together, these results demonstrate that although glucocorticoids stimulate autophagy in osteocytes, suppression of autophagy in this cell type does not worsen the negative impact of glucocorticoids on the skeleton. PMID:25700544

A high-fat diet induces bone loss in mice lacking the Alox5 gene.

PubMed

Le, Phuong; Kawai, Masanobu; Bornstein, Sheila; DeMambro, Victoria E; Horowitz, Mark C; Rosen, Clifford J

2012-01-01

5-Lipoxygenase catalyzes leukotriene generation from arachidonic acid. The gene that encodes 5-lipoxygenase, Alox5, has been identified in genome-wide association and mouse Quantitative Trait Locus studies as a candidate gene for obesity and low bone mass. Thus, we tested the hypothesis that Alox5(-/-) mice would exhibit metabolic and skeletal changes when challenged by a high-fat diet (HFD). On a regular diet, Alox5(-/-) mice did not differ in total body weight, percent fat mass, or bone mineral density compared with wild-type (WT) controls (P < 0.05). However, when placed on a HFD, Alox5(-/-) gained more fat mass and lost greater areal bone mass vs. WT (P < 0.05). Microarchitectural analyses revealed that on a HFD, WT showed increases in cortical area (P < 0.01) and trabecular thickness (P < 0.01), whereas Alox5(-/-) showed no change in cortical parameters but a decrease in trabecular number (P < 0.05) and bone volume fraction compared with WT controls (P < 0.05). By histomorphometry, a HFD did not change bone formation rates of either strain but produced an increase in osteoclast number per bone perimeter in Alox5(-/-) mice (P < 0.03). In vitro, osteoclastogenesis of marrow stromal cells was enhanced in mutant but not WT mice fed a HFD. Gene expression for Rankl, Pparg, and Cox-2 was greater in the femur of Alox5(-/-) than WT mice on a HFD (P < 0.01), but these increases were suppressed in the Alox5(-/-) mice after 8 wk of treatment with celecoxib, a cyclooxygenase-2 inhibitor. In sum, there is a strong gene by environmental interaction for bone mass when mice lacking the Alox5 gene are fed a HFD.

Quantitative analysis of the patella following the harvest of a quadriceps tendon autograft with a bone block.

PubMed

Ferrer, Gerald A; Miller, R Matthew; Murawski, Christopher D; Tashman, Scott; Irrgang, James J; Musahl, Volker; Fu, Freddie H; Debski, Richard E

2016-09-01

The objective of this study was to determine parameters associated with patellar fracture after quadriceps tendon autograft harvest. Thirteen non-fractured and five fractured patella surface models were created based on patient data obtained from a prospective randomized clinical trial in order to assess geometric parameters and bending stress. Measurements that describe the bone block harvest site geometry were used to calculate three normalized parameters. The relative depth parameter describes the thickness of the bone block harvest site with respect to the thickness of the patella at the harvest site. The asymmetry parameter defines the medial-lateral location of the bone bock harvest site. The normalized bending stress parameter assesses the bending stress experienced by the remaining bone beneath the bone block harvest site. The relative depth of the bone block harvest site in the non-fractured patellae was 27 ± 12 % and for the fractured patellae was 42 ± 14 % (p < 0.05). With a value <1 indicating a more lateral location of the harvest site, asymmetry for the non-fractured group was 1.0 ± 0.5 and 0.7 ± 0.4 for the fractured group (n.s.). The maximum bending stress experienced by the non-fractured patellae was (1.8 × 10(-3) ± 1.3 × 10(-3)) mm(-3) × M and for the fractured patellae was over three times greater (6.3 × 10(-3) ± 3.7 × 10(-3)) mm(-3) × M (p < 0.05). Based on the non-uniform geometry of the patella, an emphasis should be made on harvesting a standard percentage of patella thickness rather than a fixed depth. In order to minimize the incidence of a patellar fracture, bone blocks should not be taken laterally and should not exceed 30 % of the total patella thickness at the harvest site.

Prevention of bone loss in ovariectomized rats: the effect of Salvia miltiorrhiza extracts.

PubMed

Chae, H J; Chae, S W; Yun, D H; Keum, K S; Yoo, S K; Kim, H R

2004-02-01

The preventive effect of Salvia miltiorrhiza extracts (SMEs) on the progress of bone loss induced by ovariectomy (OVX) was studied in rats. We measured body weight and bone histomorphometry in sham, OVX or SMEs-administered OVX rats. From light microscopic analyses, a porous or erosive appearances were observed on the surface of trabecular bone of tibia in OVX rats, whereas those of the same bone in sham rats and in SMEs-administered rats were composed of fine particles. The trabecular bone area and trabecular thickness in OVX rats decreased by 50% from those in sham rats, these decreases were completely inhibited by administration of SMEs for 7 weeks. In this study, the mechanical strength in femur neck was significantly enhanced by the treatment of SMEs for 7 weeks. In OVX rats, free T3 was normal in all cases, whereas free T4 was significantly increased. Although there was no difference between OVX and SMEs-administered rats in T3 level, we have found significant difference between them in T4 level. These results strongly suggest that SMEs are effective in preventing the development of bone loss induced by OVX in rats.

Genistein treatment increases bone mass in obese, hyperglycemic mice

PubMed Central

Michelin, Richard M; Al-Nakkash, Layla; Broderick, Tom L; Plochocki, Jeffrey H

2016-01-01

Background Obesity and type 2 diabetes mellitus are associated with elevated risk of limb bone fracture. Incidences of these conditions are on the rise worldwide. Genistein, a phytoestrogen, has been shown by several studies to demonstrate bone-protective properties and may improve bone health in obese type 2 diabetics. Methods In this study, we test the effects of genistein treatment on limb bone and growth plate cartilage histomorphometry in obese, hyperglycemic ob/ob mice. Six-week-old ob/ob mice were divided into control and genistein-treated groups. Genistein-treated mice were fed a diet containing 600 mg genistein/kg for a period of 4 weeks. Cross-sectional geometric and histomorphometric analyses were conducted on tibias. Results Genistein-treated mice remained obese and hyperglycemic. However, histomorphometric comparisons show that genistein-treated mice have greater tibial midshaft diameters and ratios of cortical bone to total tissue area than the controls. Genistein-treated mice also exhibit decreased growth plate thickness of the proximal tibia. Conclusion Our results indicate that genistein treatment affects bone of the tibial midshaft in the ob/ob mouse, independent of improvements in the hyperglycemic state and body weight. PMID:27042131

IGFBP-4 regulates adult skeletal growth in a sex-specific manner

PubMed Central

DeMambro, Victoria E; Le, Phuong T; Nagano, Kenichi; Baron, Roland; Mohan, Subburaman; Rosen, Clifford J

2017-01-01

Insulin-like growth factor-1 (IGF-1) and its binding proteins are critical mediators of skeletal growth. Insulin-like growth factor-binding protein 4 (IGFBP-4) is highly expressed in osteoblasts and inhibits IGF-1 actions in vitro. Yet, in vivo studies suggest that it could potentiate IGF-1 and IGF-2 actions. In this study, we hypothesized that IGFBP-4 might potentiate the actions of IGF-1 on the skeleton. To test this, we comprehensively studied 8- and 16-week-old Igfbp4−/− mice. Both male and female adult Igfbp4−/− mice had marked growth retardation with reductions in body weight, body and femur lengths, fat proportion and lean mass at 8 and 16 weeks. Marked reductions in aBMD and aBMC were observed in 16-week-old Igfbp4−/− females, but not in males. Femoral trabecular BV/TV and thickness, cortical fraction and thickness in 16-week-old Igfbp4−/− females were significantly reduced. However, surprisingly, males had significantly more trabeculae with higher connectivity density than controls. Concordantly, histomorphometry revealed higher bone resorption and lower bone formation in Igfbp4−/− females. In contrast, Igfbp4−/− males had lower mineralized surface/bone surface. Femoral expression of Sost and circulating levels of sclerostin were reduced but only in Igfbp4−/− males. Bone marrow stromal cultures from mutants showed increased osteogenesis, whereas osteoclastogenesis was markedly increased in cells from Igfbp4−/− females but decreased in males. In sum, our results indicate that loss of Igfbp4 affects mesenchymal stromal cell differentiation, regulates osteoclastogenesis and influences both skeletal development and adult bone maintenance. Thus, IGFBP-4 modulates the skeleton in a gender-specific manner, acting as both a cell autonomous and cell non-autonomous factor. PMID:28184001

Slow versus rapid maxillary expansion in bilateral cleft lip and palate: a CBCT randomized clinical trial.

PubMed

de Almeida, Araci Malagodi; Ozawa, Terumi Okada; Alves, Arthur César de Medeiros; Janson, Guilherme; Lauris, José Roberto Pereira; Ioshida, Marilia Sayako Yatabe; Garib, Daniela Gamba

2017-06-01

The purpose of this "two-arm parallel" trial was to compare the orthopedic, dental, and alveolar bone plate changes of slow (SME) and rapid (RME) maxillary expansions in patients with complete bilateral cleft lip and palate (BCLP). Forty-six patients with BCLP and maxillary arch constriction in the late mixed dentition were randomly and equally allocated into two groups. Computer-generated randomization was used. Allocation was concealed with sequentially, numbered, sealed, opaque envelopes. The SME and RME groups comprised patients treated with quad-helix and Haas/Hyrax-type expanders, respectively. Cone-beam computed tomography (CBCT) exams were performed before expansion and 4 to 6 months post-expansion. Nasal cavity width, maxillary width, alveolar crest width, arch width, palatal cleft width, inclination of posterior teeth, alveolar crest level, and buccal and lingual bone plate thickness were assessed. Blinding was applicable for outcome assessment only. Interphase and intergroup comparisons were performed using paired t tests and t tests, respectively (p < 0.05). SME and RME similarly promoted significant increase in all the maxillary transverse dimensions at molar and premolar regions with a decreasing expanding effect from the dental arch to the nasal cavity. Palatal cleft width had a significant increase in both groups. Significant buccal inclination of posterior teeth was only observed for RME. Additionally, both expansion procedures promoted a slight reduction of the alveolar crest level and the buccal bone plate thickness. No difference was found between the orthopedic, dental, and alveolar bone plate changes of SME and RME in children with BCLP. Both appliances produced significant skeletal transverse gains with negligible periodontal bone changes. Treatment time for SME, however, was longer than the observed for RME. SME and RME can be similarly indicated to correct maxillary arch constriction in patients with BCLP in the mixed dentition.

The evaluation of bone mineral density based on nutritional status, age, and anthropometric parameters in elderly women.

PubMed

Ozeraitiene, Violeta; Būtenaite, Violeta

2006-01-01

To examine the relationship between bone mineral density and nutritional status, age, and anthropometrical data in elderly women. A validated international nutrition-risk-screening questionnaire, the Mini Nutritional Assessment, was used for evaluation of nutrition. The Mini Nutritional Assessment is a clinical tool consisting of four items: anthropometric assessment, global evaluation, dietetic assessment, and subjective assessment. Height and body weight were measured while the participants wore indoor clothes and no shoes; mid-arm and calf circumferences were measured with tape measure. The measurements of skinfold thickness on triceps, waist, and thigh were taken with a caliper. Bone mineral density was measured at distal radius of the nondominant forearm by dual x-ray absorptiometry. Our results indicate that anthropometric parameters (height, weight, body mass index, skinfold thickness) in elderly women with osteoporosis were the smallest. It was determined that more fats and proteins are reserved in the body, the greater the bone mineral density is. The nutritional status and age had a significant influence on bone mineral density. It was determined that women with osteoporosis had a tendency for greater malnutrition risk according to Mini Nutritional Assessment. Women with osteoporosis had worse appetites and suffered from cardiovascular diseases more often. It was determined that the nutritional status of elderly women, assessed by the Mini Nutritional Assessment questionnaire, reflects bone mineral density. It was found that women's age and anthropometric data, reflecting fat reserves in the body (body mass index, skinfold thickness), are significantly related to low bone mineral density.

Co-expression of DKK-1 and Sclerostin in Subchondral Bone of the Proximal Femoral Heads from Osteoarthritic Hips.

PubMed

Zarei, Allahdad; Hulley, Philippa A; Sabokbar, Afsie; Javaid, M Kassim

2017-06-01

Osteoarthritis (OA) is a progressively degenerative joint disease influenced by structural and metabolic factors. There is growing evidence that subchondral bone is involved in both symptomatic and structural progression in OA. The Wnt pathway has been implicated in the progression of OA but the expression and function of the Wnt inhibitors, Dikkopf (DKK-1) and sclerostin (SOST), are unclear. We examined the regional distribution of DKK-1 and SOST in subchondral bone of the femoral head using resection specimens following arthroplasty in patients presenting with end-stage OA. Cylindrical cores for immunohistochemistry were taken through midpoint of full thickness cartilage defect, partial cartilage defect, through base of osteophyte and through macroscopically normal cartilage. Subchondral bone was thickest in cores taken from regions with full cartilage defect and thinnest in cores taken from osteophyte regions. In subchondral bone, expression of both DKK-1 and SOST was observed exclusively in osteocytes. Expression was highest in subchondral bone in cores taken from regions with partial but not full thickness cartilage defects. DKK-1 but not SOST was expressed by chondrocytes in cores with macroscopically normal cartilage. The current study describes the regional cellular distribution of SOST and DKK-1 in hip OA. Expression was highest in the osteocytes in bone underlying partial thickness cartilage defects. It is however not clear if this is a cause or a consequence of alterations in the overlying cartilage. However, it is suggestive of an active remodeling process which might be targeted by disease-modifying agents.

Acetabular shell deformation as a function of shell stiffness and bone strength.

PubMed

Dold, Philipp; Pandorf, Thomas; Flohr, Markus; Preuss, Roman; Bone, Martin C; Joyce, Tom J; Holland, James; Deehan, David

2016-04-01

Press-fit acetabular shells used for hip replacement rely upon an interference fit with the bone to provide initial stability. This process may result in deformation of the shell. This study aimed to model shell deformation as a process of shell stiffness and bone strength. A cohort of 32 shells with two different wall thicknesses (3 and 4 mm) and 10 different shell sizes (44- to 62-mm outer diameter) were implanted into eight cadavers. Shell deformation was then measured in the cadavers using a previously validated ATOS Triple Scan III optical system. The shell-bone interface was then considered as a spring system according to Hooke's law and from this the force exerted on the shell by the bone was calculated using a combined stiffness consisting of the measured shell stiffness and a calculated bone stiffness. The median radial stiffness for the 3-mm wall thickness was 4192 N/mm (range, 2920-6257 N/mm), while for the 4-mm wall thickness the median was 9633 N/mm (range, 6875-14,341 N/mm). The median deformation was 48 µm (range, 3-187 µm), while the median force was 256 N (range, 26-916 N). No statistically significant correlation was found between shell stiffness and deformation. Deformation was also found to be not fully symmetric (centres 180° apart), with a median angle discrepancy of 11.5° between the two maximum positive points of deformation. Further work is still required to understand how the bone influences acetabular shell deformation. © IMechE 2016.

Dose in bone and tissue near bone-tissue interface from electron beam.

PubMed

Shiu, A S; Hogstrom, K R

1991-08-01

This work has quantitatively studied the variation of dose both within bone and in unit density tissue near bone-tissue interfaces. Dose upstream of a bone-tissue interface is increased because of an increase in the backscattered electrons from the bone. The magnitude of this effect was measured using a thin parallel-plate ionization chamber upstream of a polymethyl methacrylate (PMMA)-hard bone interface. The electron backscatter factor (EBF) increased rapidly with bone thickness until a full EBF was achieved. This occurred at approximately 3.5 mm at 2 MeV and 6 mm at 13.1 MeV. The full EBF at the interface ranged from approximately 1.018 at 13.1 MeV to 1.05 at 2 MeV. It was also observed that the EBF had a dependence on the energy spectrum at the interface. The penetration of the backscattered electrons in the upstream direction of PMMA was also measured. The dose penetration fell off rapidly in the upstream direction of the interface. Dose enhancement to unit density tissue in bone was measured for an electron beam by placing thermoluminescent dosimeters (TLDs) in a PMMA-bone-PMMA phantom. The maximum dose enhancement in bone was approximately 7% of the maximum dose in water. However, the pencil-beam algorithm of Hogstrom et al. predicted an increase of only 1%, primarily owing to the inverse-square correction. Film was also used to measure the dose enhancement in bone. The film plane was aligned either perpendicular or parallel to the central axis of the beam. The film data indicated that the maximum dose enhancement in bone was approximately 8% for the former film alignment (which was similarly predicted by the TLD measurements) and 13% for the latter film alignment. These results confirm that the X ray film is not suitable to be irritated "edge on" in an inhomogeneous phantom without making perturbation corrections resulting from the film acting as a long narrow inhomogeneous cavity within the bone. In addition, the results give the radiotherapist a basis for clinical judgment when electron beams are used to treat lesions behind bone or near bony structures. We feel these data enhance the ability to recognize the shortcomings of the current dose calculation algorithm used clinically.

Direct metal laser sintering (DMLS) of a customized titanium mesh for prosthetically guided bone regeneration of atrophic maxillary arches.

PubMed

Ciocca, L; Fantini, M; De Crescenzio, F; Corinaldesi, G; Scotti, R

2011-11-01

This study describes a protocol for the direct manufacturing of a customized titanium mesh using CAD-CAM procedures and rapid prototyping to augment maxillary bone and minimize surgery when severe atrophy or post-oncological deformities are present. Titanium mesh and particulate autogenous plus bovine demineralised bone were planned for patient rehabilitation. Bone augmentation planning was performed using the pre-op CT data set in relation to the prosthetic demands, minimizing the bone volume to augment at the minimum necessary for implants. The containment mesh design was used to prototype the 0.6 mm thickness customized titanium mesh, by direct metal laser sintering. The levels of regenerated bone were calculated using the post-op CT data set, through comparison with the pre-op CT data set. The mean vertical height difference of the crestal bone was 2.57 mm, while the mean buccal-palatal dimension of thickness difference was 3.41 mm. All planned implants were positioned after an 8 month healing period using two-step implant surgery, and finally restored with a partial fixed prosthesis. We present a viable and reproducible method to determine the correct bone augmentation prior to implant placement and CAD-CAM to produce a customized direct laser-sintered titanium mesh that can be used for bone regeneration.

Bone condition of the maxillary zygomatic process prior to orthodontic anchorage plate fixation.

PubMed

Präger, T M; Brochhagen, H G; Mischkowski, R; Jost-Brinkmann, P G; Müller-Hartwich, R

2015-01-01

The clinical success of orthodontic miniplates depends on the stability of the miniscrews used for fixation. For good stability, it is essential that the application site provides enough bone of good quality. This study was performed to analyze the amount of bone available for orthodontic miniplates in the zygomatic process of the maxilla. We examined 51 dental CT scans (Somatom Plus 4; Siemens, Erlangen, Germany) obtained from 51 fully dentate adult patients (mean age 24.0 ± 8.1 years; 27 male and 24 female) prior to third molar surgery. The amount of bone in the zygomatic process region at the level of the first molar root tips and at several other cranial levels as far as 15 mm from the root tips was measured Bone thickness at the root tip level averaged 4.1 ± 1.0 mm; the lowest value measured at this level in any of the patients was 2.7 mm. Bone thickness averaged 8.3 ± 1.0 mm at 15 mm cranial to the root tips; 6.9 mm was the lowest value. The zygomatic process appears to provide sufficient bone to accommodate screws for miniplate fixation. While some patients may possess a borderline amount of bone at more caudal levels, lack of volume is not a problem near the zygomatic bone.

Accelerated craniofacial bone regeneration through dense collagen gel scaffolds seeded with dental pulp stem cells

PubMed Central

Chamieh, Frédéric; Collignon, Anne-Margaux; Coyac, Benjamin R.; Lesieur, Julie; Ribes, Sandy; Sadoine, Jérémy; Llorens, Annie; Nicoletti, Antonino; Letourneur, Didier; Colombier, Marie-Laure; Nazhat, Showan N.; Bouchard, Philippe; Chaussain, Catherine; Rochefort, Gael Y.

2016-01-01

Therapies using mesenchymal stem cell (MSC) seeded scaffolds may be applicable to various fields of regenerative medicine, including craniomaxillofacial surgery. Plastic compression of collagen scaffolds seeded with MSC has been shown to enhance the osteogenic differentiation of MSC as it increases the collagen fibrillary density. The aim of the present study was to evaluate the osteogenic effects of dense collagen gel scaffolds seeded with mesenchymal dental pulp stem cells (DPSC) on bone regeneration in a rat critical-size calvarial defect model. Two symmetrical full-thickness defects were created (5 mm diameter) and filled with either a rat DPSC-containing dense collagen gel scaffold (n = 15), or an acellular scaffold (n = 15). Animals were imaged in vivo by microcomputer tomography (Micro-CT) once a week during 5 weeks, whereas some animals were sacrificed each week for histology and histomorphometry analysis. Bone mineral density and bone micro-architectural parameters were significantly increased when DPSC-seeded scaffolds were used. Histological and histomorphometrical data also revealed significant increases in fibrous connective and mineralized tissue volume when DPSC-seeded scaffolds were used, associated with expression of type I collagen, osteoblast-associated alkaline phosphatase and osteoclastic-related tartrate-resistant acid phosphatase. Results demonstrate the potential of DPSC-loaded-dense collagen gel scaffolds to benefit of bone healing process. PMID:27934940

Kefir improves bone mass and microarchitecture in an ovariectomized rat model of postmenopausal osteoporosis.

PubMed

Chen, H-L; Tung, Y-T; Chuang, C-H; Tu, M-Y; Tsai, T-C; Chang, S-Y; Chen, C-M

2015-02-01

Kefir treatment in ovariectomized (OVX) rats could significantly decrease the levels of bone turnover markers and prevent OVX-induced bone loss, deterioration of trabecular microarchitecture, and biomechanical dysfunction that may be due to increase intracellular calcium uptake through the TRPV6 calcium channel. Osteoporosis is a disease characterized by low bone mass and structural deterioration of bone tissue, leading to an increased fracture risk. The incidence of osteoporosis increases with age and occurs most frequently in postmenopausal women due to estrogen deficiency, as the balance between bone resorption and bone formation shifts towards increased levels of bone resorption. Among various methods of prevention and treatment for osteoporosis, an increase in calcium intake is the most commonly recommended preventive measure. Kefir is a fermented milk product made with kefir grains that degrade milk proteins into various peptides with health-promoting effects, including immunomodulating-, antithrombotic-, antimicrobial-, and calcium-absorption-enhancing bioactivities. The aim of this study is to investigate the effect of kefir on osteoporosis prophylaxis in an ovariectomized rat model. A total of 56 16-week-old female Sprague-Dawley (SD) rats were divided into 7 experimental groups: sham (normal), OVX/Mock, OVX/1X kefir (164 mg/kg BW/day), OVX/2X kefir (328 mg/kg BW/day), OVX/4X kefir (656 mg/kg BW/day), OVX/ALN (2.5 mg/kg BW/day), and OVX/REBONE (800 mg/kg BW/day). After 12-week treatment with kefir, the bone physiology in the OVX rat model was investigated. Accordingly, the aim of this study was to investigate the possible transport mechanism involved in calcium absorption using the Caco-2 human cell line. A 12-week treatment with kefir on the OVX-induced osteoporosis model reduced the levels of C-terminal telopeptides of type I collagen (CTx), bone turnover markers, and trabecular separation (Tb. Sp.). Additionally, treatment with kefir increased trabecular bone mineral density (BMD), bone volume (BV/TV), trabecular thickness (Tb. Th), trabecular number (Tb. N), and the biomechanical properties (hardness and modulus) of the distal femur with a dose-dependent efficacy. In addition, in in vitro assay, we found that kefir increased intracellular calcium uptake in Caco-2 cell through TRPV6 calcium channels and not through L-type voltage-operated calcium channels. The protective effect of kefir in the OVX rat model may occur through increasing intracellular calcium uptake through the TRPV6 calcium channel.

Effect of ceramic thickness and composite bases on stress distribution of inlays--a finite element analysis.

PubMed

Durand, Letícia Brandão; Guimarães, Jackeline Coutinho; Monteiro Junior, Sylvio; Baratieri, Luiz Narciso

2015-01-01

The purpose of this study was to determine the effect of cavity depth, ceramic thickness, and resin bases with different elastic modulus on von Mises stress patterns of ceramic inlays. Tridimensional geometric models were developed with SolidWorks image software. The differences between the models were: depth of pulpal wall, ceramic thickness, and presence of composite bases with different thickness and elastic modulus. The geometric models were constrained at the proximal surfaces and base of maxillary bone. A load of 100 N was applied. The stress distribution pattern was analyzed with von Mises stress diagrams. The maximum von Mises stress values ranged from 176 MPa to 263 MPa and varied among the 3D-models. The highest von Mises stress value was found on models with 1-mm-thick composite resin base and 1-mm-thick ceramic inlay. Intermediate values (249-250 MPa) occurred on models with 2-mm-thick composite resin base and 1-mm-thick ceramic inlay and 1-mm-thick composite resin base and 2-mm-thick ceramic inlay. The lowest values were observed on models restored exclusively with ceramic inlay (176 MPa to 182 MPa). It was found that thicker inlays distribute stress more favorably and bases with low elastic modulus increase stress concentrations on the internal surface of the ceramic inlay. The increase of ceramic thickness tends to present more favorable stress distribution, especially when bonded directly onto the cavity without the use of supporting materials. When the use of a composite base is required, composite resin with high elastic modulus and reduced thickness should be preferred.

Anterior maxillary and mandibular biotype: relationship between gingival thickness and width with respect to underlying bone thickness.

PubMed

La Rocca, Andres Pascual; Alemany, Antonio Santos; Levi, Paul; Juan, Monica Vicario; Molina, Jose Nart; Weisgold, Arnold S

2012-12-01

: Periodontal biotype is considered to be a significant factor related to successful dental treatments. The purpose of this study was to determine the relationship between gingival thickness (GT) and width with respect to the underlying bone thickness in the maxillary and mandibular anterior sextant. : Overall, 180 anterior teeth within healthy patients were assessed. GT and buccal bone thickness (BT) were measured at 3 locations: crestal/gingival margin, tooth apex, and a midpoint between the 2. In addition, the apicoincisal gingival width (GW) was recorded. Clinical and cone beam CT measurements were compared and correlated. : No statistically significant relations were observed between GT and BT measures at any of the 3 positions. The mean GT at crestal mid and apical position for the maxillary teeth was 1.01 (±0.58) mm, 1.06 (±0.48) mm, and 0.83 (±0.47) mm, respectively, and the corresponding mean BT was 1.24 (±0.90) mm, 0.81 (±0.33) mm, and 2.78 (±1.62) mm, respectively. The GW is directly related (R = 0.007; P < 0.05) to the crestal BT. : In this study, the GT is not linked to the BT. However, the GW seems to be associated with the crestal BT.

The peak bone mass concept: is it still relevant?

PubMed

Schönau, Eckhard

2004-08-01

The peak bone mass concept implies that optimal skeletal development during childhood and adolescence will prevent fractures in late adulthood. This concept is based on the observation that areal bone density increases with growth during childhood, is highest around 20 years of age and declines thereafter. However, it is now clear that strong bones in the youngster do not necessarily lead to a fracture-free old age. In the recent bone densitometric literature, the terms bone mass and bone density are typically used synonymously. In physics, density has been defined as the mass of a body divided by its volume. In clinical practice and science, "bone density" usually has a different meaning-the degree to which a radiation beam is attenuated by a bone, as judged from a two-dimensional projection image (areal bone density). The attenuation of a radiation beam does not only depend on physical density, but also on bone size. A small bone therefore has a lower areal bone density than a larger bone, even if the physical density is the same. Consequently, a low areal bone density value can simply reflect the small size of an otherwise normal bone. At present, bone mass analysis is very useful for epidemiological studies on factors that may have an impact on bone development. There is an ongoing discussion about whether the World Health Organization (WHO) definition of osteoporosis is over-simplistic and requires upgrading to include indices representing the distribution of bone and mineral (bone strength indices). The following suggestions and recommendations outline a new concept: bone mass should not be related to age. There is now more and more evidence that bone mass should be related to bone size or muscle function. Thus analyzed, there is no such entity as a "peak bone mass". Many studies are currently under way to evaluate whether these novel approaches increase sensitivity and specificity of fracture prediction in an individual. Furthermore, the focus of many bone researchers is shifting away from bone mass to bone geometry or bone strength. Bone mass is one surrogate marker of bone strength. Widely available techniques for measurement of bone mass, such as dual-energy X-ray absorptiometry, radiogrammetry, and computed tomography, can also be used to measure variables of bone geometry such as cortical thickness, cortical area, and moment of inertia.

Sex-related differences of bone properties of pelvic limb and bone metabolism indices in 14-month-old ostriches (Struthio camelus).

PubMed

Krupski, W; Tatara, M R; Charuta, A; Brodzki, A; Szpetnar, M; Jóźwik, A; Strzałkowska, N; Poławska, E; Łuszczewska-Sierakowska, I

2018-06-01

1. Sex-related differences of long pelvic limb bones and serum bone metabolism indices were evaluated in 14-month-old female (N = 7) and male (N = 7) ostriches of similar body weights. 2. Densitometric parameters of femur, tibia and tarsometatarsus were determined using quantitative computed tomography (volumetric bone mineral density, calcium hydroxyapatite density and mean volumetric bone mineral density) and dual energy X-ray absorptiometry (bone mineral density and bone mineral content) methods. Geometrical parameters such as cortical bone area, cross-sectional area, second moment of inertia, mean relative wall thickness and cortical index were determined in the midshaft of bones. Mechanical properties of bones (maximum elastic strength and ultimate strength) were evaluated using three-point bending test. Serum concentrations of free amino acids, osteocalcin, N-terminal propeptide of type I procollagen, C-terminal telopeptides of type II collagen and total antioxidative capacity were also determined. 3. Bone weight and relative bone weight of all bones were significantly higher in males than in females. Significantly lower values of trabecular bone mineral density and calcium hydroxyapatite density were found in the trabecular bone of tibia in males. The highest number of the sex-related differences was observed in the tarsometatarsus where bone length, bone mineral content, cortical bone area, cross-sectional area and ultimate strength were higher in males. Serum concentrations of taurine, hydroxyproline, valine and isoleucine were significantly higher in males. 4. Higher loading of the tarsometatarsus in comparison to femur and tibia may be an important factor interacting with sex hormones in regulation of bone formation and mineralisation processes. Sex-related differences of bone properties were associated with increased serum concentration of selected amino acids in males.

Rib fractures under anterior-posterior dynamic loads: experimental and finite-element study.

PubMed

Li, Zuoping; Kindig, Matthew W; Kerrigan, Jason R; Untaroiu, Costin D; Subit, Damien; Crandall, Jeff R; Kent, Richard W

2010-01-19

The purpose of this study was to investigate whether using a finite-element (FE) mesh composed entirely of hexahedral elements to model cortical and trabecular bone (all-hex model) would provide more accurate simulations than those with variable thickness shell elements for cortical bone and hexahedral elements for trabecular bone (hex-shell model) in the modeling human ribs. First, quasi-static non-injurious and dynamic injurious experiments were performed using the second, fourth, and tenth human thoracic ribs to record the structural behavior and fracture tolerance of individual ribs under anterior-posterior bending loads. Then, all-hex and hex-shell FE models for the three ribs were developed using an octree-based and multi-block hex meshing approach, respectively. Material properties of cortical bone were optimized using dynamic experimental data and the hex-shell model of the fourth rib and trabecular bone properties were taken from the literature. Overall, the reaction force-displacement relationship predicted by both all-hex and hex-shell models with nodes in the offset middle-cortical surfaces compared well with those measured experimentally for all the three ribs. With the exception of fracture locations, the predictions from all-hex and offset hex-shell models of the second and fourth ribs agreed better with experimental data than those from the tenth rib models in terms of reaction force at fracture (difference <15.4%), ultimate failure displacement and time (difference <7.3%), and cortical bone strains. The hex-shell models with shell nodes in outer cortical surfaces increased static reaction forces up to 16.6%, compared to offset hex-shell models. These results indicated that both all-hex and hex-shell modeling strategies were applicable for simulating rib responses and bone fractures for the loading conditions considered, but coarse hex-shell models with constant or variable shell thickness were more computationally efficient and therefore preferred. Copyright 2009 Elsevier Ltd. All rights reserved.

Apical stress distribution on maxillary central incisor during various orthodontic tooth movements by varying cemental and two different periodontal ligament thicknesses: a FEM study.

PubMed

Vikram, N Raj; Senthil Kumar, K S; Nagachandran, K S; Hashir, Y Mohamed

2012-01-01

During fixed orthodontic therapy, when the stress levels in the periodontal ligament (PDL) exceedsan optimum level, it could lead to root resorption. To determine an apical stress incident on the maxillary central incisor during tooth movement with varying cemental and periodontal ligament thickness by Finite Element Method (FEM) modeling. A three dimensional finite element model of a maxillary central incisor along with enamel, dentin, cementum, PDL and alveolar bone was recreated using EZIDCOM and AUTOCAD software. ALTAIR Hyper mesh 7.0 version was used to create the Finite Element meshwork of the tooth. This virtual model was transferred to Finite Element Analysis software, ANSYS where different tooth movements were performed. Cemental thickness at the root apex was varied from 200 μm to 1000 μm in increments of 200 μm. PDL thickness was varied as 0.24 mm and 0.15 mm. Intrusive, Extrusive, Rotation and Tipping forces were delivered to determine an apical stress for each set of parameters. Results indicated that an apical stress induced in the cementum and PDL, increased with an increase in cementum and PDL thickness respectively. Apical stress induced in the cementum remained the same or decreased with an increase in the PDL thickness. Apical stress induced in the PDL decreased with an increase in the cementum thickness. The study concluded that the clinical delivery of an orthodontic forces will cause stress in the cementum and PDL. Hence, it is necessary to limit the orthodontic force to prevent root resorption.

Melatonin improves bone mineral density at the femoral neck in postmenopausal women with osteopenia: a randomized controlled trial.

PubMed

Amstrup, Anne Kristine; Sikjaer, Tanja; Heickendorff, Lene; Mosekilde, Leif; Rejnmark, Lars

2015-09-01

Melatonin is known for its regulation of circadian rhythm. Recently, studies have shown that melatonin may have a positive effect on the skeleton. By increasing age, the melatonin levels decrease, which may lead to a further imbalanced bone remodeling. We aimed to investigate whether treatment with melatonin could improve bone mass and integrity in humans. In a double-blind RCT, we randomized 81 postmenopausal osteopenic women to 1-yr nightly treatment with melatonin 1 mg (N = 20), 3 mg (N = 20), or placebo (N = 41). At baseline and after 1-yr treatment, we measured bone mineral density (BMD) by dual X-ray absorptiometry, quantitative computed tomography (QCT), and high-resolution peripheral QCT (HR-pQCT) and determined calciotropic hormones and bone markers. Mean age of the study subjects was 63 (range 56-73) yr. Compared to placebo, femoral neck BMD increased by 1.4% in response to melatonin (P < 0.05) in a dose-dependent manner (P < 0.01), as BMD increased by 0.5% in the 1 mg/day group (P = 0.55) and by 2.3% (P < 0.01) in the 3 mg/day group. In the melatonin group, trabecular thickness in tibia increased by 2.2% (P = 0.04), and volumetric bone mineral density (vBMD) in the spine, by 3.6% (P = 0.04) in the 3 mg/day. Treatment did not significantly affect BMD at other sites or levels of bone turnover markers; however, 24-hr urinary calcium was decreased in response to melatonin by 12.2% (P = 0.02). In conclusion, 1-yr treatment with melatonin increased BMD at femoral neck in a dose-dependent manner, while high-dose melatonin increased vBMD in the spine. Further studies are needed to assess the mechanisms of action and whether the positive effect of nighttime melatonin will protect against fractures. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Development of a hip joint model for finite volume simulations.

PubMed

Cardiff, P; Karač, A; FitzPatrick, D; Ivanković, A

2014-01-01

This paper establishes a procedure for numerical analysis of a hip joint using the finite volume method. Patient-specific hip joint geometry is segmented directly from computed tomography and magnetic resonance imaging datasets and the resulting bone surfaces are processed into a form suitable for volume meshing. A high resolution continuum tetrahedral mesh has been generated, where a sandwich model approach is adopted; the bones are represented as a stiffer cortical shells surrounding more flexible cancellous cores. Cartilage is included as a uniform thickness extruded layer and the effect of layer thickness is investigated. To realistically position the bones, gait analysis has been performed giving the 3D positions of the bones for the full gait cycle. Three phases of the gait cycle are examined using a finite volume based custom structural contact solver implemented in open-source software OpenFOAM.

In vivo quantification of lead in bone with a portable x-ray fluorescence system--methodology and feasibility.

PubMed

Nie, L H; Sanchez, S; Newton, K; Grodzins, L; Cleveland, R O; Weisskopf, M G

2011-02-07

This study was conducted to investigate the methodology and feasibility of developing a portable x-ray fluorescence (XRF) technology to quantify lead (Pb) in bone in vivo. A portable XRF device was set up and optimal settings of voltage, current, and filter combination for bone lead quantification were selected to achieve the lowest detection limit. The minimum radiation dose delivered to the subject was calculated by Monte Carlo simulations. An ultrasound device was used to measure soft tissue thickness to account for signal attenuation, and an alternative method to obtain soft tissue thickness from the XRF spectrum was developed and shown to be equivalent to the ultrasound measurements (intraclass correlation coefficient, ICC = 0.82). We tested the correlation of in vivo bone lead concentrations between the standard KXRF technology and the portable XRF technology. There was a significant correlation between the bone lead concentrations obtained from the standard KXRF technology and those obtained from the portable XRF technology (ICC = 0.65). The detection limit for the portable XRF device was about 8.4 ppm with 2 mm soft tissue thickness. The entrance skin dose delivered to the human subject was about 13 mSv and the total body effective dose was about 1.5 µSv and should pose minimal radiation risk. In conclusion, portable XRF technology can be used for in vivo bone lead measurement with sensitivity comparable to the KXRF technology and good correlation with KXRF measurements.

In Vivo Quantification of Lead in Bone with a Portable X-ray Fluorescence (XRF) System – Methodology and Feasibility

PubMed Central

Nie, LH; Sanchez, S; Newton, K; Grodzins, L; Cleveland, RO; Weisskopf, MG

2013-01-01

This study was conducted to investigate the methodology and feasibility of developing a portable XRF technology to quantify lead (Pb) in bone in vivo. A portable XRF device was set up and optimal setting of voltage, current, and filter combination for bone lead quantification were selected to achieve the lowest detection limit. The minimum radiation dose delivered to the subject was calculated by Monte Carlo simulations. An ultrasound device was used to measure soft tissue thickness to account for signal attenuation, and an alternative method to obtain soft tissue thickness from the XRF spectrum was developed and shown to be equivalent to the ultrasound measurements (Intraclass Correlation Coefficient, ICC=0.82). We tested the correlation of in vivo bone lead concentrations between the standard KXRF technology and the portable XRF technology. There was a significant correlation between the bone lead concentrations obtained from the standard KXRF technology and those obtained from the portable XRF technology (ICC=0.65). The detection limit for the portable XRF device was about 8.4 ppm with 2 mm soft tissue thickness. The entrance skin dose delivered to the human subject was about 13 mSv and the total body effective dose was about 1.5 μSv and should pose a minimal radiation risk. In conclusion, portable XRF technology can be used for in vivo bone lead measurement with sensitivity comparable to the KXRF technology and good correlation with KXRF measurements. PMID:21242629

Simulated space radiation sensitizes bone but not muscle to the catabolic effects of mechanical unloading.

PubMed

Krause, Andrew R; Speacht, Toni L; Zhang, Yue; Lang, Charles H; Donahue, Henry J

2017-01-01

Deep space travel exposes astronauts to extended periods of space radiation and mechanical unloading, both of which may induce significant muscle and bone loss. Astronauts are exposed to space radiation from solar particle events (SPE) and background radiation referred to as galactic cosmic radiation (GCR). To explore interactions between skeletal muscle and bone under these conditions, we hypothesized that decreased mechanical load, as in the microgravity of space, would lead to increased susceptibility to space radiation-induced bone and muscle loss. We evaluated changes in bone and muscle of mice exposed to hind limb suspension (HLS) unloading alone or in addition to proton and high (H) atomic number (Z) and energy (E) (HZE) (16O) radiation. Adult male C57Bl/6J mice were randomly assigned to six groups: No radiation ± HLS, 50 cGy proton radiation ± HLS, and 50 cGy proton radiation + 10 cGy 16O radiation ± HLS. Radiation alone did not induce bone or muscle loss, whereas HLS alone resulted in both bone and muscle loss. Absolute trabecular and cortical bone volume fraction (BV/TV) was decreased 24% and 6% in HLS-no radiation vs the normally loaded no-radiation group. Trabecular thickness and mineral density also decreased with HLS. For some outcomes, such as BV/TV, trabecular number and tissue mineral density, additional bone loss was observed in the HLS+proton+HZE radiation group compared to HLS alone. In contrast, whereas HLS alone decreased muscle mass (19% gastrocnemius, 35% quadriceps), protein synthesis, and increased proteasome activity, radiation did not exacerbate these catabolic outcomes. Our results suggest that combining simulated space radiation with HLS results in additional bone loss that may not be experienced by muscle.

Effects of the phytoestrogen genistein on bone metabolism in osteopenic postmenopausal women: a randomized trial.

PubMed

Marini, Herbert; Minutoli, Letteria; Polito, Francesca; Bitto, Alessandra; Altavilla, Domenica; Atteritano, Marco; Gaudio, Agostino; Mazzaferro, Susanna; Frisina, Alessia; Frisina, Nicola; Lubrano, Carla; Bonaiuto, Michele; D'Anna, Rosario; Cannata, Maria Letizia; Corrado, Francesco; Adamo, Elena Bianca; Wilson, Steven; Squadrito, Francesco

2007-06-19

Observational studies and small trials of short duration suggest that the isoflavone phytoestrogen genistein reduces bone loss, but the evidence is not definitive. To assess the effects of genistein on bone metabolism in osteopenic postmenopausal women. Randomized, double-blind, placebo-controlled trial. 3 university medical centers in Italy. 389 postmenopausal women with a bone mineral density (BMD) less than 0.795 g/cm2 at the femoral neck and no significant comorbid conditions. After a 4-week stabilization period during which participants received a low-soy, reduced-fat diet, participants were randomly assigned to receive placebo (n = 191) or 54 mg of genistein (n = 198) daily for 24 months. Both the genistein and placebo tablets contained calcium and vitamin D. The primary outcome was BMD at the anteroposterior lumbar spine and femoral neck at 24 months. Secondary outcomes were serum levels of bone-specific alkaline phosphatase and insulin-like growth factor I, urinary excretion of pyridinoline and deoxypyridinoline, and endometrial thickness. Data on adverse events were also collected. At 24 months, BMD had increased in genistein recipients and decreased in placebo recipients at the anteroposterior lumbar spine (change, 0.049 g/cm2 [95% CI, 0.035 to 0.059] vs. -0.053 g/cm2 [CI, -0.058 to -0.035]; difference, 0.10 g/cm2 [CI, 0.08 to 0.12]; P < 0.001) and the femoral neck (change, 0.035 g/cm2 [CI, 0.025 to 0.042] vs. -0.037 g/cm2 [CI, -0.044 to -0.027]; difference, 0.062 g/cm2 [CI, 0.049 to 0.073]; P < 0.001). Genistein statistically significantly decreased urinary excretion of pyridinoline and deoxypyridinoline, increased levels of bone-specific alkaline phosphatase and insulin-like growth factor I, and did not change endometrial thickness compared with placebo. More genistein recipients than placebo recipients experienced gastrointestinal side effects (19% vs. 8%; P = 0.002) and discontinued the study. The study did not measure fractures and had limited power to evaluate adverse effects. Twenty-four months of treatment with genistein has positive effects on BMD in osteopenic postmenopausal women. ClinicalTrials.gov registration number: NCT00355953.

Prostate Cancer Metastases Alter Bone Mineral and Matrix Composition Independent of Effects on Bone Architecture in Mice A Quantitative Study Using microCT and Raman Spectroscopy

PubMed Central

Bi, Xiaohong; Sterling, Julie A.; Merkel, Alyssa R.; Perrien, Daniel S.; Nyman, Jeffry; Mahadevan-Jansen, Anita

2013-01-01

Prostate cancer is the most common primary tumor and the second leading cause of cancer-related deaths in men in the United States. Prostate cancer bone metastases are characterized by abnormal bone remodeling processes and result in a variety of skeletal morbidities. Prevention of skeletal complications is a crucial element in prostate cancer management. This study investigated prostate cancer-induced alterations in the molecular composition and morphological structure of metastasis-bearing bones in a mouse model of prostate cancer using Raman spectroscopy and micro-computed tomography (microCT). LNCaP C4-2B prostate cancer cells were injected into the right tibiae of 5-week old male SCID mice. Upon sacrifice at 8 weeks post tumor inoculation, two out of the ten tumor-bearing tibiae showed only osteoblastic lesions in the radiographs, 4 osteolytic lesions only and 4 mixed with osteoblastic and osteolytic lesions.. Carbonate substitution was significantly increased while there was a marked reduction in the level of collagen mineralization, mineral crystallinity, and carbonate:matrix ratio in the cortex of the intact tumor-bearing tibiae compared to contralateral controls. MicroCT analysis revealed a significant reduction in bone volume/total volume, trabecular number and trabecular thickness, as well as significant increase in bone surface/volume ratio in tibiae with osteolytic lesions, suggesting active bone remodeling and bone loss. None of the changes in bone compositional properties were correlated with lesion area from radiographs or the changes in bone architecture from microCT. This study indicates that LNCaP C4-2B prostate cancer metastases alter bone tissue composition independent of changes in architecture, and altered bone quality may be an important contributor to fracture risk in these patients. Raman spectroscopy may provide a new avenue of investigation into interactions between tumor and bone microenvironment. PMID:23867219

Precision of pQCT-measured total, trabecular and cortical bone area, content, density and estimated bone strength in children

PubMed Central

Duff, W.R.D.; Björkman, K.M.; Kawalilak, C.E.; Kehrig, A.M.; Wiebe, S.; Kontulainen, S.

2017-01-01

Objectives: To define pQCT precision errors, least-significant-changes, and identify associated factors for bone outcomes at the radius and tibia in children. Methods: We obtained duplicate radius and tibia pQCT scans from 35 children (8-14yrs). We report root-mean-squared coefficient of variation (CV%RMS) and 95% limits-of-agreement to characterize repeatability across scan quality and least-significant-changes for bone outcomes at distal (total and trabecular area, content and density; and compressive bone strength) and shaft sites (total area and content; cortical area content, density and thickness; and torsional bone strength). We used Spearman’s rho to identify associations between CV% and time between measurements, child’s age or anthropometrics. Results: After excluding unanalyzable scans (6-10% of scans per bone site), CV%RMS ranged from 4% (total density) to 19% (trabecular content) at the distal radius, 4% (cortical content) to 8% (cortical thickness) at the radius shaft, 2% (total density) to 14% (trabecular content) at the distal tibia and from 2% (cortical content) to 6% (bone strength) at the tibia shaft. Precision errors were within 95% limits-of-agreement across scan quality. Age was associated (rho -0.4 to -0.5, p <0.05) with CV% at the tibia. Conclusion: Bone density outcomes and cortical bone properties appeared most precise (CV%RMS <5%) in children. PMID:28574412

Pueraria mirifica alleviates cortical bone loss in naturally menopausal monkeys.

PubMed

Kittivanichkul, Donlaporn; Charoenphandhu, Narattaphol; Khemawoot, Phisit; Malaivijitnond, Suchinda

2016-11-01

Since the in vitro and in vivo anti-osteoporotic effects of Pueraria mirifica (PM) in rodents have been verified, its activity in menopausal monkeys was evaluated as required before it can be applicable for human use. In this study, postmenopausal osteoporotic monkeys were divided into two groups (five per group), and fed daily with standard diet alone (PMP0 group) or diet mixed with 1000 mg/kg body weight (BW) of PM powder (PMP1000 group) for 16 months. Every 2 months, the bone mineral density (BMD), bone mineral content (BMC) and bone geometry parameters (cortical area and thickness and periosteal and endosteal circumference) at the distal radius and proximal tibia were determined using peripheral quantitative computed tomography together with plasma and urinary bone markers. Compared with the baseline (month 0) values, the cortical, but not trabecular, BMDs and BMCs and the cortical area and thickness at the metaphysis and diaphysis of the radius and tibia of the PMP0 group continuously decreased during the 16-month study period. In contrast, PMP1000 treatment ameliorated the bone loss mainly at the cortical diaphysis by decreasing bone turnover, as indicated by the lowered plasma bone-specific alkaline phosphatase and osteocalcin levels. Generally, changes in the cortical bone geometry were in the opposite direction to the cortical bone mass after PMP1000 treatment. This study indicated that postmenopausal monkeys continuously lose their cortical bone compartment, and they have a higher possibility for long bone fractures. Oral PMP treatment could improve both the bone quantity (BMC and BMD) and quality (bone geometry). © 2016 Society for Endocrinology.

Ethanol extract of Peperomia pellucida (Piperaceae) promotes fracture healing by an anabolic effect on osteoblasts.

PubMed

Ngueguim, Florence Tsofack; Khan, Mohd Parvez; Donfack, Jean Hubert; Tewari, Deepshikha; Dimo, Theophile; Kamtchouing, Pierre; Maurya, Rakesh; Chattopadhyay, Naibedya

2013-06-21

The whole plant or some part of Peperomia pellucida (L.) HBK is used in some parts of Cameroon as a treatment for fracture healing. To evaluate the effect of ethanolic extracts of Peperomia pellucida (L.), a Cameroonian medicinal plant on bone regeneration following bone and marrow injury, and determine the mode of action. Ethanol extract of Peperomia pellucida was administered at 100 and 200mg/kg doses orally to adult female Sprague-Dawley rats having a drill hole injury (0.8mm) in the femur diaphysis. Vehicle (gum-acacia in distilled water) was given to the control group. After 12 days of treatment, animals were euthanized and femur bones collected. Confocal microscopy of calcein labeling at the drill hole site was performed to evaluate bone regeneration. 3-D microarchitecture of drill hole site was analyzed by micorocomputed tomography. Osteogenic effects of the extract were evaluated by assessing mineralized nodule formation of bone marrow stromal cells and expression of osteogenic genes (mRNA level of type-1 collagen, bone morphogenetic protein-2 and osteocalcin genes) in the femur. Ethanol extract from Peperomia Pellucida (L.) dose-dependently induced bone regeneration at the fracture site. At 200mg/kg dose, the extract significantly increased mineral deposition compared to controls. The extract also improved microarchitecture of the regenerating bone evident from increased bone volume fraction, trabecular thickness, trabecular number, and decreased trabecular separation and structure model index. In addition, the extract increased the formation of mineralized nodules from the bone marrow stromal cells. Furthermore, the extract induced the expression of osteogenic genes in the femur including type 1 collagen, osteocalcin and BMP-2, compared to control. Ethanolic extract of P. pellucid (L.) accelerates fracture repair in rats via stimulatory effects on osteoblast differentiation and mineralization, thereby justifying its traditional use. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Polycythemia is associated with bone loss and reduced osteoblast activity in mice.

PubMed

Oikonomidou, P R; Casu, C; Yang, Z; Crielaard, B; Shim, J H; Rivella, S; Vogiatzi, M G

2016-04-01

Increased fragility has been described in humans with polycythemia vera (PV). Herein, we describe an osteoporotic phenotype associated with decreased osteoblast activity in a mouse model of PV and another mouse of polycythemia and elevated circulating erythropoietin (EPO). Our results are important for patients with PV or those treated with recombinant EPO (rEPO). PV and other myeloproliferative syndromes have been recently associated with an increased risk for fractures. However, the presence of osteoporosis in these patients has not been well documented. EPO, a hormone primarily known to stimulate erythropoiesis, has been shown recently to regulate bone homeostasis in mice. The aim of this study was to examine the bone phenotype of a mouse model of PV and compare it to that of animals with polycythemia caused by elevated circulating EPO. Bone mass and remodeling were evaluated by micro-computed tomography and histomorphometry. The JAK2(V617F) knock-in mouse, a model of human PV, manifests polycythemia and low circulating EPO levels. Results from this mouse were compared to wild type (wt) controls and the tg6 transgenic mouse that shows polycythemia caused by increased constitutive expression of EPO. Compared to wt, both JAK2(V617F) and tg6 mice had a decrease in trabecular bone mass. Tg6 mice showed an additional modest decrease in cortical thickness and cortical bone volume per tissue volume (P < 0.01) suggesting a more severe bone phenotype than JAK2(V617F). Decreased osteoblast numbers and bone formation along with normal osteoclast numbers and activity were found in both mice. This study indicates that PV is associated with low bone mass and decreased osteoblast activity in mice. Our results support future studies of osteoporosis in affected humans. Polycythemia caused by chronically elevated circulating EPO also results in bone loss, and implications on patients treated with rEPO should be evaluated.

In peripubertal girls, artistic gymnastics improves areal bone mineral density and femoral bone geometry without affecting serum OPG/RANKL levels.

PubMed

Maïmoun, L; Coste, O; Mariano-Goulart, D; Galtier, F; Mura, T; Philibert, P; Briot, K; Paris, F; Sultan, C

2011-12-01

Peripubertal artistic gymnasts display elevated areal bone mineral density at various bone sites, despite delayed menarche and a high frequency of menstrual disorders, factors that may compromise bone health. The concomitant improvement in femoral bone geometry and strength suggested that this type of physical activity might have favourable clinical impact. The purpose of this study is to evaluate the effect of artistic gymnastics (GYM) on areal bone mineral density (aBMD), femoral bone geometry and bone markers and its relationship with the osteoprotegerin (OPG)/rank-ligand (RANKL) system in peripubertal girls. Forty-six girls (age 10-17.2 years) were recruited for this study: 23 elite athletes in the GYM group (training 12-30 h/week, age at start of training 5.3 years) and 23 age-matched (± 6 months; leisure physical activity ≤ 3 h/week) controls (CON). The aBMD at whole body, total proximal femur, lumbar spine, mid-radius and skull was determined using dual-X-ray absorptiometry. Hip structural analysis (HSA software) was applied at the femur to evaluate cross-sectional area (CSA, cm(2)), cross-sectional moment of inertia (CSMI, cm(4)), and the section modulus (Z, cm(3)) and buckling ratio at neck, intertrochanteric region and shaft. Markers of bone turnover and OPG/RANKL levels were also analysed. GYM had higher (5.5-16.4%) non-adjusted aBMD and adjusted aBMD for age, fat-free soft tissue and fat mass at all bone sites, skull excepted and the difference increased with age. In the three femoral regions adjusted for body weight and height, CSA (12.5-18%), CSMI (14-18%), Z (15.5-18.6%) and mean cortical thickness (13.6-21%) were higher in GYM than CON, while the buckling ratio (21-27.1%) was lower. Bone markers decreased with age in both groups and GYM presented higher values than CON only in the postmenarchal period. A similar increase in RANKL with age without OPG variation was observed for both groups. GYM is associated not only with an increase in aBMD but also an improvement in bone geometry associated with an increase in bone remodelling. These adaptations seem to be independent of the OPG/RANKL system.

A probable case of gigantism/acromegaly in skeletal remains from the Jewish necropolis of "Ronda Sur" (Lucena, Córdoba, Spain; VIII-XII centuries CE).

PubMed

Viciano, Joan; De Luca, Stefano; López-Lázaro, Sandra; Botella, Daniel; Diéguez-Ramírez, Juan Pablo

2015-01-01

Pituitary gigantism is a rare endocrine disorder caused by hypersecretion of growth hormone during growing period. Individuals with this disorder have an enormous growth in height and associated degenerative changes. The continued hypersecretion of growth hormone during adulthood leads to acromegaly, a condition related to the disproportionate bone growth of the skull, hands and feet. The skeletal remains studied belong to a young adult male from the Jewish necropolis of "Ronda Sur" in Lucena (Córdoba, Spain, VIII-XII centuries CE). The individual shows a very large and thick neurocranium, pronounced supraorbital ridges, an extremely prominent occipital protuberance, and an extremely large and massive mandible. Additional pathologies include enlargement of the vertebral bodies with degenerative changes, thickened ribs, and a slight increased length of the diaphysis with an increased cortical bone thickness of lower limbs. Comparative metric analysis of the mandible with other individuals from the same population and a contemporary Mediterranean population shows a trend toward acromegalic morphology. This case is an important contribution in paleopathological literature because it is a rare condition that has not been widely documented in ancient skeletal remains.

Hydrogen-rich saline prevents bone loss in diabetic rats induced by streptozotocin.

PubMed

Guo, Jialiang; Dong, Weichong; Jin, Lin; Wang, Pengcheng; Hou, Zhiyong; Zhang, Yingze

2017-10-01

As an antioxidant molecule, hydrogen has been received much more attention and reported to be used as the treatment strategy for various diseases. In this study, we hypothesize that systemic delivery of hydrogen saline water may improve the reservation of bone tissue in the tibias and femurs of osteoporotic rats caused by diabetes mellitus (DM), which is characterized by increased levels of oxidative stress and overproducing reactive oxygen species (ROS). The animals were divided into three groups of 12 animals and lavaged with normal saline (normal control and DM), or hydrogen saline water (DM + HRS). General status, blood glucose level, tibial and femoral mechanical strength, and micro-CT scans of the proximal tibia were recorded and analyzed. After 12 weeks, the glucose level was significantly decreased in the DM + HRS group compared with that of the DM group. Micro-CT scans showed that bone volume/total volume, connectivity density, trabecular thickness, and trabecular number were significantly increased compared with the DM group. Mechanical results of energy, stiffness and elastic modulus in the DM + HRS group were significantly higher than in the other groups for the tibia and femur. The results indicate that the systemic delivery of hydrogen saline water, which is safe and well tolerated, preserves bone volume and decreases fracture risks in streptozotocin-induced diabetic status rats, whose bone structure or inherent material properties of bone tissues are changed.

In silico biology of bone modelling and remodelling: adaptation.

PubMed

Gerhard, Friederike A; Webster, Duncan J; van Lenthe, G Harry; Müller, Ralph

2009-05-28

Modelling and remodelling are the processes by which bone adapts its shape and internal structure to external influences. However, the cellular mechanisms triggering osteoclastic resorption and osteoblastic formation are still unknown. In order to investigate current biological theories, in silico models can be applied. In the past, most of these models were based on the continuum assumption, but some questions related to bone adaptation can be addressed better by models incorporating the trabecular microstructure. In this paper, existing simulation models are reviewed and one of the microstructural models is extended to test the hypothesis that bone adaptation can be simulated without particular knowledge of the local strain distribution in the bone. Validation using an experimental murine loading model showed that this is possible. Furthermore, the experimental model revealed that bone formation cannot be attributed only to an increase in trabecular thickness but also to structural reorganization including the growth of new trabeculae. How these new trabeculae arise is still an unresolved issue and might be better addressed by incorporating other levels of hierarchy, especially the cellular level. The cellular level sheds light on the activity and interplay between the different cell types, leading to the effective change in the whole bone. For this reason, hierarchical multi-scale simulations might help in the future to better understand the biomathematical laws behind bone adaptation.

Deep tissue imaging of microfracture and non-displaced fracture of bone using the second and third near-infrared therapeutic windows

NASA Astrophysics Data System (ADS)

Sordillo, Laura A.; Pu, Yang; Sordillo, P. P.; Budansky, Yury; Alfano, Robert R.

2014-03-01

Near-infrared (NIR) light in the wavelengths of 700 nm to 2,000 nm has three NIR optical, or therapeutic, windows, which allow for deeper depth penetration in scattering tissue media. Microfractures secondary to repetitive stress, particularly in the lower extremities, are an important problem for military recruits and athletes. They also frequently occur in the elderly, or in patients taking bisphosphonates or denosumab. Microfractures can be early predictors of a major bone fracture. Using the second and third NIR therapeutic windows, we investigated the results from images of chicken bone and human tibial bone with microfractures and non-displaced fractures with and without overlying tissues of various thicknesses. Images of bone with microfractures and non-displaced fractures with tissue show scattering photons in the third NIR window with wavelengths between 1,650 nm and 1,870 nm are diminished and absorption is increased slightly from and second NIR windows. Results from images of fractured bones show the attenuation length of light through tissue in the third optical window to be larger than in the second therapeutic window. Use of these windows may aid in the detection of bone microfractures, and thus reduce the incidence of major bone fracture in susceptible groups.

Bone Marrow Oxytocin Mediates the Anabolic Action of Estrogen on the Skeleton*

PubMed Central

Colaianni, Graziana; Sun, Li; Di Benedetto, Adriana; Tamma, Roberto; Zhu, Ling-Ling; Cao, Jay; Grano, Maria; Yuen, Tony; Colucci, Sylvia; Cuscito, Concetta; Mancini, Lucia; Li, Jianhua; Nishimori, Katsuhiko; Bab, Itai; Lee, Heon-Jin; Iqbal, Jameel; Young, W. Scott; Rosen, Clifford; Zallone, Alberta; Zaidi, Mone

2012-01-01

Estrogen uses two mechanisms to exert its effect on the skeleton: it inhibits bone resorption by osteoclasts and, at higher doses, can stimulate bone formation. Although the antiresorptive action of estrogen arises from the inhibition of the MAPK JNK, the mechanism of its effect on the osteoblast remains unclear. Here, we report that the anabolic action of estrogen in mice occurs, at least in part, through oxytocin (OT) produced by osteoblasts in bone marrow. We show that the absence of OT receptors (OTRs) in OTR−/− osteoblasts or attenuation of OTR expression in silenced cells inhibits estrogen-induced osteoblast differentiation, transcription factor up-regulation, and/or OT production in vitro. In vivo, OTR−/− mice, known to have a bone formation defect, fail to display increases in trabecular bone volume, cortical thickness, and bone formation in response to estrogen. Furthermore, osteoblast-specific Col2.3-Cre+/OTRfl/fl mice, but not TRAP-Cre+/OTRfl/fl mice, mimic the OTR−/− phenotype and also fail to respond to estrogen. These data attribute the phenotype of OTR deficiency to an osteoblastic rather than an osteoclastic defect. Physiologically, feed-forward OT release in bone marrow by a rising estrogen concentration may facilitate rapid skeletal recovery during the latter phases of lactation. PMID:22761429

Additive Effects of Mechanical Marrow Ablation and PTH Treatment on de Novo Bone Formation in Mature Adult Rats

PubMed Central

Zhang, Qing; Miller, Christopher; Bible, Jesse; Li, Jiliang; Xu, Xiaoqing; Mehta, Nozer; Gilligan, James; Vignery, Agnès; Scholz, Jodi A Carlson

2012-01-01

Mechanical ablation of bone marrow in young rats induces rapid but transient bone growth, which can be enhanced and maintained for three weeks by the administration of parathyroid hormone (PTH). Additionally, marrow ablation, followed by PTH treatment for three months leads to increased cortical thickness. In this study, we sought to determine whether PTH enhances bone formation after marrow ablation in aged rats. Aged rats underwent unilateral femoral marrow ablation and treatment with PTH or vehicle for four weeks. Both femurs from each rat were analyzed by X-ray and pQCT, then analyzed either by microCT, histology or biomechanical testing. Marrow ablation alone induced transient bone formation of low abundance that persisted over four weeks, while marrow ablation followed by PTH induced bone formation of high abundance that also persisted over four weeks. Our data confirms that the osteo-inducive effect of marrow ablation and the additive effect of marrow ablation, followed by PTH, occurs in aged rats. Our observations open new avenues of investigations in the field of tissue regeneration. Local marrow ablation, in conjunction with an anabolic agent, might provide a new platform for rapid site-directed bone growth in areas of high bone loss, such as in the hip and wrist, which are subject to fracture. PMID:24710549

ECM Inspired Coating of Embroidered 3D Scaffolds Enhances Calvaria Bone Regeneration

PubMed Central

Rentsch, C.; Rentsch, B.; Heinemann, S.; Bernhardt, R.; Bischoff, B.; Förster, Y.; Scharnweber, D.; Rammelt, S.

2014-01-01

Resorbable polymeric implants and surface coatings are an emerging technology to treat bone defects and increase bone formation. This approach is of special interest in anatomical regions like the calvaria since adults lose the capacity to heal large calvarial defects. The present study assesses the potential of extracellular matrix inspired, embroidered polycaprolactone-co-lactide (PCL) scaffolds for the treatment of 13 mm full thickness calvarial bone defects in rabbits. Moreover the influence of a collagen/chondroitin sulfate (coll I/cs) coating of PCL scaffolds was evaluated. Defect areas filled with autologous bone and empty defects served as reference. The healing process was monitored over 6 months by combining a novel ultrasonographic method, radiographic imaging, biomechanical testing, and histology. The PCL coll I/cs treated group reached 68% new bone volume compared to the autologous group (100%) and the biomechanical stability of the defect area was similar to that of the gold standard. Histological investigations revealed a significantly more homogenous bone distribution over the whole defect area in the PCL coll I/cs group compared to the noncoated group. The bioactive, coll I/cs coated, highly porous, 3-dimensional PCL scaffold acted as a guide rail for new skull bone formation along and into the implant. PMID:25013767

The Erratic Behavior of Lesions in Burnt Bone.

PubMed

Collini, Federica; Amadasi, Alberto; Mazzucchi, Alessandra; Porta, Davide; Regazzola, Valeria Luisa; Garofalo, Paola; Di Blasio, Annalisa; Cattaneo, Cristina

2015-09-01

This study analyses depressed fractures (by blunt force trauma) and circular full-thickness injuries (drill injuries and gunshot wounds) in charred bones. Fifty bovine ribs (total 104 lesions) were divided into three groups. The first group consisted in 20 depressed hammer-produced fractures; in the second one, 60 round drill-holes were produced (30 circular, 30 semicircular); in the third group, 12 fleshed and 12 skeletonized ribs were hit by 9-mm bullets. Each specimen was carbonized in an electric oven up to 800°C. Morphological and metric analyses were performed before and after: morphological features were preserved, but depressed fractures showed an increase in their dimensions (p-value<0.05); the drilled holes shrunk (p-value<0.01); the charring cycle increased the number of fractures in samples with gunshot wounds differently in fleshed and defleshed ribs. This study showed the complex behavior of charred bone, for what concerns the interpretation of trauma and how caution should be applied. © 2015 American Academy of Forensic Sciences.

Effect of in vitro chondrogenic differentiation of autologous mesenchymal stem cells on cartilage and subchondral cancellous bone repair in osteoarthritis of temporomandibular joint.

PubMed

Chen, K; Man, C; Zhang, B; Hu, J; Zhu, S S

2013-02-01

This study investigated the effects of in vitro chondrogenic differentiated mesenchymal stem cells (MSCs) on cartilage and subchondral cancellous bone in temporomandibular joint osteoarthritis (TMJOA). Four weeks after induction of osteoarthritis (OA), the joints received hylartin solution, non-chondrogenic MSCs or in vitro chondrogenic differentiated MSCs. The changes in cartilage and subchondral cancellous bone were evaluated by histology, reverse transcription polymerase chain reaction and micro-computed tomography (CT). Implanted cells were tracked using Adeno-LacZ labelling. The differentiated MSC-treated group had better histology than the MSC-treated group at 4 and 12 weeks, but no difference at 24 weeks. Increased mRNA expression of collegan II, aggeran, Sox9 and decreased matrix metalloproteinase 13 (MMP13) were observed in differentiated MSC-treated groups compared to the undifferentiated MSC-treated group at 4 weeks. The differentiated MSC-treated group had decreased bone volume fraction, trabecular thickness and bone surface density, and increased trabecular spacing in the subchondral cancellous bone than the undifferentiated MSC-treated group. Transplanted cells were observed at cartilage, subchondral bone, and the synovial membrane lining at 4 weeks. Intra-articular injection of MSCs could delay the progression of TMJOA, and in vitro chondrogenic induction of MSCs could enhance the therapeutic effects. This provides new insights into the role of MSCs in cell-based therapies for TMJOA. Copyright © 2012 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Collagen Self-Assembly on Orthopedic Magnesium Biomaterials Surface and Subsequent Bone Cell Attachment

PubMed Central

Zhao, Nan; Zhu, Donghui

2014-01-01

Magnesium (Mg) biomaterials are a new generation of biodegradable materials and have promising potential for orthopedic applications. After implantation in bone tissues, these materials will directly interact with extracellular matrix (ECM) biomolecules and bone cells. Type I collagen, the major component of bone ECM, forms the architecture scaffold that provides physical support for bone cell attachment. However, it is still unknown how Mg substrate affects collagen assembly on top of it as well as subsequent cell attachment and growth. Here, we studied the effects of collagen monomer concentration, pH, assembly time, and surface roughness of two Mg materials (pure Mg and AZ31) on collagen fibril formation. Results showed that formation of fibrils would not initiate until the monomer concentration reached a certain level depending on the type of Mg material. The thickness of collagen fibril increased with the increase of assembly time. The structures of collagen fibrils formed on semi-rough surfaces of Mg materials have a high similarity to that of native bone collagen. Next, cell attachment and growth after collagen assembly were examined. Materials with rough surface showed higher collagen adsorption but compromised bone cell attachment. Interestingly, surface roughness and collagen structure did not affect cell growth on AZ31 for up to a week. Findings from this work provide some insightful information on Mg-tissue interaction at the interface and guidance for future surface modifications of Mg biomaterials. PMID:25303459

Odanacatib Restores Trabecular Bone of Skeletally Mature Female Rabbits With Osteopenia but Induces Brittleness of Cortical Bone: A Comparative Study of the Investigational Drug With PTH, Estrogen, and Alendronate.

PubMed

Khan, Mohd Parvez; Singh, Atul Kumar; Singh, Abhishek Kumar; Shrivastava, Pragya; Tiwari, Mahesh Chandra; Nagar, Geet Kumar; Bora, Himangshu Kousik; Parameswaran, Venkitanarayanan; Sanyal, Sabyasachi; Bellare, Jayesh R; Chattopadhyay, Naibedya

2016-03-01

Cathepsin K (CK), a lysosomal cysteine protease, is highly expressed in mature osteoclasts and degrades type 1 collagen. Odanacatib (ODN) is a selective and reversible CK inhibitor that inhibits bone loss in preclinical and clinical studies. Although an antiresorptive, ODN does not suppress bone formation, which led us to hypothesize that ODN may display restorative effect on the osteopenic bones. In a curative study, skeletally mature New Zealand rabbits were ovarectomized (OVX) and after induction of bone loss were given a steady-state exposure of ODN (9 mM/d) for 14 weeks. Sham-operated and OVX rabbits treated with alendronate (ALD), 17b-estradiol (E2), or parathyroid hormone (PTH) served as various controls. Efficacy was evaluated by assessing bone mineral density (BMD), bone microarchitecture (using micro-computed tomography), fluorescent labeling of bone, and biomechanical strength. Skeletal Ca/P ratio was measured by scanning electron microscopy (SEM) with X-ray microanalysis, crystallinity by X-ray diffraction, and bone mineral density distribution (tissue mineralization) by backscattered SEM. Between the sham and ODN-treated osteopenic groups, lumbar and femur metaphyseal BMD, Ca/P ratio, trabecular microstructure and geometric indices, vertebral compressive strength, trabecular lining cells, cortical parameters (femoral area and thickness and periosteal deposition), and serum P1NP were largely comparable. Skeletal improvements in ALD-treated or E2-treated groups fell significantly short of the sham/ODN/PTH group. However, the ODN group displayed reduced ductility and enhanced brittleness of central femur, which might have been contributed by higher crytallinity and tissue mineralization. Rabbit bone marrow stromal cells expressed CK and when treated with ODN displayed increased formation of mineralized nodules and decreased apoptosis in serum-deficient medium compared with control. In vivo, ODN did not suppress remodeling but inhibited osteoclast activity more than ALD. Taken together, we show that ODN reverses BMD, skeletal architecture, and compressive strength in osteopenic rabbits; however, it increases crystallinity and tissue mineralization, thus leading to increased cortical bone brittleness. © 2015 American Society for Bone and Mineral Research.

Protective effects of Tualang honey on bone structure in experimental postmenopausal rats

PubMed Central

Zaid, Siti Sarah Mohamad; Sulaiman, Siti Amrah; Othman, Nor Hayati; Soelaiman, Ima-Nirwana; Shuid, Ahmad Nazrun; Mohamad, Norazlina; Muhamad, Norliza

2012-01-01

OBJECTIVE: The objective of this study was to evaluate the effects of Tualang honey on trabecular structure and compare these effects with those of calcium supplementation in ovariectomized rats. METHODS: Forty female, Sprague-Dawley rats were randomly divided into five groups (n = 8): four controls and one test arm. The control arm comprised a baseline control, sham-operated control, ovariectomized control, and ovariectomized calcium-treated rats (receiving 1% calcium in drinking water ad libitum). The test arm was composed of ovariectomized, Tualang honey-treated rats (received 0.2 g/kg body weight of Tualang honey). Both the sham-operated control and ovariectomized control groups received vehicle treatment (deionized water), and the baseline control group was sacrificed without treatment. RESULTS: All rats were orally gavaged daily for six weeks after day one post-surgery. The bone structural analysis of rats in the test arm group showed a significant increase in the bone volume per tissue volume (BV/TV), trabecular thickness (Tb.Th) and trabecular number (Tb.N) and a significant decrease in inter-trabecular space (Tb.Sp) compared with the ovariectomized control group. The trabecular thickness (Tb.Th) in the test arm group was significantly higher compared with the ovariectomized-calcium treated group, and the inter-trabecular space (Tb.Sp) in the test arm group was significantly narrower compared with the ovariectomized-calcium treated group. CONCLUSION: In conclusion, ovariectomized rats that received Tualang honey showed more improvements in trabecular bone structure than the rats that received calcium. PMID:22892923

Protective effects of Tualang honey on bone structure in experimental postmenopausal rats.

PubMed

Zaid, Siti Sarah Mohamad; Sulaiman, Siti Amrah; Othman, Nor Hayati; Soelaiman, Ima-Nirwana; Shuid, Ahmad Nazrun; Mohamad, Norazlina; Muhamad, Norliza

2012-07-01

The objective of this study was to evaluate the effects of Tualang honey on trabecular structure and compare these effects with those of calcium supplementation in ovariectomized rats. Forty female, Sprague-Dawley rats were randomly divided into five groups (n =8): four controls and one test arm. The control arm comprised a baseline control, sham-operated control, ovariectomized control, and ovariectomized calcium-treated rats (receiving 1% calcium in drinking water ad libitum). The test arm was composed of ovariectomized, Tualang honey-treated rats (received 0.2 g/kg body weight of Tualang honey). Both the sham-operated control and ovariectomized control groups received vehicle treatment (deionized water), and the baseline control group was sacrificed without treatment. All rats were orally gavaged daily for six weeks after day one post-surgery. The bone structural analysis of rats in the test arm group showed a significant increase in the bone volume per tissue volume (BV/TV), trabecular thickness (Tb.Th) and trabecular number (Tb.N) and a significant decrease in inter-trabecular space (Tb.Sp) compared with the ovariectomized control group. The trabecular thickness (Tb.Th) in the test arm group was significantly higher compared with the ovariectomized-calcium treated group, and the inter-trabecular space (Tb.Sp) in the test arm group was significantly narrower compared with the ovariectomized-calcium treated group. In conclusion, ovariectomized rats that received Tualang honey showed more improvements in trabecular bone structure than the rats that received calcium.

Prevalence of vitamin D insufficiency among adolescents and its correlation with bone parameters using high-resolution peripheral quantitative computed tomography.

PubMed

Cheung, T F; Cheuk, K Y; Yu, F W P; Hung, V W Y; Ho, C S; Zhu, T Y; Ng, B K W; Lee, K M; Qin, L; Ho, S S Y; Wong, G W K; Cheng, J C Y; Lam, T P

2016-08-01

Vitamin D deficiency and insufficiency are highly prevalent among adolescents in Hong Kong, which is a sub-tropical city with ample sunshine. Vitamin D level is significantly correlated with key bone density and bone quality parameters. Further interventional studies are warranted to define the role of vitamin D supplementation for improvement of bone health among adolescents. The relationship between bone quality parameters and vitamin D (Vit-D) status remains undefined among adolescents. The aims of this study were to evaluate Vit-D status and its association with both bone density and bone quality parameters among adolescents. Three hundred thirty-three girls and 230 boys (12-16 years old) with normal health were recruited in summer and winter separately from local schools. Serum 25(OH) Vit-D level, bone density and quality parameters by Dual Energy X-ray Absorptiometry (DXA) and High-Resolution peripheral Quantitative Computed Tomography (HR-pQCT), dietary calcium intake, and physical activity level were assessed. Sixty-four point seven percent and 11.4 % of subjects were insufficient [25 ≤ 25(OH)Vit-D ≤ 50 nmol/L] and deficient [25(OH)Vit-D < 25 nmol/L] in Vit-D, respectively. The mean level of serum 25(OH)Vit-D in summer was significantly higher than that in winter (44.7 ± 13.6 and 35.9 ± 12.6 nmol/L, respectively) without obvious gender difference. In girls, areal bone mineral density (aBMD) and bone mineral content (BMC) of bilateral femoral necks, cortical area, cortical thickness, total volumetric bone mineral density (vBMD), and trabecular thickness were significantly correlated with 25(OH)Vit-D levels. In boys, aBMD of bilateral femoral necks, BMC of the dominant femoral neck, cortical area, cortical thickness, total vBMD, trabecular vBMD, BV/TV, and trabecular separation were significantly correlated with 25(OH)Vit-D levels. Vit-D insufficiency was highly prevalent among adolescents in Hong Kong with significant correlation between Vit-D levels and key bone density and bone quality parameters being detected in this study. Given that this is a cross-sectional study and causality relationship cannot be inferred, further interventional studies investigating the role of Vit-D supplementation on improving bone health among adolescents are warranted.

Stretch force guides finger-like pattern of bone formation in suture

PubMed Central

Kou, Xiao-Xing; Zhang, Ci; Zhang, Yi-Mei; Cui, Zhen; Wang, Xue-Dong; Liu, Yan; Liu, Da-Wei; Zhou, Yan-Heng

2017-01-01

Mechanical tension is widely applied on the suture to modulate the growth of craniofacial bones. Deeply understanding the features of bone formation in expanding sutures could help us to improve the outcomes of clinical treatment and avoid some side effects. Although there are reports that have uncovered some biological characteristics, the regular pattern of sutural bone formation in response to expansion forces is still unknown. Our study was to investigate the shape, arrangement and orientation of new bone formation in expanding sutures and explore related clinical implications. The premaxillary sutures of rat, which histologically resembles the sutures of human beings, became wider progressively under stretch force. Micro-CT detected new bones at day 3. Morphologically, these bones were forming in a finger-like pattern, projecting from the maxillae into the expanded sutures. There were about 4 finger-like bones appearing on the selected micro-CT sections at day 3 and this number increased to about 18 at day 7. The average length of these projections increased from 0.14 mm at day 3 to 0.81 mm at day 7. The volume of these bony protuberances increased to the highest level of 0.12 mm3 at day 7. HE staining demonstrated that these finger-like bones had thick bases connecting with the maxillae and thin fronts stretching into the expanded suture. Nasal sections had a higher frequency of finger-like bones occuring than the oral sections at day 3 and day 5. Masson-stained sections showed stretched fibers embedding into maxillary margins. Osteocalcin-positive osteoblasts changed their shapes from cuboidal to spindle and covered the surfaces of finger-like bones continuously. Alizarin red S and calcein deposited in the inner and outer layers of finger-like bones respectively, which showed that longer and larger bones formed on the nasal side of expanded sutures compared with the oral side. Interestingly, these finger-like bones were almost paralleling with the direction of stretch force. Inclined force led to inclined finger-like bones formation and deflection of bilateral maxillae. Additionally, heavily compressive force caused fracture of finger-like bones in the sutures. These data together proposed the special finger-like pattern of bone formation in sutures guided by stretch force, providing important implications for maxillary expansion. PMID:28472133

Comparison of bone histomorphometry and μCT for evaluating bone quality in tail-suspended rats

NASA Astrophysics Data System (ADS)

Sun, Lian-Wen; Huang, Yun-Fei; Wang, Ying; Luan, Hui-Qin; Fan, Yu-Bo

2014-10-01

Astronauts often suffer from microgravity-induced osteoporosis due to their time in space. Bone histomorphometry, the 'gold standard' technique for detecting bone quality, is widely used in the evaluation of osteoporosis. This study investigates whether μCT has the same application value as histomorphometry in the evaluation of weightlessness-induced bone loss. A total of 24 SD rats were distributed into three groups (n = 8, each): tail-suspension (TS), TS plus active exercise (TSA), and control (CON). After 21 days, bone mineral density (BMD) was measured by dual energy X-ray absorptiometry (DXA) and μCT, and microstructure was measured by μCT and histomorphometry. BMD was found to have decreased significantly in TS and TSA compared with the CON group. The results of the μCT measurements showed that a change in BMD mainly occurred in the trabecular bone, and the trabecular BMD increased significantly in the TSA compared with the TS group. The comparison of μCT and histomorphometry showed that TS led to a significant decrease in bone volume (BV/TV), trabecular thickness (Tb.Th) and trabecular number (Tb.N), and it led to an increase in trabecular separation (Tb.Sp). However, active exercise can prevent these changes. Significant differences in most parameters between TSA and CON were found by μCT but not by histomorphometry. Additionally, the parameters of these two methods are highly correlated. Therefore, the application value of μCT is as good as histomorphometry and DXA in the diagnosis of weightlessness-induced osteoporosis and is even better in evaluating the efficacy of exercise.

Dioxin-induced up-regulation of the active form of vitamin D is the main cause for its inhibitory action on osteoblast activities, leading to developmental bone toxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nishimura, Noriko; Nishimura, Hisao; Ito, Tomohiro

2009-05-01

Dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD) is known to cause bone toxicity, particularly during animal development, although its action mechanism to cause this toxicity has yet to be elucidated. Mouse pups were exposed to TCDD via dam's milk that were administered orally with 15 {mu}g TCDD/kg b.w. on postnatal day 1. Here we report that TCDD causes up-regulation of vitamin D 1{alpha}-hydroxylase in kidney, resulting in a 2-fold increase in the active form of vitamin D, 1,25-dihydroxyvitamin D{sub 3}, in serum. This action of TCDD is not caused by changes in parathyroid hormone, a decrease in vitamin D degrading enzyme, vitamin D 24-hydroxylase,more » or alterations in serum Ca{sup 2+} concentration. Vitamin D is known to affect bone mineralization. Our data clearly show that TCDD-exposed mice exhibit a marked decrease in osteocalcin and collagen type 1 as well as alkaline phosphatase gene expression in tibia by postnatal day 21, which is accompanied with a mineralization defect in the tibia, lowered activity of osteoblastic bone formation, and an increase in fibroblastic growth factor-23, a sign of increased vitamin D effect. Despite these significant effects of TCDD on osteoblast activities, none of the markers of osteoclast activities was found to be affected. Histomorphometry confirmed that osteoblastic activity, but not bone resorption activity, was altered by TCDD. A prominent lesion commonly observed in these TCDD-treated mice was impaired bone mineralization that is characterized by an increased volume and thickness of osteoids lining both the endosteum of the cortical bone and trabeculae. Together, these data suggest that the impaired mineralization resulting from reduction of the osteoblastic activity, which is caused by TCDD-induced up-regulation of vitamin D, is responsible for its bone developmental toxicity.« less

Effects of ethanol consumption and alcohol detoxification on the biomechanics and morphology the bone in rat femurs.

PubMed

Garcia, J A D; Souza, A L T; Cruz, L H C; Marques, P P; Camilli, J A; Nakagaki, W R; Esteves, A; Rossi-Junior, W C; Fernandes, G J M; Guerra, F D; Soares, E A

2015-11-01

The objective of this study was to verify the effects of ethanol consumption and alcohol detoxification on the biomechanics, area and thickness of cortical and trabecular bone in rat femur. This was an experimental study in which 18 male Wistar rats were used, with 40 days of age, weighing 179 ± 2.5 g. The rats were divided into three groups (n=06): CT (control), AC (chronic alcoholic), DT (detoxification). After experimental procedures, the animals were euthanized by an overdose of the anesthetic and their femurs were collected for mechanical testing and histological processing. All animals did not present malnutrition or dehydration during experimentation period. Morphometric analysis of cortical and trabecular bones in rat femurs demonstrated that AC animals showed inferior dimensions and alcohol detoxification (DT) allowed an enhancement in area and thickness of cortical and trabecular bone. Material and structural properties data of AC group highlighted the harmful effects of ethanol on bone mechanical properties. The results of this study demonstrated that chronic alcoholic rats (AC) presented major bone damage in all analyzed variables. Those findings suggested that alcohol detoxification is highly suggested in pre-operative planning and this corroborates to the success of bone surgery and bone tissue repair. Thanks to the financial support offered by PROBIC - UNIFENAS.

Early bone growth on the surface of titanium implants in rat femur is enhanced by an amorphous diamond coating.

PubMed

Jaatinen, Jarkko J P; Korhonen, Rami K; Pelttari, Alpo; Helminen, Heikki J; Korhonen, Hannu; Lappalainen, Reijo; Kröger, Heikki

2011-08-01

Amorphous diamond (AD) is a durable and compatible biomaterial for joint prostheses. Knowledge regarding bone growth on AD-coated implants and their early-stage osseointegration is poor. We investigated bone growth on AD-coated cementless intramedullary implants implanted in rats. Titanium was chosen as a reference due to its well-known performance. We placed AD-coated and non-coated titanium implants (R(a) ≈ 0.2 μm) into the femoral bone marrow of 25 rats. The animals were divided in 2 groups according to implant coating and they were killed after 4 or 12 weeks. The osseointegration of the implants was examined from hard tissue specimens by measuring the new bone formation on their surface. 4 weeks after the operation, the thickness of new bone in the AD-coated group was greater than that in the non-coated group (15.3 (SD 7.1) μm vs. 7.6 (SD 6.0) μm). 12 weeks after the operation, the thickness of new bone was similar in the non-coated group and in the AD-coated group. We conclude that AD coating of femoral implants can enhance bone ongrowth in rats in the acute, early stage after the operation and might be an improvement over earlier coatings.

Stem cell niches and other factors that influence the sensitivity of bone marrow to radiation-induced bone cancer and leukaemia in children and adults

PubMed Central

Richardson, Richard B

2011-01-01

Purpose: This paper reviews and reassesses the internationally accepted niches or ‘targets’ in bone marrow that are sensitive to the induction of leukaemia and primary bone cancer by radiation. Conclusions: The hypoxic conditions of the 10 μm thick endosteal/osteoblastic niche where preleukemic stem cells and hematopoietic stem cells (HSC) reside provides a radioprotective microenvironment that is 2-to 3-fold less radiosensitive than vascular niches. This supports partitioning the whole marrow target between the low haematological cancer risk of irradiating HSC in the endosteum and the vascular niches within central marrow. There is a greater risk of induced bone cancer when irradiating a 50 μm thick peripheral marrow adjacent to the remodelling/reforming portion of the trabecular bone surface, rather than marrow next to the quiescent bone surface. This choice of partitioned bone cancer target is substantiated by the greater radiosensitivity of: (i) Bone with high remodelling rates, (ii) the young, (iii) individuals with hypermetabolic benign diseases of bone, and (iv) the epidemiology of alpha-emitting exposures. Evidence is given to show that the absence of excess bone-cancer in atomic-bomb survivors may be partially related to the extremely low prevalence among Japanese of Paget's disease of bone. Radiation-induced fibrosis and the wound healing response may be implicated in not only radiogenic bone cancers but also leukaemia. A novel biological mechanism for adaptive response, and possibility of dynamic targets, is advocated whereby stem cells migrate from vascular niches to stress-mitigated, hypoxic niches. PMID:21204614

Association Between Insulin Resistance and Bone Structure in Nondiabetic Postmenopausal Women.

PubMed

Shanbhogue, Vikram V; Finkelstein, Joel S; Bouxsein, Mary L; Yu, Elaine W

2016-08-01

The clinical consequences of insulin resistance and hyperinsulinemia on bone remain largely unknown. The objective of the study was to evaluate the effect of insulin resistance on peripheral bone geometry, volumetric bone mineral density (vBMD), bone microarchitecture, and estimated bone strength. This cross-sectional study included 146 postmenopausal, nondiabetic Caucasian women (mean age 60.3 ± 2.7 y) who were participating in the Study of Women's Health Across the Nation. There were no interventions. High-resolution peripheral quantitative computed tomography was used to assess bone density and microstructure at the distal radius and tibia. Fasting insulin and glucose were measured and insulin resistance was estimated using homeostasis model assessment of insulin resistance (HOMA-IR), with higher values indicating greater insulin resistance. There was a negative association between HOMA-IR and bone size and a positive association between HOMA-IR and total vBMD, trabecular vBMD, trabecular thickness, and cortical thickness at the radius and tibia. These relationships remained, even after adjusting for body weight and other potential covariates (eg, time since menopause, cigarette smoking, physical activity, prior use of osteoporosis medications or glucocorticoids). In nondiabetic, postmenopausal women, insulin resistance was associated with smaller bone size, greater volumetric bone mineral density, and generally favorable bone microarchitecture at weight-bearing and nonweight-bearing skeletal sites. These associations were independent of body weight and other potential covariates, suggesting that hyperinsulinemia directly affects bone structure independent of obesity and may explain, in part, the higher trabecular bone density and favorable trabecular microarchitecture seen in individuals with type 2 diabetes mellitus.

Effect of Limb Lengthening on Internodal Length and Conduction Velocity of Peripheral Nerve

PubMed Central

Gillingwater, Thomas H.; Anderson, Heather; Cottrell, David; Sherman, Diane L.; Ribchester, Richard R.; Brophy, Peter J.

2013-01-01

The influences of axon diameter, myelin thickness, and internodal length on the velocity of conduction of peripheral nerve action potentials are unclear. Previous studies have demonstrated a strong dependence of conduction velocity on internodal length. However, a theoretical analysis has suggested that this relationship may be lost above a nodal separation of ∼0.6 mm. Here we measured nerve conduction velocities in a rabbit model of limb lengthening that produced compensatory increases in peripheral nerve growth. Divided tibial bones in one hindlimb were gradually lengthened at 0.7 mm per day using an external frame attached to the bone. This was associated with a significant increase (33%) of internodal length (0.95–1.3 mm) in axons of the tibial nerve that varied in proportion to the mechanical strain in the nerve of the lengthened limb. Axonal diameter, myelin thickness, and g-ratios were not significantly altered by limb lengthening. Despite the substantial increase in internodal length, no significant change was detected in conduction velocity (∼43 m/s) measured either in vivo or in isolated tibial nerves. The results demonstrate that the internode remains plastic in the adult but that increases in internodal length of myelinated adult nerve axons do not result in either deficiency or proportionate increases in their conduction velocity and support the view that the internodal lengths of nerves reach a plateau beyond which their conduction velocities are no longer sensitive to increases in internodal length. PMID:23467369

High-intensity exercise of short duration alters bovine bone density and shape.

PubMed

Hiney, K M; Nielsen, B D; Rosenstein, D; Orth, M W; Marks, B P

2004-06-01

The ability of short-duration high-intensity exercise to stimulate bone formation in confinement was investigated using immature Holstein bull calves as a model. Eighteen bull calves, 8 wk of age, were assigned to one of three treatment groups: 1) group-housed (GR, which served as a control), 2) confined with no exercise (CF), or 3) confined with exercise (EX). The exercise protocol consisted of running 50 m on a concrete surface once daily, 5 d/wk. Confined calves remained stalled for the 42-d duration of the trial. Blood samples were taken to analyze concentrations of osteocalcin and deoxypyridinoline, markers of bone formation and resorption. At the completion of the trial, calves were humanely killed, and both forelegs were collected. The fused third and fourth metacarpal bone was scanned using computed tomography for determination of cross-sectional geometry and bone mineral density. Three-point bending tests to failure were performed on metacarpal bones. The exercise protocol resulted in the formation of a rounder bone in EX as well as in increased dorsal cortex thickness compared with those in the GR and CF. The exercised calves had a significantly smaller medullary cavity than CF and GR (P < 0.01) and a larger percentage of cortical bone area than CF (P < 0.01). Dorsal, palmar, and total bone mineral density was greater in EX than in CF (P < 0.05), and palmar and total bone mineral densities were greater (P < 0.05) in EX than in GR. There was a trend for the bones of EX to have a higher fracture force than CF (P < 0.10). Osteocalcin concentrations normalized from d 0 were higher in EX than CF (P < 0.05). Therefore, the exercise protocol altered bone shape and seemed to increase bone formation comparison with the stalled and group-housed calves.

Effect of laser phototherapy on human alveolar bone repair: micro tomographic and histomorphometrical analysis

NASA Astrophysics Data System (ADS)

Romão, Marcia M. A.; Marques, Márcia M.; Cortes, Arthur R. G.; Horliana, Anna C. R. T.; Moreira, Maria S.; Lascala, Cesar A.

2015-06-01

The immediate dental implant placement in the molars region is critical, because of the high amount of bone loss and the discrepancy between the alveolar crest thickness and the dental implant platform. Laser phototherapy (LPT) improves bone repair thus could accelerate the implant placement. Twenty patients were selected for the study. Ten patients were submitted to LPT with GaAlAs diode laser (808nm) during molar extraction, immediately after, 24h, 48h, 72h, 96h and 7 days. The irradiations were applied in contact and punctual mode (100mW, 0.04cm2, 0.75J/cm2, 30s per point, 3J per point). The control group (n=10) received the same treatment; however with the power of the laser off. Forty days later samples of the tissue formed inside the sockets were obtained for further microtomography (microCTs) and histomorphometry analyses. Data were compared by the Student t test, whereas those from the different microCT parameters were compared by the Pearson correlation test (p<0.05). The relative bone volume, as well as area was significantly higher (p<0.001) in the lased than the control group. In the control group there were negative correlations between number and thickness, and between number and separation of trabecula (p<0.01). Between thickness and separation of trabecula the correlation was positive (p<0.01). The laser group showed significant negative correlation between the number and the thickness of trabecula (p<0.01). LPT accelerated bone repair. By the Pearson correlation test it was possible to infer that the lased group presented a more homogeneous trabecular configuration, which would allow earlier dental implant placement.

Hydroxyapatite coating on cobalt alloys using electrophoretic deposition method for bone implant application

NASA Astrophysics Data System (ADS)

Aminatun; M, Shovita; I, Chintya K.; H, Dyah; W, Dwi

2017-05-01

Damage on bone due to osteoporosis and cancer triggered high demand for bone implant prosthesis which is a permanent implant. Thus, a prosthesis coated with hydroxyapatite (HA) is required because it is osteoconductive that can trigger the growth of osteoblast cells. The purpose of this study is to determine the optimum concentration of HA suspension in terms of the surface morphology, coating thickness, adhesion strength and corrosion rate resulting in the HA coating with the best characteristics for bone implant. Coating using electrophoretic deposition (EPD) method with concentrations of 0.02M, 0.04M, 0.06M, 0.08M, and 0.1M was performed on the voltage and time of 120V and 30 minutes respectively. The process was followed by sintering at the temperature of 900 °C for 10 minutes. The results showed that the concentration of HA suspension influences the thickness and the adhesion of layer of HA. The higher the concentration of HA-ethanol suspension the thicker the layer of HA, but its coating adhesion strength values became lower. The concentration of HA suspension of 0.04 M is the best concentration, with characteristics that meet the standards of the bone implant prosthesis. The characteristics are HA coating thickness of 199.93 ± 4.85 μm, the corrosion rate of 0.0018 mmpy and adhesion strength of 4.175 ± 0.716 MPa.

Bone microarchitecture and estimated bone strength in men with active acromegaly.

PubMed

Silva, Paula P B; Amlashi, Fatemeh G; Yu, Elaine W; Pulaski-Liebert, Karen J; Gerweck, Anu V; Fazeli, Pouneh K; Lawson, Elizabeth; Nachtigall, Lisa B; Biller, Beverly M K; Miller, Karen K; Klibanski, Anne; Bouxsein, Mary; Tritos, Nicholas A

2017-11-01

Both acromegaly and adult growth hormone deficiency (GHD) are associated with increased fracture risk. Sufficient data are lacking regarding cortical bone microarchitecture and bone strength, as assessed by microfinite element analysis (µFEA). To elucidate both cortical and trabecular bone microarchitecture and estimated bone strength in men with active acromegaly or GHD compared to healthy controls. Cross-sectional study at a clinical research center, including 48 men (16 with acromegaly, 16 with GHD and 16 healthy controls). Areal bone mineral density (aBMD), cortical and trabecular bone microarchitecture and estimated bone strength (µFEA) at the radius and tibia. aBMD was not different between the 3 groups at any skeletal site. At the radius, patients with acromegaly had greater cortical area ( P  < 0.0001), cortical thickness ( P  = 0.0038), cortical pore volume ( P  < 0.0001) and cortical porosity ( P  = 0.0008), but lower trabecular bone density ( P  = 0.0010) compared to controls. At the tibia, patients with acromegaly had lower trabecular bone density ( P  = 0.0082), but no differences in cortical bone microstructure. Compressive strength and failure load did not significantly differ between groups. These findings persisted after excluding patients with hypogonadism. Bone microarchitecture was not deficient in patients with GHD. Both cortical and trabecular microarchitecture are altered in men with acromegaly. Our data indicate that GH excess is associated with distinct effects in cortical vs trabecular bone compartments. Our observations also affirm the limitations of aBMD testing in the evaluation of patients with acromegaly. © 2017 European Society of Endocrinology.

Involvement of CD147 in alveolar bone remodeling and soft tissue degradation in experimental periodontitis.

PubMed

Yang, D; Liu, R; Liu, L; Liao, H; Wang, C; Cao, Z

2017-08-01

The objective of this study was to investigate the possible roles of clusters of differentiation 147 (CD147) in bone resorption and mineralization through the bone markers of bone sialoprotein, osteocalcin, osteopontin and alkaline phosphatase (ALP), trabecular structure of alveolar bone and number of osteoclasts. We also investigated the effects of CD147 on inflammation and collagen breakdown. Twenty-eight male Wistar rats were randomly divided into four groups of seven animals each: healthy group, periodontitis group, periodontitis + saline group and periodontitis + anti-CD147 groups. Hematoxylin and eosin staining were used for histological assessment. Alveolar bone loss and trabecula microstructure were evaluated using micro-computed tomography. Collagen fiber breakdown was assessed via picrosirius red staining. Tartrate-resistant acid phosphatase staining was conducted for osteoclast analysis. The expressions of ALP, bone sialoprotein, osteocalcin and osteopontin were evaluated using immunohistochemistry. Anti-CD147 treatment significantly inhibited alveolar bone loss and osteoclastogenesis, and improved the bone volume/tissue volume, and the trabecular thickness of alveolar bone. Histological staining revealed that anti-CD147 significantly reduced the infiltration of inflammation and limited the fractions of degraded areas in collagen fibers. The expression of bone markers (ALP, bone sialoprotein, osteocalcin and osteopontin) was enhanced by anti-CD147 treatment. The results of the anti-CD147 treatment indicate that CD147 was involved in alveolar bone mineralization, osteoclastogenesis and trabecular microstructure. The inhibition of CD147 could increase the expression level of osteogenic markers, alveolar bone crest height and suppressed collagen fiber degradation. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Increased trabecular bone and improved biomechanics in an osteocalcin-null rat model created by CRISPR/Cas9 technology.

PubMed

Lambert, Laura J; Challa, Anil K; Niu, Aidi; Zhou, Lihua; Tucholski, Janusz; Johnson, Maria S; Nagy, Tim R; Eberhardt, Alan W; Estep, Patrick N; Kesterson, Robert A; Grams, Jayleen M

2016-10-01

Osteocalcin, also known as bone γ-carboxyglutamate protein (Bglap), is expressed by osteoblasts and is commonly used as a clinical marker of bone turnover. A mouse model of osteocalcin deficiency has implicated osteocalcin as a mediator of changes to the skeleton, endocrine system, reproductive organs and central nervous system. However, differences between mouse and human osteocalcin at both the genome and protein levels have challenged the validity of extrapolating findings from the osteocalcin-deficient mouse model to human disease. The rat osteocalcin (Bglap) gene locus shares greater synteny with that of humans. To further examine the role of osteocalcin in disease, we created a rat model with complete loss of osteocalcin using the CRISPR/Cas9 system. Rat osteocalcin was modified by injection of CRISPR/Cas9 mRNA into the pronuclei of fertilized single cell Sprague-Dawley embryos, and animals were bred to homozygosity and compound heterozygosity for the mutant alleles. Dual-energy X-ray absorptiometry (DXA), glucose tolerance testing (GTT), insulin tolerance testing (ITT), microcomputed tomography (µCT), and a three-point break biomechanical assay were performed on the excised femurs at 5 months of age. Complete loss of osteocalcin resulted in bones with significantly increased trabecular thickness, density and volume. Cortical bone volume and density were not increased in null animals. The bones had improved functional quality as evidenced by an increase in failure load during the biomechanical stress assay. Differences in glucose homeostasis were observed between groups, but there were no differences in body weight or composition. This rat model of complete loss of osteocalcin provides a platform for further understanding the role of osteocalcin in disease, and it is a novel model of increased bone formation with potential utility in osteoporosis and osteoarthritis research. © 2016. Published by The Company of Biologists Ltd.

Is there a correlation between the clinical findings and the radiological findings in chronic maxillary sinus atelectasis?

PubMed

Eyigör, Hülya; Çekiç, Bülent; Turgut Çoban, Deniz; Selçuk, Ömer Tarık; Renda, Levent; Şimşek, Emine Handan; Yılmaz, Mustafa Deniz

2016-07-01

Silent sinus syndrome (SSS) is a clinical syndrome that occurs as a result of chronic maxillary sinus atelectasis (CMA) and is seen with progressive enophthalmos and hypoglobus. The aim of this study was to investigate the correlation between radiological findings and clinical findings in patients with radiologically asymmetrical reduced maxillary sinus volume. A comparison was made of patients with CMA through evaluation of paranasal sinus computed tomography, magnetic resonance imaging examination of maxillary sinus volume of the CMA side and the contralateral side, thickness of the retroantral fat tissue, infraorbital bone curve, uncinate process lateralisation measurement, middle concha diameter, and calculation of the change in location of the inferior rectus muscle. The study included 16 patients. Although a statistically significant difference was determined between the healthy and the pathological sides in respect to maxillary sinus volume, thickness of the retroantral fat tissue, infraorbital bone curve, uncinate process lateralisation measurement, and middle concha diameter (p = 0.00, p = 0.002, p = 0.020, p = 0.020, p = 0.007), no significant difference was determined in respect to the change in location of the inferior rectus muscle (p = 0.154). A positive correlation was determined between the increase in sulcus depth and maxillary sinus volume and inferior orbital bone curve (p < 0.05). In CMA patients suspected of having SSS, radiological maxillary sinus volume analysis, determination of retroantral fat thickness, measurement of the infraorbital bone curve, and measurement of the uncinate process lateralisation can be used as objective tests. However, it should be kept in mind that radiological findings may not always be compatible with the ophthalmological examination findings. Copyright © 2016 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Feasibility of transcranial photoacoustic imaging for interventional guidance of endonasal surgeries

NASA Astrophysics Data System (ADS)

Lediju Bell, Muyinatu A.; Ostrowski, Anastasia K.; Kazanzides, Peter; Boctor, Emad

2014-03-01

Endonasal surgeries to remove pituitary tumors incur the deadly risk of carotid artery injury due to limitations with real-time visualization of blood vessels surrounded by bone. We propose to use photoacoustic imaging to overcome current limitations. Blood vessels and surrounding bone would be illuminated by an optical fiber attached to the endonasal drill, while a transducer placed on the pterional region outside of the skull acquires images. To investigate feasibility, a plastisol phantom embedded with a spherical metal target was submerged in a water tank. The target was aligned with a 1-mm optical fiber coupled to a 1064nm Nd:YAG laser. An Ultrasonix L14-5W/60 linear transducer, placed approximately 1 cm above the phantom, acquired photoacoustic and ultrasound images of the target in the presence and absence of 2- and 4-mm-thick human adult cadaveric skull specimens. Though visualized at 18 mm depth when no bone was present, the target was not detectable in ultrasound images when the 4-mm thick skull specimen was placed between the transducer and phantom. In contrast, the target was visible in photoacoustic images at depths of 17-18 mm with and without the skull specimen. To mimic a clinical scenario where cranial bone in the nasal cavity reduces optical transmission prior to drill penetration, the 2-mm-thick specimen was placed between the phantom and optical fiber, while the 4-mm specimen remained between the phantom and transducer. In this case, the target was present at depths of 15-17 mm for energies ranging 9-18 mJ. With conventional delay-and-sum beamforming, the photoacoustic signal-tonoise ratios measured 15-18 dB and the contrast measured 5-13 dB. A short-lag spatial coherence beamformer was applied to increase signal contrast by 11-27 dB with similar values for SNR at most laser energies. Results are generally promising for photoacoustic-guided endonasal surgeries.

Degeneration of the osteocyte network in the C57BL/6 mouse model of aging.

PubMed

Tiede-Lewis, LeAnn M; Xie, Yixia; Hulbert, Molly A; Campos, Richard; Dallas, Mark R; Dusevich, Vladimir; Bonewald, Lynda F; Dallas, Sarah L

2017-10-26

Age-related bone loss and associated fracture risk are major problems in musculoskeletal health. Osteocytes have emerged as key regulators of bone mass and as a therapeutic target for preventing bone loss. As aging is associated with changes in the osteocyte lacunocanalicular system, we focused on the responsible cellular mechanisms in osteocytes. Bone phenotypic analysis was performed in young-(5mo) and aged-(22mo) C57BL/6 mice and changes in bone structure/geometry correlated with alterations in osteocyte parameters determined using novel multiplexed-3D-confocal imaging techniques. Age-related bone changes analogous to those in humans were observed, including increased cortical diameter, decreased cortical thickness, reduced trabecular BV/TV and cortical porosities. This was associated with a dramatic reduction in osteocyte dendrite number and cell density, particularly in females, where osteocyte dendricity decreased linearly from 5, 12, 18 to 22mo and correlated significantly with cortical bone parameters. Reduced dendricity preceded decreased osteocyte number, suggesting dendrite loss may trigger loss of viability. Age-related degeneration of osteocyte networks may impair bone anabolic responses to loading and gender differences in osteocyte cell body and lacunar fluid volumes we observed in aged mice may lead to gender-related differences in mechanosensitivity. Therapies to preserve osteocyte dendricity and viability may be beneficial for bone health in aging.

BMP delivery complements the guiding effect of scaffold architecture without altering bone microstructure in critical-sized long bone defects: A multiscale analysis.

PubMed

Cipitria, A; Wagermaier, W; Zaslansky, P; Schell, H; Reichert, J C; Fratzl, P; Hutmacher, D W; Duda, G N

2015-09-01

Scaffold architecture guides bone formation. However, in critical-sized long bone defects additional BMP-mediated osteogenic stimulation is needed to form clinically relevant volumes of new bone. The hierarchical structure of bone determines its mechanical properties. Yet, the micro- and nanostructure of BMP-mediated fast-forming bone has not been compared with slower regenerating bone without BMP. We investigated the combined effects of scaffold architecture (physical cue) and BMP stimulation (biological cue) on bone regeneration. It was hypothesized that a structured scaffold directs tissue organization through structural guidance and load transfer, while BMP stimulation accelerates bone formation without altering the microstructure at different length scales. BMP-loaded medical grade polycaprolactone-tricalcium phosphate scaffolds were implanted in 30mm tibial defects in sheep. BMP-mediated bone formation after 3 and 12 months was compared with slower bone formation with a scaffold alone after 12 months. A multiscale analysis based on microcomputed tomography, histology, polarized light microscopy, backscattered electron microscopy, small angle X-ray scattering and nanoindentation was used to characterize bone volume, collagen fiber orientation, mineral particle thickness and orientation, and local mechanical properties. Despite different observed kinetics in bone formation, similar structural properties on a microscopic and sub-micron level seem to emerge in both BMP-treated and scaffold only groups. The guiding effect of the scaffold architecture is illustrated through structural differences in bone across different regions. In the vicinity of the scaffold increased tissue organization is observed at 3 months. Loading along the long bone axis transferred through the scaffold defines bone micro- and nanostructure after 12 months. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Multi-frequency Axial Transmission Bone Ultrasonometer

PubMed Central

Tatarinov, Alexey; Egorov, Vladimir; Sarvazyan, Noune; Sarvazyan, Armen

2014-01-01

The last decade has seen a surge in the development of axial transmission QUS (Quantitative UltraSound) technologies for the assessment of long bones using various modes of acoustic waves. The condition of cortical bones and the development of osteoporosis are determined by numerous mechanical, micro-structural, and geometrical or macro-structural bone properties like hardness, porosity and cortical thickness. Such complex manifestations of osteoporosis require the evaluation of multiple parameters with different sensitivities to the various properties of bone that are affected by the disease. This objective may be achieved by using a multi-frequency ultrasonic examination The ratio of the acoustic wavelength to the cortical thickness can be changed by varying the frequency of the ultrasonic pulse propagating through the long bone that results in the change in composition of the induced wave comprised of a set of numerous modes of guided, longitudinal, and surface acoustic waves. The multi-frequency axial transmission QUS method developed at Artann Laboratories (Trenton, NJ) is implemented in the Bone Ultrasonic Scanner (BUSS). In the current version of the BUSS, a train of ultrasonic pulses with 60, 100, 400, 800, and 1200 kHz frequencies is used. The developed technology was tested on a variety of bone phantoms simulating normal, osteopenic, and osteoporotic bones. The results of this study confirm the feasibility of the multi-frequency approach for the assessment of the processes leading to osteoporosis. PMID:24206675

Contributions of Severe Burn and Disuse to Bone Structure and Strength in Rats

PubMed Central

Baer, L.A.; Wu, X.; Tou, J. C.; Johnson, E.; Wolf, S.E.; Wade, C.E.

2012-01-01

Burn and disuse results in metabolic and bone changes associated with substantial and sustained bone loss. Such loss can lead to an increased fracture incidence and osteopenia. We studied the independent effects of burn and disuse on bone morphology, composition and strength, and microstructure of the bone alterations 14 days after injury. Sprague-Dawley rats were randomized into four groups: Sham/Ambulatory (SA), Burn/Ambulatory (BA), Sham/Hindlimb Unloaded (SH) and Burn/Hindlimb Unloaded (BH). Burn groups received a 40% total body surface area full-thickness scald burn. Disuse by hindlimb unloading was initiated immediately following injury. Bone turnover was determined in plasma and urine. Femur biomechanical parameters were measured by three-point bending tests and bone microarchitecture was determined by microcomputed tomography (uCT). On day 14, a significant reduction in body mass was observed as a result of burn, disuse and a combination of both. In terms of bone health, disuse alone and in combination affected femur weight, length and bone mineral content. Bending failure energy, an index of femur strength, was significantly reduced in all groups and maximum bending stress was lower when burn and disuse were combined. Osteocalcin was reduced in BA compared to the other groups, indicating influence of burn. The reductions observed in femur weight, BMC, biomechanical parameters and indices of bone formation are primarily responses to the combination of burn and disuse. These results offer insight into bone degradation following severe injury and disuse. PMID:23142361

Chest wall reconstruction using iliac bone allografts and muscle flaps.

PubMed

Garcia-Tutor, Emilio; Yeste, Luis; Murillo, Julio; Aubá, Cristina; Sanjulian, Mikel; Torre, Wenceslao

2004-01-01

Technically we can divide full-thickness thoracic reconstruction into 2 parts: providing a rigid support and ensuring well-vascularized coverage. Since 1986, the authors' center has had ample experience with bone banks and the use of cryopreserved bone grafts, which led them to consider the possibility of using these grafts for full-thickness chest wall reconstruction. They describe 3 patients in whom resection of the tumor and reconstruction of the thorax were carried out using iliac bone allografts covered with muscle flaps (1 pectoralis major and 2 rectus abdominis). None of the patients experienced breathing difficulties, pain, or instability after 14 months, 18 months, and 11 years of follow-up. The result of the reconstruction was excellent in all 3 patients in terms of function and aesthetics. The advantage of allografts compared with synthetic materials is their potential integration; they can become part of the host patient's living tissue.

An unusual variation in the anatomy of the uncinate process in external dacryocystorhinostomy

PubMed Central

Puri, Nitin

2008-01-01

Variations in the bony components of the nose are often encountered. One such variation was found in a 49-year-old male who had undergone conventional external dacryocystorhinostomy for adult onset nasolacrimal duct blockage. Intraoperatively, a thick bar of bone was seen beneath and parallel to the lacrimal sac fossa after a complete osteotomy had been made. Another osteotomy had to be fashioned in this bone to reach the nasal cavity. Postoperative 3D computed tomographic scan revealed the bone to be an anatomical variation of the uncinate process of the ethmoidal bone which was rather anteriorly placed, much thicker than usual, and attached to the nasal roof. The uncinate process is thin, curved and its anterior edge may frequently overlap some part of the lacrimal fossa. However, to our knowledge, the presence of such a large and thick uncinate process necessitating an additional large osteotomy has not been reported. PMID:18711272

Mandibular Inferior Cortical Bone Thickness on Panoramic Radiographs in Patients using Bisphosphonates

PubMed Central

Torres, Sandra R.; Chen, Curtis S. K.; Leroux, Brian G.; Lee, Peggy P.; Hollender, Lars G.; Lloid, Michelle; Drew, Shane Patrick; Schubert, Mark M.

2015-01-01

Objective To detect dimensional changes in the mandibular cortical bone associated with bisphosphonate (BP) use and to correlate the measurements of the cortical bone with the cumulative dose of BP therapy. Methods Mandibular inferior cortical bone thickness (MICBT) was measured under the mental foramen from panoramic radiographs of subjects using BP with and without bisphosphonate related osteonecrosis of the jaws (BRONJ) and controls. Results The highest mean MICBT was observed in BRONJ subjects 6.81 (± 1.35 mm), when compared to subjects using BP 5.44 (± 1.09 mm) and controls 4.79 (± 0.85 mm; p<0.01). The mean MICBT of BRONJ subjects was significantly higher than that of subjects using BP without BRONJ. There was a correlation between MICBT and cumulative dose of zolendronate. Conclusion The MICBT on panoramic radiograph is a potentially useful tool for the detection of dimensional changes associated with BP therapy. PMID:25864820

Combination of Weight-Bearing Training and Anti-MSTN Polyclonal Antibody Improve Bone Quality In Rats.

PubMed

Tang, Liang; Gao, Xiaohang; Yang, Xiaoying; Zhang, Didi; Zhang, Xiaojun; Du, Haiping; Han, Yanqi; Sun, Lijun

2016-12-01

Weight-bearing exercise is beneficial to bone health. Myostatin (MSTN) deficiency has a positive effect on bone formation. We wondered if a combination of weight-bearing training and polyclonal antibody for MSTN (MsAb) would augment bone formation to a greater degree than single treatment. In this study, rats were randomly assigned to four groups: Control, weight-bearing training (WT), MsAb, and WT+MsAb. The trained rats ran at 15 m/min bearing with 35% of their body weight, 40 min/day (2 min of running followed by 2 min of rest), 6 days/week, for 8 weeks. The rats with MsAb were injected once a week with MsAb for 8 weeks. MicroCT analysis showed that compared with the MsAb group, WT+MsAb significantly enhanced cortical bone mineral density (BMD) (p < .01), bone volume over total volume (BV/TV) (p < .01), trabecular thickness (p < .05), and reduced trabecular separation (Tb.Sp) (p < .01). Compared with the WT group, WT+MsAb significantly increased trabecular BMD (p < .05), BV/TV (p < .05), and decreased Tb.Sp (p < .05). Three-point bending test demonstrated that MsAb failed to improve bone biomechanical properties (p > .05), weight-bearing training significantly increased energy absorption (p < .05) and elastic modulus (p < .05). However, when they combined, biomechanical properties including maximum load (p < .05), stiffness (p < .05), elastic modulus (p < .01) and energy absorption (p < .01) were all significantly enhanced. In conclusion, the combination of weight-bearing training and MsAb have a greater positive effect on bone than treatment with either MsAb or weight-bearing training alone, suggesting that resistance training in combination with MSTN antagonists could be an effective approach for improving bone health and reducing osteoporosis risk.

Combined effects of soy isoflavone and fish oil on ovariectomy-induced bone loss in mice.

PubMed

Uchida, Raina; Chiba, Hiroshige; Ishimi, Yoshiko; Uehara, Mariko; Suzuki, Kazuharu; Kim, Hyounju; Matsumoto, Akiyo

2011-07-01

Both soy isoflavone and n-3 polyunsaturated fatty acids are known to reduce the levels of bone-resorbing cytokines; however, the synergistic effects of these food ingredients have not been examined yet. This study was performed to elucidate the effect of concomitant intake of soy isoflavone and fish oil on bone mass in ovariectomized mice. Eight-week-old ddY female mice were subjected to ovariectomy (OVX) or sham surgery, and then fed an AIN-93G with safflower oil (So) as a control lipid source, isoflavone-supplemented safflower oil (So + I), fish oil instead of safflower oil (Fo) or isoflavone-supplemented fish oil (Fo + I) for 4 weeks. Femoral bone mineral density was significantly decreased by OVX; however, this decrease was inhibited by the intake of isoflavone and/or fish oil. Histomorphometric analyses showed that bone volume and trabecular thickness in the distal femoral trabecular bone were significantly lower in the So group than in the sham group, but those were restored in the Fo + I groups. The number of osteoclasts was significantly decreased by isoflavone intake. The increased rate of bone resorption after OVX was inhibited by isoflavone and/or fish oil. The serum concentration of tumor necrosis factor alpha was increased after OVX, but was significantly lower with the combination of isoflavone with fish oil than isoflavone or fish oil alone. The results of this study indicated that the intakes of soy isoflavone and/or fish oil might have ameliorating effects on bone loss due to OVX. Further, the concomitant intake of soy isoflavone and fish oil at a low dose showed better effects on cytokines related with bone resorption.

Participation of GATA-3 in regulation of bone healing through transcriptional upregulation of bcl-xL expression

PubMed Central

Liao, Mei-Hsiu; Lin, Pei-I; Ho, Wei-Pin; Chan, Wing P; Chen, Ta-Liang; Chen, Ruei-Ming

2017-01-01

We have previously demonstrated the expression of GATA-DNA-binding protein (GATA)-3, a transcription factor, in osteoblasts and have verified its function in transducing cell survival signaling. This translational study was further designed to evaluate the roles of GATA-3 in regulating bone healing and to explore its possible mechanisms. A metaphyseal bone defect was created in the left femurs of male ICR mice. Analysis by micro-computed topography showed that the bone volume, trabecular bone number and trabecular thickness were augmented and that the trabecular pattern factor decreased. Interestingly, immunohistological analyses showed specific expression of GATA-3 in the defect area. In addition, colocalized expression of GATA-3 and alkaline phosphatase was observed at the wound site. As the fracture healed, the amounts of phosphorylated and non-phosphorylated GATA-3 concurrently increased. Separately, GATA-3 mRNA was induced during bone healing, and, levels of Runx2 mRNA and protein were also increased. The results of confocal microscopy and co-immunoprecipitation showed an association between nuclear GATA-3 and Runx2 in the area of insult. In parallel with fracture healing, Bcl-XL mRNA was significantly triggered. A bioinformatic search revealed the existence of a GATA-3-specific DNA-binding element in the promoter region of the bcl-xL gene. Analysis by chromatin immunoprecipitation assays further demonstrated transactivation activity by which GATA-3 regulated bcl-xL gene expression. Therefore, this study shows that GATA-3 participates in the healing of bone fractures via regulating bcl-xL gene expression, owing to its association with Runx2. In the clinic, GATA-3 may be used as a biomarker for diagnoses/prognoses or as a therapeutic target for bone diseases, such as bone fractures. PMID:29170477

[Assessment tools in early detection of osteoporosis in dentistry].

PubMed

Knezović Zlatarić, Dubravka; Pandurić, Josip; Korsić, Mirko; Dodig, Damir

2007-03-01

Osteoporosis, one of the major skeletal diseases in older age, is characterised by low bone mass and microarchitectural deterioration with a resulting increase in bone fragility and hence susceptibility to fracture. In this review we analyse the systemic and local factors associated with oral bone mass loss. Systemic factors most often correlated with the oral bone mass loss include osteoporosis, renal diseases, hormonal disorders, diet and the impact of different drugs on the bony structure. Chronic periodontal disease, early loss of teeth or the effect of inadequate prosthodontic appliance on the residual ridge are the local factors associated with mandibular bone loss. Different assessment tools for the assessment of mandibular oral bone loss have been proposed, such as DXA absorptiometry, quantitative computed tomography, intraoral microdensitometry, SCORE index and the assessment of the thickness and quality of the mandibular inferior cortical border. Qualitative and quantitative assessment of the mandibular bony structure is of great importance in all fields of dentistry - from periodontology to endodontics and prosthodontics, especially in dental implantology. It is important to make the correct indication prior to dental implant therapy, and taking into account the systemic and local factors mentioned above, assess both the actual quality and quantity of the mandible.

Influence of wholesale lamb marketing options and merchandising styles on retail yield and fabrication time.

PubMed

Lorenzen, C L; Martin, A M; Griffin, D B; Dockerty, T R; Walter, J P; Johnson, H K; Savell, J W

1997-01-01

Lamb carcasses (n = 94) from five packing plants, selected to vary in weight class and fat thickness, were used to determine retail yield and labor requirements of wholesale lamb fabrication. Carcasses were allotted randomly according to weight class to be fabricated as whole carcasses (n = 20), three-piece boxes (n = 22), or subprimals (n = 52). Processing times (seconds) were recorded and wholesale and retail weights (kilograms) were obtained to calculate retail yield. Subprimals were fabricated into bone-in retail cuts or boneless or semi-boneless retail cuts. Retail yield for subprimal lamb legs decreased from 85.3 +/- .6% for bone-in to 68.0 +/- .7% for a completely boneless retail product. Correspondingly, processing times increased from 126.1 +/- 5.4 s to 542.0 +/- 19.2 s for bone-in and boneless legs, respectively. For all subprimals, retail yield percentage tended to decrease and total processing time increase as cuts were fabricated to boneless or semi-boneless end points compared with a bone-in end point. Percentage retail yield did not differ (P > .05) among whole carcass, three-piece box, and subprimal marketing methods. Total processing time was shorter for subprimals (P < .05) than for the other two marketing methods.

Technical Note: Cortical thickness and density estimation from clinical CT using a prior thickness-density relationship

DOE Office of Scientific and Technical Information (OSTI.GOV)

Humbert, Ludovic, E-mail: ludohumberto@gmail.com; Hazrati Marangalou, Javad; Rietbergen, Bert van

Purpose: Cortical thickness and density are critical components in determining the strength of bony structures. Computed tomography (CT) is one possible modality for analyzing the cortex in 3D. In this paper, a model-based approach for measuring the cortical bone thickness and density from clinical CT images is proposed. Methods: Density variations across the cortex were modeled as a function of the cortical thickness and density, location of the cortex, density of surrounding tissues, and imaging blur. High resolution micro-CT data of cadaver proximal femurs were analyzed to determine a relationship between cortical thickness and density. This thickness-density relationship was usedmore » as prior information to be incorporated in the model to obtain accurate measurements of cortical thickness and density from clinical CT volumes. The method was validated using micro-CT scans of 23 cadaver proximal femurs. Simulated clinical CT images with different voxel sizes were generated from the micro-CT data. Cortical thickness and density were estimated from the simulated images using the proposed method and compared with measurements obtained using the micro-CT images to evaluate the effect of voxel size on the accuracy of the method. Then, 19 of the 23 specimens were imaged using a clinical CT scanner. Cortical thickness and density were estimated from the clinical CT images using the proposed method and compared with the micro-CT measurements. Finally, a case-control study including 20 patients with osteoporosis and 20 age-matched controls with normal bone density was performed to evaluate the proposed method in a clinical context. Results: Cortical thickness (density) estimation errors were 0.07 ± 0.19 mm (−18 ± 92 mg/cm{sup 3}) using the simulated clinical CT volumes with the smallest voxel size (0.33 × 0.33 × 0.5 mm{sup 3}), and 0.10 ± 0.24 mm (−10 ± 115 mg/cm{sup 3}) using the volumes with the largest voxel size (1.0 × 1.0 × 3.0 mm{sup 3}). A trend for the cortical thickness and density estimation errors to increase with voxel size was observed and was more pronounced for thin cortices. Using clinical CT data for 19 of the 23 samples, mean errors of 0.18 ± 0.24 mm for the cortical thickness and 15 ± 106 mg/cm{sup 3} for the density were found. The case-control study showed that osteoporotic patients had a thinner cortex and a lower cortical density, with average differences of −0.8 mm and −58.6 mg/cm{sup 3} at the proximal femur in comparison with age-matched controls (p-value < 0.001). Conclusions: This method might be a promising approach for the quantification of cortical bone thickness and density using clinical routine imaging techniques. Future work will concentrate on investigating how this approach can improve the estimation of mechanical strength of bony structures, the prevention of fracture, and the management of osteoporosis.« less

The Effect of Different Bone Marrow Stimulation Techniques on Human Talar Subchondral Bone: A Micro-Computed Tomography Evaluation.

PubMed

Gianakos, Arianna L; Yasui, Youichi; Fraser, Ethan J; Ross, Keir A; Prado, Marcelo P; Fortier, Lisa A; Kennedy, John G

2016-10-01

To evaluate morphological alterations, microarchitectural disturbances, and the extent of bone marrow access to the subchondral bone marrow compartment using micro-computed tomography analysis in different bone marrow stimulation (BMS) techniques. Nine zones in a 3 × 3 grid pattern were assigned to 5 cadaveric talar dome articular surfaces. A 1.00-mm microfracture awl (s.MFX), a 2.00-mm standard microfracture awl (l.MFX), or a 1.25-mm Kirschner wire (K-wire) drill hole was used to penetrate the subchondral bone in each grid zone. Subchondral bone holes and adjacent tissue areas were assessed by micro-computed tomography to analyze adjacent bone area destruction and communicating channels to the bone marrow. Grades 1 to 3 were assigned, where 1 = minimal compression/sclerosis; 2 = moderate compression/sclerosis; 3 = severe compression/sclerosis. Bone volume/total tissue volume, bone surface area/bone volume, trabecular thickness, and trabecular number were calculated in the region of interest. Visual assessment revealed that the s.MFX had significantly more grade 1 holes (P < .001) and that the l.MFX had significantly more poor/grade 3 holes (P = .002). Bone marrow channel assessment showed a statistically significant increase in the number of channels in the s.MFX when compared with both K-wire and l.MFX holes (P < .001). Bone volume fraction for the s.MFX was significantly less than that of the l.MFX (P = .029). BMS techniques using instruments with larger diameters resulted in increased trabecular compaction and sclerosis in areas adjacent to the defect. K-wire and l.MFX techniques resulted in less open communicating bone marrow channels, denoting a reduction in bone marrow access. The results of this study indicate that BMS using larger diameter devices results in greater microarchitecture disturbances. The current study suggests that the choice of a BMS technique should be carefully considered as the results indicate that smaller diameter hole sizes may diminish the amount of microarchitectural disturbances in the subchondral bone. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Site-specific, adult bone benefits attributed to loading during youth: A preliminary longitudinal analysis.

PubMed

Scerpella, Tamara A; Bernardoni, Brittney; Wang, Sijian; Rathouz, Paul J; Li, Quefeng; Dowthwaite, Jodi N

2016-04-01

We examined site-specific bone development in relation to childhood and adolescent artistic gymnastics exposure, comparing up to 10years of prospectively acquired longitudinal data in 44 subjects, including 31 non-gymnasts (NON) and 13 gymnasts (GYM) who participated in gymnastics from pre-menarche to ≥1.9years post-menarche. Subjects underwent annual regional and whole-body DXA scans; indices of bone geometry and strength were calculated. Anthropometrics, physical activity, and maturity were assessed annually, coincident with DXA scans. Non-linear mixed effect models centered growth in bone outcomes at menarche and adjusted for menarcheal age, height, and non-bone fat-free mass to evaluate GYM-NON differences. A POST-QUIT variable assessed the withdrawal effect of quitting gymnastics. Curves for bone area, mass (BMC), and strength indices were higher in GYM than NON at both distal radius metaphysis and diaphysis (p<0.0001). At the femoral neck, greater GYM BMC (p<0.01), narrower GYM endosteal diameter (p<0.02), and similar periosteal width (p=0.09) yielded GYM advantages in narrow neck cortical thickness and buckling ratio (both p<0.001; lower BR indicates lower fracture risk). Lumbar spine and sub-head BMC were greater in GYM than NON (p<0.036). Following gymnastics cessation, GYM slopes increased for distal radius diaphysis parameters (p≤0.01) and for narrow neck BR (p=0.02). At the distal radius metaphysis, GYM BMC and compressive strength slopes decreased, as did slopes for lumbar spine BMC, femoral neck BMC, and narrow neck cortical thickness (p<0.02). In conclusion, advantages in bone mass, geometry, and strength at multiple skeletal sites were noted across growth and into young adulthood in girls who participated in gymnastics loading to at least 1.9years post-menarche. Following gymnastics cessation, advantages at cortical bone sites improved or stabilized, while advantages at corticocancellous sites stabilized or diminished. Additional longitudinal observation is necessary to determine whether residual loading benefits enhance lifelong skeletal strength. Copyright © 2016 Elsevier Inc. All rights reserved.

Local plate/rod descriptors of 3D trabecular bone micro-CT images from medial axis topologic analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peyrin, Francoise; Attali, Dominique; Chappard, Christine

Purpose: Trabecular bone microarchitecture is made of a complex network of plate and rod structures evolving with age and disease. The purpose of this article is to propose a new 3D local analysis method for the quantitative assessment of parameters related to the geometry of trabecular bone microarchitecture. Methods: The method is based on the topologic classification of the medial axis of the 3D image into branches, rods, and plates. Thanks to the reversibility of the medial axis, the classification is next extended to the whole 3D image. Finally, the percentages of rods and plates as well as their meanmore » thicknesses are calculated. The method was applied both to simulated test images and 3D micro-CT images of human trabecular bone. Results: The classification of simulated phantoms made of plates and rods shows that the maximum error in the quantitative percentages of plate and rods is less than 6% and smaller than with the structure model index (SMI). Micro-CT images of human femoral bone taken in osteoporosis and early or advanced osteoarthritis were analyzed. Despite the large physiological variability, the present method avoids the underestimation of rods observed with other local methods. The relative percentages of rods and plates were not significantly different between osteoarthritis and osteoporotic groups, whereas their absolute percentages were in relation to an increase of rod and plate thicknesses in advanced osteoarthritis with also higher relative and absolute number of nodes. Conclusions: The proposed method is model-independent, robust to surface irregularities, and enables geometrical characterization of not only skeletal structures but entire 3D images. Its application provided more accurate results than the standard SMI on simple simulated phantoms, but the discrepancy observed on the advanced osteoarthritis group raises questions that will require further investigations. The systematic use of such a local method in the characterization of trabecular bone samples could provide new insight in bone microarchitecture changes related to bone diseases or to those induced by drugs or therapy.« less

Deficiency of retinaldehyde dehydrogenase 1 induces BMP2 and increases bone mass in vivo.

PubMed

Nallamshetty, Shriram; Wang, Hong; Rhee, Eun-Jung; Kiefer, Florian W; Brown, Jonathan D; Lotinun, Sutada; Le, Phuong; Baron, Roland; Rosen, Clifford J; Plutzky, Jorge

2013-01-01

The effects of retinoids, the structural derivatives of vitamin A (retinol), on post-natal peak bone density acquisition and skeletal remodeling are complex and compartment specific. Emerging data indicates that retinoids, such as all trans retinoic acid (ATRA) and its precursor all trans retinaldehyde (Rald), exhibit distinct and divergent transcriptional effects in metabolism. Despite these observations, the role of enzymes that control retinoid metabolism in bone remains undefined. In this study, we examined the skeletal phenotype of mice deficient in retinaldehyde dehydrogenase 1 (Aldh1a1), the enzyme responsible for converting Rald to ATRA in adult animals. Bone densitometry and micro-computed tomography (µCT) demonstrated that Aldh1a1-deficient (Aldh1a1(-/-) ) female mice had higher trabecular and cortical bone mass compared to age and sex-matched control C57Bl/6 wild type (WT) mice at multiple time points. Histomorphometry confirmed increased cortical bone thickness and demonstrated significantly higher bone marrow adiposity in Aldh1a1(-/-) mice. In serum assays, Aldh1a1(-/-) mice also had higher serum IGF-1 levels. In vitro, primary Aldh1a1(-/-) mesenchymal stem cells (MSCs) expressed significantly higher levels of bone morphogenetic protein 2 (BMP2) and demonstrated enhanced osteoblastogenesis and adipogenesis versus WT MSCs. BMP2 was also expressed at higher levels in the femurs and tibias of Aldh1a1(-/-) mice with accompanying induction of BMP2-regulated responses, including expression of Runx2 and alkaline phosphatase, and Smad phosphorylation. In vitro, Rald, which accumulates in Aldh1a1(-/-) mice, potently induced BMP2 in WT MSCs in a retinoic acid receptor (RAR)-dependent manner, suggesting that Rald is involved in the BMP2 increases seen in Aldh1a1 deficiency in vivo. Collectively, these data implicate Aldh1a1 as a novel determinant of cortical bone density and marrow adiposity in the skeleton in vivo through modulation of BMP signaling.

High-Fat Diet-Induced Obesity Promotes Expansion of Bone Marrow Adipose Tissue and Impairs Skeletal Stem Cell Functions in Mice.

PubMed

Tencerova, Michaela; Figeac, Florence; Ditzel, Nicholas; Taipaleenmäki, Hanna; Nielsen, Tina Kamilla; Kassem, Moustapha

2018-06-01

Obesity represents a risk factor for development of insulin resistance and type 2 diabetes. In addition, it has been associated with increased adipocyte formation in the bone marrow (BM) along with increased risk for bone fragility fractures. However, little is known on the cellular mechanisms that link obesity, BM adiposity, and bone fragility. Thus, in an obesity intervention study in C57BL/6J mice fed with a high-fat diet (HFD) for 12 weeks, we investigated the molecular and cellular phenotype of bone marrow adipose tissue (BMAT), BM progenitor cells, and BM microenvironment in comparison to peripheral adipose tissue (AT). HFD decreased trabecular bone mass by 29%, cortical thickness by 5%, and increased BM adiposity by 184%. In contrast to peripheral AT, BMAT did not exhibit pro-inflammatory phenotype. BM progenitor cells isolated from HFD mice exhibited decreased mRNA levels of inflammatory genes (Tnfα, IL1β, Lcn2) and did not manifest an insulin resistant phenotype evidenced by normal levels of pAKT after insulin stimulation as well as normal levels of insulin signaling genes. In addition, BM progenitor cells manifested enhanced adipocyte differentiation in HFD condition. Thus, our data demonstrate that BMAT expansion in response to HFD exerts a deleterious effect on the skeleton. Continuous recruitment of progenitor cells to adipogenesis leads to progenitor cell exhaustion, decreased recruitment to osteoblastic cells, and decreased bone formation. In addition, the absence of insulin resistance and inflammation in the BM suggest that BMAT buffers extra energy in the form of triglycerides and thus plays a role in whole-body energy homeostasis. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.

Evaluation of a New Dental Implant Cervical Design in Comparison with a Conventional Design in an Experimental American Foxhound Model

PubMed Central

Pérez-Albacete Martínez, Maria Ángeles; Maté Sánchez De Val, José Eduardo; Ramos Oltra, María Luisa; Fernández Domínguez, Manuel

2018-01-01

The aim of this study was to evaluate osseointegration and crestal bone height in implants with a triangular cervical design in comparison with a standard rounded cervical design. The control group consisted of 24 implants with a standard cervical design, and the test group of 24 implants with a triangular cervical design. The implants were inserted in healed bone in six American Foxhounds. Crestal bone height and tissue thickness in the cervical portion were measured after 12 weeks healing. Data analysis found mean crestal bone loss of: 0.31 ± 0.24 mm on the buccal side, 0.35 ± 0.14 mm on the lingual in the test group, and 0.71 ± 0.28 mm buccal loss, and 0.42 ± 0.30 mm lingual in the control group; with statistically significant differences on the buccal aspect (p = 0.0019). Mean tissue thickness in the test group was 1.98 ± 0.17 mm on the buccal aspect, and 2.43 ± 0.93 mm in the lingual; in the control group it was 2.48 ± 0.61 mm buccal thickness, and 2.88 ± 0.14 mm lingual, with significant differences on both aspects (p = 0.0043; p = 0.0029). The results suggest that greater thickness of peri-implant tissue can be expected when the triangular cervical implant design is used rather than the standard cervical design. PMID:29561788

Evaluation of a New Dental Implant Cervical Design in Comparison with a Conventional Design in an Experimental American Foxhound Model.

PubMed

Pérez-Albacete Martínez, Maria Ángeles; Pérez-Albacete Martínez, Carlos; Maté Sánchez De Val, José Eduardo; Ramos Oltra, María Luisa; Fernández Domínguez, Manuel; Calvo Guirado, Jose Luis

2018-03-21

The aim of this study was to evaluate osseointegration and crestal bone height in implants with a triangular cervical design in comparison with a standard rounded cervical design. The control group consisted of 24 implants with a standard cervical design, and the test group of 24 implants with a triangular cervical design. The implants were inserted in healed bone in six American Foxhounds. Crestal bone height and tissue thickness in the cervical portion were measured after 12 weeks healing. Data analysis found mean crestal bone loss of: 0.31 ± 0.24 mm on the buccal side, 0.35 ± 0.14 mm on the lingual in the test group, and 0.71 ± 0.28 mm buccal loss, and 0.42 ± 0.30 mm lingual in the control group; with statistically significant differences on the buccal aspect ( p = 0.0019). Mean tissue thickness in the test group was 1.98 ± 0.17 mm on the buccal aspect, and 2.43 ± 0.93 mm in the lingual; in the control group it was 2.48 ± 0.61 mm buccal thickness, and 2.88 ± 0.14 mm lingual, with significant differences on both aspects ( p = 0.0043; p = 0.0029). The results suggest that greater thickness of peri-implant tissue can be expected when the triangular cervical implant design is used rather than the standard cervical design.

Hard and soft tissue augmentation in a postorthodontic patient: a case report.

PubMed

Bonacci, Fred J

2011-02-01

A combination of hard and soft tissue grafting is used to augment a thin biotype. A 26-year-old woman with mandibular anterior flaring and Miller Class I and III recessions requested interceptive treatment. Surgery included a full-thickness buccal flap, intramarrow penetrations, bone graft placement, and primary flap closure. Postoperative visits were at 2 and 4 weeks and 2, 3, and 6 months. Stage-two surgery consisted of submerged connective tissue graft placement. Postoperative visits were completed at 2, 4, 6, and 8 weeks and 1 year. Follow-up was completed 3 years after the initial surgery. Interradicular concavities were resolved and gingival biotype was augmented. Soft tissue recession remained at 6 months. Reentry revealed clinical labial plate augmentation; 2 mm was achieved at the lateral incisors and the left central incisor and 3 mm was achieved at the right canine. No bone augmentation was achieved on the left canine and right central incisor. The dehiscence at the right central incisor appeared narrower. Overall, a 2- to 3-mm gain in alveolar bone thickness/height was observed. Two months after stage-two surgery, near complete root coverage was achieved; 1 mm of recession remained on the left central incisor. There was a soft tissue thickness gain of 2 mm without any visual difference in keratinized tissue height. Interradicular concavities were eliminated; the soft tissue was augmented and the gingival biotype was altered. Interdental soft tissue craters remained. One year after connective tissue graft placement, there was near complete root coverage at the left central incisor, which at 2 months experienced residual recession. Interradicular concavities and interdental soft tissue craters were eliminated with soft tissue augmentation, including clinical reestablishment of the mucogingival junction. Clinical stability remained 3 years after the initial surgery, with the patient noting comfort during mastication and routine oral hygiene. A clinical increase in labial plate thickness, in conjunction with soft tissue augmentation, appears to provide for continued stability and decreased potential for future clinical attachment loss.

Broiler embryo bone development is influenced by incubator temperature, oxygen concentration and eggshell conductance at the plateau stage in oxygen consumption.

PubMed

Oviedo-Rondón, E O; Small, J; Wineland, M J; Christensen, V L; Mozdziak, P S; Koci, M D; Funderburk, S V L; Ort, D T; Mann, K M

2008-11-01

1. Four experiments were conducted to evaluate the effects of temperature (TEM) and oxygen (O(2)) concentrations during the last 4 d of incubation on bone development. Fertile eggs from two strains were obtained that either exhibited Low or High eggshell conductance (G). 2. Four experimental cabinets provided either four TEM (36, 37, 38 or 39 degrees C) or four O(2) concentrations (17, 19, 21 or 23% O(2)). Data were analysed as a 2 x 2 factorial design. In the fourth experiment, two temperatures (36 and 39 degrees C), two O(2) concentrations (17 and 23%) and the same Low and High G strains were evaluated in a 2 x 2 x 2 factorial design. 3. Body weights (BW) and residual yolks were obtained, both legs were dissected. Femur, tibia and shank weights, length and thickness were recorded. Relative asymmetry (RA) of each leg section was calculated. 4. The results indicated that elevated TEM during incubation increased RA between the two legs, mainly in the Low G strain. Chickens at the lowest O(2) concentrations had lighter and shorter tibias, lighter shanks, and increased RA of femur length compared to chickens in the 23% O(2). In the fourth experiment no interactions were observed between O(2) and TEM. High TEM depressed BW of Low G broilers, but no significant effect of treatments was observed on BW of High G broilers. Nevertheless, the high TEM or low O(2) independently caused reduced femur and tibia weights and length, shank length and thickness, and both low O(2) and high TEM together increased RA in shank weight. 5. These results suggest that late incubation conditions affect long bone development in broilers.

Sclerostin alters serum vitamin D metabolite and fibroblast growth factor 23 concentrations and the urinary excretion of calcium

PubMed Central

Ryan, Zachary C.; Ketha, Hemamalini; McNulty, Melissa S.; McGee-Lawrence, Meghan; Craig, Theodore A.; Grande, Joseph P.; Westendorf, Jennifer J.; Singh, Ravinder J.; Kumar, Rajiv

2013-01-01

Inactivating mutations of the SOST (sclerostin) gene are associated with overgrowth and sclerosis of the skeleton. To determine mechanisms by which increased amounts of calcium and phosphorus are accreted to enable enhanced bone mineralization in the absence of sclerostin, we measured concentrations of calciotropic and phosphaturic hormones, and urine and serum calcium and inorganic phosphorus in mice in which the sclerostin (sost) gene was replaced by the β-D-galactosidase (lacZ) gene in the germ line. Knockout (KO) (sost−/−) mice had increased bone mineral density and content, increased cortical and trabecular bone thickness, and greater net bone formation as a result of increased osteoblast and decreased osteoclast surfaces compared with wild-type (WT) mice. β-Galactosidase activity was detected in osteocytes of sost KO mice but was undetectable in WT mice. Eight-week-old, male sost KO mice had increased serum 1α,25-dihydroxyvitamin D, decreased 24,25-dihydroxyvitamin D, decreased intact fibroblast growth factor 23, and elevated inorganic phosphorus concentrations compared with age-matched WT mice. 25-Hydroxyvitamin D 1α-hydroxylase cytochrome P450 (cyp27B1) mRNA was increased in kidneys of sost KO mice compared with WT mice. Treatment of cultured proximal tubule cells with mouse recombinant sclerostin decreased cyp27B1 mRNA transcripts. Urinary calcium and renal fractional excretion of calcium were decreased in sost KO mice compared with WT mice. Sost KO and WT mice had similar serum calcium and parathyroid hormone concentrations. The data show that sclerostin not only alters bone mineralization, but also influences mineral metabolism by altering concentrations of hormones that regulate mineral accretion. PMID:23530237

Sclerostin alters serum vitamin D metabolite and fibroblast growth factor 23 concentrations and the urinary excretion of calcium.

PubMed

Ryan, Zachary C; Ketha, Hemamalini; McNulty, Melissa S; McGee-Lawrence, Meghan; Craig, Theodore A; Grande, Joseph P; Westendorf, Jennifer J; Singh, Ravinder J; Kumar, Rajiv

2013-04-09

Inactivating mutations of the SOST (sclerostin) gene are associated with overgrowth and sclerosis of the skeleton. To determine mechanisms by which increased amounts of calcium and phosphorus are accreted to enable enhanced bone mineralization in the absence of sclerostin, we measured concentrations of calciotropic and phosphaturic hormones, and urine and serum calcium and inorganic phosphorus in mice in which the sclerostin (sost) gene was replaced by the β-D-galactosidase (lacZ) gene in the germ line. Knockout (KO) (sost(-/-)) mice had increased bone mineral density and content, increased cortical and trabecular bone thickness, and greater net bone formation as a result of increased osteoblast and decreased osteoclast surfaces compared with wild-type (WT) mice. β-Galactosidase activity was detected in osteocytes of sost KO mice but was undetectable in WT mice. Eight-week-old, male sost KO mice had increased serum 1α,25-dihydroxyvitamin D, decreased 24,25-dihydroxyvitamin D, decreased intact fibroblast growth factor 23, and elevated inorganic phosphorus concentrations compared with age-matched WT mice. 25-Hydroxyvitamin D 1α-hydroxylase cytochrome P450 (cyp27B1) mRNA was increased in kidneys of sost KO mice compared with WT mice. Treatment of cultured proximal tubule cells with mouse recombinant sclerostin decreased cyp27B1 mRNA transcripts. Urinary calcium and renal fractional excretion of calcium were decreased in sost KO mice compared with WT mice. Sost KO and WT mice had similar serum calcium and parathyroid hormone concentrations. The data show that sclerostin not only alters bone mineralization, but also influences mineral metabolism by altering concentrations of hormones that regulate mineral accretion.

Proximal Femur Mechanical Adaptation to Weight Gain in Late Adolescence: A Six-Year Longitudinal Study

PubMed Central

Petit, Moira A; Beck, Thomas J; Hughes, Julie M; Lin, Hung-Mo; Bentley, Christy; Lloyd, Tom

2008-01-01

The effect of weight gain in late adolescence on bone is not clear. Young women who consistently gained weight (n = 23) from 17 to 22 yr of age had increased BMD but a lack of subperiosteal expansion compared with stable weight peers (n = 48). Bone strength increased appropriately for lean mass in both groups but decreased relative to body weight in weight gainers, suggesting increased bone fragility in weight gainers. Introduction Weight gain leading to obesity often starts in adolescence, yet little is known about its effects on bone. We used longitudinal data to examine the effects of weight gain in late adolescence (from 17 to 22 yr of age) on proximal femur BMD, geometry, and estimates of bending strength. Materials and Methods Participants were classified as either weight gainers (WG, n = 23) or stable weight (SW, n = 48) using a random coefficients model. Weight gainers had positive increases in weight (p < 0.05) at each clinic visit from age 17 onward. Proximal femur DXA scans (Hologic QDR 2000) taken annually from 17 to 22 yr of age were analyzed for areal BMD (g/cm2), subperiosteal width (cm), and bone cross-sectional area (CSA) at the proximal femoral shaft. Cortical thickness was measured, and section modulus (Z, cm3) was calculated as a measure of bone bending strength. Total body lean (g) and fat (g) mass were measured from DXA total body scans. Results Over ages 17–22, height remained stable in both groups. Weight remained static in the SW group but increased 14% on average in the WG group (p < 0.05). After controlling for age 17 baseline values, WG had higher BMD (+2.6%), thicker cortices (+3.6%), and greater bone CSA (+2.3%). Increased BMD did not translate to greater increases in bone bending strength (Z). The SW group achieved similar gains in Z by greater subperiosteal expansion. Bone strength index (SI = Z/height) normalized for body weight remained constant in the SW group but decreased significantly in the WG group. In contrast, SI normalized to lean mass did not change over time in either group. Other variables including physical activity, nutrition, and hormone levels (estradiol, testosterone, cortisol) did not differ significantly between groups. Conclusions These data suggest that weight gain in late adolescence may inhibit the periosteal expansion known to normally occur throughout life in long bones, resulting in decreased bone strength relative to body weight. PMID:17937533

Frontonasal fold thickness-to-nasal bone length ratio as a prenatal sonographic marker for trisomy 21 in a low-risk population.

PubMed

Gonzalez, Ruben; Aedo, Socrates; Dezerega, Victor; Sepulveda, Waldo

2013-05-01

To report normative data for the fetal nasal bone length (NBL), frontonasal fold (FNF) thickness, and the FNF/NBL ratio and to study their performance in the sonographic screening of trisomy 21 in a normal, unselected Latin American population. Women undergoing a routine sonographic examination between 16 and 32 weeks' gestation at a primary health care center in Santiago, Chile, were prospectively recruited for NBL and FNF thickness measurements. Pregnancies with maternal/fetal complications were subsequently excluded from analysis. Correlations between NBL, FNF thickness, and FNF/NBL ratio and gestational age were assessed with the Spearman correlation coefficient (ρ). To generate reference percentiles for NBL and FNF thickness, adjusted regression models were derived using a statistical method for calculating reference percentiles of fetal biometric parameters. A total of 1922 cases complied with entry criteria. Both the NBL and the FNF thickness increased with gestational age. However, the FNF/NBL ratio remained constant (ρ= 0.016; P = .95), with a mean value of 0.68 and 95th and 99th percentile values of 0.84 and 0.90, respectively. During the study period, all 4 fetuses with trisomy 21 diagnosed in this low-risk population had an FNF/NBL ratio above the 99th percentile, whereas only 3 had NBL below the fifth percentile, and 3 had FNF thickness above the 95th percentile. The FNF/NBL ratio is a promising marker for the sonographic screening of trisomy 21 in the low-risk population; however, further prospective studies including larger numbers of fetuses with trisomy 21 are warranted to determine the clinical value of this marker. As the NBL is dependent on the ethnicity of the population screened, determination of normative data for NBL and the FNF/NBL ratio in different ethnic populations is also recommended before including this method in the routine screening for aneuploidy.

Optical clearing of articular cartilage: a comparison of clearing agents

NASA Astrophysics Data System (ADS)

Bykov, Alexander; Hautala, Tapio; Kinnunen, Matti; Popov, Alexey; Karhula, Sakari; Saarakkala, Simo; Nieminen, Miika T.; Tuchin, Valery

2015-07-01

Optical clearing technique was applied to the problem of OCT imaging of articular cartilage and subchondral bone. We show that optical clearing significantly enhances visualization of articular cartilage and cartilage-bone interface. The effect of different clearing agents was analyzed. For the clearing, iohexol solution and propylene glycol (PG) were used. Clearing was performed in vitro at room temperature by immersion method. Cylindrical osteochondral samples (d=4.8mm) were drilled from bovine lateral femur and stored in phosphate-buffered saline at -20°C until clearing. Monitoring of clearing process was performed using high-speed spectral-domain OCT system providing axial resolution of 5.8μm at 930nm. Total duration of experiment was 90-100min to ensure saturation of clearing. We have shown that iohexol solution and PG are capable to optically clear articular cartilage enabling reliable characterization of cartilagebone interface with OCT. Being a low osmolarity agent, iohexol provides minimal changes to the thickness of cartilage sample. Clearing saturation time for the cartilage sample with the thickness of 0.9 mm measured with OCT is of 50 min. However, less than 15 min is enough to reliably detect the rear cartilage boundary. Alternatively, PG significantly (60%) reduces the cartilage thickness enabling better visualization of subchondral bone. It was observed that PG has higher clearing rate. The clearing saturation time is of 30 min, however less than 5 min is enough to detect cartilage-bone interface. We conclude that iohexol solution is superior for OCT imaging of cartilage and cartilage-bone interface, while PG suits better for subhondral bone visualization.

Polynomial dual energy inverse functions for bone Calcium/Phosphorus ratio determination and experimental evaluation.

PubMed

Sotiropoulou, P; Fountos, G; Martini, N; Koukou, V; Michail, C; Kandarakis, I; Nikiforidis, G

2016-12-01

An X-ray dual energy (XRDE) method was examined, using polynomial nonlinear approximation of inverse functions for the determination of the bone Calcium-to-Phosphorus (Ca/P) mass ratio. Inverse fitting functions with the least-squares estimation were used, to determine calcium and phosphate thicknesses. The method was verified by measuring test bone phantoms with a dedicated dual energy system and compared with previously published dual energy data. The accuracy in the determination of the calcium and phosphate thicknesses improved with the polynomial nonlinear inverse function method, introduced in this work, (ranged from 1.4% to 6.2%), compared to the corresponding linear inverse function method (ranged from 1.4% to 19.5%). Copyright © 2016 Elsevier Ltd. All rights reserved.

A potential mechanism for allometric trabecular bone scaling in terrestrial mammals.

PubMed

Christen, Patrik; Ito, Keita; van Rietbergen, Bert

2015-03-01

Trabecular bone microstructural parameters, including trabecular thickness, spacing, and number, have been reported to scale with animal size with negative allometry, whereas bone volume fraction is animal size-invariant in terrestrial mammals. As for the majority of scaling patterns described in animals, its underlying mechanism is unknown. However, it has also been found that osteocyte density is inversely related to animal size, possibly adapted to metabolic rate, which shows a negative relationship as well. In addition, the signalling reach of osteocytes is limited by the extent of the lacuno-canalicular network, depending on trabecular dimensions and thus also on animal size. Here we propose animal size-dependent variations in osteocyte density and their signalling influence distance as a potential mechanism for negative allometric trabecular bone scaling in terrestrial mammals. Using an established and tested computational model of bone modelling and remodelling, we run simulations with different osteocyte densities and influence distances mimicking six terrestrial mammals covering a large range of body masses. Simulated trabecular structures revealed negative allometric scaling for trabecular thickness, spacing, and number, constant bone volume fraction, and bone turnover rates inversely related to animal size. These results are in agreement with previous observations supporting our proposal of osteocyte density and influence distance variation as a potential mechanism for negative allometric trabecular bone scaling in terrestrial mammals. The inverse relationship between bone turnover rates and animal size further indicates that trabecular bone scaling may be linked to metabolic rather than mechanical adaptations. © 2015 Anatomical Society.

Numerical simulation on the adaptation of forms in trabecular bone to mechanical disuse and basic multi-cellular unit activation threshold at menopause

NASA Astrophysics Data System (ADS)

Gong, He; Fan, Yubo; Zhang, Ming

2008-04-01

The objective of this paper is to identify the effects of mechanical disuse and basic multi-cellular unit (BMU) activation threshold on the form of trabecular bone during menopause. A bone adaptation model with mechanical- biological factors at BMU level was integrated with finite element analysis to simulate the changes of trabecular bone structure during menopause. Mechanical disuse and changes in the BMU activation threshold were applied to the model for the period from 4 years before to 4 years after menopause. The changes in bone volume fraction, trabecular thickness and fractal dimension of the trabecular structures were used to quantify the changes of trabecular bone in three different cases associated with mechanical disuse and BMU activation threshold. It was found that the changes in the simulated bone volume fraction were highly correlated and consistent with clinical data, and that the trabecular thickness reduced significantly during menopause and was highly linearly correlated with the bone volume fraction, and that the change trend of fractal dimension of the simulated trabecular structure was in correspondence with clinical observations. The numerical simulation in this paper may help to better understand the relationship between the bone morphology and the mechanical, as well as biological environment; and can provide a quantitative computational model and methodology for the numerical simulation of the bone structural morphological changes caused by the mechanical environment, and/or the biological environment.

Pediatric solid organ transplantation and osteoporosis: a descriptive study on bone histomorphometric findings.

PubMed

Tamminen, Inari S; Valta, Helena; Jalanko, Hannu; Salminen, Sari; Mäyränpää, Mervi K; Isaksson, Hanna; Kröger, Heikki; Mäkitie, Outi

2014-08-01

Organ transplantation may lead to secondary osteoporosis in children. This study characterized bone histomorphometric findings in pediatric solid organ transplant recipients who were assessed for suspected secondary osteoporosis. Iliac crest biopsies were obtained from 19 children (7.6-18.8 years, 11 male) who had undergone kidney (n = 6), liver (n = 9), or heart (n = 4) transplantation a median 4.6 years (range 0.6-16.3 years) earlier. All patients had received oral glucocorticoids at the time of the biopsy. Of the 19 patients, 21 % had sustained peripheral fractures and 58 % vertebral compression fractures. Nine children (47 %) had a lumbar spine BMD Z-score below -2.0. Histomorphometric analyses showed low trabecular bone volume (< -1.0 SD) in 6 children (32 %) and decreased trabecular thickness in 14 children (74 %). Seven children (37 %) had high bone turnover at biopsy, and low turnover was found in 6 children (32 %), 1 of whom had adynamic bone disease. There was a great heterogeneity in the histological findings in different transplant groups, and the results were unpredictable using non-invasive methods. The observed changes in bone quality (i.e. abnormal turnover rate, thin trabeculae) rather than the actual loss of trabecular bone, might explain the increased fracture risk in pediatric solid organ transplant recipients.

Non-linear 3D evaluation of different oral implant-abutment connections.

PubMed

Streckbein, P; Streckbein, R G; Wilbrand, J F; Malik, C Y; Schaaf, H; Howaldt, H P; Flach, M

2012-12-01

Micro-gaps and osseous overload in the implant-abutment connection are the most common causes of peri-implant bone resorption and implant failure. These undesirable events can be visualized on standardized three-dimensional finite element models and by radiographic methods. The present study investigated the influence of 7 available implant systems (Ankylos, Astra, Bego, Brånemark, Camlog, Straumann, and Xive) with different implant-abutment connections on bone overload and the appearance of micro-gaps in vitro. The individual geometries of the implants were transferred to three-dimensional finite element models. In a non-linear analysis considering the pre-loading of the occlusion screw, friction between the implant and abutment, the influence of the cone angle on bone strain, and the appearance of micro-gaps were determined. Increased bone strains were correlated with small (< 15°) cone angles. Conical implant-abutment connections efficiently avoided micro-gaps but had a negative effect on peri-implant bone strain. Bone strain was reduced in implants with greater wall thickness (Ankylos) or a smaller cone angle (Bego). The results of our in silico study provide a solid basis for the reduction of peri-implant bone strain and micro-gaps in the implant-abutment connection to improve long-term stability.

Spaceflight-Induced Bone Loss Alters Failure Mode and Reduces Bending Strength in Murine Spinal Segments

PubMed Central

Berg-Johansen, Britta; Liebenberg, Ellen C.; Li, Alfred; Macias, Brandon R.; Hargens, Alan R.; Lotz, Jeffrey C.

2017-01-01

Intervertebral disc herniation rates are quadrupled in astronauts following spaceflight. While bending motions are main contributors to herniation, the effects of microgravity on the bending properties of spinal discs are unknown. Consequently, the goal of this study was to quantify the bending properties of tail discs from mice with or without microgravity exposure. Caudal motion segments from six mice returned from a 30-day Bion M1 mission and eight vivarium controls were loaded to failure in four-point bending. After testing, specimens were processed using histology to determine the location of failure, and adjacent motion segments were scanned with micro-computed tomography (μCT) to quantify bone properties. We observed that spaceflight significantly shortened the nonlinear toe region of the force-displacement curve by 32% and reduced the bending strength by 17%. Flight mouse spinal segments tended to fail within the growth plate and epiphyseal bone, while controls tended to fail at the disc-vertebra junction. Spaceflight significantly reduced vertebral bone volume fraction, bone mineral density, and trabecular thickness, which may explain the tendency of flight specimens to fail within the epiphyseal bone. Together, these results indicate that vertebral bone loss during spaceflight may degrade spine bending properties and contribute to increased disc herniation risk in astronauts. PMID:26285046

Changes in body composition and bone of female collegiate soccer players through the competitive season and off-season.

PubMed

Minett, M M; Binkley, T B; Weidauer, L A; Specker, B L

2017-03-01

To assess body composition and bone changes pre- to post-season (pre-post) and post- to off-season (post-off) in female soccer athletes (SC). Outcomes were assessed using DXA and pQCT in 23 SC and 17 controls at three times throughout season. SC, non-starters in particular, lost lean mass pre-post (-0.9±0.2 kg, p<0.01; not different from controls, p=0.2) and gained fat mass post-off (1.4±0.3 kg, p<0.01; differed from controls, p=0.01). Baseline femoral neck and hip aBMD were higher in SC than controls (both,p<0.04), but increased in controls more than SC in pre-post and decreased post-off. SC cortical bone mineral content (BMC), cortical area and periosteal circumference increased pre-post (all, p<0.01; differed from controls, p<0.05) and trabecular vBMD decreased post-off (-3.0±1.3 mg/cm 3 ; p=0.02; not different from controls, p=0.4). Both SC and controls increased cortical BMC, cortical area, and thickness post-off (all, p<0.01). Soccer players lost lean mass over the competitive season that was not recovered during off-season. Bone size increased pre- to post-season. Female soccer athletes experience body composition and bone geometry changes that differ depending on the time of season and on athlete's playing status. Evaluations of athletes at key times across the training season are necessary to understand changes that occur.

Changes in body composition and bone of female collegiate soccer players through the competitive season and off-season

PubMed Central

Minett, M.M.; Binkley, T.B.; Weidauer, L.A.; Specker, B.L.

2017-01-01

Objectives: To assess body composition and bone changes pre- to post-season (pre-post) and post- to off-season (post-off) in female soccer athletes (SC). Methods: Outcomes were assessed using DXA and pQCT in 23 SC and 17 controls at three times throughout season. Results: SC, non-starters in particular, lost lean mass pre-post (-0.9±0.2 kg, p<0.01; not different from controls, p=0.2) and gained fat mass post-off (1.4±0.3 kg, p<0.01; differed from controls, p=0.01). Baseline femoral neck and hip aBMD were higher in SC than controls (both, p<0.04), but increased in controls more than SC in pre-post and decreased post-off. SC cortical bone mineral content (BMC), cortical area and periosteal circumference increased pre-post (all, p<0.01; differed from controls, p<0.05) and trabecular vBMD decreased post-off (-3.0±1.3 mg/cm3; p=0.02; not different from controls, p=0.4). Both SC and controls increased cortical BMC, cortical area, and thickness post-off (all, p<0.01). Conclusion: Soccer players lost lean mass over the competitive season that was not recovered during off-season. Bone size increased pre- to post-season. Female soccer athletes experience body composition and bone geometry changes that differ depending on the time of season and on athlete’s playing status. Evaluations of athletes at key times across the training season are necessary to understand changes that occur. PMID:28250243

Effect of gingival fibroblasts and ultrasound on dogs' root resorption during orthodontic treatment.

PubMed

Crossman, Jacqueline; Hassan, Ali H; Saleem, Ali; Felemban, Nayef; Aldaghreer, Saleh; Fawzi, Elham; Farid, Mamdouh; Abdel-Ghaffar, Khaled; Gargoum, Ausama; El-Bialy, Tarek

2017-01-01

To investigate the effect of using osteogenic induced gingival fibroblasts (OIGFs) and low intensity pulsed ultrasound (LIPUS) on root resorption lacunae volume and cementum thickness in beagle dogs that received orthodontic tooth movement. Seven beagle dogs were used, from which gingival cells (GCs) were obtained and were induced osteogenically to produce OIGFs. Each third and fourth premolar was randomly assigned to one of the five groups, namely, LIPUS, OIGFs, bone morphogenetic protein-2 (BMP-2), OIGFs + LIPUS, and control. All groups received 4 weeks of bodily tooth movement, then LIPUS-treated groups received LIPUS for 20 min/day for 4 weeks, and OIGFs groups received an injection of OIGFs near the root apex. Microcomputed tomography analysis was used to calculate root resorption lacunae volume and histomorphometric analysis was performed to measure the cementum thickness of each root at 3 root levels on compression and tension sides. There was no significant difference in resorption volume between the treatment groups. OIGFs + LIPUS increased cementum thickness ( P > 0.05) in third premolars near the apex, and LIPUS increased cementum thickness ( P > 0.05) in fourth premolars near the apex. Furthermore, BMP2 increased cementum thickness at the coronal third at the compression side. OIGFs, LIPUS, and BMP-2 can be potential treatments for orthodontically induced root resorption, however, improvements in experimental design and treatment parameters are required to further investigate these repair modalities.

Rabbiteye blueberry prevents osteoporosis in ovariectomized rats.

PubMed

Li, Tao; Wu, Shou-Mian; Xu, Zhi-Yuan; Ou-Yang, Sheng

2014-08-08

It has been forecasted that the rabbiteye blueberry could inhibit osteoporosis. However, the inhibition and prevention of osteoporosis via rabbiteye blueberry are still elusive. This study was aim to evaluate the anti-osteoporosis effects of rabbiteye blueberry in ovariectomized rats. Thirty rats were randomly divided into three groups of ten rats each as follows: sham-operated group (SG), ovariectomized model control group (OMG), and ovariectomized rabbiteye blueberry treatment group (OBG). The blood mineral levels, the alkaline phosphatase (ALP) activity, and osteoprotegerin (OPG) level were determined. The expression analyses of type I collagen, integrin-β1, and focal adhesion kinase (FAK) were performed. Besides, the bone mineral density (BMD) and bone histomorphometry (BH) were measured. The ALP activity in SG and OBG was significantly lower than that in OMG. For the OPG level, the significant increase of OPG level in OBG was indicated compared with the other groups. The mRNA expression levels of type I collagen, integrin-β1, and FAK in OMG were significantly lower than those in other groups. The BMD in OMG were all significantly lower than those in SG and OBG. For BH, blueberry significantly improved the trabecular bone volume fraction, trabecular thickness, mean trabecular bone number, and bone formation rate, and decreased the trabecular separation, the percent of bone resorption perimeter, and mean osteoclast number in OBG compared with OMG. The rabbiteye blueberries had an effective inhibition in bone resorption, bone loss, and reduction of bone strength of ovariectomized rats and could improve the BMD, osteogenic activity, and trabecular bone structure.

Successful treatment of unicameral bone cyst by single percutaneous injection of alpha-BSM.

PubMed

Thawrani, Dinesh; Thai, Chia Che; Welch, Robert D; Copley, Lawson; Johnston, Charles E

2009-01-01

Unicameral bone cyst (UBC) is a benign bone lesion, recognized for its high rate of recurrence and need for repeat procedures to achieve healing. We hypothesized that the osteoconductive material apatitic calcium phosphate (alpha-BSM) could be effective in filling and stimulating resolution of UBC. The purpose of this study was to evaluate clinical and radiographic outcomes of UBC treated by a single injection of alpha-BSM. Thirteen patients (6 male, 7 female) with a mean age of 10.5 years, underwent single percutaneous injection of alpha-BSM for presumed UBC. The aspiration of the cysts was followed by vigorous saline lavage using 2 wide bore needles to disrupt the cyst walls. alpha-BSM "paste" was then injected under fluoroscopic guidance. Radiographs were digitized to measure cystic area (millimeter squares) on 2 orthogonal views. Healing was rated according to a modified Neer outcome grading system. Nine of the 13 patients had had pathologic fractures in the past. Eleven of the 13 patients had had past unsuccessful treatment: multiple steroid injections in 6, curettage and bone grafting in 3, and bone marrow and demineralized bone matrix (Grafton) injection in 2. Five cysts were grade 1 (healed 100%), 6 grade 2 (healed >50%), 2 grade 3 (healed <50% with increased cortical thickness), and none grade 4 (recurrence/enlargement). The average resolution of cystic area in 11/13 cysts was 85.7% at final follow-up of 35.8 months (P=0.0001) with 2.8 mm of average gain in cortical thickness (P=0.0018). None of the 13 lesions required an additional procedure or repeat injection. All patients were clinically asymptomatic at latest follow-up. This is the first study quantifying cyst resolution objectively according to actual decrease in area (millimeter squares). A single injection of alpha-BSM is a safe, minimally invasive and efficacious method to treat UBC in the pediatric population.

[Carpal canal ultrasound examination in patients with mild hand-arm vibration disease].

PubMed

Liu, Y Z; Ye, Z H; Yang, W L; Zhu, J X; Lu, Q J; Su, W L

2016-08-20

Objective: To investigate the clinical value of ultrasound examination of carpal canal structure in patients with mild hand-arm vibration disease. Methods: A total of 29 patients (58 wrists) with mild hand-arm vibration disease who were treated in Shenzhen Prevention and Treatment Center for Occupational Diseases from May to December, 2015 were enrolled as observation group, and 20 healthy volunteers (40 wrists) were enrolled as the control group. Color Doppler ultrasound was used to observe the morphology and echo of the median nerve in the carpal canal and 9 muscle tendons and transverse carpal ligament. The thickness of transverse carpal ligament and diameter of the median nerve at the level of the hamulus of hamate bone were measured, as well as the cross-sectional area of the median nerve at the level of pisiform bone. Results: In the 29 patients with hand-arm vibration disease patients in the observation group, 8 experienced entrapment of the median nerve in the carpal canal, among whom 5 had entrapment in both wrists; there were 13 wrists (23%) with nerve entrapment and 45 wrists (77%) without nerve entrapment. Compared with the control group, the patients with hand-arm vibration disease and nerve entrapment in the observation group showed significant thickening of the transverse carpal ligament at the level of the hamulus of hamate bone and a significant increase in the cross-sectional area of the median nerve at the level of pisiform bone ( P <0.05) , while there were no significant differences in the thickness of transverse carpal ligament at the level of the hamulus of hamate bone and the cross-sectional area of the median nerve at the level of pisiform bone ( t=- 9.397 and -4.385, both P >0.05) . Conclusion: Ultrasound examination can clearly show the radiological changes of carpal canal contents in patients with mild hand-arm vibration disease and has a certain diagnostic value in nerve damage in patients with hand-arm vibration disease.

Association Between Insulin Resistance and Bone Structure in Nondiabetic Postmenopausal Women

PubMed Central

Finkelstein, Joel S.; Bouxsein, Mary L.; Yu, Elaine W.

2016-01-01

Context: The clinical consequences of insulin resistance and hyperinsulinemia on bone remain largely unknown. Objective: The objective of the study was to evaluate the effect of insulin resistance on peripheral bone geometry, volumetric bone mineral density (vBMD), bone microarchitecture, and estimated bone strength. Design, Setting, and Participants: This cross-sectional study included 146 postmenopausal, nondiabetic Caucasian women (mean age 60.3 ± 2.7 y) who were participating in the Study of Women's Health Across the Nation. Interventions: There were no interventions. Main Outcome Measures: High-resolution peripheral quantitative computed tomography was used to assess bone density and microstructure at the distal radius and tibia. Fasting insulin and glucose were measured and insulin resistance was estimated using homeostasis model assessment of insulin resistance (HOMA-IR), with higher values indicating greater insulin resistance. Results: There was a negative association between HOMA-IR and bone size and a positive association between HOMA-IR and total vBMD, trabecular vBMD, trabecular thickness, and cortical thickness at the radius and tibia. These relationships remained, even after adjusting for body weight and other potential covariates (eg, time since menopause, cigarette smoking, physical activity, prior use of osteoporosis medications or glucocorticoids). Conclusions: In nondiabetic, postmenopausal women, insulin resistance was associated with smaller bone size, greater volumetric bone mineral density, and generally favorable bone microarchitecture at weight-bearing and nonweight-bearing skeletal sites. These associations were independent of body weight and other potential covariates, suggesting that hyperinsulinemia directly affects bone structure independent of obesity and may explain, in part, the higher trabecular bone density and favorable trabecular microarchitecture seen in individuals with type 2 diabetes mellitus. PMID:27243136

Improvement of cancellous bone microstructure in patients on teriparatide following alendronate pretreatment.

PubMed

Fahrleitner-Pammer, Astrid; Burr, David; Dobnig, Harald; Stepan, Jan J; Petto, Helmut; Li, Jiliang; Krege, John H; Pavo, Imre

2016-08-01

An increase in procollagen type I amino-terminal propeptide (PINP) early after teriparatide initiation was shown to correlate with increased lumbar spine areal BMD and is a good predictor of the anabolic response to teriparatide. Few data exist correlating PINP and bone microstructure, and no data exist in patients on teriparatide following prior potent antiresorptive treatment. This exploratory analysis aimed to investigate the effects of teriparatide on cancellous bone microstructure and correlations of bone markers with microstructure in alendronate-pretreated patients. This was a post hoc analysis of changes in bone markers and three-dimensional indices of bone microstructure in paired iliac crest biopsies from a prospective teriparatide treatment study in postmenopausal women with osteoporosis who were either treatment-naïve (TN, n=16) or alendronate-pretreated (ALN, n=29) at teriparatide initiation. Teriparatide (20μg/day) was given for 24months; biopsies were taken at baseline and endpoint, and serum concentrations of PINP and type 1 collagen cross-linked C-telopeptide (βCTX) were measured at intervals up to 24months. In the TN and ALN groups, respectively, mean (SD) increases in three-dimensional bone volume/tissue volume were 105 (356)% (P=0.039) and 55 (139)% (P<0.005) and trabecular thickness 30.4 (30)% (P<0.001) and 30.8 (53)% (P<0.001). No significant changes were observed in trabecular number or separation. In the ALN patients, 3-month change of neither PINP nor βCTX correlated with indices of cancellous bone microstructure. However, 12-month changes in biochemical bone markers correlated significantly with improvements in bone volume/tissue volume, r=0.502 (P<0.01) and r=0.378 (P<0.05), trabecular number, r=0.559 (P<0.01) and r=0.515 (P<0.01), and reduction of trabecular separation, r=-0.432 (P<0.05) and r=-0.530 (P<0.01), for PINP and βCTX, respectively. We conclude that cancellous bone microstructure improved with teriparatide therapy irrespective of prior antiresorptive use. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Segmentation of cortical bone using fast level sets

NASA Astrophysics Data System (ADS)

Chowdhury, Manish; Jörgens, Daniel; Wang, Chunliang; Smedby, Årjan; Moreno, Rodrigo

2017-02-01

Cortical bone plays a big role in the mechanical competence of bone. The analysis of cortical bone requires accurate segmentation methods. Level set methods are usually in the state-of-the-art for segmenting medical images. However, traditional implementations of this method are computationally expensive. This drawback was recently tackled through the so-called coherent propagation extension of the classical algorithm which has decreased computation times dramatically. In this study, we assess the potential of this technique for segmenting cortical bone in interactive time in 3D images acquired through High Resolution peripheral Quantitative Computed Tomography (HR-pQCT). The obtained segmentations are used to estimate cortical thickness and cortical porosity of the investigated images. Cortical thickness and Cortical porosity is computed using sphere fitting and mathematical morphological operations respectively. Qualitative comparison between the segmentations of our proposed algorithm and a previously published approach on six images volumes reveals superior smoothness properties of the level set approach. While the proposed method yields similar results to previous approaches in regions where the boundary between trabecular and cortical bone is well defined, it yields more stable segmentations in challenging regions. This results in more stable estimation of parameters of cortical bone. The proposed technique takes few seconds to compute, which makes it suitable for clinical settings.

Predicting bone strength with ultrasonic guided waves

PubMed Central

Bochud, Nicolas; Vallet, Quentin; Minonzio, Jean-Gabriel; Laugier, Pascal

2017-01-01

Recent bone quantitative ultrasound approaches exploit the multimode waveguide response of long bones for assessing properties such as cortical thickness and stiffness. Clinical applications remain, however, challenging, as the impact of soft tissue on guided waves characteristics is not fully understood yet. In particular, it must be clarified whether soft tissue must be incorporated in waveguide models needed to infer reliable cortical bone properties. We hypothesize that an inverse procedure using a free plate model can be applied to retrieve the thickness and stiffness of cortical bone from experimental data. This approach is first validated on a series of laboratory-controlled measurements performed on assemblies of bone- and soft tissue mimicking phantoms and then on in vivo measurements. The accuracy of the estimates is evaluated by comparison with reference values. To further support our hypothesis, these estimates are subsequently inserted into a bilayer model to test its accuracy. Our results show that the free plate model allows retrieving reliable waveguide properties, despite the presence of soft tissue. They also suggest that the more sophisticated bilayer model, although it is more precise to predict experimental data in the forward problem, could turn out to be hardly manageable for solving the inverse problem. PMID:28256568

Correction of metabolic acidosis with potassium citrate in renal transplant patients and its effect on bone quality.

PubMed

Starke, Astrid; Corsenca, Alf; Kohler, Thomas; Knubben, Johannes; Kraenzlin, Marius; Uebelhart, Daniel; Wüthrich, Rudolf P; von Rechenberg, Brigitte; Müller, Ralph; Ambühl, Patrice M

2012-09-01

Acidosis and transplantation are associated with increased risk of bone disturbances. This study aimed to assess bone morphology and metabolism in acidotic patients with a renal graft, and to ameliorate bone characteristics by restoration of acid/base homeostasis with potassium citrate. This was a 12-month controlled, randomized, interventional trial that included 30 renal transplant patients with metabolic acidosis (S-[HCO(3)(-)] <24 mmol/L) undergoing treatment with either potassium citrate to maintain S-[HCO(3)(-)] >24 mmol/L, or potassium chloride (control group). Iliac crest bone biopsies and dual-energy X-ray absorptiometry were performed at baseline and after 12 months of treatment. Bone biopsies were analyzed by in vitro micro-computed tomography and histomorphometry, including tetracycline double labeling. Serum biomarkers of bone turnover were measured at baseline and study end. Twenty-three healthy participants with normal kidney function comprised the reference group. Administration of potassium citrate resulted in persisting normalization of S-[HCO(3)(-)] versus potassium chloride. At 12 months, bone surface, connectivity density, cortical thickness, and cortical porosity were better preserved with potassium citrate than with potassium chloride, respectively. Serological biomarkers and bone tetracycline labeling indicate higher bone turnover with potassium citrate versus potassium chloride. In contrast, no relevant changes in bone mineral density were detected by dual-energy X-ray absorptiometry. Treatment with potassium citrate in renal transplant patients is efficient and well tolerated for correction of metabolic acidosis and may be associated with improvement in bone quality. This study is limited by the heterogeneity of the investigated population with regard to age, sex, and transplant vintage.

Effects of 16-month treatment with the cathepsin K inhibitor ONO-5334 on bone markers, mineral density, strength and histomorphometry in ovariectomized cynomolgus monkeys.

PubMed

Yamada, Hiroyuki; Ochi, Yasuo; Mori, Hiroshi; Nishikawa, Satoshi; Hashimoto, Yasuaki; Nakanishi, Yasutomo; Tanaka, Makoto; Bruce, Mark; Deacon, Steve; Kawabata, Kazuhito

2016-05-01

We examined the effects of ONO-5334, a cathepsin K inhibitor, on bone markers, BMD, strength and histomorphometry in ovariectomized (OVX) cynomolgus monkeys. ONO-5334 (1.2, 6 and 30mg/kg/day, p.o.), alendronate (0.05mg/kg/2weeks, i.v.), or vehicle was administered to OVX monkeys (all groups N=20) for 16months. A concurrent Sham group (N=20) was also treated with vehicle for 16months. OVX significantly increased bone resorption and formation markers and decreased BMD in lumbar vertebra, femoral neck, proximal tibia and distal radius. Alendronate suppressed these parameters to a level similar to that in the Sham-operated monkeys. ONO-5334 at doses 6 and 30mg/kg decreased bone resorption markers to a level roughly half of that in the Sham group, while keeping bone formation markers level above that in the Sham monkeys. Changes in DXA BMD confirmed that ONO-5334 at doses 6 and 30mg/kg increased BMD to a level greater than that in the Sham group in all examined sites. In the proximal tibia, in vivo pQCT analysis showed that ONO-5334 at doses 6 and 30mg/kg suppressed trabecular BMD loss to the sham level. However, ONO-5334 increased cortical BMD, cortical area and cortical thickness to a level greater than that in the Sham group, suggesting that ONO-5334 improves both cortical BMD and cortical geometry. Histomorphometric analysis revealed that ONO-5334 suppressed bone formation rate (BFR) at osteonal site in the midshaft femur but did not influence OVX-induced increase in BFR at either the periosteal or endocortical surfaces. Unlike alendronate, ONO-5334 increased osteoclasts surface (Oc.S/BS) and serum tartrate-resistant acid phosphatise 5b (TRAP5b) activity, highlighting the difference in the mode of action between these two drugs. Our results suggest that ONO-5334 has therapeutic potential not only in vertebral bones, but also in non-vertebral bones. Copyright © 2016 Elsevier Inc. All rights reserved.

A role for subchondral bone changes in the process of osteoarthritis; a micro-CT study of two canine models.

PubMed

Sniekers, Yvonne H; Intema, Femke; Lafeber, Floris P J G; van Osch, Gerjo J V M; van Leeuwen, Johannes P T M; Weinans, Harrie; Mastbergen, Simon C

2008-02-12

This study evaluates changes in peri-articular bone in two canine models for osteoarthritis: the groove model and the anterior cruciate ligament transection (ACLT) model. Evaluation was performed at 10 and 20 weeks post-surgery and in addition a 3-weeks time point was studied for the groove model. Cartilage was analysed, and architecture of the subchondral plate and trabecular bone of epiphyses was quantified using micro-CT. At 10 and 20 weeks cartilage histology and biochemistry demonstrated characteristic features of osteoarthritis in both models (very mild changes at 3 weeks). The groove model presented osteophytes only at 20 weeks, whereas the ACLT model showed osteophytes already at 10 weeks. Trabecular bone changes in the groove model were small and not consistent. This contrasts the ACLT model in which bone volume fraction was clearly reduced at 10 and 20 weeks (15-20%). However, changes in metaphyseal bone indicate unloading in the ACLT model, not in the groove model. For both models the subchondral plate thickness was strongly reduced (25-40%) and plate porosity was strongly increased (25-85%) at all time points studied. These findings show differential regulation of subchondral trabecular bone in the groove and ACLT model, with mild changes in the groove model and more severe changes in the ACLT model. In the ACLT model, part of these changes may be explained by unloading of the treated leg. In contrast, subchondral plate thinning and increased porosity were very consistent in both models, independent of loading conditions, indicating that this thinning is an early response in the osteoarthritis process.

Augmenting the osseointegration of endoprostheses using laser-sintered porous collars: an in vivo study.

PubMed

Mumith, A; Coathup, M; Chimutengwende-Gordon, M; Aston, W; Briggs, T; Blunn, G

2017-02-01

Massive endoprostheses rely on extra-cortical bone bridging (ECBB) to enhance fixation. The aim of this study was to investigate the role of selective laser sintered (SLS) porous collars in augmenting the osseointegration of these prostheses. The two novel designs of porous SLS collars, one with small pores (Ø700 μm, SP) and one with large pores (Ø1500 μm, LP), were compared in an ovine tibial diaphyseal model. Osseointegration of these collars was compared with that of a clinically used solid, grooved design (G). At six months post-operatively, the ovine tibias were retrieved and underwent radiological and histological analysis. Porous collars provided a significantly greater surface (p < 0.001) for the ingrowth of bone than the standard grooved design. Significantly greater extracortical pedicle formation was seen radiologically around the grooved design (length p = 0.002, thickness p < 0.001, surface area p = 0.002) than around the porous collars. However, the ingrowth of bone occurred from the transection site into the porous structure of both types of collar. A fivefold increase in integration was seen with the SP and a threefold increase in the LP design when compared with G (p < 0.001). SLS porous collars allow the direct ingrowth of more bone and are better than current designs which rely on surface ongrowth and ECBB. Cite this article: Bone Joint J 2017;99-B:276-82. ©2017 The British Editorial Society of Bone & Joint Surgery.

Yellow-bellied Marmots (Marmota flaviventris) preserve bone strength and microstructure during hibernation

PubMed Central

Wojda, Samantha J.; McGee-Lawrence, Meghan E.; Gridley, Richard A.; Auger, Janene; Black, Hal L.; Donahue, Seth W.

2012-01-01

Reduced skeletal loading typically results in decreased bone strength and increased fracture risk for humans and many other animals. Previous studies have shown bears are able to prevent bone loss during the disuse that occurs during hibernation. Studies with smaller hibernators, which arouse intermittently during hibernation, show that they may lose bone at the microstructural level. These small hibernators, like bats and squirrels, do not utilize intracortical remodeling. However, slightly larger mammals like marmots do. In this study we examined the effects of hibernation on bone structural, mineral, and mechanical properties in yellow-bellied marmots (Marmota flaviventris). This was done by comparing cortical bone properties in femurs and trabecular bone properties in tibias from marmots killed before hibernation (fall) and after hibernation (spring). Age data were not available for this study; however, based on femur length the post-hibernation marmots were larger than the pre-hibernation marmots. Thus, cross-sectional properties were normalized by allometric functions of bone length for comparisons between pre- and post-hibernation. Cortical thickness and normalized cortical area were higher in post-hibernation samples; no other normalized cross-sectional properties were different. No cortical bone microstructural loss was evident in osteocyte lacunar measurements, intracortical porosity, or intracortical remodeling cavity density. Osteocyte lacunar area, porosity, and density were surprisingly lower in post-hibernation samples. Trabecular bone volume fraction was not different between pre- and post-hibernation. Measures of both trabecular and cortical bone mineral content were higher in post-hibernation samples. Three-point bending failure load, failure energy, elastic energy, ultimate stress, and yield stress were all higher in post-hibernation samples. These results support the idea that, like bears, marmots are able to prevent disuse osteoporosis during hibernation, thus preventing increased fracture risk and promoting survival of the extreme environmental conditions that occur in hibernation. PMID:22037004

Yellow-bellied marmots (Marmota flaviventris) preserve bone strength and microstructure during hibernation.

PubMed

Wojda, Samantha J; McGee-Lawrence, Meghan E; Gridley, Richard A; Auger, Janene; Black, Hal L; Donahue, Seth W

2012-01-01

Reduced skeletal loading typically results in decreased bone strength and increased fracture risk for humans and many other animals. Previous studies have shown bears are able to prevent bone loss during the disuse that occurs during hibernation. Studies with smaller hibernators, which arouse intermittently during hibernation, show that they may lose bone at the microstructural level. These small hibernators, like bats and squirrels, do not utilize intracortical remodeling. However, slightly larger mammals like marmots do. In this study we examined the effects of hibernation on bone structural, mineral, and mechanical properties in yellow-bellied marmots (Marmota flaviventris). This was done by comparing cortical bone properties in femurs and trabecular bone properties in tibias from marmots killed before hibernation (fall) and after hibernation (spring). Age data were not available for this study; however, based on femur length the post-hibernation marmots were larger than the pre-hibernation marmots. Thus, cross-sectional properties were normalized by allometric functions of bone length for comparisons between pre- and post-hibernation. Cortical thickness and normalized cortical area were higher in post-hibernation samples; no other normalized cross-sectional properties were different. No cortical bone microstructural loss was evident in osteocyte lacunar measurements, intracortical porosity, or intracortical remodeling cavity density. Osteocyte lacunar area, porosity, and density were surprisingly lower in post-hibernation samples. Trabecular bone volume fraction was not different between pre- and post-hibernation. Measures of both trabecular and cortical bone mineral content were higher in post-hibernation samples. Three-point bending failure load, failure energy, elastic energy, ultimate stress, and yield stress were all higher in post-hibernation samples. These results support the idea that, like bears, marmots are able to prevent disuse osteoporosis during hibernation, thus preventing increased fracture risk and promoting survival of the extreme environmental conditions that occur in hibernation. Copyright © 2011 Elsevier Inc. All rights reserved.

In vivo performance of two different hydroxyapatite coatings on titanium prepared by discharging in electrolytes.

PubMed

Yamamoto, Hiroki; Shibata, Yo; Tachikawa, Tetsuhiko; Miyazaki, Takashi

2006-07-01

This study reports a discharging method for bone-like carbonated HA (cHA)-coating (Ca/P 1.71) and stoichiometric HA (sHA)-coating (Ca/P 1.67) with micrometer order thicknesses on titanium plates, using modified body fluid and acidic calcium phosphate solutions, respectively. In vivo histological performance of the HA coatings prepared by discharging in electrolytes was evaluated. Bone-contact indexes of HA coatings were measured microscopically. Additionally, bone-coating interface was analyzed by scanning electron microscopy and the use of an electron probe microanalyzer. Results demonstrated that there was no significant difference in contact index between HA coatings. However, the cHA coating was practically replaced by immature bone, and the titanium metal substrate was directly connected to the bone structure whereas the sHA coating layer remained and was partially detached from the titanium metal substrate. Since detached coating particles are pathogens, and can cause peri-implantitis, the cHA coating was more favorable than the sHA coating even if contact index was equivalent to that of the sHA coating. It is thought that coating thickness and chemical composition of coatings are important for biological stability of implants. In conclusion, since bone-like thin cHA coating showed high osteoconductivity and bone replacement, bone-like HA is superior to sHA coating for use in dental implants.

Contribution of trochanteric soft tissues to fall force estimates, the factor of risk, and prediction of hip fracture risk.

PubMed

Bouxsein, Mary L; Szulc, Pawel; Munoz, Fracoise; Thrall, Erica; Sornay-Rendu, Elizabeth; Delmas, Pierre D

2007-06-01

We compared trochanteric soft tissue thickness, femoral aBMD, and the ratio of fall force to femoral strength (i.e., factor of risk) in 21 postmenopausal women with incident hip fracture and 42 age-matched controls. Reduced trochanteric soft tissue thickness, low femoral aBMD, and increased ratio of fall force to femoral strength (i.e., factor of risk) were associated with increased risk of hip fracture. The contribution of trochanteric soft tissue thickness to hip fracture risk is incompletely understood. A biomechanical approach to assessing hip fracture risk that compares forces applied to the hip during a sideways fall to femoral strength may by improved by incorporating the force-attenuating effects of trochanteric soft tissues. We determined the relationship between femoral areal BMD (aBMD) and femoral failure load in 49 human cadaveric specimens, 53-99 yr of age. We compared femoral aBMD, trochanteric soft tissue thickness, and the ratio of fall forces to bone strength (i.e., the factor of risk for hip fracture, phi), before and after accounting for the force-attenuating properties of trochanteric soft tissue in 21 postmenopausal women with incident hip fracture and 42 age-matched controls. Femoral aBMD correlated strongly with femoral failure load (r2 = 0.73-0.83). Age, height, and weight did not differ; however, women with hip fracture had lower total femur aBMD (OR = 2.06; 95% CI, 1.19-3.56) and trochanteric soft tissue thickness (OR = 1.82; 95% CI, 1.01, 3.31). Incorporation of trochanteric soft tissue thickness measurements reduced the estimates of fall forces by approximately 50%. After accounting for force-attenuating properties of trochanteric soft tissue, the ratio of fall forces to femoral strength was 50% higher in cases than controls (0.92 +/- 0.44 versus 0.65 +/- 0.50, respectively; p = 0.04). It is possible to compute a biomechanically based estimate of hip fracture risk by combining estimates of femoral strength based on an empirical relationship between femoral aBMD and bone strength in cadaveric femora, along with estimates of loads applied to the hip during a sideways fall that account for thickness of trochanteric soft tissues. Our findings suggest that trochanteric soft tissue thickness may influence hip fracture risk by attenuating forces applied to the femur during a sideways fall and provide rationale for developing improved measurements of trochanteric soft tissue and for studying a larger cohort to determine whether trochanteric soft tissue thickness contributes to hip fracture risk independently of aBMD.

Androgens have antiresorptive effects on trabecular disuse osteopenia independent from muscle atrophy.

PubMed

Laurent, Michaël R; Jardí, Ferran; Dubois, Vanessa; Schollaert, Dieter; Khalil, Rougin; Gielen, Evelien; Carmeliet, Geert; Claessens, Frank; Vanderschueren, Dirk

2016-12-01

Aging hypogonadal men are at increased risk of osteoporosis and sarcopenia. Testosterone is a potentially appealing strategy to prevent simultaneous bone and muscle loss. The androgen receptor (AR) mediates antiresorptive effects on trabecular bone via osteoblast-lineage cells, as well as muscle-anabolic actions. Sex steroids also modify the skeletal response to mechanical loading. However, it is unclear whether the effects of androgens on bone remain effective independent of mechanical stimulation or rather require indirect androgen effects via muscle. This study aims to characterize the effects and underlying mechanisms of androgens on disuse osteosarcopenia. Adult male mice received a unilateral botulinum toxin (BTx) injection, and underwent sham surgery or orchidectomy (ORX) without or with testosterone (ORX+T) or dihydrotestosterone (ORX+DHT) replacement. Compared to the contralateral internal control hindlimb, acute trabecular number and bone volume loss was increased by ORX and partially prevented DHT. T was more efficient and increased BV/TV in both hindlimbs over sham values, although it did not reduce the detrimental effect of BTx. Both androgens and BTx regulated trabecular osteoclast surface as well as tartrate-resistant acid phosphatase expression. Androgens also prevented BTx-induced body weight loss but did not significantly influence paralysis or muscle atrophy. BTx and ORX both reduced cortical thickness via endosteal expansion, which was prevented by T but not DHT. In long-term follow-up, the residual trabecular bone volume deficit in sham-BTx hindlimbs was prevented by DHT but T restored it more efficiently to pre-treatment levels. Conditional AR deletion in late osteoblasts and osteocytes or in the satellite cell lineage increased age-related trabecular bone loss in both hindlimbs without influencing the effect of BTx on trabecular osteopenia. We conclude that androgens have antiresorptive effects on trabecular disuse osteopenia which do not require AR actions on bone via muscle or via osteocytes. Copyright © 2016 Elsevier Inc. All rights reserved.

Moderate weight loss in obese and overweight men preserves bone quality12345

PubMed Central

Pop, L Claudia; Sukumar, Deeptha; Tomaino, Katherine; Schlussel, Yvette; Schneider, Stephen H; Gordon, Chris L; Wang, Xiangbing; Shapses, Sue A

2015-01-01

Background: Weight loss (WL) negatively affects bone mineral density (BMD) in older populations and has specifically been shown in women. Objective: In this prospective controlled trial, we examined variables of bone quality and endocrine changes after intentional WL in men. Design: Thirty-eight overweight and obese [mean ± SD body mass index (in kg/m2): 31.9 ± 4.4; age: 58 ± 6 y] men were recruited to either WL through caloric restriction or weight maintenance (WM) for 6 mo. Results: There was a −7.9 ± 4.4% and +0.2 ± 1.6% change in body weight in the WL and WM groups, respectively. There was a greater increase in femoral neck and total body BMD and bone mineral content (BMC) in the WM group than in the WL group (P-interaction effect < 0.05). In contrast, there was a trend for the tibia cortical thickness and area to decrease more in the WM group than in the WL group (P ≤ 0.08). There was a decrease in the periosteal circumference in both groups over time (P < 0.01) and no statistically significant changes in trabecular bone. Circulating total, free, and bioavailable estradiol decreased in the WL group compared with the WM group, and changes were different between groups (P < 0.05). Serum total and bioavailable testosterone increased in both groups (P < 0.01). Serum 25-hydroxyvitamin D increased to a similar extent in both groups (P < 0.05). Conclusions: Moderate WL in overweight and obese men did not decrease BMD at any anatomical site or alter cortical and trabecular bone and geometry. Also, despite increased BMD at some sites when maintaining excess body weight, cortical bone showed a trend in the opposite direction. This trial was registered at clinicaltrials.gov as NCT00472745. PMID:25733651

Hypophosphatemic osteomalacia induced by tenofovir in HIV-infected patients.

PubMed

Mateo, Lourdes; Holgado, Susana; Mariñoso, Maria Luisa; Pérez-Andrés, Ricard; Bonjoch, Anna; Romeu, Joan; Olivé, Alejandro

2016-05-01

Tenofovir disoproxil fumarate (TDF) is an adenine analogue reverse transcription inhibitor widely used in first-line treatment of human immunodeficiency virus (HIV) infection and also in hepatitis B virus infection. Its use has been linked to sporadic Fanconi syndrome, renal failure and bone disease. We present the clinical characteristics of tenofovir-induced osteomalacia, discuss bone biopsy findings, describe predisposing factors and compare our results with other reported cases. We describe five cases of hypophosphatemic osteomalacia induced by TDF and recorded at the rheumatology service of a university hospital between 2010 and 2014. We also report the characteristics of bone biopsies of this pathology, which have not been previously described. We include a review of published cases of proximal renal tubulopathy (PRT) and osteomalacia induced by TDF (PubMed 1995-2014; keywords: osteomalacia, tenofovir, Fanconi syndrome, hypophosphatemic osteomalacia, proximal renal tubulopathy, bone biopsy). Five HIV patients who developed hypophosphatemic osteomalacia under TDF treatment (>5 years) presented increasing bone pain and a progressive inability to walk without assistance as a result of multiple insufficiency fractures. Bone biopsy performed in three patients after tetracycline labelling showed increased osteoid thickness, confirming osteomalacia. A literature review retrieved 17 publications on this condition, including 53 cases: 26 patients developed isolated PRT, 25 presented PRT and with multiple insufficiency fractures and two presented isolated bone disease, including osteomalacia and osteoporosis. Rheumatologists should be alert to this complication in patients receiving tenofovir. The main complaint reported by these patients is diffuse pain, predominantly in the lower limbs, indicating multiple stress fractures. Serum phosphate and appropriate screening for abnormal proximal tubule function should be monitored. Bone scintigraphy should be carried out in cases of limb pain before the occurrence of more severe complications.

Effect of swimming exercise on three-dimensional trabecular bone microarchitecture in ovariectomized rats.

PubMed

Ju, Yong-In; Sone, Teruki; Ohnaru, Kazuhiro; Tanaka, Kensuke; Fukunaga, Masao

2015-11-01

Swimming is generally considered ineffective for increasing bone mass in humans, at least compared with weight-bearing sports. However, swimming exercise has sometimes been shown to have a strong positive effect on bone mass in small animals. This study investigated the effects of swimming on bone mass, strength, and microarchitecture in ovariectomized (OVX) rats. OVX or sham operations were performed on 18-wk-old female Fisher 344 rats. Rats were randomly divided into four groups: sham sedentary (Sham-CON), sham swimming exercised (Sham-SWI), OVX sedentary (OVX-CON), and OVX swimming exercised (OVX-SWI). Rats in exercise groups performed swimming in a water bath for 60 min/day, 5 days/wk, for 12 wk. Bone mineral density (BMD) in right femurs was analyzed using dual-energy X-ray absorptiometry. Three-dimensional trabecular architecture at the distal femoral metaphysis was analyzed using microcomputed tomography (μCT). Geometrical properties of diaphyseal cortical bone were evaluated in the midfemoral region using μCT. The biomechanical properties of femurs were analyzed using three-point bending. Femoral BMD was significantly decreased following ovariectomy. This change was suppressed by swimming. Trabecular bone thickness, number, and connectivity were decreased by ovariectomy, whereas structure model index (i.e., ratio of rod-like to plate-like trabeculae) increased. These changes were also suppressed by swimming exercise. Femurs displayed greater cortical width and maximum load in SWI groups than in CON groups. Together, these results demonstrate that swimming exercise drastically alleviated both OVX-induced decreases in bone mass and mechanical strength and the deterioration of trabecular microarchitecture in rat models of osteoporosis. Copyright © 2015 the American Physiological Society.

Vitamin E provides protection for bone in mature hindlimb unloaded male rats

NASA Technical Reports Server (NTRS)

Smith, B. J.; Lucas, E. A.; Turner, R. T.; Evans, G. L.; Lerner, M. R.; Brackett, D. J.; Stoecker, B. J.; Arjmandi, B. H.

2005-01-01

The deleterious effects of skeletal unloading on bone mass and strength may, in part, result from increased production of oxygen-derived free radicals and proinflammatory cytokines. This study was designed to evaluate the ability of vitamin E (alpha-tocopherol), a free-radical scavenger with antiinflammatory properties, to protect against bone loss caused by skeletal unloading in mature male Sprague-Dawley rats. A 2 x 3 factorial design was used with either hindlimb unloading (HU) or normal loading (ambulatory; AMB), and low-dose (LD; 15 IU/kg diet), adequate-dose (AD; 75 IU/kg diet), or high-dose (HD; 500 IU/kg diet) vitamin E (DL-alpha-tocopherol acetate). To optimize the effects of vitamin E on bone, dietary treatments were initiated 9 weeks prior to unloading and continued during the 4-week unloading period, at which time animals were euthanized and blood and tissue samples were collected. Serum vitamin E was dose-dependently increased, confirming the vitamin E status of animals. The HD treatment improved oxidation parameters, as indicated by elevated serum ferric-reducing ability and a trend toward reducing tissue lipid peroxidation. Histomorphometric analysis of the distal femur revealed significant reductions in trabecular thickness (TbTh), double-labeled surface (dLS/BS), and rate of bone formation to bone volume (BFR/BV) due by HU. AMB animals on the HD diet and HU animals on the LD diet had reduced bone surface normalized to tissue volume (BS/TV) and trabecular number (TbN); however, the HD vitamin E protected against these changes in the HU animals. Our findings suggest that vitamin E supplementation provides modest bone protective effects during skeletal unloading.

Tributyltin induces distinct effects on cortical and trabecular bone in female C57Bl/6J mice.

PubMed

Watt, James; Baker, Amelia H; Meeks, Brett; Pajevic, Paola D; Morgan, Elise F; Gerstenfeld, Louis C; Schlezinger, Jennifer J

2018-09-01

The retinoid X receptors (RXR), peroxisome proliferator activated receptor gamma (PPARγ), and liver X receptors (LXR) all have been shown to regulate bone homeostasis. Tributyltin (TBT) is an environmental contaminant that is a dual RXRα/β and PPARγ agonist. TBT induces RXR, PPARγ, and LXR-mediated gene transcription and suppresses osteoblast differentiation in vitro. Bone marrow multipotent mesenchymal stromal cells derived from female C57BL/6J mice were more sensitive to suppression of osteogenesis by TBT than those derived from male mice. In vivo, oral gavage of 12 week old female, C57Bl/6J mice with 10 mg/kg TBT for 10 weeks resulted in femurs with a smaller cross-sectional area and thinner cortex. Surprisingly, TBT induced significant increases in trabecular thickness, number, and bone volume fraction. TBT treatment did not change the Rankl:Opg RNA ratio in whole bone, and histological analyses showed that osteoclasts in the trabecular space were minimally reduced. In contrast, expression of cardiotrophin-1, an osteoblastogenic cytokine secreted by osteoclasts, increased. In primary bone marrow macrophage cultures, TBT marginally inhibited the number of osteoclasts that differentiated, in spite of significantly suppressing expression of osteoclast markers Nfatc1, Acp5, and Ctsk and resorptive activity. TBT induced expression of RXR- and LXR-dependent genes in whole bone and in vitro osteoclast cultures. However, only an RXR antagonist, but not an LXR antagonist, significantly inhibited TBTs ability to suppress osteoclast differentiation. These results suggest that TBT has distinct effects on cortical versus trabecular bone, likely resulting from independent effects on osteoblast and osteoclast differentiation that are mediated through RXR. © 2018 Wiley Periodicals, Inc.

Finite element analysis of osteoporosis models based on synchrotron radiation

NASA Astrophysics Data System (ADS)

Xu, W.; Xu, J.; Zhao, J.; Sun, J.

2016-04-01

With growing pressure of social aging, China has to face the increasing population of osteoporosis patients as well as the whole world. Recently synchrotron radiation has become an essential tool for biomedical exploration with advantage of high resolution and high stability. In order to study characteristic changes in different stages of primary osteoporosis, this research focused on the different periods of osteoporosis of rats based on synchrotron radiation. Both bone histomorphometry analysis and finite element analysis were then carried on according to the reconstructed three dimensional models. Finally, the changes of bone tissue in different periods were compared quantitatively. Histomorphometry analysis showed that the structure of the trabecular in osteoporosis degraded as the bone volume decreased. For femurs, the bone volume fraction (Bone volume/ Total volume, BV/TV) decreased from 69% to 43%. That led to the increase of the thickness of trabecular separation (from 45.05μ m to 97.09μ m) and the reduction of the number of trabecular (from 7.99 mm-1 to 5.97mm-1). Simulation of various mechanical tests with finite element analysis (FEA) indicated that, with the exacerbation of osteoporosis, the bones' ability of resistance to compression, bending and torsion gradually became weaker. The compression stiffness of femurs decreased from 1770.96 Fμ m-1 to 697.41 Fμ m-1, the bending and torsion stiffness were from 1390.80 Fμ m-1 to 566.11 Fμ m-1 and from 2957.28N.m/o to 691.31 N.m/o respectively, indicated the decrease of bone strength, and it matched the histomorphometry analysis. This study suggested that FEA and synchrotron radiation were excellent methods for analysing bone strength conbined with histomorphometry analysis.

A study on porous super austenitic stainless steel coating for improvement of bone ingrowth

NASA Astrophysics Data System (ADS)

Oh, Keun Taek; Park, Yong Soo

1998-02-01

In this study, the prostheses were provided with the bone ingrowth site by coating the super stainless steel powder on the same substrate (S32050) using plasma spraying method. Plasma current and powder feed rate varied in this study based on the optimum conditions of previous experiments. The optimum conditions for satisfying the requirements of the porous coatings were found. The characteristics of the coatings were observed according to the experimental parameters. It was found that plasma current influenced the chemical composition (the oxides, Cr component), melting and flattening degree of the sprayed particle (surface roughness, thickness of the splat, pores) and corrosion -resistance. The powder feed rate also influenced the coating thickness and efficiency. The amount of Cr was increased, but Ni, Mo, Fe were decreased with plasma current. An increase of Cr in the coating surface corresponded to an increase in the amount of the formed oxides. The coated specimen in 400A had a high corrosion-resistance owing to a dense coating. The coated specimen in 500A formed many types of oxides. In 300A current, the coating was rough with many pores, and corrosion-resistance of the coating showed a large variation according to the oxidation and compositional change. Specifically at 100 g/min powder feed rate in a 300A current, the coating was rough and porous, nevertheless, it had high corrosion resistance.

Influence of bone density on the cement fixation of femoral hip resurfacing components.

PubMed

Bitsch, Rudi G; Jäger, Sebastian; Lürssen, Marcus; Loidolt, Travis; Schmalzried, Thomas P; Clarius, Michael

2010-08-01

In clinical outcome studies, small component sizes, female gender, femoral shape, focal bone defects, bad bone quality, and biomechanics have been associated with failures of resurfacing arthroplasties. We used a well-established experimental setup and human bone specimens to analyze the effects of bone density on cement fixation of femoral hip resurfacing components. Thirty-one fresh frozen femora were prepared for resurfacing using the original instruments. ASR resurfacing prostheses were implanted after dual-energy X-ray densitometer scans. Real-time measurements of pressure and temperature during implantation, analyses of cement penetration, and measurements of micro motions under torque application were performed. The associations of bone density and measurement data were examined calculating regression lines and multiple correlation coefficients; acceptability was tested with ANOVA. We found significant relations between bone density and micro motion, cement penetration, cement mantle thickness, cement pressure, and interface temperature. Mean bone density of the femora was 0.82 +/- 0.13 g/cm(2), t-score was -0.7 +/- 1.0, and mean micro motion between bone and femoral resurfacing component was 17.5 +/- 9.1 microm/Nm. The regression line between bone density and micro motion was equal to -56.7 x bone density + 63.8, R = 0.815 (p < 0.001). Bone density scans are most helpful for patient selection in hip resurfacing, and a better bone quality leads to higher initial component stability. A sophisticated cementing technique is recommended to avoid vigorous impaction and incomplete seating, since increasing bone density also results in higher cement pressures, lower cement penetration, lower interface temperatures, and thicker cement mantles. Copyright 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Placenta hominis protects osteoporosis in ovariectomized rats.

PubMed

Chae, H J; Choi, K H; Chae, S W; Kim, H M; Shin, T K; Lee, G Y; Jeong, G S; Park, H R; Choi, H I; Kim, S B; Yoo, S K; Kim, H R

2006-01-01

In China, Japan, and Korea, placenta hominis extracts (PHEs) are used clinically for the treatment of osteoporosis. The anti-osteoporotic effect of PHEs was studied. The trabecular bone area and thickness in OVX rats decreased by 50% from those in sham-operated rats; these decreases were completely inhibited by administration of PHEs for 7 weeks. Osteoclast numbers and the osteoblast surface were enhanced in OVX rats, but PHEs had no effect on these phenomena. Serum phosphorus and alkaline phosphatase in OVX rats increased compared to those in sham-operated rats, but the increases were not affected by the administration of PHEs. Thyroxine (T4) level was stimulated in OVX rats. The extracts inhibited the T4 level in the OVX rats. These results strongly suggest that PHEs be effective in preventing the development of bone loss induced by OVX in rats.

Effects of in utero pestivirus infection on bovine fetal bone geometry, biomechanical properties and composition.

PubMed

Webb, Brett T; McGilvray, Kirk C; Smirnova, Natalia P; Hansen, Thomas R; Norrdin, Robert W

2013-11-01

Transplacental viral infection of the fetus can result in abnormal trabecular and cortical bone modeling in long bones through impaired bone resorption and formation. Although such infections are frequently associated with neonatal fractures in humans and animals, their effect on the biomechanical properties of the developing skeleton remain poorly understood. The goal of this study was to determine the effects of transplacental bovine viral diarrhea virus (BVDV) infection on the biomechanical properties of fetal femora. Pregnant heifers were inoculated intranasally with non-cytopathic BVDV or media alone on day 75 of gestation to produce persistently infected (PI) and control fetuses, respectively, which were then removed on days 192 and 245 of gestation. Histomorphometry, compositional analysis and 'four-point bending until failure' were performed on fetal femora. Altered cortical geometry largely accounted for differences in calculated elastic modulus (PI vs. control, and day 192 vs. day 245) and ultimate stress (day 192 vs. day 245). Fetal infection with BVDV did not significantly impair inherent biomechanical properties of bone but rather resulted in decreased periosteal apposition rates, manifested as smaller femoral mid-diaphyseal diameters. There were no differences between PI and control fetuses in cortical thickness ratio, ash density or calcium/phosphorous content; however, cortical thickness ratio decreased with fetal age. Thus even when cortical thickness ratios are similar, differences in mid-diaphyseal diameter affect the error associated with the calculation of stress and strain by classical beam theory equations. Copyright © 2013. Published by Elsevier Ltd.

Comparison between complete denture and implant-retained overdenture: effect of different mucosa thickness and resiliency on stress distribution.

PubMed

Assunção, Wirley Gonçalves; Barão, Valentim Adelino Ricardo; Tabata, Lucas Fernando; de Sousa, Edson Antonio Capello; Gomes, Erica Alves; Delben, Juliana Aparecida

2009-12-01

The effect of different mucosa characteristics on stress distribution of complete dentures and overdentures remains unknown. The aim of this study was to evaluate the effect of different mucosa thickness and resiliency on the stress distribution of complete dentures and implant-retained overdentures using a two-dimensional finite element analysis. Representative models of the edentulous mandible were constructed on AutoCAD software according to the groups' characteristics. In group CD, a model of the edentulous mandible supporting a complete denture was obtained while in group IO, a model of edentulous mandible supporting an overdenture over two unsplinted implants with an o' ring system was constructed. In each group, mucosa assumed three characteristics of thickness (1, 3 and 5 mm) corresponding to the resiliencies hard, resilient and soft respectively. Evaluation was performed on Ansys software with 100N vertical load applied on central incisor teeth. The principal stress was used as analysis criteria. Group IO showed higher stress values than group CD regardless of mucosal thickness and resiliency. Stress decreased at the supporting tissues in both groups as the thickness and resiliency of mucosa increased. In relation to the supporting tissues, cortical bone showed the highest stress values. It was concluded that the use of an attachment system increases stress values and the thickness and resiliency of mucosa influence more on these values.

A High-Fat Diet Induces Bone Loss in Mice Lacking the Alox5 Gene

PubMed Central

Le, Phuong; Kawai, Masanobu; Bornstein, Sheila; DeMambro, Victoria E.; Horowitz, Mark C.

2012-01-01

5-Lipoxygenase catalyzes leukotriene generation from arachidonic acid. The gene that encodes 5-lipoxygenase, Alox5, has been identified in genome-wide association and mouse Quantitative Trait Locus studies as a candidate gene for obesity and low bone mass. Thus, we tested the hypothesis that Alox5−/− mice would exhibit metabolic and skeletal changes when challenged by a high-fat diet (HFD). On a regular diet, Alox5−/− mice did not differ in total body weight, percent fat mass, or bone mineral density compared with wild-type (WT) controls (P < 0.05). However, when placed on a HFD, Alox5−/− gained more fat mass and lost greater areal bone mass vs. WT (P < 0.05). Microarchitectural analyses revealed that on a HFD, WT showed increases in cortical area (P < 0.01) and trabecular thickness (P < 0.01), whereas Alox5−/− showed no change in cortical parameters but a decrease in trabecular number (P < 0.05) and bone volume fraction compared with WT controls (P < 0.05). By histomorphometry, a HFD did not change bone formation rates of either strain but produced an increase in osteoclast number per bone perimeter in Alox5−/− mice (P < 0.03). In vitro, osteoclastogenesis of marrow stromal cells was enhanced in mutant but not WT mice fed a HFD. Gene expression for Rankl, Pparg, and Cox-2 was greater in the femur of Alox5−/− than WT mice on a HFD (P < 0.01), but these increases were suppressed in the Alox5−/− mice after 8 wk of treatment with celecoxib, a cyclooxygenase-2 inhibitor. In sum, there is a strong gene by environmental interaction for bone mass when mice lacking the Alox5 gene are fed a HFD. PMID:22128029

Long-Duration Spaceflight During the Bion-M1 Spaceflight Experiment Resulted in Significant Bone Loss in the Femoral Head and Alterations in Stem Cell Differentiation Potential in Male Mice

NASA Astrophysics Data System (ADS)

Blaber, Elizabeth; Almeida, Eduardo; Grigoryan, Eleonora; Globus, Ruth

Scientific understanding of the effects of microgravity on mammalian physiology has been limited to short duration spaceflight experiments (10-15 days). As long duration and inter-planetary missions are being initiated, there is a great need to understand the long-term effects of spaceflight on various physiological processes, including stem cell-based tissue regeneration. Bion-M1, for the first time, enabled the possibility of studying the effects of 30-days of microgravity exposure on a mouse model with sufficient sample size to enable statistical analysis. In this experiment, we hypothesized that microgravity negatively impacts stem cell based tissue regeneration, such as bone remodeling and regeneration from hematopoietic and mesenchymal precursors, thereby resulting in tissue degeneration in mice exposed to spaceflight. To test this hypothesis we collected the pelvis and proximal femur from space-flown mice and asynchronous ground controls and analyzed bone and bone marrow using techniques including Microcomputed Tomography (MicroCT), and in-vitro differentiation and differentiating cell motility assays. To determine the effects of 30-days spaceflight on bone tissue mass, we used MicroCT to analyze the trabecular bone of the femoral head and the cortical bone of the femoral neck and mid-shaft. We found that spaceflight caused a 45% decrease in bone volume ratio, a 17% decrease in trabecular thickness, a 25% decrease in trabecular number, and a 17% increase in trabecular spacing of trabecular bone. Furthermore, structural model index and trabecular pattern factor were increased by 32% and 82% respectively indicating that 30-days spaceflight resulted not only in a large loss of trabecular bone but also in a decrease of bone strength indicators. Analysis of the femoral neck cortical bone showed an increase in marrow area and cortical porosity indicating an overall widening of the femoral neck. Interestingly, no significant alterations were found in the cortical bone of the femoral mid-shaft. To determine the regenerative potential of osteoblasts derived from mesenchymal stem cells flown in microgravity we conducted post-flight in-vitro osteoblastogenesis and mineralized nodule formation assays. We found an increase in post-flight differentiation and mineralization of microgravity-flown osteogenic cells, suggesting an accumulation of precursor cells that fail to fully differentiate in space, and then resume vigorous osteogenesis upon reloading at 1g. Overall, these preliminary results indicate that exposure to 30-days spaceflight causes significant trabecular bone loss in the femoral head, a decrease in trabecular bone strength indicators, and compensatory widening of the femoral neck. These results, coupled with diminished regenerative potential of bone marrow stem cells during mechanical unloading in microgravity, have potentially serious implications for bone health and fracture risk during long-duration spaceflight.

Changes in jawbones of male patients with chronic renal failure on digital panoramic radiographs.

PubMed

Dagistan, Saadettin; Miloglu, Ozkan; Caglayan, Fatma

2016-01-01

To compare the existence of gonial cortical bone thickness, antegonial index, mandibular canal bone resorption and gonial angle values and pathologies like ground-glass appearance in jawbones and brown tumor in male patients undergoing dialysis due to chronic renal failure and men from the healthy control group on panoramic radiographs. Panoramic radiographs were taken from 80 male individuals in total (40 normal and 40 dialysis patients). Values obtained from the right and left sides of the mandible were summed and their means were calculated. Gonial cortical thickness, antegonial index and gonial angle values were assessed with the Student's t-test, mandibular canal wall resorption with the Chi-square test, and pathologies such as ground-glass appearance and Brown tumor as "available" or "not available." Statistically significant differences were observed among the antegonial index (P < 0.001), gonial cortical bone thickness (P < 0.001), and gonial angle (P < 0.001) values of study and control groups. Besides, mandibular canal wall resorption (P < 0.001) was also statistically significant. In the study group, pathologies with ground-glass appearance were encountered in mandible, but no radiographic findings were observed similar to brown tumor. Compared to the control group, decreases were found in gonial cortical bone thicknesses, antegonial index values, mandibular canal wall resorption, and gonial angle values of the patients receiving dialysis treatment due to chronic renal failure. Although it is not statistically significant, pathology with ground-glass appearance was detected in a patient, but no pathologies like brown tumor were observed. These findings from patients with chronic renal failure must be evaluated in panoramic radiography.

Does chemical composition of antler bone reflect the physiological effort made to grow it?

PubMed

Landete-Castillejos, T; Estevez, J A; Martínez, A; Ceacero, F; Garcia, A; Gallego, L

2007-04-01

In a previous study, antler bone chemical composition was found to differ between base and tip. If such variation is in part due to the physiological effort made to grow the antler, composition trends should differ between antlers from deer population differing in mineral or food availability, or body reserves. To assess this, we examined cortical thickness and bone composition along the antler shaft, and compared trends between antlers from two populations: captive, well-fed, health-managed deer (n=15), and free-ranging deer with lower food quality and no health treatment (n=10). Significant and clear divergent trends supporting greater physiological exhaustion in free-ranging deer and high or moderate predictive models were found for cortical thickness (R(2)=61.8%), content of Na (R(2)=68.6%), Mg (R(2)=56.3%), K (R(2)=40.0%), and Zn (34.6%); lower predictive power was found for protein (R(2)=25.6%) and ash content (R(2)=19.5%); and poor predictive power was found for Ca (R(2)=4.3%), Fe (R(2)=11.1%), and Si (R(2)=4.7%). A second part of the study assessed similar antler structures grown at the beginning (brow tine) and end (top tine) of antler growth within captive deer. Greater cortical thickness and ash content was found for brow tine, as well as a smaller protein, K and Mg content. In contrast, no difference was found for Ca, Na, Zn, Fe or Si. The results suggest that thickness and mineral composition reflect the physiological effort made to build antler bone.

A Biomechanical Approach to Assessing Hip Fracture Risk

NASA Technical Reports Server (NTRS)

Ellman, Rachel

2009-01-01

Bone loss in microgravity is well documented, but it is difficult to quantify how declines in bone mineral density (BMD) contribute to an astronaut's overall risk of fracture upon return. This study uses a biomechanical approach to assessing hip fracture risk, or Factor of Risk (Phi), which is defined as the ratio of applied load to bone strength. All long-duration NASA astronauts from Expeditions 1-18 were included in this study (n=25), while crewmembers who flew twice (n=2) were treated as separate subjects. Bone strength was estimated based on an empirical relationship between areal BMD at the hip, as measured by DXA, and failure load, as determined by mechanical testing of cadaver femora. Fall load during a sideways fall was calculated from a previously developed biomechanical model, which takes into account body weight, height, gender, and soft tissue thickness overlying the lateral aspect of the hip that serves to attenuate the impact force. While no statistical analyses have been performed yet, preliminary results show that males in this population have a higher FOR than females, with a post- flight Phi of 0.87 and 0.36, respectively. FOR increases 5.1% from preflight to postflight, while only one subject crossed the fracture "threshold" of Phi = 1, for a total of 2 subjects with a postflight Phi > 1. These results suggest that men may be at greater risk for hip fracture due largely in part to their relatively thin soft tissue padding as compared to women, since soft tissue thickness has the highest correlation (R(exp 2)= .53) with FOR of all subject-specific parameters. Future work will investigate changes in FOR during recovery to see if baseline risk levels are restored upon return to 1-g activity. While dual x-ray absorptiometry (DXA) is the most commonly used clinical measure of bone health, it fails to provide compartment-specific information that is useful in assessing changes to bone quality as a result of microgravity exposure. Peripheral quantitative computed tomography (pQCT) accomplishes this by imaging transverse "slices" of the long bones. This project was a re-analysis of a 90 day bed rest study to determine if changes to cortical and trabecular compartments could be detected in the distal tibia with statistical significance using a new pQCT image analysis method. Nearly all changes in bone mineral density (BMD) and cross sectional area (CSA) measures were seen with statistical significance, with the exception of a change in cortical BMD. Total bone CSA increased by 1.1 % (p =0.01), cortical CSA decreased by - 5.6% (p<0.001) and trabecular CSA increased by 1.76% (p=0.007); the combination of which suggests bone resorption occurred at the endocortical surface in response to mechanical unloading by bed rest. Furthermore, total BMD and trabecular BMD decreased (-3.8%, p=0.001 and -2.8%, p =0.007, respectively), while decreases in cortical BMD failed to reach significance (-1.2%, p=0.07). Given that compartment-specific changes are seen with significance and are likely to influence bone strength, it is recommended that pQCT remain a standard measure used in bed rest because it provides a unique measure by which to better evaluate the efficacy of countermeasures to microgravity-induced bone loss.

Autologous chondrocyte implantation in knee joint: MR imaging and histologic features at 1-year follow-up.

PubMed

Tins, Bernhard J; McCall, Iain W; Takahashi, Tomoki; Cassar-Pullicino, Victor; Roberts, Sally; Ashton, Brian; Richardson, James

2005-02-01

To evaluate magnetic resonance (MR) imaging features of autologous chondrocyte implantation (ACI) grafts and compare these with graft histologic features 1 year after ACI for treatment of femoral condylar defects. This study was approved by the regional ethics committee, and all patients gave informed consent. Forty-one patients (mean age, 35 years; 30 men, 11 women) underwent ACI for treatment of femoral condylar defects. One year later, knee joint MR imaging and graft biopsy were performed. Graft biopsy results were categorized into those showing hyaline, mixed fibrohyaline cartilage, fibrocartilage, and fibrous tissue. Standard T1-, T2-, T2*-, and intermediate-weighted sequences were performed, as well as three-dimensional (3D) fast low-angle shot (FLASH) and double-echo steady-state sequences for cartilage assessment. ACI grafts were assessed for signal intensity (with FLASH sequence), thickness, overgrowth, surface smoothness, integration to adjacent cartilage and underlying bone, bone marrow edema underneath graft, and contour of bone underneath graft. MR images were assessed by two observers, first independently and then in consensus. MR imaging findings were correlated with histologic findings. All 41 grafts were present at 1-year follow-up. The graft consisted of hyaline cartilage in four, mixed fibrohyaline cartilage in 10, fibrocartilage in 25, and fibrous tissue in two cases. Graft signal intensity was virtually always lower than adjacent normal cartilage signal intensity, and there was no relationship between graft signal intensity and histologic appearance (P = .34). Graft thickness (P = .83), overgrowth (P = .69), surface smoothness (P = .28), and integration with adjacent cartilage and underlying bone (P = .90); edema in bone marrow underneath graft (P = .63); and bone contour underneath graft (P = .94) at MR imaging had no correlation with graft histologic appearance. Graft overgrowth (n = 16; 39%) and edema-like signal in bone marrow underneath graft (n = 23; 56%) were common. The origin of graft overgrowth remains unclear. With the methods presented here, MR imaging findings cannot predict ACI graft histologic features, and graft histologic appearance determined at biopsy was not related to graft signal intensity, graft thickness, overgrowth, surface smoothness, integration with adjacent cartilage or underlying bone, signal intensity change in underlying bone marrow, or underlying bone contour. Overgrowth and bone marrow changes underneath the graft were common. (c) RSNA, 2004.

Hominid cranial bone structure: a histological study of Omo 1 specimens from Ethiopia using different microscopic techniques.

PubMed

Bartsiokas, Antonis

2002-05-01

The microstructure of a hominid cranial vault has not previously been studied to determine its tissue histology, and differences in comparison with that of modern humans. We selected the parietals of Omo-Kibish 1, regarded as one of the oldest (about 130,000 years old) anatomically modern humans, and Omo 1 (Howell), which is a very recent human (about 2,000 years old)-both from the same area of Ethiopia. A combination of macrophotography, polarizing microscopy in the incident and transmission illumination mode, and confocal laser scanning microscopy (CLSM) was employed to examine thin sections, as well as polished and unpolished block faces of unembedded bone fragments, to minimize specimen destruction as much as possible. The methods enabled remarkably detailed information on bone microstructure and remodeling to be gleaned from tiny fragments of bone. The best method for examining fossilized human bones was shown to be that of incident light microscopy, which was the least destructive while producing the most amount of information. Unless the above methods are used, bone-filling minerals, such as calcite, can cause erroneous estimations of bone thickness, as observations with the naked eye or even a magnifying glass cannot determine the limit between the cortex and the diploe. This is particularly important for sciences such as paleoanthropology, in which, for instance, a thick cranial bone of Homo erectus may be confused with a pathological one of H. sapiens and vice versa. Cross sections of parietal bones revealed differences between Omo-Kibish 1 and Omo 1 (Howell) in diploic histology and in the relative thickness between the cortex and diploe, with the former specimen having an H. erectus ratio despite its H. sapiens gross anatomy. Omo-Kibish 1 may still retain some affinities with H. erectus despite its being classified as H. sapiens. Newly described histological structures, such as the reverse type II osteons, the multicanalled osteons, and the osteocytomata are presented here. A modern human skeletal anatomy does not necessarily imply a modern human cranial bone histology. The outer circumferential lamellae of cranial bones are in essence growth lines. Cranial histology of hominids may provide useful information concerning their taxonomy and life history, including such factors as growth rate, developmental stress, and diet. Copyright 2002 Wiley-Liss, Inc.

Abnormal subchondral bone microstructure following steroid administration is involved in the early pathogenesis of steroid-induced osteonecrosis.

PubMed

Wang, L; Zhang, L; Pan, H; Peng, S; Zhao, X; Lu, W W

2016-01-01

Loss of bone microstructure integrity is thought to be related to osteonecrosis. But the relationship between the time when bone microstructure integrity loss appears and the onset of osteonecrosis has not yet been determined. Our study demonstrated abnormal changes of subchondral bone microstructure involved in the early pathogenesis of osteonecrosis. Using a rabbit model, we investigated the changes of subchondral bone microstructure following steroid administration to identify the onset of abnormal bone microstructure development in steroid-induced osteonecrosis. Fifty-five adult female Japanese White rabbits (mean body weight 3.5 kg; mean age 24 months) were used and randomly divided among three time points (3, 7, and 14 days) consisting of 15 rabbits each, received a single intramuscular injection of methylprednisolone acetate (MP; Pfizer Manufacturing Belgium NV) at a dose of 4 mg/kg, and a control group consisting of 10 rabbits was fed and housed under identical conditions but were not given steroid injections. A micro-CT scanner was applied to detect changes in the trabecular region of subchondral bone of excised femoral head samples. Parameters including bone volume fraction (BV/TV), bone surface (BS), trabecular bone pattern factor (Tb.Pf), trabecular thickness/number/separation (Tb.Th, Tb.N, and Tb.Sp), and structure model index (SMI) were evaluated using the software CTAn (SkyScan). After micro-CT scans, bilateral femoral heads were cut in the coronal plane at a thickness of 4 μm. The sections were then stained with haematoxylin-eosin and used for the diagnosis of osteonecrosis and the rate of development of osteonecrosis. The BV/TV, BS, Tb.Th and Tb.N demonstrated a time-dependent decline from 3, 7, and 14 days compared with the control group, while the Tb.Pf, Tb.Sp and SMI demonstrated an increase at 3, 7, and 14 days compared with the control group. For the histopathology portion, osteonecrosis was not seen 3 days after steroid treatment, but was present 7 days after treatment and was obvious 14 days after treatment. Furthermore, the rate of osteonecrosis appearing between 7 and 14 days was not significantly different. In addition, the presence and variation of BV/TV, BS, Tb.Pf, Tb.Th, Tb.N, and SMI demonstrated significant changes at 7 days compared with the control group except Tb.Sp (at 14 days) and this is the time when osteonecrosis is thought to occur in this model. This study demonstrated that osteonecrosis in rabbits is chronologically associated with changes in subchondral bone microstructure.

TH-AB-209-02: Gadolinium Measurements in Human Bone Using in Vivo K X-Ray Fluorescence (KXRF) Technique

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mostafaei, F; Nie, L

Purpose: Improvement in an in vivo K x-ray fluorescence system, based on 109Cd source, for the detection of gadolinium (Gd) in bone has been investigated. Series of improvements to the method is described. Gd is of interest because of the extensive use of Gd-based contrast agents in MR imaging and the potential toxicity of Gd exposure. Methods: A set of seven bone equivalent phantoms with different amount of Gd concentrations (from 0–100 ppm) has been developed. Soft tissue equivalent plastic plates were used to simulate the soft tissue overlaying the tibia bone in an in vivo measurement. A new 5more » GBq 109Cd source was used to improve the source activity in comparison to the previous study (0.17 GBq). An improved spectral fitting program was utilized for data analysis. Results: The previous published minimum detection limit (MDL) for Gd doped phantom measurements using KXRF system was 3.3 ppm. In this study the MDL for bare bone phantoms was found to be 0.8 ppm. Our previous study used only three layers of plastic (0.32, 0.64 and 0.96 mm) as soft tissue equivalent materials and obtained the MDL of 4–4.8 ppm. In this study the plastic plates with more realistic thicknesses to simulate the soft tissue covering tibia bone (nine thicknesses ranging from 0.61–6.13 mm) were used. The MDLs for phantoms were determined to be 1.8–3.5 ppm. Conclusion: With the improvements made to the technology (stronger source, improved data analysis algorithm, realistic soft tissue thicknesses), the MDL of the KXRF system to measure Gd in bare bone was improved by a factor of 4.1. The MDL is at the level of the bone Gd concentration reported in literature. Hence, the system is ready to be tested on human subjects to investigate the use of bone Gd as a biomarker for Gd toxicity.« less

Sinus floor elevation from a maxillary molar tooth extraction socket in a patient with chronic inflammation.

PubMed

Tözüm, Tolga F; Dursun, Erhan; Tulunoglu, Ibrahim

2009-03-01

The compromised nature of the residual interradicular bone after extraction of periodontally hopeless maxillary molars often requires a sinus elevation procedure to ideally place the implants to accept future prosthesis. Maxillary sinus elevation surgery is a procedure used to increase the volume of bone mass so that dental implants can be placed. This article documents a sinus floor elevation technique through an extraction socket in a 65-year-old white male with chronic inflammation to increase the bone mass after the extraction of a periodontally involved maxillary molar tooth. Computerized tomography revealed an increased thickness of the sinus membrane, which was attributed to possible chronic sinus inflammation and periodontal inflammation. After consultation with the Department of Otolaryngology, it was diagnosed as chronic inflammation without any contraindication for sinus elevation surgery or implant placement. One month after the extraction, the sinus floor elevation surgery was performed through the extraction socket, and implants were placed 4 months later. An uneventful healing was noted after 6 months of osseointegration; two porcelain-fused-to-metal crowns were fabricated. Clinical follow-up took place every 3 months for 3 years, and successful healing was achieved. The patient was satisfied with the esthetic and functional results of the oral rehabilitation. Sinus floor elevation through an extraction socket without any residual bone, followed by dental implant placement, provided successful functional results and acceptable stability.

Deregulation of arginase induces bone complications in high-fat/high-sucrose diet diabetic mouse model

PubMed Central

Bhatta, Anil; Sangani, Rajnikumar; Kolhe, Ravindra; Toque, Haroldo A.; Cain, Michael; Wong, Abby; Howie, Nicole; Shinde, Rahul; Elsalanty, Mohammed; Yao, Lin; Chutkan, Norman; Hunter, Monty; Caldwell, Ruth B.; Isales, Carlos; Caldwell, R. William; Fulzele, Sadanand

2016-01-01

A balanced diet is crucial for healthy development and prevention of musculoskeletal related diseases. Diets high in fat content are known to cause obesity, diabetes and a number of other disease states. Our group and others have previously reported that activity of the urea cycle enzyme arginase is involved in diabetes-induced dysregulation of vascular function due to decreases in nitric oxide formation. We hypothesized that diabetes may also elevate arginase activity in bone and bone marrow, which could lead to bone-related complications. To test this we determined the effects of diabetes on expression and activity of arginase, in bone and bone marrow stromal cells (BMSCs). We demonstrated that arginase 1 is abundantly present in the bone and BMSCs. We also demonstrated that arginase activity and expression in bone and bone marrow is up-regulated in models of diabetes induced by HFHS diet and streptozotocin (STZ). HFHS diet down-regulated expression of healthy bone metabolism markers (BMP2, COL-1, ALP, and RUNX2) and reduced bone mineral density, bone volume and trabecular thickness. However, treatment with an arginase inhibitor (ABH) prevented these bone-related complications of diabetes. In-vitro study of BMSCs showed that high glucose treatment increased arginase activity and decreased nitric oxide production. These effects were reversed by treatment with an arginase inhibitor (ABH). Our study provides evidence that deregulation of L-arginine metabolism plays a vital role in HFHS diet-induced diabetic complications and that these complications can be prevented by treatment with arginase inhibitors. The modulation of L-arginine metabolism in disease could offer a novel therapeutic approach for osteoporosis and other musculoskeletal related diseases. PMID:26704078

Effect of simvastatin injections on temporomandibular joint inflammation in growing rats.

PubMed

George, Mark D; Owen, Callista M; Reinhardt, Adam L; Giannini, Peter J; Marx, David B; Reinhardt, Richard A

2013-05-01

Juvenile idiopathic arthritis often affects the temporomandibular joint (TMJ), resulting in facial deformities, and intra-articular injections of anti-inflammatory steroids used in treatment may inhibit bone growth in the developing condyle. The purpose of this pilot study was to evaluate the anti-inflammatory properties of simvastatin (SIM), a bone anabolic drug, compared with the common steroid triamcinolone hexacetonide (TH) in experimental TMJ arthritis of growing rats. Joint inflammation was induced by injecting complete Freund's adjuvant (CFA) into the TMJs of 32 growing (4-week-old) Sprague-Dawley rats while simultaneously receiving 1) ethanol drug carrier, 2) 0.1 mg of SIM, 3) 0.5 mg of SIM, or 4) 0.15 mg of TH. Six rats had no treatment to the TMJ. Animals were euthanized 28 days later, and TMJs were decalcified and stained with hematoxylin-eosin. Histopathologic TMJ results showed that CFA injection along with drug carrier induced increased thickness of the articular layer on the head of the condyle and inflammation of the retrodiscal area (CFA and ethanol). Although both TH and SIM reduced the articular layer thickness, 0.5 mg of SIM was more effective at reducing subsynovial inflammation. Intra-articular simvastatin showed anti-inflammatory properties in this TMJ model, prompting its further study in the growing TMJ, where bone anabolic properties would be important. Copyright © 2013 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.