IGF-1 Regulates Vertebral Bone Aging Through Sex-Specific and Time-Dependent Mechanisms.

PubMed

Ashpole, Nicole M; Herron, Jacquelyn C; Mitschelen, Matthew C; Farley, Julie A; Logan, Sreemathi; Yan, Han; Ungvari, Zoltan; Hodges, Erik L; Csiszar, Anna; Ikeno, Yuji; Humphrey, Mary Beth; Sonntag, William E

2016-02-01

Advanced aging is associated with increased risk of bone fracture, especially within the vertebrae, which exhibit significant reductions in trabecular bone structure. Aging is also associated with a reduction in circulating levels of insulin-like growth factor (IGF-1). Studies have suggested that the reduction in IGF-1 compromises healthspan, whereas others report that loss of IGF-1 is beneficial because it increases healthspan and lifespan. To date, the effect of decreases in circulating IGF-1 on vertebral bone aging has not been thoroughly investigated. Here, we delineate the consequences of a loss of circulating IGF-1 on vertebral bone aging in male and female Igf(f/f) mice. IGF-1 was reduced at multiple specific time points during the mouse lifespan: early in postnatal development (crossing albumin-cyclic recombinase [Cre] mice with Igf(f/f) mice); and in early adulthood and in late adulthood using hepatic-specific viral vectors (AAV8-TBG-Cre). Vertebrae bone structure was analyzed at 27 months of age using micro-computed tomography (μCT) and quantitative bone histomorphometry. Consistent with previous studies, both male and female mice exhibited age-related reductions in vertebral bone structure. In male mice, reduction of circulating IGF-1 induced at any age did not diminish vertebral bone loss. Interestingly, early-life loss of IGF-1 in females resulted in a 67% increase in vertebral bone volume fraction, as well as increased connectivity density and increased trabecular number. The maintenance of bone structure in the early-life IGF-1-deficient females was associated with increased osteoblast surface and an increased ratio of osteoprotegerin/receptor-activator of NF-κB-ligand (RANKL) levels in circulation. Within 3 months of a loss of IGF-1, there was a 2.2-fold increase in insulin receptor expression within the vertebral bones of our female mice, suggesting that local signaling may compensate for the loss of circulating IGF-1. Together, these data suggest the age-related loss of vertebral bone density in females can be reduced by modifying circulating IGF-1 levels early in life. © 2015 American Society for Bone and Mineral Research.

The protective effect of Rhizoma Dioscoreae extract against alveolar bone loss in ovariectomized rats via regulating Wnt and p38 MAPK signaling.

PubMed

Zhang, Zhiguo; Xiang, Lihua; Bai, Dong; Wang, Wenlai; Li, Yan; Pan, Jinghua; Liu, Hong; Wang, Shaojun; Xiao, Gary Guishan; Ju, Dahong

2014-12-12

The aim of this study was to evaluate the osteoprotective effect of aqueous Rhizoma Dioscoreae extract (RDE) on the alveolar bone of rats with ovariectomy-induced bone loss. Female Wistar rats were subjected to either ovariectomy or a sham operation (SHAM). The ovariectomized (OVX) rats were treated with vehicle (OVX) or RDE by oral gavage or with 17β-estradiol (E2) subcutaneously. After treatments, the bone mineral density (BMD), the three-dimensional bone architecture of the alveolar bone and the plasma biomarkers of bone turnover were analyzed to assess bone metabolism, and the histomorphometry of the alveolar bone was observed. Microarrays were used to evaluate gene expression profiles in alveolar bone from RDE-treated and OVX rats. The differential expression of genes was further analyzed using Ingenuity Pathway Analysis (IPA). The key findings were verified using real-time quantitative RT-PCR (qRT-PCR). Our results showed that RDE inhibited alveolar bone loss in OVX rats. Compared to the OVX rats, the RDE-treated rats showed upregulated expression levels of 207 genes and downregulated expression levels of 176 genes in the alveolar bone. The IPA showed that several genes had the potential to code for proteins that were involved in the Wnt/β-catenin signaling pathway (Wnt7a, Fzd2, Tcf3, Spp1, Frzb, Sfrp2 and Sfrp4) and the p38 MAPK signaling pathway (Il1rn and Mapk14). These experiments revealed that RDE could inhibit ovariectomy-induced alveolar bone loss in rats. The mechanism of this anti-osteopenic effect in alveolar bone may be involved in the reduced abnormal bone remodeling, which is associated with the modulation of the Wnt/β-catenin and the p38 MAPK signaling pathways via gene regulation.

IGF-1 REGULATES VERTEBRAL BONE AGING THROUGH SEX-SPECIFIC AND TIME-DEPENDENT MECHANISMS

PubMed Central

Ashpole, Nicole M; Herron, Jacquelyn C; Mitschelen, Matthew C; Farley, Julie A; Logan, Sreemathi; Yan, Han; Ungvari, Zoltan; Hodges, Erik L.; Csiszar, Anna; Ikeno, Yuji; Humphrey, Mary Beth; Sonntag, William E

2016-01-01

Advanced aging is associated with increased risk of bone fracture, especially within the vertebrae, which exhibit significant reductions in trabecular bone structure. Aging is also associated with a reduction in circulating levels of insulin-like growth factor (IGF-1). Studies have suggested that the reduction in IGF-1 compromises healthspan, while others report that loss of IGF-1 is beneficial as it increases healthspan and lifespan. To date, the effect of decreases in circulating IGF-1 on vertebral bone aging has not been thoroughly investigated. Here, we delineate the consequences of a loss of circulating IGF-1 on vertebral bone aging in male and female Igff/f mice. IGF-1 was reduced at multiple specific time points during the mouse lifespan- early in postnatal development (crossing albumin-Cre mice with Igff/f mice), or early adulthood, and late adulthood using hepatic-specific viral vectors (AAV8-TBG-Cre). Vertebrae bone structure was analyzed at 27 months of age using microCT and quantitative bone histomorphometry. Consistent with previous studies, both male and female mice exhibited age-related reductions in vertebral bone structure. In male mice, reduction of circulating IGF-1 induced at any age did not diminish vertebral bone loss. Interestingly, early-life loss of IGF-1 in females resulted in a 67% increase in vertebral bone volume fraction, as well as increased connectivity density and increased trabecular number. The maintenance of bone structure in the early-life IGF-1-deficient females was associated with increased osteoblast surface and an increased ratio of osteoprotegerin/receptor-activator of NFkB-ligand levels in circulation. Within 3 months of a loss of IGF-1, there was a 2.2 fold increase in insulin receptor expression within the vertebral bones of our female mice, suggesting that local signaling may compensate for the loss of circulating IGF-1. Together, these data suggest the age-related loss of vertebral bone density in females can be reduced by modifying circulating IGF-1 levels early in life. PMID:26260312

Voxel-based modeling and quantification of the proximal femur using inter-subject registration of quantitative CT images.

PubMed

Li, Wenjun; Kezele, Irina; Collins, D Louis; Zijdenbos, Alex; Keyak, Joyce; Kornak, John; Koyama, Alain; Saeed, Isra; Leblanc, Adrian; Harris, Tamara; Lu, Ying; Lang, Thomas

2007-11-01

We have developed a general framework which employs quantitative computed tomography (QCT) imaging and inter-subject image registration to model the three-dimensional structure of the hip, with the goal of quantifying changes in the spatial distribution of bone as it is affected by aging, drug treatment or mechanical unloading. We have adapted rigid and non-rigid inter-subject registration techniques to transform groups of hip QCT scans into a common reference space and to construct composite proximal femoral models. We have applied this technique to a longitudinal study of 16 astronauts who on average, incurred high losses of hip bone density during spaceflights of 4-6 months on the International Space Station (ISS). We compared the pre-flight and post-flight composite hip models, and observed the gradients of the bone loss distribution. We performed paired t-tests, on a voxel by voxel basis, corrected for multiple comparisons using false discovery rate (FDR), and observed regions inside the proximal femur that showed the most significant bone loss. To validate our registration algorithm, we selected the 16 pre-flight scans and manually marked 4 landmarks for each scan. After registration, the average distance between the mapped landmarks and the corresponding landmarks in the target scan was 2.56 mm. The average error due to manual landmark identification was 1.70 mm.

Enhancer of Zeste Homolog 2 Inhibition Stimulates Bone Formation and Mitigates Bone Loss Caused by Ovariectomy in Skeletally Mature Mice*

PubMed Central

Dudakovic, Amel; Camilleri, Emily T.; Riester, Scott M.; Paradise, Christopher R.; Gluscevic, Martina; O'Toole, Thomas M.; Thaler, Roman; Evans, Jared M.; Yan, Huihuang; Subramaniam, Malayannan; Hawse, John R.; Stein, Gary S.; Montecino, Martin A.; McGee-Lawrence, Meghan E.; Westendorf, Jennifer J.; van Wijnen, Andre J.

2016-01-01

Perturbations in skeletal development and bone degeneration may result in reduced bone mass and quality, leading to greater fracture risk. Bone loss is mitigated by bone protective therapies, but there is a clinical need for new bone-anabolic agents. Previous work has demonstrated that Ezh2 (enhancer of zeste homolog 2), a histone 3 lysine 27 (H3K27) methyltransferase, suppressed differentiation of osteogenic progenitors. Here, we investigated whether inhibition of Ezh2 can be leveraged for bone stimulatory applications. Pharmacologic inhibition and siRNA knockdown of Ezh2 enhanced osteogenic commitment of MC3T3 preosteoblasts. Next generation RNA sequencing of mRNAs and real time quantitative PCR profiling established that Ezh2 inactivation promotes expression of bone-related gene regulators and extracellular matrix proteins. Mechanistically, enhanced gene expression was linked to decreased H3K27 trimethylation (H3K27me3) near transcriptional start sites in genome-wide sequencing of chromatin immunoprecipitations assays. Administration of an Ezh2 inhibitor modestly increases bone density parameters of adult mice. Furthermore, Ezh2 inhibition also alleviated bone loss in an estrogen-deficient mammalian model for osteoporosis. Ezh2 inhibition enhanced expression of Wnt10b and Pth1r and increased the BMP-dependent phosphorylation of Smad1/5. Thus, these data suggest that inhibition of Ezh2 promotes paracrine signaling in osteoblasts and has bone-anabolic and osteoprotective potential in adults. PMID:27758858

The Protective Effect of Rhizoma Dioscoreae Extract against Alveolar Bone Loss in Ovariectomized Rats via Regulating Wnt and p38 MAPK Signaling

PubMed Central

Zhang, Zhiguo; Xiang, Lihua; Bai, Dong; Wang, Wenlai; Li, Yan; Pan, Jinghua; Liu, Hong; Wang, Shaojun; Xiao, Gary Guishan; Ju, Dahong

2014-01-01

Aim: The aim of this study was to evaluate the osteoprotective effect of aqueous Rhizoma Dioscoreae extract (RDE) on the alveolar bone of rats with ovariectomy-induced bone loss. Methods: Female Wistar rats were subjected to either ovariectomy or a sham operation (SHAM). The ovariectomized (OVX) rats were treated with vehicle (OVX) or RDE by oral gavage or with 17β-estradiol (E2) subcutaneously. After treatments, the bone mineral density (BMD), the three-dimensional bone architecture of the alveolar bone and the plasma biomarkers of bone turnover were analyzed to assess bone metabolism, and the histomorphometry of the alveolar bone was observed. Microarrays were used to evaluate gene expression profiles in alveolar bone from RDE-treated and OVX rats. The differential expression of genes was further analyzed using Ingenuity Pathway Analysis (IPA). The key findings were verified using real-time quantitative RT-PCR (qRT-PCR). Results: Our results showed that RDE inhibited alveolar bone loss in OVX rats. Compared to the OVX rats, the RDE-treated rats showed upregulated expression levels of 207 genes and downregulated expression levels of 176 genes in the alveolar bone. The IPA showed that several genes had the potential to code for proteins that were involved in the Wnt/β-catenin signaling pathway (Wnt7a, Fzd2, Tcf3, Spp1, Frzb, Sfrp2 and Sfrp4) and the p38 MAPK signaling pathway (Il1rn and Mapk14). Conclusion: These experiments revealed that RDE could inhibit ovariectomy-induced alveolar bone loss in rats. The mechanism of this anti-osteopenic effect in alveolar bone may be involved in the reduced abnormal bone remodeling, which is associated with the modulation of the Wnt/β-catenin and the p38 MAPK signaling pathways via gene regulation. PMID:25514564

Quantitation of mandibular symphysis volume as a source of bone grafting.

PubMed

Verdugo, Fernando; Simonian, Krikor; Smith McDonald, Roberto; Nowzari, Hessam

2010-06-01

Autogenous intramembranous bone graft present several advantages such as minimal resorption and high concentration of bone morphogenetic proteins. A method for measuring the amount of bone that can be harvested from the symphysis area has not been reported in real patients. The aim of the present study was to intrasurgically quantitate the volume of the symphysis bone graft that can be safely harvested in live patients and compare it with AutoCAD (version 16.0, Autodesk, Inc., San Rafael, CA, USA) tomographic calculations. AutoCAD software program quantitated symphysis bone graft in 40 patients using computerized tomographies. Direct intrasurgical measurements were recorded thereafter and compared with AutoCAD data. The bone volume was measured at the recipient sites of a subgroup of 10 patients, 6 months post sinus augmentation. The volume of bone graft measured by AutoCAD averaged 1.4 mL (SD 0.6 mL, range: 0.5-2.7 mL). The volume of bone graft measured intrasurgically averaged 2.3 mL (SD 0.4 mL, range 1.7-2.8 mL). The statistical difference between the two measurement methods was significant. The bone volume measured at the recipient sites 6 months post sinus augmentation averaged 1.9 mL (SD 0.3 mL, range 1.3-2.6 mL) with a mean loss of 0.4 mL. AutoCAD did not overestimate the volume of bone that can be safely harvested from the mandibular symphysis. The use of the design software program may improve surgical treatment planning prior to sinus augmentation.

Bisphosphonate as a Countermeasure to Space Flight-Induced Bone Loss

NASA Technical Reports Server (NTRS)

Spector, Elisabeth; LeBlanc, A.; Sibonga, J.; Matsumoto, T.; Jones, J.; Smith, S. M.; Shackelford, L.; Shapiro, J.; Lang, T.; Evans, H.;

Rsk2, the Kinase Mutated in Coffin-Lowry Syndrome, Controls Cementum Formation.

PubMed

Koehne, T; Jeschke, A; Petermann, F; Seitz, S; Neven, M; Peters, S; Luther, J; Schweizer, M; Schinke, T; Kahl-Nieke, B; Amling, M; David, J-P

2016-07-01

The ribosomal S6 kinase RSK2 is essential for osteoblast function, and inactivating mutations of RSK2 cause osteopenia in humans with Coffin-Lowry syndrome (CLS). Alveolar bone loss and premature tooth exfoliation are also consistently reported symptoms in CLS patients; however, the pathophysiologic mechanisms are unclear. Therefore, aiming to identify the functional relevance of Rsk2 for tooth development, we analyzed Rsk2-deficient mice. Here, we show that Rsk2 is a critical regulator of cementoblast function. Immunohistochemistry, histology, micro-computed tomography imaging, quantitative backscattered electron imaging, and in vitro assays revealed that Rsk2 is activated in cementoblasts and is necessary for proper acellular cementum formation. Cementum hypoplasia that is observed in Rsk2-deficient mice causes detachment and disorganization of the periodontal ligament and was associated with significant alveolar bone loss with age. Moreover, Rsk2-deficient mice display hypomineralization of cellular cementum with accumulation of nonmineralized cementoid. In agreement, treatment of the cementoblast cell line OCCM-30 with a Rsk inhibitor reduces formation of mineralization nodules and decreases the expression of cementum markers. Western blot analyses based on antibodies against Rsk1, Rsk2, and an activated form of the 2 kinases confirmed that Rsk2 is expressed and activated in differentiating OCCM-30 cells. To discriminate between periodontal bone loss and systemic bone loss, we additionally crossed Rsk2-deficient mice with transgenic mice overexpressing the osteoanabolic transcription factor Fra1. Fra1 overexpression clearly increases systemic bone volume in Rsk2-deficient mice but does not protect from alveolar bone loss. Our results indicate that cell autonomous cementum defects are causing early tooth loss in CLS patients. Moreover, we identify Rsk2 as a nonredundant regulator of cementum homeostasis, alveolar bone maintenance, and periodontal health, with all these features being independent of Rsk2 function in systemic bone formation. © International & American Associations for Dental Research 2016.

Accelerated bone loss in older men: Effects on bone microarchitecture and strength.

PubMed

Cauley, J A; Burghardt, A J; Harrison, S L; Cawthon, P M; Schwartz, A V; Connor, E Barrett; Ensrud, Kristine E; Langsetmo, Lisa; Majumdar, S; Orwoll, E

2018-05-11

Accelerated bone loss (ABL) shown on routine dual-energy X-ray absorptiometry (DXA) may be accompanied by microarchitectural changes, increased cortical porosity and lower bone strength. To test this hypothesis, we performed a cross-sectional study and used high resolution peripheral quantitative computed tomography (HR-pQCT) scans (SCANCO, Inc., Switzerland) to measure estimated bone strength and microarchitecture in the distal radius and distal and diaphyseal tibia. We studied 1628 men who attended the Year 14 exam of the Osteoporotic Fractures in Men (MrOS) study. We retrospectively characterized areal (a) bone mineral density (BMD) change from the Year 7 to Year 14 exam in 3 categories: "accelerated" >10% loss at either the total hip or femoral neck, (N = 299, 18.4%); "expected" loss, <10%, (N = 1061, 65.2%) and "maintained" BMD, ≥0%, (N = 268, 16.5%). The ABL cutoff was a safety alert established for MrOS. We used regression models to calculate adjusted mean HR-pQCT parameters in men with ABL, expected loss or maintained BMD. Men who experienced ABL were older and had a lower body mass index and aBMD and experienced greater weight loss compared to other men. Total volumetric BMD and trabecular and cortical volumetric BMD were lower in men with ABL compared to the expected or maintained group. Men with ABL had significantly lower trabecular bone volume fraction (BV/TV), fewer trabeculae and greater trabecular separation at both the distal radius and tibia than men with expected loss or who maintained aBMD, all p trend <0.001. Men with ABL had lower cortical thickness and lower estimated bone strength but there was no difference in cortical porosity except at the tibia diaphyseal site In summary, men with ABL have lower estimated bone strength, poorer trabecular microarchitecture and thinner cortices than men without ABL but have similar cortical porosity. These impairments may lead to an increased risk of fracture. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

The association between bone health indicated by calcaneal quantitative ultrasound and metabolic syndrome in Malaysian men.

PubMed

Chin, Kok-Yong; Ima-Nirwana, Soelaiman; Mohamed, Isa Naina; Ahmad, Fairus; Mohd Ramli, Elvy Suhana; Aminuddin, Amilia; Wan Ngah, Wan Zurinah

2015-01-01

Previous studies on the relationship between bone health and metabolic syndrome (MS) have revealed heterogeneous results. There are limited studies employing bone quantitative ultrasonometry in evaluating this relationship. This study aimed to determine the relationship between MS and bone health in a group of Malaysian middle-aged and elderly men using bone quantitative ultrasonometry. This cross-sectional study recruited 309 free living Chinese and Malay men aged 40 years and above residing in Klang Valley, Malaysia. Their demographic and anthropometric data were collected. Their calcaneal speed of sound (SOS) was measured using a CM-200 bone ultrasonometer. Their blood was collected for the evaluation of lipid profile, total testosterone and sex hormone-binding globulin. The joint interim MS definition was used for the classification of subjects. Multiple linear regression analysis was used to assess the association between SOS and indicators of MS and the presence of MS, with suitable adjustment for confounders. There was no significant difference in SOS value between MS and non-MS subjects (p > 0.05). The SOS values among subjects with different MS scores did not differ significantly (p > 0.05). There were no significant associations between SOS values and indicators of MS or the presence of MS (p > 0.05). The relationship between bone health and MS is not significant in Malaysian middle-aged and elderly men. A longitudinal study should be conducted to evaluate the association between bone loss and MS to confirm this finding.

Prediction of trabecular bone qualitative properties using scanning quantitative ultrasound

NASA Astrophysics Data System (ADS)

Qin, Yi-Xian; Lin, Wei; Mittra, Erik; Xia, Yi; Cheng, Jiqi; Judex, Stefan; Rubin, Clint; Müller, Ralph

2013-11-01

Microgravity induced bone loss represents a critical health problem in astronauts, particularly occurred in weight-supporting skeleton, which leads to osteopenia and increase of fracture risk. Lack of suitable evaluation modality makes it difficult for monitoring skeletal status in long term space mission and increases potential risk of complication. Such disuse osteopenia and osteoporosis compromise trabecular bone density, and architectural and mechanical properties. While X-ray based imaging would not be practical in space, quantitative ultrasound may provide advantages to characterize bone density and strength through wave propagation in complex trabecular structure. This study used a scanning confocal acoustic diagnostic and navigation system (SCAN) to evaluate trabecular bone quality in 60 cubic trabecular samples harvested from adult sheep. Ultrasound image based SCAN measurements in structural and strength properties were validated by μCT and compressive mechanical testing. This result indicated a moderately strong negative correlations observed between broadband ultrasonic attenuation (BUA) and μCT-determined bone volume fraction (BV/TV, R2=0.53). Strong correlations were observed between ultrasound velocity (UV) and bone's mechanical strength and structural parameters, i.e., bulk Young's modulus (R2=0.67) and BV/TV (R2=0.85). The predictions for bone density and mechanical strength were significantly improved by using a linear combination of both BUA and UV, yielding R2=0.92 for BV/TV and R2=0.71 for bulk Young's modulus. These results imply that quantitative ultrasound can characterize trabecular structural and mechanical properties through measurements of particular ultrasound parameters, and potentially provide an excellent estimation for bone's structural integrity.

Body fat loss induced by calcium in co-supplementation with conjugated linoleic acid is associated with increased expression of bone formation genes in adult mice.

PubMed

Chaplin, Alice; Palou, Andreu; Serra, Francisca

2015-12-01

The potential of conjugated linoleic acids (CLA) and calcium in weight management in animal models and human studies has been outlined, as well as their use to prevent bone loss at critical stages. In addition, it has been suggested that bone remodeling and energy metabolism are regulated by shared pathways and involve common hormones such as leptin. We have previously shown that supplementation with CLA and calcium in adult obese mice decreases body weight and body fat. The aim of the present study was to assess the effects of these two compounds on bone and energy metabolism markers on bone. Mice (C57BL/6J) were divided into five groups according to diet and treatment (up to 56 days): control (C), high-fat diet (HF), HF+CLA (CLA), HF+calcium (Ca) and HF with both compounds (CLA+Ca). At the end of treatment, bone formation markers were determined in plasma and expression of selected bone and energy markers was determined in tibia by quantitative polymerase chain reaction. Results show that CLA was associated with decreased tibia weight and minor impact on bone markers, whereas calcium, either alone or co-supplemented with CLA, maintained bone weight and promoted the expression of bone formation genes such as bone gamma-carboxyglutamate protein 2 (Bglap2) and collagen Iα1 (Col1a1). Furthermore, it had a significant effect on key players in energy metabolism, in particular leptin and adiponectin tibia receptors. Overall, in addition to the weight loss promoting properties of calcium, on its own or co-supplemented with CLA, our results support beneficial effects on bone metabolism in mice. Copyright © 2015. Published by Elsevier Inc.

Osteoporosis of the slender smoker. Vertebral compression fractures and loss of metacarpal cortex in relation to postmenopausal cigarette smoking and lack of obesity.

PubMed

Daniell, H W

1976-03-01

A group of thirty-eight women under age 70 who sustained vertebral compression fractures during minor trauma included more postmenopausal smokers than a group of 34 similar women with fractures resulting from major trauma and more than a group of 572 other women. Advanced idiopathic osteoporosis occurring before age 65 was found rarely among nonsmokers. The percent cortical area at the second metacarpal midpoint was measured in 103 white women aged 40 to 49 years, and 208 white women aged 60 to 69 years. In the younger group, no quantitative differences were demonstrated between bones of the obese and the nonobese or between smokers and nonsmokers. In contrast, among the older group, postmenopausal smokers exhibited much more bone loss than did nonsmokers (P less than .001), and nonobese women demonstrated much more bone loss than did obese women, this difference being most striking among smokers.

The effect of clomiphene on disuse bone loss

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

LeBlanc, A.; Marsh, C.; Spira, M.

1984-01-01

Clomiphene is a synthetic estrogen agonist/antagonist used for many years to induce ovulation in anovulatory women. A recent study demonstrated that clomiphene had a protective effect against bone loss in ovariectomized aged rats. The purpose was to determine if this drug retards resorption of bone associated with disuse in rats with intact ovaries. Eleven adult (300-350g) female rats received a pedicle bone graft (disuse) in one femur with the opposite limb serving as control. Of these, 6 received weekly 10 mg injections of clomiphone (Rx). Three Rx and three untreated (unRx) were sacrificed at 6 weeks while the remainder (3more » Rx, 2 unRx) were sacrificed at 10 weeks after surgery. All received quantitative injections of MDP 24 hrs. before sacrifice and labeled microspheres (5) just prior to sacrifice. The % uptakes of MDP and S, total bone mineral (BMC) and regional BMC (RBMC) were determined. Results are expressed as a ratio of the pedicle bone to the bone from the opposite limb. At 6 weeks, MDP and S are elevated in both groups indicating that metabolic activity is elevated. The Rx group shows no change in BMC while the unRx lost 13%. At 10 weeks, MDP and S are close to one in both groups. The Rx group lost 13% BMC while the unRx lost 29%. The RBMC indicates that the early loss of mineral is located primarily in the metaphysis, a region rich in trabecular bone. These results indicate that clomiphene retards resorption of bone resulting from disuse.« less

Inner ear changes in mucopolysaccharidosis type I/Hurler syndrome.

PubMed

Kariya, Shin; Schachern, Patricia A; Nishizaki, Kazunori; Paparella, Michael M; Cureoglu, Sebahattin

2012-10-01

Mucopolysaccharidosis type I/Hurler syndrome is an autosomal recessive disease caused by a deficiency of α-L-iduronidase activity. Recurrent middle ear infections and hearing loss are common complications in Hurler syndrome. Although sensorineural and conductive components occur, the mechanism of sensorineural hearing loss has not been determined. The purpose of this study is to evaluate the quantitative inner ear histopathology of the temporal bones of patients with Hurler syndrome. Eleven temporal bones from 6 patients with Hurler syndrome were examined. Age-matched healthy control samples consisted of 14 temporal bones from 7 cases. Temporal bones were serially sectioned in the horizontal plane and stained with hematoxylin and eosin. The number of spiral ganglion cells, loss of cochlear hair cells, area of stria vascularis, and cell density of spiral ligament were evaluated using light microscopy. There was no significant difference between Hurler syndrome and healthy controls in the number of spiral ganglion cells, area of stria vascularis, or cell density of spiral ligament. The number of cochlear hair cells in Hurler syndrome was significantly decreased compared with healthy controls. Auditory pathophysiology in the central nerve system in Hurler syndrome remains unknown; however, decreased cochlear hair cells may be one of the important factors for the sensorineural component of hearing loss.

Rhizoma Dioscoreae Extract Protects against Alveolar Bone Loss in Ovariectomized Rats via microRNAs Regulation

PubMed Central

Zhang, Zhiguo; Song, Changheng; Zhang, Fangzhen; Xiang, Lihua; Chen, Yanjing; Li, Yan; Pan, Jinghua; Liu, Hong; Xiao, Gary Guishan; Ju, Dahong

2015-01-01

The aim of this study was to evaluate the osteoprotective effect of aqueous Rhizoma Dioscoreae extract (RDE) on the alveolar bone of rats with ovariectomy-induced bone loss. Female Wistar rats underwent either ovariectomy or sham operation (SHAM). The ovariectomized (OVX) rats were treated with vehicle (OVX), estradiol valerate (EV), or RDE. After treatments, the bone mineral density (BMD) and the three-dimensional microarchitecture of the alveolar bone were analyzed to assess bone mass. Microarrays were used to evaluate microRNA expression profiles in alveolar bone from RDE-treated and OVX rats. The differential expression of microRNAs was validated using real-time quantitative RT-PCR (qRT-PCR), and the target genes of validated microRNAs were predicted and further analyzed using Ingenuity Pathway Analysis (IPA). The key findings were verified using qRT-PCR. Our results show that RDE inhibits alveolar bone loss in OVX rats. Compared to the OVX rats, the RDE-treated rats showed upregulated expression levels of 8 microRNAs and downregulated expression levels of 8 microRNAs in the alveolar bone in the microarray analysis. qRT-PCR helped validate 13 of 16 differentially expressed microRNAs, and 114 putative target genes of the validated microRNAs were retrieved. The IPA showed that these putative target genes had the potential to code for proteins that were involved in the transforming growth factor (TGF)-β/bone morphogenetic proteins (BMPs)/Smad signaling pathway (Tgfbr2/Bmpr2, Smad3/4/5, and Bcl-2) and interleukin (IL)-6/oncostatin M (OSM)/Jak1/STAT3 signaling pathway (Jak1, STAT3, and Il6r). These experiments revealed that RDE could inhibit ovariectomy-induced alveolar bone loss in rats. The mechanism of this anti-osteopenic effect in alveolar bone may involve the simultaneous inhibition of bone formation and bone resorption, which is associated with modulation of the TGF-β/BMPs/Smad and the IL-6/OSM/Jak1/STAT3 signaling pathways via microRNA regulation. PMID:25690421

Rhizoma Dioscoreae extract protects against alveolar bone loss in ovariectomized rats via microRNAs regulation.

PubMed

Zhang, Zhiguo; Song, Changheng; Zhang, Fangzhen; Xiang, Lihua; Chen, Yanjing; Li, Yan; Pan, Jinghua; Liu, Hong; Xiao, Gary Guishan; Ju, Dahong

2015-02-16

The aim of this study was to evaluate the osteoprotective effect of aqueous Rhizoma Dioscoreae extract (RDE) on the alveolar bone of rats with ovariectomy-induced bone loss. Female Wistar rats underwent either ovariectomy or sham operation (SHAM). The ovariectomized (OVX) rats were treated with vehicle (OVX), estradiol valerate (EV), or RDE. After treatments, the bone mineral density (BMD) and the three-dimensional microarchitecture of the alveolar bone were analyzed to assess bone mass. Microarrays were used to evaluate microRNA expression profiles in alveolar bone from RDE-treated and OVX rats. The differential expression of microRNAs was validated using real-time quantitative RT-PCR (qRT-PCR), and the target genes of validated microRNAs were predicted and further analyzed using Ingenuity Pathway Analysis (IPA). The key findings were verified using qRT-PCR. Our results show that RDE inhibits alveolar bone loss in OVX rats. Compared to the OVX rats, the RDE-treated rats showed upregulated expression levels of 8 microRNAs and downregulated expression levels of 8 microRNAs in the alveolar bone in the microarray analysis. qRT-PCR helped validate 13 of 16 differentially expressed microRNAs, and 114 putative target genes of the validated microRNAs were retrieved. The IPA showed that these putative target genes had the potential to code for proteins that were involved in the transforming growth factor (TGF)-β/bone morphogenetic proteins (BMPs)/Smad signaling pathway (Tgfbr2/Bmpr2, Smad3/4/5, and Bcl-2) and interleukin (IL)-6/oncostatin M (OSM)/Jak1/STAT3 signaling pathway (Jak1, STAT3, and Il6r). These experiments revealed that RDE could inhibit ovariectomy-induced alveolar bone loss in rats. The mechanism of this anti-osteopenic effect in alveolar bone may involve the simultaneous inhibition of bone formation and bone resorption, which is associated with modulation of the TGF-β/BMPs/Smad and the IL-6/OSM/Jak1/STAT3 signaling pathways via microRNA regulation.

Triiodothyronine increases calcium loss in a bed rest antigravity model for space flight.

PubMed

Smith, Steven R; Lovejoy, Jennifer C; Bray, George A; Rood, Jennifer; Most, Marlene M; Ryan, Donna H

2008-12-01

Bed rest has been used as a model to simulate the effects of space flight on bone metabolism. Thyroid hormones accelerate bone metabolism. Thus, supraphysiologic doses of this hormone might be used as a model to accelerate bone metabolism during bed rest and potentially simulate space flight. The objective of the study was to quantitate the changes in bone turnover after low doses of triiodothyronine (T(3)) added to short-term bed rest. Nine men and 5 women were restricted to bed rest for 28 days with their heads positioned 6 degrees below their feet. Subjects were randomly assigned to receive either placebo or oral T(3) at doses of 50 to 75 microg/d in a single-blind fashion. Calcium balance was measured over 5-day periods; and T(3), thyroxine, thyroid-stimulating hormone, immunoreactive parathyroid hormone, osteocalcin, bone alkaline phosphatase, and urinary deoxypyridinoline were measured weekly. Triiodothyronine increased 2-fold in the men and 5-fold in the women during treatment, suppressing both thyroxine and thyroid-stimulating hormone. Calcium balance was negative by 300 to 400 mg/d in the T(3)-treated volunteers, primarily because of the increased fecal loss that was not present in the placebo group. Urinary deoxypyridinoline to creatinine ratio, a marker of bone resorption, increased 60% in the placebo group during bed rest, but more than doubled in the T(3)-treated subjects (P < .01), suggesting that bone resorption was enhanced by treatment with T(3). Changes in serum osteocalcin and bone-specific alkaline phosphatase, markers of bone formation, were similar in T(3)- and placebo-treated subjects. Triiodothyronine increases bone resorption and fecal calcium loss in subjects at bed rest.

Efficacy of bone substitute material in preserving volume when placing a maxillary immediate complete denture: study protocol for the PANORAMIX randomized controlled trial.

PubMed

Rignon-Bret, Christophe; Hadida, Alain; Aidan, Alexis; Nguyen, Thien-Huong; Pasquet, Gerard; Fron-Chabouis, Helene; Wulfman, Claudine

2016-05-20

Bone preservation is an essential issue in the context of last teeth extraction and complete edentulism. The intended treatment, whether a complete denture or an implant placement, is facilitated with a voluminous residual ridge. Bone resorption after multiple extractions has not been as well studied as the bone resorption that occurs after the extraction of a single tooth. Recent advances in bone substitute materials have revived this issue. The purpose of this study is to evaluate the interest in using bone substitute material to fill the socket after last teeth extraction in a maxillary immediate complete denture procedure compared with the conventional protocol without socket filling. A randomized, controlled, clinical trial was designed. The 34 participants eligible for maxillary immediate complete denture were divided into two groups. Complete dentures were prepared despite persistence of the last anterior teeth. The control group received a conventional treatment including denture placement immediately after extractions. In the experimental group, in addition to the immediate denture placement, a xenograft bone-substitute material (Bio-Oss Collagen®) was placed in the fresh sockets. The primary outcome of the study is to compare mean bone ridge height loss 1 year after maxillary immediate complete denture placement, with or without bone-substitute material, in incisor and canine sockets. The secondary outcomes are to compare the average bone ridge height and width loss for each extraction site. An original quantitative evaluation method using cone beam computed tomography was designed for reproducible measurements, with a radio-opaque denture duplicate. Two independent operators perform the radiologic measurements. The immediate complete denture technique limits bone resorption in multiple extraction situations and thus allows better denture retention and better options for implant placement. To compare the benefit of using any bone socket-filling material, we proposed a quantitative evaluation protocol of resorption in the specific case of the last anterior maxillary teeth extraction with immediate denture placement. ClinicalTrials.gov, NCT02120053 . Registered on 18 April 2014.

Astronaut Bones: Stable Calcium Isotopes in Urine as a Biomarker of Bone Mineral Balance

NASA Astrophysics Data System (ADS)

Skulan, J.; Gordon, G. W.; Romaniello, S. J.; Anbar, A. D.; Smith, S. M.; Zwart, S.

2016-12-01

Bone loss is a common health concern, in conditions ranging from osteoporosis to cancer. Bone loss due to unloading is also an important health issue for astronauts. We demonstrate stable calcium isotopes, a tool developed in geochemistry, are capable of detecting real-time quantitative changes in net bone mineral balance (BMB) using serum and urine [1]. We validated this technique by comparing with DEXA and biomarker data in subjects during bed rest, a ground-based analog of space flight effects [2-4]. We now apply this tool to assess changes in astronauts' BMB before, during and after 4-6 month space missions. There is stable isotope fractionation asymmetry between bone formation and resorption. During bone formation there is a mass-dependent preference for "lighter" calcium isotopes to be removed from serum and incorporated into bone mineral. During bone resorption, there is no measurable isotopic discrimination between serum and bone. Hence, when bone formation rates exceed that of resorption, serum and urine become isotopically "heavy" due to the sequestration of "light" calcium in bone. Conversely, when bone resorption exceeds bone formation, serum and urine become isotopically "light" due to the release of the sequestered light calcium from bone. We measured Ca isotopes in urine of thirty International Space Station astronauts. Average Ca isotope values in astronauts' urine shift isotopically lighter during microgravity, consistent with negative net BMB. Within a month of return to Earth, astronauts returned to within error of their δ44Ca value prior to departure. Urine samples from astronauts testing bone loss countermeasures showed bisphosphonates provide a viable pharmacological countermeasure. Some, but not all, individuals appear able to resist bone loss through diet and intensive resistive exercise alone. This is a promising new technique for monitoring BMB in astronauts, and hopefully someday on the way to/from Mars, this also has important clinical applications for human health and terrestrial medicine [5]. REFERENCES [1] Morgan, J.L. et al (2011) Anal Chem 83, 6956-6962. [2] Skulan, J.L. et al. (2007) Clin Chem 53, 1155-1158. [3] Morgan, J.L. et al (2012) PNAS 109, 9989-9994. [4] Channon, M.B. et al (2015) Bone 77, 69-74. [5] Gordon, G.W. et al (2014) Leukemia 28, 2112-2115.

A mathematical model of cortical bone remodeling at cellular level under mechanical stimulus

NASA Astrophysics Data System (ADS)

Qin, Qing-Hua; Wang, Ya-Nan

2012-12-01

A bone cell population dynamics model for cortical bone remodeling under mechanical stimulus is developed in this paper. The external experiments extracted from the literature which have not been used in the creation of the model are used to test the validity of the model. Not only can the model compare reasonably well with these experimental results such as the increase percentage of final values of bone mineral content (BMC) and bone fracture energy (BFE) among different loading schemes (which proves the validity of the model), but also predict the realtime development pattern of BMC and BFE, as well as the dynamics of osteoblasts (OBA), osteoclasts (OCA), nitric oxide (NO) and prostaglandin E2 (PGE2) for each loading scheme, which can hardly be monitored through experiment. In conclusion, the model is the first of its kind that is able to provide an insight into the quantitative mechanism of bone remodeling at cellular level by which bone cells are activated by mechanical stimulus in order to start resorption/formation of bone mass. More importantly, this model has laid a solid foundation based on which future work such as systemic control theory analysis of bone remodeling under mechanical stimulus can be investigated. The to-be identified control mechanism will help to develop effective drugs and combined nonpharmacological therapies to combat bone loss pathologies. Also this deeper understanding of how mechanical forces quantitatively interact with skeletal tissue is essential for the generation of bone tissue for tissue replacement purposes in tissue engineering.

Quantitative trait locus on chromosome 1q influences bone loss in young Mexican American adults

PubMed Central

Shaffer, John R.; Kammerer, Candace M.; Bruder, Jan M.; Cole, Shelley A.; Dyer, Thomas D.; Almasy, Laura; MacCluer, Jean W.; Blangero, John; Bauer, Richard L.; Mitchell, Braxton D.

2009-01-01

Introduction Bone loss occurs as early as the third decade and its cumulative effect throughout adulthood may impact risk for osteoporosis in later life, however the genes and environmental factors influencing early bone loss are largely unknown. We investigated the role of genes in the change in bone mineral density (BMD) in participants of the San Antonio Family Osteoporosis Study. Materials and Methods BMD change in 327 Mexican Americans (ages 25–45 years) from 32 extended pedigrees was calculated from DXA measurements at baseline and follow-up (3.5 to 8.9 years later). Family-based likelihood methods were used to estimate heritability (h2) and perform autosome-wide linkage analysis for BMD change of the proximal femur and forearm, and estimate heritability for BMD change of lumbar spine. Results BMD change was significantly heritable for total hip, ultradistal radius and 33% radius (h2 = 0.34, 0.34, 0.27, respectively, p < 0.03 for all), modestly heritable for femoral neck (h2 = 0.22, p = 0.06) and not heritable for spine BMD. Covariates associated with BMD change included age, sex, baseline BMD, menopause, body mass index, and interim BMI change, and accounted for 6% to 24% of phenotype variation. A significant quantitative trait locus (LOD = 3.6) for femoral neck BMD change was observed on chromosome 1q23. Conclusions We observed that change in BMD in young adults is heritable, and performed one of the first linkage studies for BMD change. Linkage to chromosome 1q23 suggests this region may harbor one or more genes involved in regulating early BMD change of the femoral neck. PMID:19067020

Prediction of trabecular bone qualitative properties using scanning quantitative ultrasound

PubMed Central

Qin, Yi-Xian; Lin, Wei; Mittra, Erik; Xia, Yi; Cheng, Jiqi; Judex, Stefan; Rubin, Clint; Müller, Ralph

2012-01-01

Microgravity induced bone loss represents a critical health problem in astronauts, particularly occurred in weight-supporting skeleton, which leads to osteopenia and increase of fracture risk. Lack of suitable evaluation modality makes it difficult for monitoring skeletal status in long term space mission and increases potential risk of complication. Such disuse osteopenia and osteoporosis compromise trabecular bone density, and architectural and mechanical properties. While X-ray based imaging would not be practical in space, quantitative ultrasound may provide advantages to characterize bone density and strength through wave propagation in complex trabecular structure. This study used a scanning confocal acoustic diagnostic and navigation system (SCAN) to evaluate trabecular bone quality in 60 cubic trabecular samples harvested from adult sheep. Ultrasound image based SCAN measurements in structural and strength properties were validated by μCT and compressive mechanical testing. This result indicated a moderately strong negative correlations observed between broadband ultrasonic attenuation (BUA) and μCT-determined bone volume fraction (BV/TV, R2=0.53). Strong correlations were observed between ultrasound velocity (UV) and bone’s mechanical strength and structural parameters, i.e., bulk Young’s modulus (R2=0.67) and BV/TV (R2=0.85). The predictions for bone density and mechanical strength were significantly improved by using a linear combination of both BUA and UV, yielding R2=0.92 for BV/TV and R2=0.71 for bulk Young’s modulus. These results imply that quantitative ultrasound can characterize trabecular structural and mechanical properties through measurements of particular ultrasound parameters, and potentially provide an excellent estimation for bone’s structural integrity. PMID:23976803

Rapidly assessing changes in bone mineral balance using natural stable calcium isotopes

PubMed Central

Morgan, Jennifer L. L.; Skulan, Joseph L.; Gordon, Gwyneth W.; Romaniello, Stephen J.; Smith, Scott M.; Anbar, Ariel D.

2012-01-01

The ability to rapidly detect changes in bone mineral balance (BMB) would be of great value in the early diagnosis and evaluation of therapies for metabolic bone diseases such as osteoporosis and some cancers. However, measurements of BMB are hampered by difficulties with using biochemical markers to quantify the relative rates of bone resorption and formation and the need to wait months to years for altered BMB to produce changes in bone mineral density large enough to resolve by X-ray densitometry. We show here that, in humans, the natural abundances of Ca isotopes in urine change rapidly in response to changes in BMB. In a bed rest experiment, use of high-precision isotope ratio MS allowed the onset of bone loss to be detected in Ca isotope data after about 1 wk, long before bone mineral density has changed enough to be detectable with densitometry. The physiological basis of the relationship between Ca isotopes and BMB is sufficiently understood to allow quantitative translation of changes in Ca isotope abundances to changes in bone mineral density using a simple model. The rate of change of bone mineral density inferred from Ca isotopes is consistent with the rate observed by densitometry in long-term bed rest studies. Ca isotopic analysis provides a powerful way to monitor bone loss, potentially making it possible to diagnose metabolic bone disease and track the impact of treatments more effectively than is currently possible. PMID:22652567

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.

Age-related differences in volumetric bone mineral density, microarchitecture, and bone strength of distal radius and tibia in Chinese women: a high-resolution pQCT reference database study.

PubMed

Hung, V W Y; Zhu, T Y; Cheung, W-H; Fong, T-N; Yu, F W P; Hung, L-K; Leung, K-S; Cheng, J C Y; Lam, T-P; Qin, L

2015-06-01

In a cohort of 393 Chinese women, by using high-resolution peripheral quantitative computed tomography (HR-pQCT), we found that significant cortical bone loss occurred after midlife. Prominent increase in cortical porosity began at the fifth decade but reached a plateau before the sixth decade. Trabecular bone loss was already evident in young adulthood and continued throughout life. This study aimed to investigate age-related differences in volumetric bone mineral density (vBMD), microarchitecture, and estimated bone strength at peripheral skeleton in Chinese female population. In a cross-sectional cohort of 393 Chinese women aged 20-90 years, we obtained vBMD, microarchtecture, and micro-finite element-derived bone strength at distal radius and tibia using HR-pQCT. The largest predictive age-related difference was found for cortical porosity (Ct.Po) which showed over four-fold and two-fold differences at distal radius and tibia, respectively, over the adulthood. At both sites, cortical bone area, vBMD, and thickness showed significant quadratic association with age with significant decrease beginning after midlife. Change of Ct.Po became more prominent between age of 50 and 57 (0.26 %/year at distal radius, 0.54 %/year at distal tibia, both p ≤ 0.001) but thereafter, reached a plateau (0.015 and 0.028 %/year, both p > 0.05). In contrast, trabecular vBMD and microarchitecture showed linear association with age with significant deterioration observed throughout adulthood. Estimated age of peak was around age of 20 for trabecular vBMD and microarchitecture and Ct.Po and age of 40 for cortical vBMD and microarchitecture. Estimated stiffness and failure load peaked at mid-30s at the distal radius and at age 20 at distal tibia. Age-related differences in vBMD and microarchitecture in Chinese women differed by bone compartments. Significant cortical bone loss occurred after midlife. Prominent increase in Ct.Po began at the fifth decade but appeared to be arrested before the sixth decade. Loss of trabecular bone was already evident in young adulthood and continued throughout life.

Spaceflight-relevant types of ionizing radiation and cortical bone: Potential LET effect?

NASA Astrophysics Data System (ADS)

Lloyd, Shane A. J.; Bandstra, Eric R.; Travis, Neil D.; Nelson, Gregory A.; Bourland, J. Daniel; Pecaut, Michael J.; Gridley, Daila S.; Willey, Jeffrey S.; Bateman, Ted A.

2008-12-01

Extended exposure to microgravity conditions results in significant bone loss. Coupled with radiation exposure, this phenomenon may place astronauts at a greater risk for mission-critical fractures. In a previous study, we identified a profound and prolonged loss of trabecular bone (29-39%) in mice following exposure to an acute, 2 Gy dose of radiation simulating both solar and cosmic sources. However, because skeletal strength depends on trabecular and cortical bone, accurate assessment of strength requires analysis of both bone compartments. The objective of the present study was to examine various properties of cortical bone in mice following exposure to multiple types of spaceflight-relevant radiation. Nine-week old, female C57BL/6 mice were sacrificed 110 days after exposure to a single, whole body, 2 Gy dose of gamma, proton, carbon, or iron radiation. Femora were evaluated with biomechanical testing, microcomputed tomography, quantitative histomorphometry, percent mineral content, and micro-hardness analysis. Compared to non-irradiated controls, there were significant differences compared to carbon or iron radiation for only fracture force, medullary area and mineral content. A greater differential effect based on linear energy transfer (LET) level may be present: high-LET (carbon or iron) particle irradiation was associated with a decline in structural properties (maximum force, fracture force, medullary area, and cortical porosity) and mineral composition compared to low-LET radiation (gamma and proton). Bone loss following irradiation appears to be largely specific to trabecular bone and may indicate unique biological microenvironments and microdosimetry conditions. However, the limited time points examined and non-haversian skeletal structure of the mice employed highlight the need for further investigation.

Measurement of Bone: Diagnosis of SCI-Induced Osteoporosis and Fracture Risk Prediction

PubMed Central

Morse, Leslie R.

2015-01-01

Background: Spinal cord injury (SCI) is associated with a rapid loss of bone mass, resulting in severe osteoporosis and a 5- to 23-fold increase in fracture risk. Despite the seriousness of fractures in SCI, there are multiple barriers to osteoporosis diagnosis and wide variations in treatment practices for SCI-induced osteoporosis. Methods: We review the biological and structural changes that are known to occur in bone after SCI in the context of promoting future research to prevent or reduce risk of fracture in this population. We also review the most commonly used methods for assessing bone after SCI and discuss the strengths, limitations, and clinical applications of each method. Conclusions: Although dual-energy x-ray absorptiometry assessments of bone mineral density may be used clinically to detect changes in bone after SCI, 3-dimensional methods such as quantitative CT analysis are recommended for research applications and are explained in detail. PMID:26689691

Measurement of Bone: Diagnosis of SCI-Induced Osteoporosis and Fracture Risk Prediction.

PubMed

Troy, Karen L; Morse, Leslie R

2015-01-01

Spinal cord injury (SCI) is associated with a rapid loss of bone mass, resulting in severe osteoporosis and a 5- to 23-fold increase in fracture risk. Despite the seriousness of fractures in SCI, there are multiple barriers to osteoporosis diagnosis and wide variations in treatment practices for SCI-induced osteoporosis. We review the biological and structural changes that are known to occur in bone after SCI in the context of promoting future research to prevent or reduce risk of fracture in this population. We also review the most commonly used methods for assessing bone after SCI and discuss the strengths, limitations, and clinical applications of each method. Although dual-energy x-ray absorptiometry assessments of bone mineral density may be used clinically to detect changes in bone after SCI, 3-dimensional methods such as quantitative CT analysis are recommended for research applications and are explained in detail.

Quantitative two-dimensional ultrashort echo time magnetization transfer (2D UTE-MT) imaging of cortical bone.

PubMed

Ma, Ya-Jun; Tadros, Anthony; Du, Jiang; Chang, Eric Y

2018-04-01

To investigate quantitative 2D ultrashort echo time magnetization transfer (UTE-MT) imaging in ex vivo bovine cortical bone and in vivo human tibial cortical bone. Data were acquired from five fresh bovine cortical bone samples and five healthy volunteer tibial cortical bones using a 2D UTE-MT sequence on a clinical 3T scanner. The 2D UTE-MT sequence used four or five MT powers with five frequency offsets. Results were analyzed with a two-pool quantitative MT model, providing measurements of macromolecular fraction (f), macromolecular proton transverse relaxation times (T 2m ), proton exchange rates from water/macromolecular to the macromolecular/water pool (RM 0m /RM 0w ), and spin-lattice relaxation rate of water pool (R 1w ). A sequential air-drying study for a small bovine cortical bone chip was used to investigate whether above MT modeling parameters were sensitive to the water loss. Mean fresh bovine cortical bone values for f, T 2m , R 1w , RM 0m , and RM 0w were 59.9 ± 7.3%, 14.6 ± 0.3 μs, 9.9 ± 2.4 s -1 , 17.9 ± 3.6 s -1 , and 11.8 ± 2.0 s -1 , respectively. Mean in vivo human cortical bone values for f, T 2m , R 1w , RM 0m and RM 0w were 54.5 ± 4.9%, 15.4 ± 0.6 μs, 8.9 ± 1.1 s -1 , 11.5 ± 3.5 s -1 , and 9.5 ± 1.9 s -1 , respectively. The sequential air-drying study shows that f, RM 0m , and R 1w were increased with longer drying time. UTE-MT two-pool modeling provides novel and useful quantitative information for cortical bone. Magn Reson Med 79:1941-1949, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

Low cortical bone density measured by computed tomography in children and adolescents with untreated hyperthyroidism.

PubMed

Numbenjapon, Nawaporn; Costin, Gertrude; Gilsanz, Vicente; Pitukcheewanont, Pisit

2007-05-01

To determine whether increased thyroid hormones levels have an effect on various bone components (cortical vs cancellous bone). The anthropometric and 3-dimensional quantitative computed tomography (CT) bone measurements, including bone density (BD), cross-sectional area (CSA) of the lumbar spine and femur, and cortical bone area (CBA) of the femur, of 18 children and adolescents with untreated hyperthyroidism were reviewed and compared with those of age-, sex-, and ethnicity-matched historical controls. No significant differences in height, weight, body mass index (BMI), or pubertal staging between patients and controls were found. Cortical BD was significantly lower (P < .001) in children and adolescents with hyperthyroidism compared with historical controls. After adjusting for weight and height, no difference in femur CSA between hyperthyroid children and historical controls was evident. No significant correlations among thyroid hormone levels, antithyroid antibody levels, and cortical BD values were found. As determined by CT, cortical bone is the preferential site of bone loss in children and adolescents with untreated hyperthyroidism.

Voluntary exercise in pregnant rats improves post-lactation maternal bone parameters but does not affect offspring outcomes in early life.

PubMed

Rosa, B V; Blair, H T; Vickers, M H; Morel, P C; Cockrem, J F; Firth, E C

2012-12-01

The objectives of this study were to examine the effects of voluntary exercise during pregnancy on maternal post-lactation bone parameters and offspring growth. Pregnant Wistar rats were housed in conventional cages (control), or were housed in raised cages requiring them to rise to an erect, bipedal stance to obtain food/water, throughout pregnancy. Dual energy X-ray absorptiometry and peripheral quantitative computed tomography scans were performed pre-mating and post-weaning. Maternal stress was assessed by fecal corticosterone measurement. Offspring weights were assessed at postnatal days 1 and 25 (weaning). Changes in bone mineral over the pregnancy/lactation period were site-specific. Exercise did not affect loss of bone mineral from the lumbar spine, but did attenuate the loss of trabecular bone mineral from the tibial metaphysis and enhance the strength strain index and cross-sectional moment of inertia at the tibial diaphysis (P≤0.05) in dams in the exercised group. Fecal corticosterone did not differ between dam groups. There were no significant differences in offspring weight between the exercised and control group at either time point. Voluntary exercise in the pregnant rat can improve some post-lactation bone parameters and does not adversely affect early postnatal outcomes of the offspring.

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.

Studies of indirect and direct effects of hypervitaminosis A on rat bone by comparing free access to food and pair-feeding.

PubMed

Lind, Thomas; Lind, P Monica; Hu, Lijuan; Melhus, Håkan

2018-04-26

The most prominent features of hypervitaminosis A in rats are spontaneous fractures and anorexia. Since caloric restriction induces alterations in bone, some effects could be secondary to loss of appetite. To clarify the mechanisms behind vitamin A-induced bone fragility it is necessary to distinguish between direct and indirect effects. In this study we compared rats fed high doses of vitamin A both with pair-fed controls, which were fed the same amount of chow as that consumed by the vitamin A group to keep food intake the same, and to controls with free access to food. In contrast to the pair-fed animals, rats in the free access group fed high doses of vitamin A for 7 days had 13% lower food intake, 15% lower body weight, and 2.7% shorter femurs compared with controls. In addition, serum biomarkers of bone turnover were reduced. Peripheral quantitative computed tomography of the femurs showed that the bone mineral content, cross sectional area, and periosteal circumference were similarly reduced in the pair-fed and free access groups. However, bone mineral density (BMD) and cortical parameters were only significantly decreased in the free access group. Our data indicate that the major direct short-term effect of high doses of vitamin A on rat bone is a reduced bone diameter, whereas the effects on bone length, serum biomarkers of bone turnover, BMD, and bone cortex appear to be mainly indirect, caused by a systemic toxicity with loss of appetite, reduced food intake, and general effects on growth.

Optimal Serum Cholesterol Concentrations are Associated with Accelerated Bone Loss in African Ancestry Men

PubMed Central

Kuipers, Allison L.; Miljkovic, Iva; Evans, Rhobert; Bunker, Clareann H.; Patrick, Alan L.; Zmuda, Joseph M.

2016-01-01

Purpose Studies of lipid and lipoprotein cholesterol associations with bone mineral density (BMD) and bone loss have been inconclusive, and longitudinal data are sparse. Therefore, the aim of this study was to test if fasting serum lipid and lipoprotein cholesterol levels are associated with areal and volumetric BMD and BMD change, Methods We determined the association of serum triglycerides, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol concentrations with cross-sectional and longitudinal (mean follow-up: 6.1 years) measures of BMD in a cohort of 1289 in African ancestry men (mean age: 56.4 years). Fasting serum triglycerides, HDL and LDL were measured at baseline concurrent with BMD assessments. Dual-energy X-ray absorptiometry was used to quantify integral hip BMD and peripheral quantitative computed tomography at the radius and tibia was used to quantify volumetric BMD. Men were categorized as optimal, borderline or high-risk for triglyceride, HDL and LDL concentrations based on adult treatment panel III guidelines. Results Lower serum triglyceride or LDL and higher HDL concentrations were associated with lower trabecular BMD at baseline (all p<0.05). Similarly, men classified as having optimal levels of LDL, HDL or triglycerides at baseline experienced the greatest integral BMD loss at the hip and trabecular BMD loss at the tibia (all p<0.05), independent of potential confounding factors. Conclusions We found that clinically optimal serum lipid and lipoprotein cholesterol concentrations were associated with accelerated bone loss among Afro-Caribbean men. Further studies are needed to better understand the mechanisms involved and potential clinical significance of these findings. PMID:26602914

The Role of Nutrition in the Changes in Bone and Calcium Metabolism During Space Flight

NASA Technical Reports Server (NTRS)

Morey-Holton, Emily R.; Arnaud, Sara B.

1995-01-01

On Earth, the primary purpose of the skeleton is provide structural support for the body. In space, the support function of the skeleton is reduced since, without gravity, structures have only mass and no weight. The adaptation to space flight is manifested by shifts in mineral distribution, altered bone turnover, and regional mineral deficits in weight-bearing bones. The shifts in mineral distribution appear to be related to the cephalic fluid shift. The redistribution of mineral from one bone to another or to and from areas in the same bone in response to alterations in gravitational loads is more likely to affect skeletal function than quantitative whole body losses and gains. The changes in bone turnover appear dependent upon changes in body weight with weight loss tending to increase bone resorption as well as decrease bone formation. During bedrest, the bone response to unloading varies depending upon the routine activity level of the subjects with more active subjects showing a greater suppression of bone formation in the iliac crest with inactivity. Changes in body composition during space flight are predicted by bedrest studies on Earth which show loss of lean body mass and increase tn body fat in adult males after one month. In ambulatory studies on Earth, exercising adult males of the same age, height, g weight, body mass index, and shoe size show significantly higher whole body mineral and lean body mass. than non-exercising subjects. Nutritional preference appears to change with activity level. Diet histories in exercisers and nonexercisers who maintain identical body weights show no differences in nutrients except for slightly higher carbohydrate intake in the exercisers. The absence of differences in dietary calcium in men with higher total body calcium is noteworthy. In this situation, the increased bone mineral content was facilitated by the calcium endocrine system. This regulatory system can be by-passed by raising dietary calcium. Increased calcium intake can increase the calcium content in normally loaded bone. However, bone with a higher calcium content still decreases proportionally to normal bone during unloading. Nutritional requirements in space should be reevaluated with respect to these adaptive changes to loading and physical activity.

Atg12 Maintains Skeletal Integrity by Modulating Pro-Osteoclastogenic Signals and Chondrocyte Differentiation

NASA Technical Reports Server (NTRS)

Tahimic, Candice; Bahl, Disha; Shirazi-Fard, Yasaman; Marsh, Timothy; Schreurs, Anne-Sofie; Rael, Victoria E.; Glikbarg, Chloe; Debnath, Jayantha; Globus, Ruth K.

2016-01-01

Weightlessness and radiation, two unique elements of space, profoundly decreases bone mass. This bone loss is attributed to increased activity of bone-resorbing osteoclasts and functional changes in bone-forming osteoblasts, cells that give rise to mature osteocytes. Our long-term goal is to identify signaling pathways that may be targeted to mitigate bone loss in scenarios of space exploration, radiotherapy and accidental radiation exposure. We have previously shown that exposure of MLO-Y4 osteocyte-like cells to simulated space radiation (56Fe) increased the expression of the pro-osteoclastogenic gene rankl and decreased protein levels of LC3B-II, a key player in autophagy. In this current study, we aimed to further elucidate the role of autophagy in maintaining structural integrity of the skeleton. We hypothesize that loss of autophagy in bone leads to an imbalance in pro-osteoclastogenic and pro-osteogenic signals, resulting in net bone loss. To test our hypothesis we performed global postnatal deletion of Atg12 using tamoxifeninducible Cre recombinase under the control of the CAG promoter. Six-week-old CAGCreERT2/ FloxAtg12 animals were treated daily with Tamoxifen or Vehicle (Control, oil only) for five days and euthanasia performed two weeks after the onset of treatment. Percent change in body weights (prior to treatment and at euthanasia) was not significantly different between treatment groups within the same gender. Compared to Vehicle (Control) groups, Tamoxifen (Atg12 iKO) groups showed decreased LC3B-I to II conversion and increased p62 protein levels, consistent with loss of autophagy. Quantitative PCR revealed increased expression of proosteoclastogenic cytokines mcp1 and rankl in bone and marrow respectively in male iKOs compared to male controls. Expression levels of these genes were not significantly altered in the Atg12 iKO females compared to females controls. Microcomputed tomography of tibiae revealed decreased cortical bone volume, cortical thickness and periosteal perimeter consistent with bone loss; and a longer primary spongiosa in male Atg12 iKOs display compared to male controls. These decrements were less pronounced in the female Atg12 iKOs. Cancellous bone structure was not significantly different between iKOs and controls in both genders. Histological analysis also revealed that compared to male controls, male iKOs showed a profound increase in chondrocyte column length of the growth plate with hyper-expansion of both proliferating and hypertrophic zones. Taken together, these findings indicate that autophagy plays an important role in the maintenance of bone structural integrity by mediating the production of proosteoclastogenic signals and regulating chondrocyte proliferation and differentiation.

Clinical Imaging of Bone Microarchitecture with HR-pQCT

PubMed Central

Nishiyama, Kyle K.; Shane, Elizabeth

2014-01-01

Osteoporosis, a disease characterized by loss of bone mass and structural deterioration, is currently diagnosed by dual-energy x-ray absorptiometry (DXA). However, DXA does not provide information about bone microstructure, which is a key determinant of bone strength. Recent advances in imaging permit the assessment of bone microstructure in vivo using high-resolution peripheral quantitative computed tomography (HR-pQCT). From these data, novel image processing techniques can be applied to characterize bone quality and strength. To date, most HR-pQCT studies are cross-sectional comparing subjects with and without fracture. These studies have shown that HR-pQCT is capable of discriminating fracture status independent of DXA. Recent longitudinal studies present new challenges in terms of analyzing the same region of interest and multisite calibrations. Careful application of analysis techniques and educated clinical interpretation of HR-pQCT results have improved our understanding of various bone-related diseases and will no doubt continue to do so in the future. PMID:23504496

Fermented dairy products consumption is associated with attenuated cortical bone loss independently of total calcium, protein, and energy intakes in healthy postmenopausal women.

PubMed

Biver, E; Durosier-Izart, C; Merminod, F; Chevalley, T; van Rietbergen, B; Ferrari, S L; Rizzoli, R

2018-05-03

A longitudinal analysis of bone microstructure in postmenopausal women of the Geneva Retirees Cohort indicates that age-related cortical bone loss is attenuated at non-bearing bone sites in fermented dairy products consumers, not in milk or ripened cheese consumers, independently of total energy, calcium, or protein intakes. Fermented dairy products (FDP), including yogurts, provide calcium, phosphorus, and proteins together with prebiotics and probiotics, all being potentially beneficial for bone. In this prospective cohort study, we investigated whether FDP, milk, or ripened cheese consumptions influence age-related changes of bone mineral density (BMD) and microstructure. Dietary intakes were assessed at baseline and after 3.0 ± 0.5 years with a food frequency questionnaire in 482 postmenopausal women enrolled in the Geneva Retirees Cohort. Cortical (Ct) and trabecular (Tb) volumetric (v) BMD and microstructure at the distal radius and tibia were assessed by high-resolution peripheral quantitative computerized tomography, in addition to areal (a) BMD and body composition by dual-energy X-ray absorptiometry, at the same time points. At baseline, FDP consumers had lower abdominal fat mass and larger bone size at the radius and tibia. Parathyroid hormone and β-carboxyterminal cross-linked telopeptide of type I collagen levels were inversely correlated with FDP consumption. In the longitudinal analysis, FDP consumption (mean of the two assessments) was associated with attenuated loss of radius total vBMD and of Ct vBMD, area, and thickness. There was no difference in aBMD and at the tibia. These associations were independent of total energy, calcium, or protein intakes. For other dairy products categories, only milk consumption was associated with lower decrease of aBMD and of failure load at the radius. In this prospective cohort of healthy postmenopausal women, age-related Ct bone loss was attenuated at non-bearing bone sites in FDP consumers, not in milk or ripened cheese consumers, independently of total energy, calcium, or protein intakes. ISRCTN11865958 ( http://www.isrctn.com ).

A multi-method assessment of bone maintenance and loss in an Imperial Roman population: Implications for future studies of age-related bone loss in the past.

PubMed

Beauchesne, Patrick; Agarwal, Sabrina C

2017-09-01

One of the hallmarks of contemporary osteoporosis and bone loss is dramatically higher prevalence of loss and fragility in females post-menopause. In contrast, bioarchaeological studies of bone loss have found a greater diversity of age- and sex-related patterns of bone loss in past populations. We argue that the differing findings may relate to the fact that most studies use only a single methodology to quantify bone loss and do not account for the heterogeneity and complexity of bone maintenance across the skeleton and over the life course. We test the hypothesis that bone mass and maintenance in trabecular bone sites versus cortical bone sites will show differing patterns of age-related bone loss, with cortical bone sites showing sex difference in bone loss that are similar to contemporary Western populations, and trabecular bone loss at earlier ages. We investigated this hypothesis in the Imperial Roman population of Velia using three methods: radiogrammetry of the second metacarpal (N = 71), bone histology of ribs (N = 70), and computerized tomography of trabecular bone architecture (N = 47). All three methods were used to explore sex and age differences in patterns of bone loss. The suite of methods utilized reveal differences in the timing of bone loss with age, but all methods found no statistically significant differences in age-related bone loss. We argue that a multi-method approach reduces the influence of confounding factors by building a reconstruction of bone turnover over the life cycle that a limited single-method project cannot provide. The implications of using multiple methods beyond studies of bone loss are also discussed. © 2017 Wiley Periodicals, Inc.

Volumetric topological analysis: a novel approach for trabecular bone classification on the continuum between plates and rods.

PubMed

Saha, Punam K; Xu, Yan; Duan, Hong; Heiner, Anneliese; Liang, Guoyuan

2010-11-01

Trabecular bone (TB) is a complex quasi-random network of interconnected plates and rods. TB constantly remodels to adapt to the stresses to which it is subjected (Wolff's Law). In osteoporosis, this dynamic equilibrium between bone formation and resorption is perturbed, leading to bone loss and structural deterioration. Both bone loss and structural deterioration increase fracture risk. Bone's mechanical behavior can only be partially explained by variations in bone mineral density, which led to the notion of bone structural quality. Previously, we developed digital topological analysis (DTA) which classifies plates, rods, profiles, edges, and junctions in a TB skeletal representation. Although the method has become quite popular, a major limitation of DTA is that it provides only hard classifications of different topological entities, failing to distinguish between narrow and wide plates. Here, we present a new method called volumetric topological analysis (VTA) for regional quantification of TB topology. At each TB location, the method uniquely classifies its topology on the continuum between perfect plates and perfect rods, facilitating early detections of TB alterations from plates to rods according to the known etiology of osteoporotic bone loss. Several new ideas, including manifold distance transform, manifold scale, and feature propagation have been introduced here and combined with existing DTA and distance transform methods, leading to the new VTA technology. This method has been applied to multidetector computed tomography (CT) and micro-computed tomography ( μCT) images of four cadaveric distal tibia and five distal radius specimens. Both intra- and inter-modality reproducibility of the method has been examined using repeat CT and μCT scans of distal tibia specimens. Also, the method's ability to predict experimental biomechanical properties of TB via CT imaging under in vivo conditions has been quantitatively examined and the results found are very encouraging.

Heel Ultrasound Can Assess Maintenance of Bone Mass in Women with Breast Cancer

PubMed Central

Langmann, Gabrielle A.; Vujevich, Karen T.; Medich, Donna; Miller, Megan E.; Perera, Subashan; Greenspan, Susan L.

2016-01-01

Postmenopausal women with early-stage breast cancer are at increased risk for bone loss and fractures. Bisphosphonates can prevent bone loss, but little data are available on changes in bone mass assessed by heel quantitative ultrasound (QUS). Our objectives were to determine if (1) heel QUS would provide a reliable and accessible method for evaluation of changes in bone mass in women with breast cancer as compared to the current standard of bone mass measurement, dual-energy x-ray absorptiometry (DXA), and (2) oral risedronate could affect these changes. Eighty-six newly postmenopausal (up to 8 years) women with nonmetastatic breast cancer were randomized to risedronate, 35 mg once weekly or placebo. Outcomes were changes in heel QUS bone mass measurements and conventional dual-energy x-ray absorptiometry (DXA) derived bone mineral density (BMD). Over 2 years, bone mass assessed by heel QUS remained stable in women on risedronate, while women on placebo had a 5.2% decrease (p ≤ 0.05) in heel QUS bone mass. Both total hip BMD and femoral neck BMD assessed by DXA decreased by 1.6% (p ≤ 0.05) in the placebo group and remained stable with risedronate. Spine BMD remained stable in both groups. Heel QUS was moderately associated with BMD measured by DXA at the total hip (r = 0.50), femoral neck (r = 0.40), and spine (r = 0.46) at baseline (all p ≤ 0.001). In conclusion, risedronate helps to maintain skeletal integrity as assessed by heel QUS for women with early-stage breast cancer. Heel QUS is associated with DXA-derived BMD at other major axial sites and may be used to follow skeletal health and bone mass changes in these women. PMID:22425507

Determinants of prevalent vertebral fractures and progressive bone loss in long-term hemodialysis patients.

PubMed

Mares, Jan; Ohlidalova, Kristina; Opatrna, Sylvie; Ferda, Jiri

2009-01-01

Skeletal fractures are common in hemodialysis (HD) patients. However, consensus regarding technique and site of bone examination has not been reached in HD patients. Seventy-two patients (44% females) aged 65 (1.4) years, treated with HD for 43 (4.6) months were examined with quantitative computed tomography and 53 of them re-examined after 1 year. Bone mineral density (BMD) of lumbar spine was established separately for cortical and trabecular bone, prevalent vertebral fractures were determined. Data are given as mean (standard error). At least one vertebral fracture was discovered in 15 (21%) patients. In a logistic regression model, fractures were best predicted by cortical BMD: OR 0.96 (CI 0.94, 0.99), p < 0.005. With a multiple regression analysis, time on dialysis was found to be independently correlated to cortical BMD (R = 0.35, p < 0.005). On follow-up, a decrease of BMD was detected, which occurred only in the cortical region and was significantly greater in females than in males: -7% (1.7) versus 1.2% (1.9), p < 0.005. A time-dependent loss of vertebral cortical bone occurs in HD patients, especially in females. This decrement may impose an increased risk of fractures on long-term dialysis patients.

Maxillary sinus augmentation by crestal access: a retrospective study on cavity size and outcome correlation.

PubMed

Spinato, Sergio; Bernardello, Fabio; Galindo-Moreno, Pablo; Zaffe, Davide

2015-12-01

Cone-beam computed tomography (CBCT) and radiographic outcomes of crestal sinus elevation, performed using mineralized human bone allograft, were analyzed to correlate results with maxillary sinus size. A total of 60 sinus augmentations in 60 patients, with initial bone ≤5 mm, were performed. Digital radiographs were taken at surgical implant placement time up to post-prosthetic loading follow-up (12-72 months), when CBCT evaluation was carried out. Marginal bone loss (MBL) was radiographically analyzed at 6 months and follow-up time post-loading. Sinus size (BPD), implant distance from palatal (PID) and buccal wall (BID), and absence of bone coverage of implant (intra-sinus bone loss--IBL) were evaluated and statistically evaluated by ANOVA and linear regression analyses. MBL increased as a function of time. MBL at final follow-up was statistically associated with MBL at 6 months. A statistically significant correlation of IBL with wall distance and of IBL/mm with time was identified with greater values in wide sinuses (WS ≥ 13.27 mm) than in narrow sinuses (NS < 13.27 mm). This study is the first quantitative and statistically significant confirmation that crestal technique with residual ridge height <5 mm is more appropriate and predictable, in terms of intra-sinus bone coverage, in narrow than in WS. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Sex Steroids and Bone Health Status in Men

PubMed Central

Chin, Kok-Yong; Ima-Nirwana, Soelaiman

2012-01-01

Male osteoporosis is a health problem which deserves more attention as nearly 30% of osteoporotic fractures happen in men aged 50 years and above. Although men do not experience an accelerated bone loss phase and testosterone deficiency is not a universal characteristic for aged men, osteoporosis due to age-related testosterone deficiency does have a negative impact on bone health status of men. Observations from epidemiological studies indicate that elderly men with higher testosterone can preserve their BMD better and thus are less prone to fracture. Observations on men with estrogen resistance or aromatase deficiency indicate that estrogen is equally important in the maintenance of bone health status. This had been validated in several epidemiological studies which found that the relationships between estrogen and bone health indices are significant and sometimes stronger than testosterone. Studies on the relationship between quantitative ultrasound and bone remodeling markers suggest that testosterone and estrogen may have differential effects on bone, but further evidence was needed. In conclusion, both testosterone and estrogen are important in the maintenance of bone health in men. PMID:23150727

Calcium tracer kinetics show decreased irreversible flow to bone in glucocorticoid treated patients.

PubMed

Goans, R E; Weiss, G H; Abrams, S A; Perez, M D; Yergey, A L

1995-06-01

Osteopenia resulting from pharmacologic doses of glucocorticoids is well known. Previously, there has been no satisfactory quantitative model describing the kinetics of calcium flow in subjects on chronic steroid use. A mathematical model of calcium isotope interaction with bone is described and applied to determine an estimate of kinetic parameters characterizing these changes. Calcium tracer dilution kinetics after a bolus injection of 42Ca were measured in 14 subjects with juvenile dermatomyositis, 6 on prednisone regimens and 8 on treatment regimens without prednisone. Irreversible tracer loss from plasma bone is found to be significantly reduced (P = 0.043) in the glucocorticoid-treated patients compared with patients on nonsteroid regimens. Reversible flow to bone is noted to be similar in the two groups. These results suggest a direct effect of glucocorticoids on osteoblast function.

Sex-specific patterns in cortical and trabecular bone microstructure in the Kirsten Skeletal Collection, South Africa.

PubMed

Beresheim, Amy C; Pfeiffer, Susan K; Grynpas, Marc D; Alblas, Amanda

2018-02-07

The purpose of this study was to provide bone histomorphometric reference data for South Africans of the Western Cape who likely dealt with health issues under the apartheid regime. The 206 adult individuals ( n female = 75, n male = 131, mean = 47.9 ± 15.8 years) from the Kirsten Skeletal Collection, U. Stellenbosch, lived in the Cape Town metropole from the late 1960s to the mid-1990s. To study age-related changes in cortical and trabecular bone microstructure, photomontages of mid-thoracic rib cross-sections were quantitatively examined. Variables include relative cortical area (Rt.Ct.Ar), osteon population density (OPD), osteon area (On.Ar), bone volume fraction (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), and trabecular spacing (Tb.Sp). All cortical variables demonstrated significant relationships with age in both sexes, with women showing stronger overall age associations. Peak bone mass was compromised in some men, possibly reflecting poor nutritional quality and/or substance abuse issues throughout adolescence and early adulthood. In women, greater predicted decrements in On.Ar and Rt.Ct.Ar suggest a structural disadvantage with age, consistent with postmenopausal bone loss. Age-related patterns in trabecular bone microarchitecture are variable and difficult to explain. Except for Tb.Th, there are no statistically significant relationships with age in women. Men demonstrate significant negative correlations between BV/TV, Tb.N, and age, and a significant positive correlation between Tb.Sp and age. This research highlights sex-specific differences in patterns of age-related bone loss, and provides context for discussion of contemporary South African bone health. While the study sample demonstrates indicators of poor bone quality, osteoporosis research continues to be under-prioritized in South Africa. © 2018 Wiley Periodicals, Inc.

Normative Standards for HRpQCT Parameters in Chinese Men and Women.

PubMed

Zhu, Tracy Y; Yip, Benjamin Hk; Hung, Vivian Wy; Choy, Carol Wy; Cheng, Ka-Lo; Kwok, Timothy Cy; Cheng, Jack Cy; Qin, Ling

2018-06-12

Assessing bone architecture using high resolution peripheral quantitative computed tomography (HRpQCT) has the potential to improve fracture risk assessment. The Normal Reference Study aimed to establish sex-specific reference centile curves for HRpQCT parameters. This was an age-stratified cross-sectional study and 1,072 ambulatory Chinese men (n = 544) and women (n = 528) aged 20-79yrs, who were free from conditions and medications that could affect bone metabolism and had no history of fragility fracture, were recruited from local communities of Hong Kong. Reference centile curves for each HRpQCT parameter were constructed using Generalized Additive Models for Location, Scale and Shape with age as the only explanatory variable. Patterns of reference centile curves reflected age-related changes of bone density, microarchitecture, and estimated bone strength. In both sexes, loss of cortical bone was only evident in mid-adulthood, particularly in women with a more rapid fashion probably concurrent with the onset of menopause. In contrast, loss of trabecular bone was subtle or gradual or occurred at an earlier age. Expected values of HRpQCT parameters for a defined sex and age, and a defined percentile or z-score were obtained from these curves. T-scores were calculated using the population with the peak values as the reference and reflected age- or menopause-related bone loss in an older individual or the room to reach the peak potential in a younger individual. These reference centile curves produced a standard describing a norm or desirable target that enables value clinical judgements. Percentiles, z-scores and T-scores would be helpful in detecting abnormalities in bone density and microarchitecture arising from various conditions and establishing entry criteria for clinical trials. They also hold the potential to refine the diagnosis of osteoporosis and assessment of fracture risk. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Non-synonymous FGD3 Variant as Positional Candidate for Disproportional Tall Stature Accounting for a Carcass Weight QTL (CW-3) and Skeletal Dysplasia in Japanese Black Cattle

PubMed Central

Takasuga, Akiko; Sato, Kunio; Nakamura, Ryouichi; Saito, Yosuke; Sasaki, Shinji; Tsuji, Takehito; Suzuki, Akio; Kobayashi, Hiroshi; Matsuhashi, Tamako; Setoguchi, Koji; Okabe, Hiroshi; Ootsubo, Toshitake; Tabuchi, Ichiro; Fujita, Tatsuo; Watanabe, Naoto; Hirano, Takashi; Nishimura, Shota; Watanabe, Toshio; Hayakawa, Makio; Sugimoto, Yoshikazu; Kojima, Takatoshi

2015-01-01

Recessive skeletal dysplasia, characterized by joint- and/or hip bone-enlargement, was mapped within the critical region for a major quantitative trait locus (QTL) influencing carcass weight; previously named CW-3 in Japanese Black cattle. The risk allele was on the same chromosome as the Q allele that increases carcass weight. Phenotypic characterization revealed that the risk allele causes disproportional tall stature and bone size that increases carcass weight in heterozygous individuals but causes disproportionately narrow chest width in homozygotes. A non-synonymous variant of FGD3 was identified as a positional candidate quantitative trait nucleotide (QTN) and the corresponding mutant protein showed reduced activity as a guanine nucleotide exchange factor for Cdc42. FGD3 is expressed in the growth plate cartilage of femurs from bovine and mouse. Thus, loss of FDG3 activity may lead to subsequent loss of Cdc42 function. This would be consistent with the columnar disorganization of proliferating chondrocytes in chondrocyte-specific inactivated Cdc42 mutant mice. This is the first report showing association of FGD3 with skeletal dysplasia. PMID:26306008

Multiscale alterations in bone matrix quality increased fragility in steroid induced osteoporosis

PubMed Central

Karunaratne, A.; Xi, L.; Bentley, L.; Sykes, D.; Boyde, A.; Esapa, C.T.; Terrill, N.J.; Brown, S.D.M.; Cox, R.D.; Thakker, R.V.; Gupta, H.S.

2016-01-01

A serious adverse clinical effect of glucocorticoid steroid treatment is secondary osteoporosis, enhancing fracture risk in bone. This rapid increase in bone fracture risk is largely independent of bone loss (quantity), and must therefore arise from degradation of the quality of the bone matrix at the micro- and nanoscale. However, we lack an understanding of both the specific alterations in bone quality n steroid-induced osteoporosis as well as the mechanistic effects of these changes. Here we demonstrate alterations in the nanostructural parameters of the mineralized fibrillar collagen matrix, which affect bone quality, and develop a model linking these to increased fracture risk in glucocorticoid induced osteoporosis. Using a mouse model with an N-ethyl-N-nitrosourea (ENU)-induced corticotrophin releasing hormone promoter mutation (Crh− 120/+) that developed hypercorticosteronaemia and osteoporosis, we utilized in situ mechanical testing with small angle X-ray diffraction, synchrotron micro-computed tomography and quantitative backscattered electron imaging to link altered nano- and microscale deformation mechanisms in the bone matrix to abnormal macroscopic mechanics. We measure the deformation of the mineralized collagen fibrils, and the nano-mechanical parameters including effective fibril modulus and fibril to tissue strain ratio. A significant reduction (51%) of fibril modulus was found in Crh− 120/+ mice. We also find a much larger fibril strain/tissue strain ratio in Crh− 120/+ mice (~ 1.5) compared to the wild-type mice (~ 0.5), indicative of a lowered mechanical competence at the nanoscale. Synchrotron microCT show a disruption of intracortical architecture, possibly linked to osteocytic osteolysis. These findings provide a clear quantitative demonstration of how bone quality changes increase macroscopic fragility in secondary osteoporosis. PMID:26657825

Estrogen regulates the rate of bone turnover but bone balance in ovariectomized rats is modulated by prevailing mechanical strain

NASA Technical Reports Server (NTRS)

Westerlind, K. C.; Wronski, T. J.; Ritman, E. L.; Luo, Z. P.; An, K. N.; Bell, N. H.; Turner, R. T.

1997-01-01

Estrogen deficiency induced bone loss is associated with increased bone turnover in rats and humans. The respective roles of increased bone turnover and altered balance between bone formation and bone resorption in mediating estrogen deficiency-induced cancellous bone loss was investigated in ovariectomized rats. Ovariectomy resulted in increased bone turnover in the distal femur. However, cancellous bone was preferentially lost in the metaphysis, a site that normally experiences low strain energy. No bone loss was observed in the epiphysis, a site experiencing higher strain energy. The role of mechanical strain in maintaining bone balance was investigated by altering the strain history. Mechanical strain was increased and decreased in long bones of ovariectomized rats by treadmill exercise and functional unloading, respectively. Functional unloading was achieved during orbital spaceflight and following unilateral sciatic neurotomy. Increasing mechanical loading reduced bone loss in the metaphysis. In contrast, decreasing loading accentuated bone loss in the metaphysis and resulted in bone loss in the epiphysis. Finally, administration of estrogen to ovariectomized rats reduced bone loss in the unloaded and prevented loss in the loaded limb following unilateral sciatic neurotomy in part by reducing indices of bone turnover. These results suggest that estrogen regulates the rate of bone turnover, but the overall balance between bone formation and bone resorption is influenced by prevailing levels of mechanical strain.

The Digital Astronaut Project Computational Bone Remodeling Model (Beta Version) Bone Summit Summary Report

NASA Technical Reports Server (NTRS)

Pennline, James; Mulugeta, Lealem

2013-01-01

Under the conditions of microgravity, astronauts lose bone mass at a rate of 1% to 2% a month, particularly in the lower extremities such as the proximal femur [1-3]. The most commonly used countermeasure against bone loss in microgravity has been prescribed exercise [4]. However, data has shown that existing exercise countermeasures are not as effective as desired for preventing bone loss in long duration, 4 to 6 months, spaceflight [1,3,5,6]. This spaceflight related bone loss may cause early onset of osteoporosis to place the astronauts at greater risk of fracture later in their lives. Consequently, NASA seeks to have improved understanding of the mechanisms of bone demineralization in microgravity in order to appropriately quantify this risk, and to establish appropriate countermeasures [7]. In this light, NASA's Digital Astronaut Project (DAP) is working with the NASA Bone Discipline Lead to implement well-validated computational models to help predict and assess bone loss during spaceflight, and enhance exercise countermeasure development. More specifically, computational modeling is proposed as a way to augment bone research and exercise countermeasure development to target weight-bearing skeletal sites that are most susceptible to bone loss in microgravity, and thus at higher risk for fracture. Given that hip fractures can be debilitating, the initial model development focused on the femoral neck. Future efforts will focus on including other key load bearing bone sites such as the greater trochanter, lower lumbar, proximal femur and calcaneus. The DAP has currently established an initial model (Beta Version) of bone loss due to skeletal unloading in femoral neck region. The model calculates changes in mineralized volume fraction of bone in this segment and relates it to changes in bone mineral density (vBMD) measured by Quantitative Computed Tomography (QCT). The model is governed by equations describing changes in bone volume fraction (BVF), and rates of changes in bone cell populations that remove and replace bone in packets within the bone region. The DAP bone model is unique in several respects. In particular in takes former models of volume fraction changes one step higher in fidelity and separates BVF into separate equations for mineralized and osteoid volume fractions governed by a mineralization rate. This more closely follows the physiology of the remodeling unit cycles where bone is first resorbed and then followed by the action of osteoblasts to lay down collagen matrix which eventually becomes mineralized. In another respect, the modules allow the functional description of the time rate of change of other parameters and variables in the model during a computational simulation. More detailed description of the model, preliminary validation results, current limitation and caveats, and planned advancements are provided in sections 2 through 5. The DAP bone model is being developed primarily as a research tool, and not as a clinical tool like QCT. Even if it transitions to a clinical tool, it is not intended to replace QCT or any other clinical tool. Moreover, the DAP bone model does not predict bone fracture. Its purpose is to provide valuable additional data via "forward prediction" simulations for during and after spaceflight missions to gain insight on, (1) mechanisms of bone demineralization in microgravity, and (2) the volumetric changes at the various bone sites in response to in-flight and post-flight exercise countermeasures. This data can then be used as input to the Keyak [8] (or equivalent) FE analysis method to gain insight on how bone strength may change during and after flight. This information can also be useful to help optimize exercise countermeasure protocols to minimize changes in bone strength during flight, and improve regain of bone strength post-flight. To achieve this goal, the bone model will be integrated with DAP's exercise countermeasure models to simulate the effect of exercise prescriptions on preserving bone. More specifically, the model will accept loading history due to muscle and joint force on bone and produce quantified remodeling within the bone region under influence of the applied stress. Furthermore, because they tend to respond differently, the bone remodeling model includes both trabecular bone and cortical bone.

Mechanical signaling in the development of postmenopausal osteoporosis

NASA Technical Reports Server (NTRS)

Turner, R. T.

1999-01-01

Estrogen deficiency results in increased bone turnover and net bone loss in rats as well as humans. The respective roles of bone turnover and mechanical strain in mediating estrogen deficiency-induced cancellous bone loss were investigated in ovariectomized rats. Ovariectomy resulted in increased bone turnover in long bones. However, cancellous bone was preferentially lost in the metaphysis, a site that experiences low strain energy during normal physical activity. No bone loss was observed in the epiphysis, a site experiencing higher strain energy, despite a similar increase in bone turnover. The role of mechanical strain in maintaining bone balance was investigated by altering the strain history. Mechanical strain was increased or decreased in long bones of ovariectomized rats by treadmill exercise or functional unloading, respectively. Increasing mechanical loading reduced bone loss in the metaphysis. In contrast, decreasing weight bearing accentuated bone loss in the metaphysis and resulted in bone loss in the epiphysis. Finally, administration of estrogen to ovariectomized rats reduced bone loss in unloaded limbs and prevented bone loss in the loaded limbs. These results suggest that estrogen alters the mechanosensory (mechanostat) set point for skeletal adaptation, effectively reducing the minimum strain energy levels at which bone is added. Additionally, these studies suggest that physical activity as well as endocrine status play an important role in maintenance of the female skeleton during aging.

Assessment of metabolic bone diseases by quantitative computed tomography

NASA Technical Reports Server (NTRS)

Richardson, M. L.; Genant, H. K.; Cann, C. E.; Ettinger, B.; Gordan, G. S.; Kolb, F. O.; Reiser, U. J.

1985-01-01

Advances in the radiologic sciences have permitted the development of numerous noninvasive techniques for measuring the mineral content of bone, with varying degrees of precision, accuracy, and sensitivity. The techniques of standard radiography, radiogrammetry, photodensitometry, Compton scattering, neutron activation analysis, single and dual photon absorptiometry, and quantitative computed tomography (QCT) are described and reviewed in depth. Results from previous cross-sectional and longitudinal QCT investigations are given. They then describe a current investigation in which they studied 269 subjects, including 173 normal women, 34 patients with hyperparathyroidism, 24 patients with steroid-induced osteoporosis, and 38 men with idiopathic osteoporosis. Spinal quantitative computed tomography, radiogrammetry, and single photon absorptiometry were performed, and a spinal fracture index was calculated on all patients. The authors found a disproportionate loss of spinal trabecular mineral compared to appendicular mineral in the men with idiopathic osteoporosis and the patients with steroid-induced osteoporosis. They observed roughly equivalent mineral loss in both the appendicular and axial regions in the hyperparathyroid patients. The appendicular cortical measurements correlated moderately well with each other but less well with spinal trabecular QCT. The spinal fracture index correlated well with QCT and less well with the appendicular measurements. Knowledge of appendicular cortical mineral status is important in its own right but is not a valid predictor of axial trabecular mineral status, which may be disproportionately decreased in certain diseases. Quantitative CT provides a reliable means of assessing the latter region of the skeleton, correlates well with the spinal fracture index (a semiquantitative measurement of end-organ failure), and offers the clinician a sensitive means of following the effects of therapy.

Assessment of Alveolar Bone Status in Middle Aged Chinese (40-59 Years) with Chronic Periodontitis--Using CBCT.

PubMed

Zhao, Haijiao; Li, Chen; Lin, Li; Pan, Yaping; Wang, Hongyan; Zhao, Jian; Tan, Lisi; Pan, Chunling; Song, Jia; Zhang, Dongmei

2015-01-01

This study used con-beam computed tomography (CBCT) to investigate the prevalence and severity of alveolar bone loss in middle-aged (40-59 years) Chinese with chronic periodontitis. The study group comprised 145 dentate individuals aged 40 to 59 years residing in China who suffered from chronic periodontitis. CBCT and the application of NNT software were used to examine the level and location of alveolar bone loss. The study revealed that 40-59 year old patients with chronic periodontitis had severe bone loss. At 5,286 sites (34.7%), alveolar bone loss was mild; severe alveolar bone loss was found at 5,978 sites (39.2%). A comparison of bone loss in different jaws revealed that the area with the highest degree of bone loss was on the lingual side of the maxillary molar (56.3 ± 7.2%), and that the area with the lowest degree was primarily on the lingual side of the mandibular canine (27.5 ± 6.3%). There was a lower degree of alveolar bone loss in males than females. Differences were observed when comparing the incidence of bone loss between males and females (P < 0.05). Menopause in females and smoking in both genders may affect the level of bone loss. Male smokers experienced a greater degree of bone loss (41.67 ± 5.76%) than male non-smokers (32.95 ± 4.31%). A 42.23 ± 6.34% bone loss was found in menopausal females versus 31.35 ± 3.62% in non-menopausal females. The study revealed that different sites and teeth exhibited a diverse degree of bone loss. In middle-aged patients with chronic periodontitis, the highest degrees of bone loss in the incisors, premolars, and molars were on the lingual side, mesial side and lingual side, respectively. Menopause in females and smoking may affect the level of bone loss.

Characterization of microgravity effects on bone structure and strength using fractal analysis

NASA Technical Reports Server (NTRS)

Acharya, Raj S.; Shackelford, Linda

1995-01-01

The effect of micro-gravity on the musculoskeletal system has been well studied. Significant changes in bone and muscle have been shown after long term space flight. Similar changes have been demonstrated due to bed rest. Bone demineralization is particularly profound in weight bearing bones. Much of the current techniques to monitor bone condition use bone mass measurements. However, bone mass measurements are not reliable to distinguish Osteoporotic and Normal subjects. It has been shown that the overlap between normals and osteoporosis is found for all of the bone mass measurement technologies: single and dual photon absorptiometry, quantitative computed tomography and direct measurement of bone area/volume on biopsy as well as radiogrammetry. A similar discordance is noted in the fact that it has not been regularly possible to find the expected correlation between severity of osteoporosis and degree of bone loss. Structural parameters such as trabecular connectivity have been proposed as features for assessing bone conditions. In this report, we use fractal analysis to characterize bone structure. We show that the fractal dimension computed with MRI images and X-Ray images of the patella are the same. Preliminary experimental results show that the fractal dimension computed from MRI images of vertebrae of human subjects before bedrest is higher than during bedrest.

Marginal bone loss around non-submerged implants is associated with salivary microbiome during bone healing.

PubMed

Duan, Xiao-Bo; Wu, Ting-Xi; Guo, Yu-Chen; Zhou, Xue-Dong; Lei, Yi-Ling; Xu, Xin; Mo, An-Chun; Wang, Yong-Yue; Yuan, Quan

2017-06-01

Marginal bone loss during bone healing exists around non-submerged dental implants. The aim of this study was to identify the relationship between different degrees of marginal bone loss during bone healing and the salivary microbiome. One hundred patients were recruited, and marginal bone loss around their implants was measured using cone beam computed tomography during a 3-month healing period. The patients were divided into three groups according to the severity of marginal bone loss. Saliva samples were collected from all subjected and were analysed using 16S MiSeq sequencing. Although the overall structure of the microbial community was not dramatically altered, the relative abundance of several taxonomic groups noticeably changed. The abundance of species in the phyla Spirochaeta and Synergistetes increased significantly as the bone loss became more severe. Species within the genus Treponema also exhibited increased abundance, whereas Veillonella, Haemophilus and Leptotrichia exhibited reduced abundances, in groups with more bone loss. Porphyromonasgingivalis, Treponemadenticola and Streptococcus intermedius were significantly more abundant in the moderate group and/or severe group. The severity of marginal bone loss around the non-submerged implant was associated with dissimilar taxonomic compositions. An increased severity of marginal bone loss was related to increased proportions of periodontal pathogenic species. These data suggest a potential role of microbes in the progression of marginal bone loss during bone healing.

Associated among endocrine, inflammatory, and bone markers, body composition and weight loss induced bone loss

USDA-ARS?s Scientific Manuscript database

Weight loss reduces co-¬morbidities of obesity but decreases bone mass. Our aims were to determine whether adequate dairy intake could prevent weight loss related bone loss and to evaluate the contribution of energy-related hormones and inflammatory markers to bone metabolism. Overweight and obese w...

Participation in High-Impact Sports Predicts Bone Mineral Density in Senior Olympic Athletes

PubMed Central

Leigey, Daniel; Irrgang, James; Francis, Kimberly; Cohen, Peter; Wright, Vonda

2009-01-01

Background: Loss of bone mineral density (BMD) and resultant fractures increase with age in both sexes. Participation in resistance or high-impact sports is a known contributor to bone health in young athletes; however, little is known about the effect of participation in impact sports on bone density as people age. Hypothesis: To test the hypothesis that high-impact sport participation will predict BMD in senior athletes, this study evaluated 560 athletes during the 2005 National Senior Games (the Senior Olympics). Study Design: Cross-sectional methods. The athletes completed a detailed health history questionnaire and underwent calcaneal quantitative ultrasound to measure BMD. Athletes were classified as participating in high impact sports (basketball, road race [running], track and field, triathalon, and volleyball) or non-high-impact sports. Stepwise linear regression was used to determine the influence of high-impact sports on BMD. Results: On average, participants were 65.9 years old (range, 50 to 93). There were 298 women (53.2%) and 289 men (51.6%) who participated in high-impact sports. Average body mass index was 25.6 ± 3.9. The quantitative ultrasound-generated T scores, a quantitative measure of BMD, averaged 0.4 ± 1.3 and −0.1 ± 1.4 for the high-impact and non-high-impact groups, respectively. After age, sex, obesity, and use of osteoporosis medication were controlled, participation in high-impact sports was a significant predictor of BMD (R2 change 3.2%, P < .001). Conclusions: This study represents the largest sample of BMD data in senior athletes to date. Senior participation in high-impact sports positively influenced bone health, even in the oldest athletes. Clinical Relevance: These data imply that high-impact exercise is a vital tool to maintain healthy BMD with active aging. PMID:23015914

Vegetarian diets and bone status.

PubMed

Tucker, Katherine L

2014-07-01

Osteoporosis is a common chronic condition associated with progressive loss of bone mineral density (BMD) and compromised bone strength, with increasing risk of fracture over time. Vegetarian diets have been shown to contain lower amounts of calcium, vitamin D, vitamin B-12, protein, and n-3 (ω-3) fatty acids, all of which have important roles in maintaining bone health. Although zinc intakes are not necessarily lower quantitatively, they are considerably less bioavailable in vegetarian diets, which suggests the need for even higher intakes to maintain adequate status. At the same time, healthy vegetarian diets tend to contain more of several protective nutrients, including magnesium, potassium, vitamin K, and antioxidant and anti-inflammatory phytonutrients. On balance, there is evidence that vegetarians, and particularly vegans, may be at greater risk of lower BMD and fracture. Attention to potential shortfall nutrients through the careful selection of foods or fortified foods or the use of supplements can help ensure healthy bone status to reduce fracture risk in individuals who adhere to vegetarian diets. © 2014 American Society for Nutrition.

A Cross-Sectional Study of the Association between Autoantibodies and Qualitative Ultrasound Index of Bone in an Elderly Sample without Clinical Autoimmune Disease

PubMed Central

McEvoy, Mark; Kelly, Brian; Agnew, Linda; Walker, Frederick R.; Boyle, Michael

2018-01-01

Bone loss is characteristic of the ageing process and a common complication of many autoimmune diseases. Research has highlighted a potential role of autoantibodies in pathologic bone loss. The confounding effects of immunomodulatory drugs make it difficult to establish the contribution of autoantibodies amongst autoimmune disease sufferers. We attempted to examine the relationship between autoantibodies and bone mass in a population of 2812 elderly participants without clinical autoimmune disease. Serum samples were assayed for a panel of autoantibodies (anti-nuclear, extractable nuclear antigen, anti-neutrophil cytoplasmic, thyroid peroxidase, tissue transglutaminase, anti-cardiolipin, rheumatoid factor, and cyclic citrullinated peptide). Bone mass was measured using quantitative ultrasound (QUS) of the calcaneus. The relationship between each autoantibody and bone mass was determined using linear regression models. Anti-nuclear autoantibodies were the most prevalent, positive in approximately 11%, and borderline in roughly 23% of our sample. They were also the only autoantibody observed to be significantly associated with QUS index in the univariate analysis (n = 1628; r = −0.20; 95% CI: −0.40–0.00; p = 0.046). However, statistical significance was lost after adjustment for various other potential confounders. None of the other autoantibodies was associated with QUS index in either univariate or multivariate analysis. We are limited by the cross-sectional nature of the study and the low prevalence of autoantibodies in our nonclinical sample. PMID:29854851

Operculum bone carp (cyprinus carprio sp.) scaffold is a new potential xenograft material: a preliminary study

NASA Astrophysics Data System (ADS)

Kartiwa, A.; Abbas, B.; Pandansari, P.; Prahasta, A.; Nandini, M.; Fadhlillah, M.; Subroto, T.; Panigoro, R.

2017-02-01

Orbital floor fracture with extensive bone loss, would cause herniation of the orbital tissue into the maxillary sinus. Graft implantation should be done on the orbital fracture with extensive bone loss. Different types of grafts have their own characteristics and advantages. Xenograft has been widely studied for use in bone defects. This study was to investigate cyprinus carprio sp. opercula bone as a potential xenograft. The aim of this study was to investigate based on EDS chemical analysis using a ZAF Standardless Method of Quantitative Analysis (Oxide) and SEM examination conducted in the laboratory of Mathematics, Institute of Technology Bandung. Particularly the mass ratio of Ca and P (5.8/3:47), the result is 1.67. This is equivalent to the stoichiometric Hydroxyapatite (HA) (Aoki H, 1991, Science and medical applications of hydroxyapatite, Tokyo: Institute for Medical and Engineering, Tokyo Medical and Dental University). C N O that there is an element of protein/amino acid collagen compound, serves as a matrix together with HA. As shown in the SEM analysis that the matrix is a porous sheet-shaped (oval) that interconnect with each other, which is good scaffold. The pore is composed of large pores >200 microns and smaller pores between the large pores with a size smaller or equal to 10 microns that can serve for the attachment of osteoblast cell. In conclusion, Opercula bone carp (cyprinus carprio sp.) scaffold could be a new potential xenograft material.

Serum Albumin and Body Weight as Biomarkers for the Antemortem Identification of Bone and Gastrointestinal Disease in the Common Marmoset

PubMed Central

Baxter, Victoria K.; Shaw, Gillian C.; Sotuyo, Nathaniel P.; Carlson, Cathy S.; Olson, Erik J.; Zink, M. Christine; Mankowski, Joseph L.; Adams, Robert J.

2013-01-01

The increasing use of the common marmoset (Callithrix jacchus) in research makes it important to diagnose spontaneous disease that may confound experimental studies. Bone disease and gastrointestinal disease are two major causes of morbidity and mortality in captive marmosets, but currently no effective antemortem tests are available to identify affected animals prior to the terminal stage of disease. In this study we propose that bone disease and gastrointestinal disease are associated disease entities in marmosets and aim to establish the efficacy of several economical antemortem tests in identifying and predicting disease. Tissues from marmosets were examined to define affected animals and unaffected controls. Complete blood count, serum chemistry values, body weight, quantitative radiographs, and tissue-specific biochemical markers were evaluated as candidate biomarkers for disease. Bone and gastrointestinal disease were associated, with marmosets being over seven times more likely to have either concurrent bone and gastrointestinal disease or neither disease as opposed to lesions in only one organ system. When used in tandem, serum albumin <3.5 g/dL and body weight <325 g identified 100% of the marmosets affected with concurrent bone and gastrointestinal disease. Progressive body weight loss of 0.05% of peak body weight per day predicted which marmosets would develop disease prior to the terminal stage. Bone tissue-specific tests, such as quantitative analysis of radiographs and serum parathyroid hormone levels, were effective for distinguishing between marmosets with bone disease and those without. These results provide an avenue for making informed decisions regarding the removal of affected marmosets from studies in a timely manner, preserving the integrity of research results. PMID:24324827

Distinctive Tooth-Extraction Socket Healing: Bisphosphonate Versus Parathyroid Hormone Therapy

PubMed Central

Kuroshima, Shinichiro; Mecano, Rodan B.; Tanoue, Ryuichiro; Koi, Kiyono; Yamashita, Junro

2014-01-01

Background Patients with osteoporosis who receive tooth extractions are typically on either oral bisphosphonate or parathyroid hormone (PTH) therapy. Currently, the consequence of these therapies on hard- and soft-tissue healing in the oral cavity is not clearly defined. The aim of this study is to determine the differences in the therapeutic effect on tooth-extraction wound healing between bisphosphonate and PTH therapies. Methods Maxillary second molars were extracted in Sprague Dawley rats (n = 30), and either bisphosphonate (zoledronate [Zol]), PTH, or saline (vehicle control [VC]) was administered for 10 days (n = 10 per group). Hard-tissue healing was evaluated by microcomputed tomography and histomorphometric analyses. Collagen, blood vessels, inflammatory cell infiltration, and cathepsin K expression were assessed in soft tissue using immunohistochemistry, quantitative polymerase chain reaction, and immunoblotting. Results Both therapies significantly increased bone fill and suppressed vertical bone loss. However, considerably more devital bone was observed in the sockets of rats on Zol versus VC. Although Zol increased the numbers of blood vessels, the total blood vessel area in soft tissue was significantly smaller than in VC. PTH therapy increased osteoblastic bone formation and suppressed osteoclasts. PTH therapy promoted soft-tissue maturation by suppressing inflammation and stimulating collagen deposition. Conclusion Zoledronate therapy deters whereas PTH therapy promotes hard- and soft-tissue healing in the oral cavity, and both therapies prevent vertical bone loss. PMID:23688101

An open randomized controlled clinical trial to evaluate ridge preservation and repair using SocketKAP(™) and SocketKAGE(™) : part 2 - three-dimensional alveolar bone volumetric analysis of CBCT imaging.

PubMed

Abdelhamid, Alaa; Omran, Mostafa; Bakhshalian, Neema; Tarnow, Dennis; Zadeh, Homayoun H

2016-06-01

The aims of this study were (i) to evaluate the efficacy of ridge preservation and repair procedures involving the application of SocketKAP(™) and SocketKAGE(™) devices following tooth removal and (ii) to evaluate alveolar bone volumetric changes at 6 months post-extraction in intact sockets or those with facial wall dehiscence defects using 3-dimensional pre- and postoperative CBCT data. Thirty-six patients required 61 teeth extracted. Five cohorts were established: Group A: Intact Socket Negative Control Group B: Intact Socket + SocketKAP(™) Group C: Intact Socket Filled with Anorganic Bovine Bone Mineral (ABBM) + SocketKAP(™) Group D: Facial Dehiscence Socket Negative Control Group E: Facial Dehiscence Socket Filled with ABBM + SocketKAP(™) + SocketKAGE(™) . Preoperative CBCT scans were obtained followed by digital subtraction of the test teeth. At 6 months post-extraction, another CBCT scan was obtained. The pre- and postoperative scans were then superimposed, allowing highly accurate quantitative determination of the 3D volumetric alveolar bone volume changes from baseline through 6 months. Significant volumetric bone loss occurred in all sockets, localized mainly in the 0-3 mm zone apical to the ridge crest. For intact sockets, SocketKAP(™) + ABBM treatment led to a statistically significant greater percentage of remaining mineralized tissue volume when compared to negative control group. A significant difference favoring SocketKAP(™) + SocketKAGE(™) + ABBM treatment was observed for sockets with facial dehiscence defects compared to the negative control group. SocketKAP(™) , with ABBM, appears effective in limiting post-extraction volumetric bone loss in intact sockets, while SocketKAP(™) + SocketKAGE + ABBM appears effective in limiting post-extraction bone loss in sockets with dehiscence defects. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Experiment requirements: Vitamin D metabolites and bone demineralization, Spacelab 2, experiment no. 1

NASA Technical Reports Server (NTRS)

Schnoes, H. K.; Holton, E. M.; Thirolf, R. G.

1978-01-01

As a contribution toward an understanding of the molecular basis of bone loss, mineral imbalance, and increasing fecal calcium under conditions of prolonged space flight, the blood levels of biologically active vitamin D metabolites of flight crew members will be quantitatively measured. Prior to the mission, the refinement of existing and the development of new techniques for the assay of all vitamin D metabolites will provide an arsenal of methods suitable for a wide range of metabolite levels. In terms of practical application, the analysis of human and animal plasma samples, Spacelab crew plasma samples, and flight hardware are envisioned.

Marginal Bone Loss after Ten Years in an Adult Danish Population: A Radiographic Study.

PubMed

Bahrami, Golnosh; Vaeth, Michael; Wenzel, Ann; Isidor, Flemming

To evaluate marginal bone loss over a 10-year period in individuals and in tooth groups in relation to age and level of marginal bone. In 1997, 616 randomly selected individuals (mean age: 42 years, range: 21-63 years) underwent a full-mouth radiographic survey. In 2008, the survey was repeated in 362 of the same individuals (182 women and 180 men). The marginal bone level of each tooth was measured in mm from the cementoenamel junction to the marginal bone. These measurements were used to calculate marginal bone loss during the 10-year period for individuals and tooth groups in relation to age and to baseline marginal bone level, calculated as the average between measurements in 1997 and 2008 to circumvent regression towards the mean. The average annual marginal bone loss was 0.09 mm (SD ± 0.04 mm) during the 10-year study period. The association between marginal bone loss and baseline marginal bone level was more pronounced in the youngest age group, compared to the other age groups. Molars displayed the most severe bone loss during the study period. Marginal bone loss over a 10-year period is associated with age and baseline marginal bone level. Younger individuals with a reduced marginal bone level were at higher risk for further bone loss. Molars lose marginal bone more rapidly than other tooth groups.

Age-associated bone loss and intraskeletal variability in the Imperial Romans.

PubMed

Cho, Helen; Stout, Sam Darrel

2011-01-01

An Imperial Roman sample from the Isola Sacra necropolis (100-300 A.D.) offered an opportunity to histologically examine bone loss and intraskeletal variability in an urban archaeological population. Rib and femur samples were analyzed for static indices of bone remodeling and measures of bone mass. The Imperial Romans experienced normal age-associated bone loss via increased intracortical porosity and endosteal expansion, with females exhibiting greater bone loss and bone turnover rates than in males. Life events such as menopause and lactation coupled with cultural attitudes and practices regarding gender and food may have led to increased bone loss in females. Remodeling dynamics differ between the rib and femur and the higher remodeling rates in the rib may be attributed to different effective age of the adult compacta or loading environment. This study demonstrates that combining multiple methodologies to examine bone loss is necessary to shed light on the biocultural factors that influence bone mass and bone loss.

QUANTITATIVE PLUTONIUM MICRODISTRIBUTION IN BONE TISSUE OF VERTEBRA FROM A MAYAK WORKER

PubMed Central

Lyovkina, Yekaterina V.; Miller, Scott C.; Romanov, Sergey A.; Krahenbuhl, Melinda P.; Belosokhov, Maxim V.

2010-01-01

The purpose was to obtain quantitative data on plutonium microdistribution in different structural elements of human bone tissue for local dose assessment and dosimetric models validation. A sample of the thoracic vertebra was obtained from a former Mayak worker with a rather high plutonium burden. Additional information was obtained on occupational and exposure history, medical history, and measured plutonium content in organs. Plutonium was detected in bone sections from its fission tracks in polycarbonate film using neutron-induced autoradiography. Quantitative analysis of randomly selected microscopic fields on one of the autoradiographs was performed. Data included fission fragment tracks in different bone tissue and surface areas. Quantitative information on plutonium microdistribution in human bone tissue was obtained for the first time. From these data, quantitative relationship of plutonium decays in bone volume to decays on bone surface in cortical and trabecular fractions were defined as 2.0 and 0.4, correspondingly. The measured quantitative relationship of decays in bone volume to decays on bone surface does not coincide with recommended models for the cortical bone fraction by the International Commission on Radiological Protection. Biokinetic model parameters of extrapulmonary compartments might need to be adjusted after expansion of the data set on quantitative plutonium microdistribution in other bone types in human as well as other cases with different exposure patterns and types of plutonium. PMID:20838087

Microbiological outcome of two screw-shaped titanium implant systems placed following a split-mouth randomised protocol, at the 12th year of follow-up after loading.

PubMed

Van Assche, Nele; Pittayapat, Pisha; Jacobs, Reinhilde; Pauwels, Martine; Teughels, Wim; Quirynen, Marc

2011-01-01

To compare the subgingival microbiota around two differently designed implant systems that were in function for more than 12 years in a randomised split-mouth study design, and to compare the outcome with natural dentition. A total of 18 partially edentulous patients received at least two TiOblast™ (Astra Tech) and two Brånemark (Nobel Biocare) implants following a split-mouth design. At the last follow-up visit, periodontal parameters (probing depth, bleeding on probing and plaque) were recorded and intraoral radiographs were taken to calculate bone loss. Subgingival plaque samples were collected for culture, qPCR and checkerboard DNA-DNA hybridisation analysis. These data were related to implant design and bone loss. This study setup allowed a comparison of 34 Astra Tech (Impl A) with 32 Brånemark (Impl B) implants. During the 12-year follow up, five patients dropped out. One Brånemark implant was lost before abutment connection in a dropout patient. Mean bone loss between loading and year 12 was 0.7 mm (range: -0.8-5.8) (Impl A), and 0.4 mm (range: -1.1-4.1) (Impl B). No significant microbiological differences (qualitative and quantitative) could be observed between both implant types. Compared to teeth, subgingival plaque samples from implants did not reach the concentration of pathogens, even after 12 years of function. These data show that both implant systems (with differences in macro-design and surface characteristics), in patients with good oral hygiene and a stable periodontal condition, can maintain a successful treatment outcome without significant subgingival microbiological differences after 12 years of loading. The presence of periodontopathogens did not necessarily result in bone loss.

Measurement of Strain Distributions in Mouse Femora with 3D-Digital Speckle Pattern Interferometry

PubMed Central

Yang, Lianxiang; Zhang, Ping; Liu, Sheng; Samala, Praveen R; Su, Min; Yokota, Hiroki

2007-01-01

Bone is a mechanosensitive tissue that adapts its mass, architecture and mechanical properties to external loading. Appropriate mechanical loads offer an effective means to stimulate bone remodeling and prevent bone loss. A role of in situ strain in bone is considered essential in enhancement of bone formation, and establishing a quantitative relationship between 3D strain distributions and a rate of local bone formation is important. Digital speckle pattern interferometry (DSPI) can achieve whole-field, non-contacting measurements of microscopic deformation for high-resolution determination of 3D strain distributions. However, the current system does not allow us to derive accurate strain distributions because of complex surface contours inherent to biological samples. Through development of a custom-made piezoelectric loading device as well as a new DSPI-based force calibration system, we built an advanced DSPI system and integrated local contour information to deformation data. Using a mouse femur in response to a knee loading modality as a model system, we determined 3D strain distributions and discussed effectiveness and limitations of the described system. PMID:18670581

Low-dosage micronized 17 beta-estradiol prevents bone loss in postmenopausal women

NASA Technical Reports Server (NTRS)

Ettinger, B.; Genant, H. K.; Steiger, P.; Madvig, P.

1992-01-01

With the use of a double-blind, randomized, dose-ranging design, we tested during an 18-month period the degree of protection against postmenopausal bone loss afforded by micronized 17 beta-estradiol in dosages of 0.5, 1.0, and 2.0 mg. All subjects received supplementation to ensure a minimum of 1500 mg calcium daily. Fifty-one subjects completed at least 1 year of follow-up bone density measurements by quantitative computed tomography and by single- and dual-photon absorptiometry. In the placebo group spinal trabecular bone density decreased 4.9% annually (p less than 0.001), whereas in those taking micronized 17 beta-estradiol bone density tended to increase (annual increases of 0.3% in the 0.5 mg micronized 17 beta-estradiol group, 1.8% in the 1.0 mg micronized 17 beta-estradiol group, and 2.5% in the 2.0 mg micronized 17 beta-estradiol group). After completing the double-blind phase, 41 subjects completed an additional 18 months of follow-up while taking 1.0 mg micronized 17 beta-estradiol. During this time one third of the subjects were randomly assigned to discontinue calcium supplements. Among those who previously received placebo, trabecular bone density increased 4.3% annually, whereas among those who had used micronized 17 beta-estradiol, trabecular bone density response was inversely related to the dosage previously used. Additionally and independently, the level of calcium intake showed a statistically significant correlation with the change in spinal trabecular bone density (r = 0.37, p = 0.02). We conclude that micronized 17 beta-estradiol has a continuous skeletal dose-response effect in the range of 0.5 to 2.0 mg and that calcium intake positively modifies the skeletal response to 1.0 mg micronized 17 beta-estradiol.

Massive Bone Loss Due to Orchidectomy and Localized Disuse: Preventive Effects of a Biosphonsphonate

NASA Astrophysics Data System (ADS)

Libouban, H.; Moreau, M. F.; Chappard, D.

2008-06-01

Orchidectomy (ORX) and hindlimb paralysis induced by botulinum neurotoxin (BTX) were combined to see if their effects were cumulative and if bone loss could be prevented by an antiresorptive agent (risedronate) or testosterone. Four groups of mature rats were studied for 1 month: SHAM operated; ORX and right hindlimb immobilization (BTX); ORX+BTX+risedronate or testosterone. Bone loss and microarchitecture deterioration were maximized on the immobilized bone. Risedronate but not testosterone prevented trabecular bone loss but was less effective on cortical bone loss. ORX and BTX had additive effects on bone loss which can be prevented by risedronate but not testosterone.

Bed Rest and Immobilization: Risk Factors for Bone Loss

MedlinePlus

... Loss Bed Rest and Immobilization: Risk Factors for Bone Loss Like muscle, bone is living tissue that ... bones adjust to the state of weightlessness. Maintaining Bone Health In general, healthy people who undergo prolonged ...

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.

Systematic strength training as a model of therapeutic intervention. A controlled trial in postmenopausal women with osteopenia.

PubMed

Hartard, M; Haber, P; Ilieva, D; Preisinger, E; Seidl, G; Huber, J

1996-01-01

Physical exercise is often recommended as a therapeutic tool to combat pre- and postmenopausal loss of bone density. However, the relationship between training dosage (intensity, duration, frequency) and the effect on bone density still is undergoing discussion. Furthermore, the exercise quantification programs are often described so inadequately that they are neither quantitatively nor qualitatively reproducible. The aim of this investigation was to determine whether a clearly defined training of muscle strength, under defined safety aspects, performed only twice weekly, can counteract bone density loss in women with postmenopausal osteopenia. Data from 16 women in the training group (age, 63.6 +/- 6.2 yr) and 15 women in the control group (age, 67.4 +/-9.7 yr), of comparable height and weight, were evaluated. Strength training was performed for 6 mo as continually adapted strength training, providing an intensity of about 70% of each test person's one repetition maximum. Bone mineral density of lumbar vertebrae 2 to 4 and the femoral neck was measured by dual-energy x-ray absorptiometry. Maximum performance in watts and parameters of hemodynamics were controlled with a bicycle ergometer test to maximal effort. In addition, metabolic data were assessed. In the lumbar spine and femoral neck, the training group showed no significant changes, whereas the control group demonstrated a significant loss of bone mineral density, especially in the femoral neck (P<0.05). The strength increase was highly significant in all exercised muscle groups, rising to about 70% above the pretraining status (P<0.001). Heart rate and blood pressure data indicated a slight economization, metabolism was not significantly influenced. Based on these findings, we conclude that continually adapted strength training is an effective, safe, reproducible, and adaptable method of therapeutic strength training, following only two exercise sessions per week.

MRI-guided attenuation correction in whole-body PET/MR: assessment of the effect of bone attenuation.

PubMed

Akbarzadeh, A; Ay, M R; Ahmadian, A; Alam, N Riahi; Zaidi, H

2013-02-01

Hybrid PET/MRI presents many advantages in comparison with its counterpart PET/CT in terms of improved soft-tissue contrast, decrease in radiation exposure, and truly simultaneous and multi-parametric imaging capabilities. However, the lack of well-established methodology for MR-based attenuation correction is hampering further development and wider acceptance of this technology. We assess the impact of ignoring bone attenuation and using different tissue classes for generation of the attenuation map on the accuracy of attenuation correction of PET data. This work was performed using simulation studies based on the XCAT phantom and clinical input data. For the latter, PET and CT images of patients were used as input for the analytic simulation model using realistic activity distributions where CT-based attenuation correction was utilized as reference for comparison. For both phantom and clinical studies, the reference attenuation map was classified into various numbers of tissue classes to produce three (air, soft tissue and lung), four (air, lungs, soft tissue and cortical bones) and five (air, lungs, soft tissue, cortical bones and spongeous bones) class attenuation maps. The phantom studies demonstrated that ignoring bone increases the relative error by up to 6.8% in the body and up to 31.0% for bony regions. Likewise, the simulated clinical studies showed that the mean relative error reached 15% for lesions located in the body and 30.7% for lesions located in bones, when neglecting bones. These results demonstrate an underestimation of about 30% of tracer uptake when neglecting bone, which in turn imposes substantial loss of quantitative accuracy for PET images produced by hybrid PET/MRI systems. Considering bones in the attenuation map will considerably improve the accuracy of MR-guided attenuation correction in hybrid PET/MR to enable quantitative PET imaging on hybrid PET/MR technologies.

Horizontal alveolar bone loss: A periodontal orphan

PubMed Central

Jayakumar, A.; Rohini, S.; Naveen, A.; Haritha, A.; Reddy, Krishnanjeneya

2010-01-01

Background: Attempts to successfully regenerate lost alveolar bone have always been a clinician’s dream. Angular defects, at least, have a fairer chance, but the same cannot be said about horizontal bone loss. The purpose of the present study was to evaluate the prevalence of horizontal alveolar bone loss and vertical bone defects in periodontal patients; and later, to correlate it with the treatment modalities available in the literature for horizontal and vertical bone defects. Materials and Methods: The study was conducted in two parts. Part I was the radiographic evaluation of 150 orthopantomographs (OPGs) (of patients diagnosed with chronic periodontitis and seeking periodontal care), which were digitized and read using the AutoCAD 2006 software. All the periodontitis-affected teeth were categorized as teeth with vertical defects (if the defect angle was ≤45° and defect depth was ≥3 mm) or as having horizontal bone loss. Part II of the study comprised search of the literature on treatment modalities for horizontal and vertical bone loss in four selected periodontal journals. Results: Out of the 150 OPGs studied, 54 (36%) OPGs showed one or more vertical defects. Totally, 3,371 teeth were studied, out of which horizontal bone loss was found in 3,107 (92.2%) teeth, and vertical defects were found only in 264 (7.8%) of the teeth, which was statistically significant (P<.001). Search of the selected journals revealed 477 papers have addressed the treatment modalities for vertical and horizontal types of bone loss specifically. Out of the 477 papers, 461 (96.3%) have addressed vertical bone loss, and 18 (3.7%) have addressed treatment options for horizontal bone loss. Two papers have addressed both types of bone loss and are included in both categories. Conclusion: Horizontal bone loss is more prevalent than vertical bone loss but has been sidelined by researchers as very few papers have been published on the subject of regenerative treatment modalities for this type of bone loss. This study should be an impetus for greater attention to an otherwise ubiquitous periodontal challenge. PMID:21760673

Factors Associated with Bone Health in Malaysian Middle-Aged and Elderly Women Assessed via Quantitative Ultrasound.

PubMed

Chin, Kok-Yong; Low, Nie Yen; Dewiputri, Wan Ilma; Ima-Nirwanaa, Soelaiman

2017-07-06

Risk factors for osteoporosis may vary according to different populations. We aimed to investigate the relationship between risk factors of osteoporosis and bone health indices determined via calcaneal quantitative ultrasound (QUS) in a group of Malaysian women aged 50 years or above. A cross-sectional study was performed on 344 Malaysian women recruited from a tertiary medical centre in Kuala Lumpur, Malaysia. They answered a self-administered questionnaire on their social-demographic details, medical history, lifestyle, and physical activity status. Their height was measured using a stadiometer, and their body composition estimated using a bioelectrical impedance device. Their bone health status was determined using a water-based calcaneal QUS device that generated three indices, namely speed of sound (SOS), broadband ultrasound attenuation (BUA), and stiffness index (SI). A T-score was computed from SI values using a reference database from a mainland Chinese population. Women with three or more lifetime pregnancies, who were underweight and not drinking coffee had a significantly lower BUA. Stepwise multiple linear regression showed that SOS was predicted by age alone, BUA and SI by years since menopause, body mass index (BMI), and number of lifetime pregnancies, and T-score by years since menopause and percentage of body fat. As a conclusion, suboptimal bone health in middle-aged and elderly Malaysian women as indicated by QUS is associated with old age, being underweight, having a high body fat percentage, and a high number of lifetime pregnancies. Women having several risk factors should be monitored more closely to protect their bones against accelerated bone loss.

Autoradiographic method for quantitation of deposition and distribution of radiocalcium in bone

PubMed Central

Lawrence Riggs, B; Bassingthwaighte, James B.; Jowsey, Jenifer; Peter Pequegnat, E

2010-01-01

A method is described for quantitating autoradiographs of bone-seeking isotopes in microscopic sections of bone. Autoradiographs of bone sections containing 45Ca and internal calibration standards are automatically scanned with a microdensitometer. The digitized optical density output is stored on magnetic tape and is converted by computer to equivalent activity of 45Ca per gram of bone. The computer determines the total 45Ca uptake in the bone section and, on the basis of optical density and anatomic position, quantitatively divides the uptake into 4 components, each representing a separate physiologic process (bone formation, secondary mineralization, diffuse long-term exchange, and surface short-term exchange). The method is also applicable for quantitative analysis of microradiographs of bone sections for mineral content and density. PMID:5416906

Regulation of bone mineral loss during lactation

NASA Technical Reports Server (NTRS)

Brommage, R.; Deluca, H. F.

1985-01-01

The effects of varyng dietary calcium and phosphorous levels, vitamin D deficiency, oophorectomy, adrenalectomy, and simultaneous pregnancy on bone mineral loss during lactation in rats are studied. The experimental procedures and evaluations are described. The femur ash weight of lactating and nonlactating rats are calculated. The data reveals that a decrease in dietary calcium of 0.02 percent results in an increased loss of bone mineral, an increase in calcium to 1.4 percent does not lessen bone mineral loss, and bone mineral loss in vitamin D deficient rats is independent of calcium levels. It is observed that changes in dietary phosphorous level, oophorectomy, adrenalectomy, and simultaneous pragnancy do not reduce bone mineral loss during lactation. The analysis of various hormones to determine the mechanism that triggers bone mineral loss during lactation is presented.

Amount of bone loss in relation to time around the final menstrual period and follicle-stimulating hormone staging of the transmenopause.

PubMed

Sowers, MaryFran R; Zheng, Huiyong; Jannausch, Mary L; McConnell, Daniel; Nan, Bin; Harlow, Sioban; Randolph, John F

2010-05-01

The objective of the study was to describe bone loss rates across the transmenopause related to FSH staging and the final menstrual period (FMP). This was a population-based cohort of 629 women (baseline age 24-44 yr) with annual data points over 15 yr. Measures were bone mineral density (BMD), FSH to define four FSH stages, and menstrual bleeding cessation to define the FMP. Bone loss rates were reported by obesity status. Annualized rates of lumbar spine bone loss began in FSH stage 3, which occurs approximately 2 yr prior to the FMP (1.67%/yr); bone loss continued into FSH stage 4 (1.21%/yr). Mean spine BMD in FSH stage 4 was 6.4% less than spine BMD value in FSH stage 1. Annualized rates of femoral neck (FN) bone loss began in FSH stage 3 (0.55%/yr) and continued into FSH stage 4 (0.72%/yr). The FN difference between mean values in FSH stage 1 and FSH stage 4 was 5%. Annualized rates of spine bone loss in the 2 yr prior to the FMP were 1.7%/yr, 3.3%/yr in the 2 yr after the FMP, and 1.1%/yr in the 2- to 7-yr period after the FMP. Nonobese women had lower BMD levels and greater bone loss rates. Spine and FN bone loss accelerates in FSH stage 3. Bone loss also began to accelerate 2 yr before the FMP with the greatest loss occurring in the 2 yr after the FMP. Bone loss rates in both spine and FN BMD were greater in nonobese women than obese women.

Bone loss of vertebral bodies at the operative segment after cervical arthroplasty: a potential complication?

PubMed

Heo, Dong Hwa; Lee, Dong Chan; Oh, Jong Yang; Park, Choon Keun

2017-02-01

OBJECTIVE Bony overgrowth and spontaneous fusion are complications of cervical arthroplasty. In contrast, bone loss or bone remodeling of vertebral bodies at the operation segment after cervical arthroplasty has also been observed. The purpose of this study is to investigate a potential complication-bone loss of the anterior portion of the vertebral bodies at the surgically treated segment after cervical total disc replacement (TDR)-and discuss the clinical significance. METHODS All enrolled patients underwent follow-up for more than 24 months after cervical arthroplasty using the Baguera C disc. Clinical evaluations included recording demographic data and measuring the visual analog scale and Neck Disability Index scores. Radiographic evaluations included measurements of the functional spinal unit's range of motion and changes such as bone loss and bone remodeling. The grading of the bone loss of the operative segment was classified as follows: Grade 1, disappearance of the anterior osteophyte or small minor bone loss; Grade 2, bone loss of the anterior portion of the vertebral bodies at the operation segment without exposure of the artificial disc; or Grade 3, significant bone loss with exposure of the anterior portion of the artificial disc. RESULTS Forty-eight patients were enrolled in this study. Among them, bone loss developed in 29 patients (Grade 1 in 15 patients, Grade 2 in 6 patients, and Grade 3 in 8 patients). Grade 3 bone loss was significantly associated with postoperative neck pain (p < 0.05). Bone loss was related to the motion preservation effect of the operative segment after cervical arthroplasty in contrast to heterotopic ossification. CONCLUSIONS Bone loss may be a potential complication of cervical TDR and affect early postoperative neck pain. However, it did not affect mid- to long-term clinical outcomes or prosthetic failure at the last follow-up. Also, this phenomenon may result in the motion preservation effect in the operative segment after cervical TDR.

Bone, body weight, and weight reduction: what are the concerns?

PubMed

Shapses, Sue A; Riedt, Claudia S

2006-06-01

Of the U.S. population, 65% is either overweight or obese, and weight loss is recommended to reduce co-morbid conditions. However, bone mobilization and loss may also occur with weight loss. The risk for bone loss depends on initial body weight, age, gender, physical activity, and conditions of dieting such as the extent of energy restriction and specific levels of nutrient intake. Older populations are more prone to bone loss with weight loss; in women, this is due at least in part to a reduced dietary Ca intake and/or efficiency of absorption. Potential hormonal mechanisms regulating bone loss during weight loss are discussed, including decreases in estrogen, leptin, glucagon-like peptide-2, growth hormone, and insulin-like growth factor-1, or an increase in cortisol. In contrast, the rise in adiponectin and ghrelin with weight reduction should not be detrimental to bone. Combining energy restriction with exercise does not necessarily prevent bone loss, but may attenuate loss as was shown with additional Ca intake or osteoporosis medications. Future controlled weight loss trials should be designed to further address mechanisms influencing the density and quality of bone sites vulnerable to fracture, in the prevention of osteoporosis.

Sostdc1 deficiency accelerates fracture healing by promoting the expansion of periosteal mesenchymal stem cells [Sostdc1 Participates in Bone Maintenance and Fracture Repair

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

Collette, Nicole M.; Yee, Cristal S.; Hum, Nicholas R.

Loss of Sostdc1, a growth factor paralogous to Sost, causes the formation of ectopic incisors, fused molars, abnormal hair follicles, and resistance to kidney disease. Sostdc1 is expressed in the periosteum, a source of osteoblasts, fibroblasts and mesenchymal progenitor cells, which are critically important for fracture repair. Here, we investigated the role of Sostdc1 in bone metabolism and fracture repair. Mice lacking Sostdc1 ( Sostdc1 –/–) had a low bone mass phenotype associated with loss of trabecular bone in both lumbar vertebrae and in the appendicular skeleton. In contrast, Sostdc1 –/– cortical bone measurements revealed larger bones with higher BMD,more » suggesting that Sostdc1 exerts differential effects on cortical and trabecular bone. Mid-diaphyseal femoral fractures induced in Sostdc1 –/– mice showed that the periosteal population normally positive for Sostdc1 rapidly expands during periosteal thickening and these cells migrate into the fracture callus at 3 days post fracture. Quantitative analysis of mesenchymal stem cell (MSC) and osteoblast populations determined that MSCs express Sostdc1, and that Sostdc1 –/– 5 day calluses harbor > 2-fold more MSCs than fractured wildtype controls. Histologically a fraction of Sostdc1-positive cells also expressed nestin and α-smooth muscle actin, suggesting that Sostdc1 marks a population of osteochondral progenitor cells that actively participate in callus formation and bone repair. Elevated numbers of MSCs in D5 calluses resulted in a larger, more vascularized cartilage callus at day 7, and a more rapid turnover of cartilage with significantly more remodeled bone and a thicker cortical shell at 21 days post fracture. In conclusion, these data support accelerated or enhanced bone formation/remodeling of the callus in Sostdc1 –/– mice, suggesting that Sostdc1 may promote and maintain mesenchymal stem cell quiescence in the periosteum.« less

Sostdc1 deficiency accelerates fracture healing by promoting the expansion of periosteal mesenchymal stem cells [Sostdc1 Participates in Bone Maintenance and Fracture Repair

DOE PAGES

Collette, Nicole M.; Yee, Cristal S.; Hum, Nicholas R.; ...

2016-04-19

Loss of Sostdc1, a growth factor paralogous to Sost, causes the formation of ectopic incisors, fused molars, abnormal hair follicles, and resistance to kidney disease. Sostdc1 is expressed in the periosteum, a source of osteoblasts, fibroblasts and mesenchymal progenitor cells, which are critically important for fracture repair. Here, we investigated the role of Sostdc1 in bone metabolism and fracture repair. Mice lacking Sostdc1 ( Sostdc1 –/–) had a low bone mass phenotype associated with loss of trabecular bone in both lumbar vertebrae and in the appendicular skeleton. In contrast, Sostdc1 –/– cortical bone measurements revealed larger bones with higher BMD,more » suggesting that Sostdc1 exerts differential effects on cortical and trabecular bone. Mid-diaphyseal femoral fractures induced in Sostdc1 –/– mice showed that the periosteal population normally positive for Sostdc1 rapidly expands during periosteal thickening and these cells migrate into the fracture callus at 3 days post fracture. Quantitative analysis of mesenchymal stem cell (MSC) and osteoblast populations determined that MSCs express Sostdc1, and that Sostdc1 –/– 5 day calluses harbor > 2-fold more MSCs than fractured wildtype controls. Histologically a fraction of Sostdc1-positive cells also expressed nestin and α-smooth muscle actin, suggesting that Sostdc1 marks a population of osteochondral progenitor cells that actively participate in callus formation and bone repair. Elevated numbers of MSCs in D5 calluses resulted in a larger, more vascularized cartilage callus at day 7, and a more rapid turnover of cartilage with significantly more remodeled bone and a thicker cortical shell at 21 days post fracture. In conclusion, these data support accelerated or enhanced bone formation/remodeling of the callus in Sostdc1 –/– mice, suggesting that Sostdc1 may promote and maintain mesenchymal stem cell quiescence in the periosteum.« less

A study on OPG/RANK/RANKL axis in osteoporotic bile duct-ligated rats and the involvement of nitrergic and opioidergic systems.

PubMed

Doustimotlagh, Amir Hossein; Dehpour, Ahmad Reza; Etemad-Moghadam, Shahroo; Alaeddini, Mojgan; Ostadhadi, Sattar; Golestani, Abolfazl

2018-06-01

Chronic liver disease (CLD) affects millions of people and its impact on bone loss has become a subject of interest. Nitric oxide and endogenous opioids are suggested to increase during cholestasis/cirrhosis and may impact bone resorption by different mechanisms. The receptor activator of nuclear factor-κB (RANK)/RANK-ligand (RANKL)/osteoprotegerin (OPG) signaling pathway regulates bone resorption, but its role in metabolic bone disease subsequent to CLD is unknown. We aimed to investigate the involvement of nitrergic and opioidergic systems in bone loss relative to the RANK/RANKL/OPG pathway, in bile duct-ligated (BDL) rats. Eighty BDL/sham-operated (SO) rats received injections of 3 mg/kg/day Nω-Nitro-L-arginine methyl ester ± naltrexone (10 mg/kg/day) or saline for 28 days. Plasma bone turnover markers, OPG, RANK, and RANKL along with mRNA expression levels of the latter three were assessed. Plasma bone turnover markers and OPG level increased, but RANKL decreased in the BDL group compared with their SO controls (both: P ≤ 0.05). Administration of naltrexone reduced bone turnover markers and OPG level while increased RANKL content in comparison to BDL rats ( P ≤ 0.05). As compared to untreated BDL rats, nitric oxide inhibition showed no effect on bone turnover marker i.e. OPG, RANK, and RANKL levels. BDL significantly increased RANK mRNA, but had no significant effect on RANKL and OPG mRNA expression. The lack of association between plasma levels and quantitative gene expression of RANKL and OPG suggests an indirect function of these markers in BDL rats. Considering that opioid receptor blockage by naltrexone in BDL animals caused a significant decrease in OPG and an increase in RANKL plasma contents, it could be postulated that the opioidergic system may have a regulatory effect on these bone markers.

The Effects of Partial Mechanical Loading and Ibandronate on Skeletal Tissues in the Adult Rat Hindquarter Suspension Model for Microgravity

NASA Technical Reports Server (NTRS)

Schultheis, Lester W.

1999-01-01

We report initial data from a suspended rat model that quantitatively relates chronic partial weightbearing to bone loss. Chronic partial weightbearing is our simulation of the effect of limited artificial gravity aboard spacecraft or reduced planetary gravity. Preliminary analysis of bone by PQCT, histomorphometry, mechanical testing and biochemistry suggest that chronic exposure to half of Earth gravity is insufficient to prevent severe bone loss. The effect of episodic full weightbearing activity (Earth Gravity) on rats otherwise at 50% weightbearing was also explored. This has similarity to treatment by an Earth G-rated centrifuge on a spacecraft that normally maintained artificial gravity at half of Earth G. Our preliminary evidence, using the above techniques to analyze bone, indicate that 2 hours daily of full weightbearing was insufficient to prevent the bone loss observed in 50% weightbearing animals. The effectiveness of partial weightbearing and episodic full weightbearing as potential countermeasures to bone loss in spaceflight was compared with treatment by ibandronate. Ibandronate, a long-acting potent bisphosphonate proved more effective in preventing bone loss and associated functionality based upon structure than our first efforts at mechanical countermeasures. The effectiveness of ibandronate was notable by each of the testing methods we used to study bone from gross structure and strength to tissue and biochemistry. These results appear to be independent of generalized systemic stress imposed by the suspension paradigm. Preliminary evidence does not suggest that blood levels of vitamin D were affected by our countermeasures. Despite the modest theraputic benefit of mechanical countermeasures of partial weightbearing and episodic full weightbearing, we know that some appropriate mechanical signal maintains bone mass in Earth gravity. Moreover, the only mechanism that correctly assigns bone mass and strength to oppose regionally specific force applied to bone is mechanical, a process based upon bone strain. Substantial evidence indicates that the specifics of dynamic loading i.e. time-varying forces are critical. Bone strain history is a predictor of the effect that mechanical conditions have on bone structure mass and strength. Using servo-controlled force plates on suspended rats with implanted strain gauges we manipulated impact forces of ambulation in the frequency (Fourier) domain. Our results indicate that high frequency components of impact forces are particularly potent in producing bone strain independent of the magnitude of the peak force or peak energy applied to the leg. Because a servo-system responds to forces produced by the rat's own muscle activity during ambulation, the direction of ground-reaction loads act on bone through the rat's own musculature. This is in distinction to passive vibration of the floor where forces reach bone through the natural filters of soft tissue and joints. Passive vibration may also be effective, but it may or may not increase bone in the appropriate architectural pattern to oppose the forces of normal ambulatory activity. Effectiveness of high frequency mechanical stimulation in producing regional (muscle directed) bone response will be limited by 1. the sensitivity of bone to a particular range of frequencies and 2. the inertia of the muscles, limiting their response to external forces by increasing tension along insertions. We have begun mathematical modeling of normal ambulatory activity. Effectiveness of high frequency mechanical stimulation in producing regional (muscle directed) bone response will be limited by 1. the sensitivity of bone to a particular range of frequencies and 2. the inertia of the muscles, limiting their response to external forces by increasing tension along insertions. We have begun mathematical modeling of the rat forelimb as a transfer function between impact force and bone strain to predict optimal dynamic loading conditions for this system. We plan additional studies of mechanical counter-measures that incorporate improved dynamic loading, features relevant to anticipated evaluation of artificial gravity, exercise regimens and exposure to Martian gravity, The combination of mechanical countermeasures with ibandronate will also be investigated for signs of synergy.

Non-Invasive Investigation of Bone Adaptation in Humans to Mechanical Loading

NASA Technical Reports Server (NTRS)

Whalen, R.

1999-01-01

Experimental studies have identified peak cyclic forces, number of loading cycles, and loading rate as contributors to the regulation of bone metabolism. We have proposed a theoretical model that relates bone density to a mechanical stimulus derived from average daily cumulative peak cyclic 'effective' tissue stresses. In order to develop a non-invasive experimental model to test the theoretical model we need to: (1) monitor daily cumulative loading on a bone, (2) compute the internal stress state(s) resulting from the imposed loading, and (3) image volumetric bone density accurately, precisely, and reproducibly within small contiguous volumes throughout the bone. We have chosen the calcaneus (heel) as an experimental model bone site because it is loaded by ligament, tendon and joint contact forces in equilibrium with daily ground reaction forces that we can measure; it is a peripheral bone site and therefore more easily and accurately imaged with computed tomography; it is composed primarily of cancellous bone; and it is a relevant site for monitoring bone loss and adaptation in astronauts and the general population. This paper presents an overview of our recent advances in the areas of monitoring daily ground reaction forces, biomechanical modeling of the forces on the calcaneus during gait, mathematical modeling of calcaneal bone adaptation in response to cumulative daily activity, accurate and precise imaging of the calcaneus with quantitative computed tomography (QCT), and application to long duration space flight.

Longitudinal study of bone loss in pre- and perimenopausal women: evidence for bone loss in perimenopausal women.

PubMed

Chapurlat, R D; Garnero, P; Sornay-Rendu, E; Arlot, M E; Claustrat, B; Delmas, P D

2000-01-01

Bone loss before and around the time of menopause is not well characterized by longitudinal studies. We measured bone mineral density at various skeletal sites--total body, femoral neck, trochanter, anteroposterior (AP) and lateral spine, and forearm--with dual-energy X-ray absorptiometry in a large prospective cohort of 272 untreated pre- and perimenopausal women aged 31-59 years, at 1 year intervals for 3 years. Sex steroids and the following markers of bone remodeling were measured: serum osteocalcin (OC), procollagen I carboxyterminal extension peptide, bone alkaline phosphatase (BAP) and urinary crosslinks (CTX and NTX). Seventy-six women were classified as perimenopausal and 196 as premenopausal. Over the 3 years, premenopausal women had no significant bone loss at any site and a small but significant increase in bone mineral density at the trochanter, total hip, AP spine and radius. Perimenopausal women significantly lost bone from cancellous and cortical sites, i.e., the femoral neck, trochanter and lumbar spine. In perimenopausal women with increased follicle stimulating hormone, the rate of bone loss at the femoral neck correlated negatively with OC and BAP. In perimenopausal women, serum estradiol levels decreased during the 3 years of follow-up and bone loss from the trochanter and the AP spine was correlated with serum estradiol after 3 years. In conclusion, among premenopausal women there is no bone loss. In contrast, there is a rapid and diffuse bone loss in perimenopausal women, related to decreased estrogen secretion. Bone markers may be useful to identify these women losing bone.

The Triple Functions of D2 Silencing in Treatment of Periapical Disease.

PubMed

Pan, Jie; Wang, Jue; Hao, Liang; Zhu, Guochun; Nguyen, Diep N; Li, Qian; Liu, Yuehua; Zhao, Zhihe; Li, Yi-Ping; Chen, Wei

2017-02-01

Dental caries is the most widespread chronic infectious disease. Inflammation in pulp tissues caused by dental caries will lead to periapical granulomas, bone erosion, loss of the tooth, and severe pain. Despite numerous efforts in recent studies to develop effective treatments for dental caries, the need for a potent therapy is still urgent. In this study, we applied a gene-based therapy approach by administering recombinant adeno-associated virus (AAV)-mediated Atp6v0d2 (d2) RNA interference knockdown of d2 gene expression to prevent periapical bone loss and suppress periapical inflammation simultaneously. The results showed that d2 depletion is simultaneously capable of reducing bone resorption with 75% protection through reducing osteoclasts, enhancing bone formation by increasing osterix expression, and inhibiting inflammation by decreasing T-cell infiltration. Notably, AAV-mediated gene therapy of d2 knockdown significantly reduced proinflammatory cytokine expression, including tumor necrosis factor α, interferon-γ, interleukin-1α, and interleukin 6 levels in periapical diseases caused by bacterial infection. Quantitative real-time polymerase chain reaction revealed that d2 knockdown reduced osteoclast-specific functional genes (ie, Acp5 and Ctsk) and increased osteoblast marker genes (ie, Osx and Opg) in periapical tissues. Collectively, our results showed that AAV-mediated d2 depletion in the periapical lesion area can prevent the progression of endodontic disease and bone erosion while significantly reducing the inflammatory over-response. These findings show that the depletion of d2 simultaneously reduces bone resorption, enhances bone formation, and inhibits inflammation caused by periapical diseases and provide significant insights into the potential effectiveness of AAV-sh-d2-mediated d2 silencing gene therapy as a major endodontic treatment. Copyright © 2016. Published by Elsevier Inc.

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

USDA-ARS?s Scientific Manuscript database

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 prote...

Contribution of Serum Inflammatory Markers to Changes in Bone Mineral Content and Density in Postmenopausal Women: A 1-Year Investigation

PubMed Central

Gertz, ER; Silverman, NE; Wise, KS; Hanson, KB; Alekel, DL; Stewart, JW; Perry, CD; Bhupathiraju, SN; Kohut, ML; Van Loan, MD

2010-01-01

Bone formation and resorption are influenced by inflammatory processes. We examined the relationships among inflammatory markers and bone mineral content and density (BMC, BMD) and determined the contribution of inflammatory markers to 1-year changes in BMC and BMD in healthy postmenopausal women. This analysis included 242 women at baseline from our parent Soy Isoflavones for Reducing Bone Loss (SIRBL) project who were randomly assigned to one of three treatment groups: placebo, 80 mg/d soy isoflavones, or 120 mg/d soy isoflavones. BMD and BMC from the lumbar spine (LS), total proximal femur (hip), and whole body were measured by dual energy x-ray absorptiometry (DXA) and the 4% distal tibia (DT) by peripheral quantitative computed tomography (pQCT). Serum inflammatory markers (C-reactive protein (CRP), interleukin (IL)-1β, IL-6, tumor necrosis factor-alpha (TNF-α), and white blood cell count (WBC)) were measured at baseline, 6 and 12 months. Due to attrition or missing values, data analysis at 12 months includes only 235 women. Significant associations among Il-6, TNF-α, and WBC were observed with percent change in LS, hip, and whole body BMC and BMD. Multiple regression analysis indicated that in combination inflammatory markers accounted for 1.1% to 6.1% of the variance to the observed 12 month changes in BMC and BMD. Our results suggest that modifying inflammatory markers, even in healthy postmenopausal women, may possibly reduce bone loss. PMID:20605499

Grizzly bears (Ursus arctos horribilis) and black bears (Ursus americanus) prevent trabecular bone loss during disuse (hibernation).

PubMed

McGee-Lawrence, Meghan E; Wojda, Samantha J; Barlow, Lindsay N; Drummer, Thomas D; Castillo, Alesha B; Kennedy, Oran; Condon, Keith W; Auger, Janene; Black, Hal L; Nelson, O Lynne; Robbins, Charles T; Donahue, Seth W

2009-12-01

Disuse typically causes an imbalance in bone formation and bone resorption, leading to losses of cortical and trabecular bone. In contrast, bears maintain balanced intracortical remodeling and prevent cortical bone loss during disuse (hibernation). Trabecular bone, however, is more detrimentally affected than cortical bone in other animal models of disuse. Here we investigated the effects of hibernation on bone remodeling, architectural properties, and mineral density of grizzly bear (Ursus arctos horribilis) and black bear (Ursus americanus) trabecular bone in several skeletal locations. There were no differences in bone volume fraction or tissue mineral density between hibernating and active bears or between pre- and post-hibernation bears in the ilium, distal femur, or calcaneus. Though indices of cellular activity level (mineral apposition rate, osteoid thickness) decreased, trabecular bone resorption and formation indices remained balanced in hibernating grizzly bears. These data suggest that bears prevent bone loss during disuse by maintaining a balance between bone formation and bone resorption, which consequently preserves bone structure and strength. Further investigation of bone metabolism in hibernating bears may lead to the translation of mechanisms preventing disuse-induced bone loss in bears into novel treatments for osteoporosis.

Grizzly bears (Ursus arctos horribilis) and black bears (Ursus americanus) prevent trabecular bone loss during disuse (hibernation)

PubMed Central

McGee-Lawrence, Meghan E.; Wojda, Samantha J.; Barlow, Lindsay N.; Drummer, Thomas D.; Castillo, Alesha B.; Kennedy, Oran; Condon, Keith W.; Auger, Janene; Black, Hal L.; Nelson, O. Lynne; Robbins, Charles T.; Donahue, Seth W.

2009-01-01

Disuse typically causes an imbalance in bone formation and bone resorption, leading to losses of cortical and trabecular bone. In contrast, bears maintain balanced intracortical remodeling and prevent cortical bone loss during disuse (hibernation). Trabecular bone, however, is more detrimentally affected than cortical bone in other animal models of disuse. Here we investigated the effects of hibernation on bone remodeling, architectural properties, and mineral density of grizzly bear (Ursus arctos horribilis) and black bear (Ursus americanus) trabecular bone in several skeletal locations. There were no differences in bone volume fraction or tissue mineral density between hibernating and active bears or between pre- and post-hibernation bears in the ilium, distal femur, or calcaneus. Though indices of cellular activity level (mineral apposition rate, osteoid thickness) decreased, trabecular bone resorption and formation indices remained balanced in hibernating grizzly bears. These data suggest that bears prevent bone loss during disuse by maintaining a balance between bone formation and bone resorption, which consequently preserves bone structure and strength. Further investigation of bone metabolism in hibernating bears may lead to the translation of mechanisms preventing disuse induced bone loss in bears into novel treatments for osteoporosis. PMID:19703606

Male Astronauts Have Greater Bone Loss and Risk of Hip Fracture Following Long Duration Spaceflights than Females

NASA Technical Reports Server (NTRS)

Ellman, Rachel; Sibonga, Jean; Bouxsein, Mary

2010-01-01

This slide presentation reviews bone loss in males and compares it to female bone loss during long duration spaceflight. The study indicates that males suffer greater bone loss than females and have a greater risk of hip fracture. Two possible reason for the greater male bone loss are that the pre-menopausal females have the estrogen protection and the greater strength of men max out the exercise equipment that provide a limited resistance to 135 kg.

Anabolic Steroids as a Novel Therapeutic Strategy for the Prevention of Bone Loss after Spinal Cord Injury: Animal Model and Molecular Mechanism

DTIC Science & Technology

2012-10-01

bone loss. At present, there is no practical treatment to delay or prevent bone loss in individuals with motor-complete SCI. Hypogonadism is common...TERMS- Spinal cord injuries, Nandrolone, Androgens, Hypogonadism , Bone loss, Wnt signaling 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF...At present, there is no practical treatment to delay or prevent bone loss in individuals with motor-complete SCI. Hypogonadism is common in men

Presence, location, type and size of denuded areas of subchondral bone in the knee as a function of radiographic stage of OA - data from the OA initiative.

PubMed

Frobell, R B; Wirth, W; Nevitt, M; Wyman, B T; Benichou, O; Dreher, D; Davies, R Y; Lee, J H; Baribaud, F; Gimona, A; Hudelmaier, M; Cotofana, S; Eckstein, F

2010-05-01

To assess the presence, location, type and size of denuded areas of subchondral bone (dAB) in the femorotibial joint, measured quantitatively with 3T MRI, in a large subset of OAI participants. One knee of 633 subjects (250 men, 383 women, aged 61.7+/-9.6 y) were studied, spanning all radiographic osteoarthritis (OA) stages. dABs were determined quantitatively using segmentations of coronal FLASHwe images, representing areas where the subchondral bone was not covered by cartilage. Post hoc visual examination of segmented images determined whether dABs represented full thickness cartilage loss or internal osteophyte. 7% Of the knees were Kellgren & Lawrence (KL) grade 0, 6% grade 1, 41% grade 2, 41% grade 3, and 5% grade 4. 39% Of the participants (48% of the men and 33% of the women) displayed dABs; 61% of the dABs represented internal osteophytes. 1/47 Participants with KL grade 0 displayed 'any' dAB whereas 29/32 of the KL grade 4 knees were affected. Even as early as KL grade 1, 29% of the participants showed dABs. There were significant relationships of dAB with increasing KL grades (P<0.001) and with ipsi-compartimental JSN (P< or =0.001). Internal osteophytes were more frequent laterally (mainly posterior tibia and internal femur) whereas full thickness cartilage loss was more frequent medially (mainly external tibia and femur). dABs occur already at earliest stages of radiographic OA (KL grades 1 and 2) and become more common (and larger) with increasing disease severity. Almost all KL grade 4 knees exhibited dABs, with cartilage loss being more frequent than internal osteophytes. Copyright 2010 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Skeletal health in long-duration astronauts: nature, assessment, and management recommendations from the NASA Bone Summit.

PubMed

Orwoll, Eric S; Adler, Robert A; Amin, Shreyasee; Binkley, Neil; Lewiecki, E Michael; Petak, Steven M; Shapses, Sue A; Sinaki, Mehrsheed; Watts, Nelson B; Sibonga, Jean D

2013-06-01

Concern about the risk of bone loss in astronauts as a result of prolonged exposure to microgravity prompted the National Aeronautics and Space Administration to convene a Bone Summit with a panel of experts at the Johnson Space Center to review the medical data and research evidence from astronauts who have had prolonged exposure to spaceflight. Data were reviewed from 35 astronauts who had served on spaceflight missions lasting between 120 and 180 days with attention focused on astronauts who (1) were repeat fliers on long-duration missions, (2) were users of an advanced resistive exercise device (ARED), (3) were scanned by quantitative computed tomography (QCT) at the hip, (4) had hip bone strength estimated by finite element modeling, or (5) had lost >10% of areal bone mineral density (aBMD) at the hip or lumbar spine as measured by dual-energy X-ray absorptiometry (DXA). Because of the limitations of DXA in describing the effects of spaceflight on bone strength, the panel recommended that the U.S. space program use QCT and finite element modeling to further study the unique effects of spaceflight (and recovery) on bone health in order to better inform clinical decisions. Copyright © 2013 American Society for Bone and Mineral Research.

High-Dose α-Tocopherol Supplementation Does Not Induce Bone Loss in Normal Rats

PubMed Central

Kasai, Shunji; Ito, Akemi; Shindo, Kaori; Toyoshi, Tohru; Bando, Masahiro

2015-01-01

Oxidative stress affects bone turnover. Preventative effects of antioxidants such as vitamin E on reduced bone mineral density and fractures associated with aging, osteoporosis, and smoking have been examined in animals and humans. The effects of vitamin E (α-tocopherol; αT) on bone health have yielded conflicting and inconclusive results from animal studies. In this study, to determine the bone effects of αT, we investigated the in vivo effects of αT on the bone mineral density, bone mass, bone microstructure, bone resorption, and osteogenesis through peripheral quantitative computed tomography (pQCT) measurements, micro-computed tomography (micro-CT) analyses, and bone histomorphometry of lumbar vertebrae and femurs in normal female Wistar rats fed diets containing αT in different quantities (0, 30, 120, or 600 mg/kg diet) for 8 weeks. To validate our hypotheses regarding bone changes, we examined ovariectomized rats as an osteoporosis model and control sham-operated rats in parallel. As expected, ovariectomized rats had reduced bone mineral density in lumbar vertebrae and the distal metaphyses of their femurs, reduced bone mass and deteriorated microstructure of cancellous bones in the vertebral body and distal femur metaphyses, and reduced bone mass due to resorption-dominant enhanced bone turnover in secondary cancellous bones in these sites. In comparison, αT administered to normal rats, even at the highest dose, did not induce reduced bone mineral density of lumbar vertebrae and femurs or a reduced bone mass or fragile microstructure of cancellous bones of the vertebral body and distal femur metaphyses. Instead, αT-fed rats showed a tendency for an osteogenesis-dominant bone mass increase in secondary cancellous bones in the vertebral body, in which active bone remodeling occurs. Thus, αT consumption may have beneficial effects on bone health. PMID:26147575

Nandrolone slows hindlimb bone loss in a rat model of bone loss due to denervation.

PubMed

Cardozo, Christopher P; Qin, Weiping; Peng, Yuanzhen; Liu, Xuan; Wu, Yong; Pan, Jiangping; Bauman, William A; Zaidi, Mone; Sun, Li

2010-03-01

Nandrolone is an anabolic steroid that has been demonstrated to reduce the loss of bone and muscle from hindlimb unweighting and to slow muscle atrophy after nerve transection. To determine whether nandrolone has the ability to protect bone against loss due to disuse after denervation, male rats underwent sciatic nerve transaction, followed 28 days later by treatment with nandrolone or vehicle for 28 days. Bone mineral density (BMD) was determined 28 days later or 56 days after nerve transection. Denervation led to reductions in BMD of 7% and 12% for femur and tibia, respectively. Nandrolone preserved 80% and 60% of BMD in femur and tibia, respectively, demonstrating that nandrolone administration significantly reduced loss of BMD from denervation. This study offers a potential novel pharmacological strategy for use of nandrolone to reduce bone loss in severe disuse- and denervation-related bone loss, such as that which occurs after spinal cord injury.

An improved cost-effective, reproducible method for evaluation of bone loss in a rodent model.

PubMed

Fine, Daniel H; Schreiner, Helen; Nasri-Heir, Cibele; Greenberg, Barbara; Jiang, Shuying; Markowitz, Kenneth; Furgang, David

2009-02-01

This study was designed to investigate the utility of two "new" definitions for assessment of bone loss in a rodent model of periodontitis. Eighteen rats were divided into three groups. Group 1 was infected by Aggregatibacter actinomycetemcomitans (Aa), group 2 was infected with an Aa leukotoxin knock-out, and group 3 received no Aa (controls). Microbial sampling and antibody titres were determined. Initially, two examiners measured the distance from the cemento-enamel-junction to alveolar bone crest using the three following methods; (1) total area of bone loss by radiograph, (2) linear bone loss by radiograph, (3) a direct visual measurement (DVM) of horizontal bone loss. Two "new" definitions were adopted; (1) any site in infected animals showing bone loss >2 standard deviations above the mean seen at that site in control animals was recorded as bone loss, (2) any animal with two or more sites in any quadrant affected by bone loss was considered as diseased. Using the "new" definitions both evaluators independently found that infected animals had significantly more disease than controls (DVM system; p<0.05). The DVM method provides a simple, cost effective, and reproducible method for studying periodontal disease in rodents.

Space flight and bone formation.

PubMed

Doty, St B

2004-12-01

Major physiological changes which occur during spaceflight include bone loss, muscle atrophy, cardiovascular and immune response alterations. When trying to determine the reason why bone loss occurs during spaceflight, one must remember that all these other changes in physiology and metabolism may also have impact on the skeletal system. For bone, however, the role of normal weight bearing is a major concern and we have found no adequate substitute for weight bearing which can prevent bone loss. During the study of this problem, we have learned a great deal about bone physiology and increased our knowledge about how normal bone is formed and maintained. Presently, we do not have adequate ground based models which can mimic the tissue loss that occurs in spaceflight but this condition closely resembles the bone loss seen with osteoporosis. Although a normal bone structure will respond to application of mechanical force and weight bearing by forming new bone, a weakened osteoporotic bone may have a tendency to fracture. The study of the skeletal system during weightless conditions will eventually produce preventative measures and form a basis for protecting the crew during long term space flight. The added benefit from these studies will be methods to treat bone loss conditions which occur here on earth.

Space flight and bone formation

NASA Technical Reports Server (NTRS)

Doty, St B.

2004-01-01

Major physiological changes which occur during spaceflight include bone loss, muscle atrophy, cardiovascular and immune response alterations. When trying to determine the reason why bone loss occurs during spaceflight, one must remember that all these other changes in physiology and metabolism may also have impact on the skeletal system. For bone, however, the role of normal weight bearing is a major concern and we have found no adequate substitute for weight bearing which can prevent bone loss. During the study of this problem, we have learned a great deal about bone physiology and increased our knowledge about how normal bone is formed and maintained. Presently, we do not have adequate ground based models which can mimic the tissue loss that occurs in spaceflight but this condition closely resembles the bone loss seen with osteoporosis. Although a normal bone structure will respond to application of mechanical force and weight bearing by forming new bone, a weakened osteoporotic bone may have a tendency to fracture. The study of the skeletal system during weightless conditions will eventually produce preventative measures and form a basis for protecting the crew during long term space flight. The added benefit from these studies will be methods to treat bone loss conditions which occur here on earth.

The effects of simulated bone loss on the implant-abutment assembly and likelihood of fracture: an in vitro study.

PubMed

Manzoor, Behzad; Suleiman, Mahmood; Palmer, Richard M

2013-01-01

The crestal bone level around a dental implant may influence its strength characteristics by offering protection against mechanical failures. Therefore, the present study investigated the effect of simulated bone loss on modes, loads, and cycles to failure in an in vitro model. Different amounts of bone loss were simulated: 0, 1.5, 3.0, and 4.5 mm from the implant head. Forty narrow-diameter (3.0-mm) implant-abutment assemblies were tested using compressive bending and cyclic fatigue testing. Weibull and accelerated life testing analysis were used to assess reliability and functional life. Statistical analyses were performed using the Fisher-Exact test and the Spearman ranked correlation. Compressive bending tests showed that the level of bone loss influenced the load-bearing capacity of implant-abutment assemblies. Fatigue testing showed that the modes, loads, and cycles to failure had a statistically significant relationship with the level of bone loss. All 16 samples with bone loss of 3.0 mm or more experienced horizontal implant body fractures. In contrast, 14 of 16 samples with 0 and 1.5 mm of bone loss showed abutment and screw fractures. Weibull and accelerated life testing analysis indicated a two-group distribution: the 0- and 1.5-mm bone loss samples had better functional life and reliability than the 3.0- and 4.5-mm samples. Progressive bone loss had a significant effect on modes, loads, and cycles to failure. In addition, bone loss influenced the functional life and reliability of the implant-abutment assemblies. Maintaining crestal bone levels is important in ensuring biomechanical sustainability and predictable long-term function of dental implant assemblies.

PULSED FOCUSED ULTRASOUND TREATMENT OF MUSCLE MITIGATES PARALYSIS-INDUCED BONE LOSS IN THE ADJACENT BONE: A STUDY IN A MOUSE MODEL

PubMed Central

Poliachik, Sandra L.; Khokhlova, Tatiana D.; Wang, Yak-Nam; Simon, Julianna C.; Bailey, Michael R.

2015-01-01

Bone loss can result from bed rest, space flight, spinal cord injury or age-related hormonal changes. Current bone loss mitigation techniques include pharmaceutical interventions, exercise, pulsed ultrasound targeted to bone and whole body vibration. In this study, we attempted to mitigate paralysis-induced bone loss by applying focused ultrasound to the midbelly of a paralyzed muscle. We employed a mouse model of disuse that uses onabotulinumtoxinA-induced paralysis, which causes rapid bone loss in 5 d. A focused 2 MHz transducer applied pulsed exposures with pulse repetition frequency mimicking that of motor neuron firing during walking (80 Hz), standing (20 Hz), or the standard pulsed ultrasound frequency used in fracture healing (1 kHz). Exposures were applied daily to calf muscle for 4 consecutive d. Trabecular bone changes were characterized using micro-computed tomography. Our results indicated that application of certain focused pulsed ultrasound parameters was able to mitigate some of the paralysis-induced bone loss. PMID:24857416

Preliminary evidence of early bone resorption in a sheep model of acute burn injury: an observational study.

PubMed

Klein, Gordon L; Xie, Yixia; Qin, Yi-Xian; Lin, Liangjun; Hu, Minyi; Enkhbaatar, Perenlei; Bonewald, Lynda F

2014-03-01

Treatment with bisphosphonates within the first 10 days of severe burn injury completely prevents bone loss. We therefore postulated that bone resorption occurs early post burn and is the primary explanation for acute bone loss in these patients. Our objective was to assess bone for histological and biomechanical evidence of early resorption post burn. We designed a randomized controlled study utilizing a sheep model of burn injury. Three sheep received a 40 % total body surface area burn under isoflurane anesthesia, and three other sheep received cotton-smoke inhalation and served as control. Burned sheep were killed 5 days post procedure and controls were killed 2 days post procedure. Backscatter scanning electron microscopy was performed on iliac crests obtained immediately postmortem along with quantitative histomorphometry and compression testing to determine bone strength (Young's modulus). Blood ionized Ca was also determined in the first 24 h post procedure as was urinary CTx. Three of three sheep killed at 5 days had evidence of scalloping of the bone surface, an effect of bone resorption, whereas none of the three sheep killed at 2 days post procedure had scalloping. One of the three burned sheep killed at 5 days showed quantitative doubling of the eroded surface and halving of the bone volume compared to sham controls. Mean values of Young's modulus were approximately one third lower in the burned sheep killed at 5 days compared to controls, p = 0.08 by unpaired t test, suggesting weaker bone. These data suggest early post-burn bone resorption. Urine CTx normalized to creatinine did not differ between groups at 24 h post procedure because the large amounts of fluids received by the burned sheep may have diluted urine creatinine and CTx and because the urine volume produced by the burned sheep was threefold that of the controls. We calculated 24 h urinary CTx excretion, and with this calculation CTx excretion/24 h in the burned sheep was nearly twice that of the controls. Moreover, whole blood ionized Ca measured at 3- to 6-h intervals over the first 24 h in both burn and control sheep showed a 6 % reduction versus baseline in the burned sheep with <1 % reduction in the control animals. This sheep model was previously used to demonstrate upregulation of the parathyroid calcium-sensing receptor within the timeframe of the present study. Because both early bone resorption, supported by this study, and calcium-sensing receptor upregulation, consistent with the observed reduction in blood ionized Ca, are mediated by proinflammatory cytokines that are present as part of the post-burn systemic inflammatory response, we may postulate that post-burn upregulation of the parathyroid calcium-sensing receptor may be an adaptive response to clear the blood of excess calcium liberated by cytokine-mediated bone resorption.

Quantitative MRI and spectroscopy of bone marrow

PubMed Central

Ruschke, Stefan; Dieckmeyer, Michael; Diefenbach, Maximilian; Franz, Daniela; Gersing, Alexandra S.; Krug, Roland; Baum, Thomas

2017-01-01

Bone marrow is one of the largest organs in the human body, enclosing adipocytes, hematopoietic stem cells, which are responsible for blood cell production, and mesenchymal stem cells, which are responsible for the production of adipocytes and bone cells. Magnetic resonance imaging (MRI) is the ideal imaging modality to monitor bone marrow changes in healthy and pathological states, thanks to its inherent rich soft‐tissue contrast. Quantitative bone marrow MRI and magnetic resonance spectroscopy (MRS) techniques have been also developed in order to quantify changes in bone marrow water–fat composition, cellularity and perfusion in different pathologies, and to assist in understanding the role of bone marrow in the pathophysiology of systemic diseases (e.g. osteoporosis). The present review summarizes a large selection of studies published until March 2017 in proton‐based quantitative MRI and MRS of bone marrow. Some basic knowledge about bone marrow anatomy and physiology is first reviewed. The most important technical aspects of quantitative MR methods measuring bone marrow water–fat composition, fatty acid composition, perfusion, and diffusion are then described. Finally, previous MR studies are reviewed on the application of quantitative MR techniques in both healthy aging and diseased bone marrow affected by osteoporosis, fractures, metabolic diseases, multiple myeloma, and bone metastases. Level of Evidence: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:332–353. PMID:28570033

Fabric dependence of wave propagation in anisotropic porous media

PubMed Central

Cowin, Stephen C.; Cardoso, Luis

2012-01-01

Current diagnosis of bone loss and osteoporosis is based on the measurement of the Bone Mineral Density (BMD) or the apparent mass density. Unfortunately, in most clinical ultrasound densitometers: 1) measurements are often performed in a single anatomical direction, 2) only the first wave arriving to the ultrasound probe is characterized, and 3) the analysis of bone status is based on empirical relationships between measurable quantities such as Speed of Sound (SOS) and Broadband Ultrasound Attenuation (BUA) and the density of the porous medium. However, the existence of a second wave in cancellous bone has been reported, which is an unequivocal signature of poroelastic media, as predicted by Biot’s poroelastic wave propagation theory. In this paper the governing equations for wave motion in the linear theory of anisotropic poroelastic materials are developed and extended to include the dependence of the constitutive relations upon fabric - a quantitative stereological measure of the degree of structural anisotropy in the pore architecture of a porous medium. This fabric-dependent anisotropic poroelastic approach is a theoretical framework to describe the microarchitectural-dependent relationship between measurable wave properties and the elastic constants of trabecular bone, and thus represents an alternative for bone quality assessment beyond BMD alone. PMID:20461539

Fabric dependence of quasi-waves in anisotropic porous media.

PubMed

Cardoso, Luis; Cowin, Stephen C

2011-05-01

Assessment of bone loss and osteoporosis by ultrasound systems is based on the speed of sound and broadband ultrasound attenuation of a single wave. However, the existence of a second wave in cancellous bone has been reported and its existence is an unequivocal signature of poroelastic media. To account for the fact that ultrasound is sensitive to microarchitecture as well as bone mineral density (BMD), a fabric-dependent anisotropic poroelastic wave propagation theory was recently developed for pure wave modes propagating along a plane of symmetry in an anisotropic medium. Key to this development was the inclusion of the fabric tensor--a quantitative stereological measure of the degree of structural anisotropy of bone--into the linear poroelasticity theory. In the present study, this framework is extended to the propagation of mixed wave modes along an arbitrary direction in anisotropic porous media called quasi-waves. It was found that differences between phase and group velocities are due to the anisotropy of the bone microarchitecture, and that the experimental wave velocities are more accurately predicted by the poroelastic model when the fabric tensor variable is taken into account. This poroelastic wave propagation theory represents an alternative for bone quality assessment beyond BMD.

Estrogen prevents bone loss through transforming growth factor β signaling in T cells

PubMed Central

Gao, Yuhao; Qian, Wei-Ping; Dark, Kimberly; Toraldo, Gianluca; Lin, Angela S. P.; Guldberg, Robert E.; Flavell, Richard A.; Weitzmann, M. Neale; Pacifici, Roberto

2004-01-01

Estrogen (E) deficiency leads to an expansion of the pool of tumor necrosis factor (TNF)-producing T cells through an IFN-γ-dependent pathway that results in increased levels of the osteoclastogenic cytokine TNF in the bone marrow. Disregulated IFN-γ production is instrumental for the bone loss induced by ovariectomy (ovx), but the responsible mechanism is unknown. We now show that mice with T cell-specific blockade of type β transforming growth factor (TGFβ) signaling are completely insensitive to the bone-sparing effect of E. This phenotype results from a failure of E to repress IFN-γ production, which, in turn, leads to increased T cell activation and T cell TNF production. Furthermore, ovx blunts TGFβ levels in the bone marrow, and overexpression of TGFβ in vivo prevents ovx-induced bone loss. These findings demonstrate that E prevents bone loss through a TGFβ-dependent mechanism, and that TGFβ signaling in T cells preserves bone homeostasis by blunting T cell activation. Thus, stimulation of TGFβ production in the bone marrow is a critical “upstream” mechanism by which E prevents bone loss, and enhancement of TGFβ levels in vivo may constitute a previously undescribed therapeutic approach for preventing bone loss. PMID:15531637

Digital radiographic evaluation of alveolar bone loss, density and lamina dura integrity on post splinting mandibular anterior with chronic periodontitis

NASA Astrophysics Data System (ADS)

Rafini, F.; Priaminiarti, M.; Sukardi, I.; Lessang, R.

2017-08-01

The healing of periodontal splinting can be detected both with clinical and radiographic examination. In this study, the alveolar bone was evaluated by radiographic digital periapical analysis. Periodontal tooth splinting is periodontal support therapy used to prevent periodontal injury during repair and regeneration of periodontal therapy. Radiographic digital periapical analysis of alveolar bone in the mandibular anterior region with chronic periodontitis and 2/3 cervical bone loss after three months of periodontal splinting. Eighty four proximal site (43 mesial and 41 distal) from 16 patients with chronic periodontitis and treated with spinting were examined by taking periapical digital radiographic at day 1 and 91. The bone loss, bone density and utility of lamina dura were evaluated. The statistical analysis after three months evaluation using T-test for bone loss, Wilcoxon sign rank test for bone density and utility lamina dura showed no significantly differences (p<0.05) (p=0.44, 0.256 and 0.059). No radiographic change in bone loss, bone density and utility of lamina dura from chronic periodontitis with 2/3 alveolar bone loss after three months splinting.

Skeletal effects of estrogen deficiency as induced by an aromatase inhibitor in an aged male rat model.

PubMed

Vanderschueren, D; Boonen, S; Ederveen, A G; de Coster, R; Van Herck, E; Moermans, K; Vandenput, L; Verstuyf, A; Bouillon, R

2000-11-01

Aromatization of androgens into estrogens may be important for maintenance of the male skeleton. To address this hypothesis, we evaluated the skeletal effects of selective estrogen deficiency as induced by the aromatase inhibitor vorozole (Vor), with or without 17beta-estradiol (E(2)) administration (1.35 microg/day), in aged (12-month-old) male rats. A baseline group was killed at the start of the experiment (Base). The control group (Control), the group treated with vorozole alone (Vor), the group treated with E(2) alone (E(2)), or the group with a combination of both (Vor + E(2)) were killed 15 weeks later. Vorozole significantly increased serum testosterone (T) and reduced serum E(2) compared with Control. Body weight gain and serum insulin-like growth factor-I (IGF-I) were also lower in Vor, whereas significant weight loss and decrease of serum IGF-I occurred as a result of E(2) administration. Bone formation as assessed by serum osteocalcin was unaffected but osteoid surface in the proximal metaphysis of the tibia was increased in Vor-treated rats. Bone resorption as evaluated by urinary deoxypyridinoline excretion was increased in Vor. Biochemical parameters of bone turnover were reduced significantly in all E(2) treated rats. Premature closure of the growth plates and decreased osteoid and mineralizing surfaces were also observed in E(2) and Vor + E(2). Apparent bone density of lumbar vertebrae and femur, as measured by dual-energy X-ray absorptiometry (DXA), was significantly reduced in Vor. Vorozole decreased femoral bone density mainly in the distal femur (trabecular and cortical region). This decrease of bone density was not present in E(2) and Vor + E(2). Similar findings were observed when bone density was assessed by peripheral quantitative computed tomography (pQCT); that is, trabecular density of the distal femur, the proximal tibia, and the distal lumbar vertebra were all lower in Vor. This decrease in density was not observed in all E(2)-treated animals. In conclusion, administration of the aromatase inhibitor, vorozole, to aged male rats induces net trabecular bone loss in both the appendicular and axial skeleton, despite a concomitant increase in serum testosterone. E(2) administration is able to prevent this trabecular bone loss in vorozole-treated animals.

Redefining "Critical" Bone Loss in Shoulder Instability: Functional Outcomes Worsen With "Subcritical" Bone Loss.

PubMed

Shaha, James S; Cook, Jay B; Song, Daniel J; Rowles, Douglas J; Bottoni, Craig R; Shaha, Steven H; Tokish, John M

2015-07-01

Glenoid bone loss is a common finding in association with anterior shoulder instability. This loss has been identified as a predictor of failure after operative stabilization procedures. Historically, 20% to 25% has been accepted as the "critical" cutoff where glenoid bone loss should be addressed in a primary procedure. Few data are available, however, on lesser, "subcritical" amounts of bone loss (below the 20%-25% range) on functional outcomes and failure rates after primary arthroscopic stabilization for shoulder instability. To evaluate the effect of glenoid bone loss, especially in subcritical bone loss (below the 20%-25% range), on outcomes assessments and redislocation rates after an isolated arthroscopic Bankart repair for anterior shoulder instability. Cohort study; Level of evidence, 3. Subjects were 72 consecutive anterior instability patients (73 shoulders) who underwent isolated anterior arthroscopic labral repair at a single military institution by 1 of 3 sports medicine fellowship-trained orthopaedic surgeons. Data were collected on demographics, the Western Ontario Shoulder Instability (WOSI) score, Single Assessment Numeric Evaluation (SANE) score, and failure rates. Failure was defined as recurrent dislocation. Glenoid bone loss was calculated via a standardized technique on preoperative imaging. The average bone loss across the group was calculated, and patients were divided into quartiles based on the percentage of glenoid bone loss. Outcomes were analyzed for the entire cohort, between the quartiles, and within each quartile. Outcomes were then further stratified between those sustaining a recurrence versus those who remained stable. The mean age at surgery was 26.3 years (range, 20-42 years), and the mean follow-up was 48.3 months (range, 23-58 months). The cohort was divided into quartiles based on bone loss. Quartile 1 (n = 18) had a mean bone loss of 2.8% (range, 0%-7.1%), quartile 2 (n = 19) had 10.4% (range, 7.3%-13.5%), quartile 3 (n = 18) had 16.1% (range, 13.5%-19.8%), and quartile 4 (n = 18) had 24.5% (range, 20.0%-35.5%). The overall mean WOSI score was 756.8 (range, 0-2097). The mean WOSI score correlated with SANE scores and worsened as bone loss increased in each quartile. There were significant differences (P < .05) between quartile 1 (mean WOSI/SANE, 383.3/62.1) and quartile 2 (mean, 594.0/65.2), between quartile 2 and quartile 3 (mean, 839.5/52.0), and between quartile 3 and quartile 4 (mean, 1187.6/46.1). Additionally, between quartiles 2 and 3 (bone loss, 13.5%), the WOSI score increased to rates consistent with a poor clinical outcome. There was an overall failure rate of 12.3%. The percentage of glenoid bone loss was significantly higher among those repairs that failed versus those that remained stable (24.7% vs 12.8%, P < .01). There was no significant difference in failure rate between quartiles 1, 2, and 3, but there was a significant increase in failure (P < .05) between quartiles 1, 2, and 3 (7.3%) when compared with quartile 4 (27.8%). Notably, even when only those patients who did not sustain a recurrent dislocation were compared, bone loss was predictive of outcome as assessed by the WOSI score, with each quartile's increasing bone loss predictive of a worse functional outcome. While critical bone loss has yet to be defined for arthroscopic Bankart reconstruction, our data indicate that "critical" bone loss should be lower than the 20% to 25% threshold often cited. In our population with a high level of mandatory activity, bone loss above 13.5% led to a clinically significant decrease in WOSI scores consistent with an unacceptable outcome, even in patients who did not sustain a recurrence of their instability. © 2015 The Author(s).

Single- and dual-photon absorptiometry in osteoporosis and osteomalacia

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

Wahner, H.W.

Single- and dual-photon absorptiometric methods have been used in the past to identify populations at risk for bone loss, to define the osteoporotic syndrome in terms of bone mass, and to evaluate treatment regimens to prevent bone loss. Technical improvements have made these procedures available for the nontraumatic measurement of bone mineral in the management of the individual patient suspected of having osteoporosis or other bone loss. This requires a different approach to data interpretation because decisions have to be made on the basis of a single measurement. Osteoporosis and osteomalacia cannot be distinguished by bone mineral measurements because bothmore » are characterized by a decrease in content of bone mineral. Bone mineral measurements can be used to assess the risk of fracture and, with it, the severity of bone loss. This allows treatment decisions to be made. Repeated measurements made under well-defined conditions allow estimation of long-term rate of bone loss and monitoring of treatment effect. 38 references.« less

Prevalence of Dental Implants and Evaluation of Peri-implant Bone Levels in Patients Presenting to a Dental School: A Radiographic Cross-Sectional 2-Year Study.

PubMed

Alkan, Eylem Ayhan; Mau, Lian Ping; Schoolfield, John; Guest, Gary F; Cochran, David L

To evaluate the number of patients with dental implants who present to a dental school clinic for screening and to report the prevalence of peri-implant bone level change detected on digital panoramic radiographs of those subjects. Patient screening files for 9,422 patients over a 2-year period were examined to see how many patients presented with dental implants. Those patients with at least one implant were further evaluated by measuring the bone level on the mesial and distal sides of the implant using the screening radiograph. A total of 187 patients (2%) had at least one implant. In regard to implants, 423 were examined and 146 (33%) had no detectable bone loss defined as bone level below the top of the implant. When thresholds of bone loss were evaluated, 109 implants (25%) had ≥ 2 mm of bone loss on either the mesial or distal sides or both. The median bone loss was 1.74 mm for the 277 implants with detectable bone loss and 2.97 mm for the 109 implants that had ≥ 2 mm bone loss. Interestingly, patients who were ≥ 70 years of age had significantly (P = .03) more bone loss in the mandible compared with the maxilla, while patients who were 60 to 69 years of age had significantly greater loss in the maxilla. These data reveal that for patients presenting to the dental school for a screening over a 2-year period, 1.98% had one or more dental implants. Furthermore, those patients with implants had a minimum amount of bone loss as measured from the top of the implant.

Synergistic Phytochemicals Fail to Protect Against Ovariectomy Induced Bone Loss in Rats.

PubMed

Ambati, Suresh; Miller, Colette N; Bass, Erica F; Hohos, Natalie M; Hartzell, Diane L; Kelso, Emily W; Trunnell, Emily R; Yang, Jeong-Yeh; Della-Fera, Mary Anne; Baile, Clifton A; Rayalam, Srujana

2018-05-24

Menopause induces a loss of bone as a result of estrogen deficiency. Despite pharmaceutical options for the treatment of osteopenia and osteoporosis, many aging women use dietary supplements with estrogenic activity to prevent bone loss and other menopausal-related symptoms. Such supplements are yet to be tested for efficacy against a Food and Drug Administration (FDA) approved medication for menopausal bone loss such as zoledronic acid (ZA). The postmenopausal rat model was used to investigate the efficacy of various synergistic phytochemical blends mixed into the diet for 16 weeks. Retired-breeder, Fischer 344 rats were randomly assigned to sham or ovariectomy surgery and 4 treatment groups: ZA; genistein supplementation; and a low dose and high dose blend of genistein, resveratrol, and quercetin. Ovariectomy resulted in a loss of both trabecular and cortical bone which was prevented with ZA. The phytochemical blends tested were unable to reverse these losses. Despite the lack of effectiveness in preventing bone loss, a significant dose-response trend was observed in the phytochemical-rich diets in bone adipocyte number compared to ovariectomized control rats. Data from this study indicate that estrogenic phytochemicals are not as efficacious as ZA in preventing menopausal-related bone loss but may have beneficial effects on bone marrow adiposity in rats.

Sox10 Expressing Cells in the Lateral Wall of the Aged Mouse and Human Cochlea

PubMed Central

Hao, Xinping; Xing, Yazhi; Moore, Michael W.; Zhang, Jianning; Han, Demin; Schulte, Bradley A.; Dubno, Judy R.; Lang, Hainan

2014-01-01

Age-related hearing loss (presbycusis) is a common human disorder, affecting one in three Americans aged 60 and over. Previous studies have shown that presbyacusis is associated with a loss of non-sensory cells in the cochlear lateral wall. Sox10 is a transcription factor crucial to the development and maintenance of neural crest-derived cells including some non-sensory cell types in the cochlea. Mutations of the Sox10 gene are known to cause various combinations of hearing loss and pigmentation defects in humans. This study investigated the potential relationship between Sox10 gene expression and pathological changes in the cochlear lateral wall of aged CBA/CaJ mice and human temporal bones from older donors. Cochlear tissues prepared from young adult (1–3 month-old) and aged (2–2.5 year-old) mice, and human temporal bone donors were examined using quantitative immunohistochemical analysis and transmission electron microscopy. Cells expressing Sox10 were present in the stria vascularis, outer sulcus and spiral prominence in mouse and human cochleas. The Sox10+ cell types included marginal and intermediate cells and outer sulcus cells, including those that border the scala media and those extending into root processes (root cells) in the spiral ligament. Quantitative analysis of immunostaining revealed a significant decrease in the number of Sox10+ marginal cells and outer sulcus cells in aged mice. Electron microscopic evaluation revealed degenerative alterations in the surviving Sox10+ cells in aged mice. Strial marginal cells in human cochleas from donors aged 87 and older showed only weak immunostaining for Sox10. Decreases in Sox10 expression levels and a loss of Sox10+ cells in both mouse and human aged ears suggests an important role of Sox10 in the maintenance of structural and functional integrity of the lateral wall. A loss of Sox10+ cells may also be associated with a decline in the repair capabilities of non-sensory cells in the aged ear. PMID:24887110

Serum markers of bone turnover are increased by modest weight loss with or without weight-bearing exercise in overweight premenopausal women.

PubMed

Rector, R Scott; Loethen, Joanne; Ruebel, Meghan; Thomas, Tom R; Hinton, Pamela S

2009-10-01

Weight loss improves metabolic fitness and reduces morbidity and mortality; however, weight reduction also reduces bone mineral density (BMD) and increases bone turnover. Weight-bearing aerobic exercise may preserve bone mass and maintain normal bone turnover during weight reduction. We investigated the impact of weight-bearing and nonweight-bearing exercise on serum markers of bone formation and breakdown during short-term, modest weight loss in overweight premenopausal women. Subjects (n = 36) were assigned to 1 of 3 weight-loss interventions designed to produce a 5% reduction in body weight over 6 weeks: (i) energy restriction only (n = 11; DIET); (ii) energy restriction plus nonweight-bearing exercise (n = 12, CYCLE); or (iii) energy restriction plus weight-bearing exercise (n = 13, RUN). Bone turnover markers were measured in serum collected at baseline and after weight loss. All groups achieved a ~5% reduction in body weight (DIET = 5.2%; CYCLE = 5.0%; RUN = 4.7%). Osteocalcin (OC) and C-terminal telopeptide of type I collagen (CTX) increased with weight loss in all 3 groups (p < 0.05), whereas bone alkaline phosphatase was unaltered by the weight-loss interventions. At baseline, OC and CTX were positively correlated (r = 0.36, p = 0.03), but the strength of this association was diminished (r = 0.30, p = 0.06) after weight loss. Modest weight loss, regardless of method, resulted in a significant increase in both OC and CTX. Low-impact, weight-bearing exercise had no effect on serum markers of bone formation or resorption in premenopausal women during weight loss. Future studies that examine the effects of high-impact, weight-bearing activity on bone turnover and BMD during weight loss are warranted.

[Bone loss in lactating women and post-pregnancy osteoporosis].

PubMed

Hirata, Go; Chaki, Osamu

2011-09-01

Measurement of the bone mineral density have shown that lactating women had 1 to 3% decrease in bone mineral density. Post pregnancy osteoporosis is rare condition that causes fragile fracture mostly in vertebrae. The bone loss in lactating women is caused by calcium loss, decrease in estrogen level, and increase in PTHrP (parathyroid hormone related protein) level. Some data have shown that extended lactation and amenorrhea had an association with the degree of bone loss. Mostly, the bone loss of the lactating women recovers to the baseline level, soon after the weaning, and there is no long term effect. Post pregnancy osteoporosis should be concerned, when we see a lactating woman with fragile fracture of the vertebrae.

A crucial role for thiol antioxidants in estrogen-deficiency bone loss

PubMed Central

Lean, Jenny M.; Davies, Julie T.; Fuller, Karen; Jagger, Christopher J.; Kirstein, Barrie; Partington, Geoffrey A.; Urry, Zoë L.; Chambers, Timothy J.

2003-01-01

The mechanisms through which estrogen prevents bone loss are uncertain. Elsewhere, estrogen exerts beneficial actions by suppression of reactive oxygen species (ROS). ROS stimulate osteoclasts, the cells that resorb bone. Thus, estrogen might prevent bone loss by enhancing oxidant defenses in bone. We found that glutathione and thioredoxin, the major thiol antioxidants, and glutathione and thioredoxin reductases, the enzymes responsible for maintaining them in a reduced state, fell substantially in rodent bone marrow after ovariectomy and were rapidly normalized by exogenous 17-β estradiol. Moreover, administration of N-acetyl cysteine (NAC) or ascorbate, antioxidants that increase tissue glutathione levels, abolished ovariectomy-induced bone loss, while L-buthionine-(S,R)-sulphoximine (BSO), a specific inhibitor of glutathione synthesis, caused substantial bone loss. The 17-β estradiol increased glutathione and glutathione and thioredoxin reductases in osteoclast-like cells in vitro. Furthermore, in vitro NAC prevented osteoclast formation and NF-κB activation. BSO and hydrogen peroxide did the opposite. Expression of TNF-α, a target for NF-κB and a cytokine strongly implicated in estrogen-deficiency bone loss, was suppressed in osteoclasts by 17-β estradiol and NAC. These observations strongly suggest that estrogen deficiency causes bone loss by lowering thiol antioxidants in osteoclasts. This directly sensitizes osteoclasts to osteoclastogenic signals and entrains ROS-enhanced expression of cytokines that promote osteoclastic bone resorption. PMID:12975476

Prostaglandin E2 Prevents Ovariectomy-Induced Cancellous Bone Loss in Rats

NASA Technical Reports Server (NTRS)

Ke, Hua Zhu; Li, Mei; Jee, Webster S. S.

1992-01-01

The object of this study was to determine whether prostaglandin E2, (PGE2) can prevent ovariectomy induced cancellous bone loss. Thirty-five 3-month-old female Sprague-Dawley rats were divided into two groups. The rats in the first group were ovariectomized (OVX) while the others received sham operation (sham-OVX). The OVX group was further divided into three treatment groups. The daily doses for the three groups were 0,1 and 6 mg PGE2/kg for 90 days. Bone histomorphometric analyses were performed on double-fluorescent-labeled undecalcified proximal tibial metaphysis (PTM). We confirmed that OVX induces massive cancellous bone loss (-80%) and a higher bone turnover (+143%). The new findings from the present study demonstrate that bone loss due to ovarian hormone deficiency can be prevented by a low-dose (1 mg) daily administration of PGE2. Furthermore, a higher-dose (6 mg) daily administration of PGE2 not only prevents bone loss but also adds extra bone to the proximal tibial metaphyses. PGE, at the 1-mg dose level significantly increased trabecular bone area, trabecular width, trabecular node density, density of node to node, ratio of node to free end, and thus significantly decreased trabecular separation from OVX controls. At this dose level, these same parameters did not differ significantly from sham-OVX controls. However, at the 6-mg dose level PGE2, there were significant increases in trabecular bone area, trabecular width, trabecular node density, density of node to node, and ratio of node to free end, while there was significant decrease in trabecular separation from both OVX and sham-operated controls. The changes in indices of trabecular bone microanatomical structure indicated that PGE2 prevented bone loss as well as the disconnection of existing trabeculae. In summary, PGE2, administration to OVX rats decreased bone turnover and increased bone formation parameters resulting in a positive bone balance that prevented bone loss (in both lower and higher doses) and added extra bone to metaphyses of OVX rats (in higher dose). These findings support the strategy of the use of bone stimulation agents in the prevention of estrogen depletion bone loss (postmenopausal osteoporosis).

Animal Models of Bone Loss in Inflammatory Arthritis: from Cytokines in the Bench to Novel Treatments for Bone Loss in the Bedside-a Comprehensive Review.

PubMed

Alves, C Henrique; Farrell, Eric; Vis, Marijn; Colin, Edgar M; Lubberts, Erik

2016-08-01

Throughout life, bone is continuously remodelled. Bone is formed by osteoblasts, from mesenchymal origin, while osteoclasts induce bone resorption. This process is tightly regulated. During inflammation, several growth factors and cytokines are increased inducing osteoclast differentiation and activation, and chronic inflammation is a condition that initiates systemic bone loss. Rheumatoid arthritis (RA) is a chronic inflammatory auto-immune disease that is characterised by active synovitis and is associated with early peri-articular bone loss. Peri-articular bone loss precedes focal bone erosions, which may progress to bone destruction and disability. The incidence of generalised osteoporosis is associated with the severity of arthritis in RA and increased osteoporotic vertebral and hip fracture risk. In this review, we will give an overview of different animal models of inflammatory arthritis related to RA with focus on bone erosion and involvement of pro-inflammatory cytokines. In addition, a humanised endochondral ossification model will be discussed, which can be used in a translational approach to answer osteoimmunological questions.

Horticultural activity predicts later localized limb status in a contemporary pre-industrial population.

PubMed

Stieglitz, Jonathan; Trumble, Benjamin C; Kaplan, Hillard; Gurven, Michael

2017-07-01

Modern humans may have gracile skeletons due to low physical activity levels and mechanical loading. Tests using pre-historic skeletons are limited by the inability to assess behavior directly, while modern industrialized societies possess few socio-ecological features typical of human evolutionary history. Among Tsimane forager-horticulturalists, we test whether greater activity levels and, thus, increased loading earlier in life are associated with greater later-life bone status and diminished age-related bone loss. We used quantitative ultrasonography to assess radial and tibial status among adults aged 20+ years (mean ± SD age = 49 ± 15; 52% female). We conducted systematic behavioral observations to assess earlier-life activity patterns (mean time lag between behavioural observation and ultrasound = 12 years). For a subset of participants, physical activity was again measured later in life, via accelerometry, to determine whether earlier-life time use is associated with later-life activity levels. Anthropometric and demographic data were collected during medical exams. Structural decline with age is reduced for the tibia (female: -0.25 SDs/decade; male: 0.05 SDs/decade) versus radius (female: -0.56 SDs/decade; male: -0.20 SDs/decade), which is expected if greater loading mitigates bone loss. Time allocation to horticulture, but not hunting, positively predicts later-life radial status (β Horticulture  = 0.48, p = 0.01), whereas tibial status is not significantly predicted by subsistence or sedentary leisure participation. Patterns of activity- and age-related change in bone status indicate localized osteogenic responses to loading, and are generally consistent with the logic of bone functional adaptation. Nonmechanical factors related to subsistence lifestyle moderate the association between activity patterns and bone structure. © 2017 Wiley Periodicals, Inc.

MicroRNA-29a mitigates glucocorticoid induction of bone loss and fatty marrow by rescuing Runx2 acetylation.

PubMed

Ko, Jih-Yang; Chuang, Pei-Chin; Ke, Huei-Jin; Chen, Yu-Shan; Sun, Yi-Chih; Wang, Feng-Sheng

2015-12-01

Glucocorticoid treatment reportedly increases the morbidity of osteoporotic or osteonecrotic disorders. Exacerbated bone acquisition and escalated marrow adipogenesis are prominent pathological features of glucocorticoid-mediated skeletal disorders. MicroRNAs reportedly modulate tissue metabolism and remodeling. This study was undertaken to investigate the biological roles of microRNA-29a (miR-29a) in skeletal and fat metabolism in the pathogenesis of glucocorticoid-induced osteoporosis. Transgenic mice overexpressing miR-29a precursor or wild-type mice were given methylprednisolone. Bone mass, microarchitecture and histology were assessed by dual energy X-ray absorptiometry, μCT and histomorphometry. Differential gene expression and signaling components were delineated by quantitative RT-PCR and immunoblotting. Glucocorticoid treatment accelerated bone loss and marrow fat accumulation in association with decreased miR-29a expression. The miR-29a transgenic mice had high bone mineral density, trabecular microarchitecture and cortical thickness. miR-29a overexpression mitigated the glucocorticoid-induced impediment of bone mass, skeletal microstructure integrity and mineralization reaction and attenuated fatty marrow histopathology. Ex vivo, miR-29a increased osteogenic differentiation capacity and alleviated the glucocorticoid-induced promotion of adipocyte formation in primary bone-marrow mesenchymal progenitor cell cultures. Through inhibition of histone deacetylase 4 (HDAC4) expression, miR-29a restored acetylated Runx2 and β-catenin abundances and reduced RANKL, leptin and glucocorticoid receptor expression in glucocorticoid-mediated osteoporosis bone tissues. Taken together, glucocorticoid suppression of miR-29a signaling disturbed the balances between osteogenic and adipogenic activities, and thereby interrupted bone formation and skeletal homeostasis. miR-29a inhibition of HDAC4 stabilized the acetylation state of Runx2 and β-catenin that ameliorated the detrimental effects of glucocorticoid on mineralization and lipogenesis reactions in bone tissue microenvironments. This study highlighted emerging skeletal-anabolic actions of miR-29a signaling in the progression of glucocorticoid-induced bone tissue destruction. Sustaining miR-29a actions is beneficial in protecting against glucocorticoid-mediated osteoporosis. Copyright © 2015 Elsevier Inc. All rights reserved.

Individual Trabecula Segmentation (ITS)-Based Morphological Analyses and Micro Finite Element Analysis of HR-pQCT Images Discriminate Postmenopausal Fragility Fractures Independent of DXA Measurements

PubMed Central

Liu, X. Sherry; Stein, Emily M.; Zhou, Bin; Zhang, Chiyuan A.; Nickolas, Thomas L.; Cohen, Adi; Thomas, Valerie; McMahon, Donald J.; Cosman, Felicia; Nieves, Jeri; Shane, Elizabeth; Guo, X. Edward

2011-01-01

Osteoporosis is typically diagnosed by dual energy x-ray absorptiometry (DXA) measurements of areal bone mineral density (aBMD). Emerging technologies, such as high-resolution peripheral quantitative computed tomography (HR-pQCT), may increase the diagnostic accuracy of DXA and enhance our mechanistic understanding of decreased bone strength in osteoporosis. Women with (n=68) and without (n=101) a history of postmenopausal fragility fracture had aBMD measured by DXA, trabecular plate and rod microarchitecture measured by HR-pQCT image-based individual trabeculae segmentation (ITS) analysis, and whole bone and trabecular bone stiffness by micro finite element analysis (μFEA) of HR-pQCT images at the radius and tibia. DXA T-scores were similar in women with and without fractures at the spine, hip and 1/3 radius, but lower in fracture subjects at the ultradistal radius. Trabecular microarchitecture of fracture subjects was characterized by preferential reductions in trabecular plate bone volume, number, and connectivity over rod trabecular parameters, loss of axially aligned trabeculae, and a more rod-like trabecular network. In addition, decreased thickness and size of trabecular plates were observed at the tibia. The differences between groups were greater at the radius than the tibia for plate number, rod bone volume fraction and number and plate-rod and rod-rod junction densities. Most differences between groups remained after adjustment for T-score by DXA. At a fixed bone volume fraction, trabecular plate volume, number and connectivity were directly associated with bone stiffness. In contrast, rod volume, number and connectivity were inversely associated with bone stiffness. In summary, HR-pQCT-based ITS and μFEA measurements discriminate fracture status in postmenopausal women independent of DXA measurements. Moreover, these results suggest that preferential loss of plate-like trabeculae contribute to lower trabecular bone and whole bone stiffness in women with fractures. We conclude that HR-pQCT-based ITS and μFEA measurements increase our understanding of the microstructural pathogenesis of fragility fracture in postmenopausal women. PMID:22072446

Preservation of volumetric bone density and geometry in trans women during cross-sex hormonal therapy: a prospective observational study.

PubMed

Van Caenegem, E; Wierckx, K; Taes, Y; Schreiner, T; Vandewalle, S; Toye, K; Kaufman, J-M; T'Sjoen, G

2015-01-01

Although trans women before the start of hormonal therapy have a less bone and muscle mass compared with control men, their bone mass and geometry are preserved during the first 2 years of hormonal therapy, despite of substantial muscle loss, illustrating the major role of estrogen in the male skeleton. The aim of this study is to examine the evolution of areal and volumetric bone density, geometry, and turnover in trans women undergoing sex steroid changes, during the first 2 years of hormonal therapy. In a prospective observational study, we examined 49 trans women (male-to-female) before and after 1 and 2 years of cross-sex hormonal therapy (CSH) in comparison with 49 age-matched control men measuring grip strength (hand dynamometer), areal bone mineral density (aBMD), and total body fat and lean mass using dual X-ray absorptiometry (DXA), bone geometry and volumetric bone mineral density, regional fat, and muscle area at the forearm and calf using peripheral quantitative computed tomography. Standardized treatment regimens were used with oral estradiol valerate, 4 mg daily (or transdermal 17-β estradiol 100 μg/24 h for patients >45 years old), both combined with oral cyproterone acetate 50 mg daily. Prior to CSH, trans women had lower aBMD at all measured sites (all p < 0.001), smaller cortical bone size (all p < 0.05), and lower muscle mass and strength and lean body mass (all p < 0.05) compared with control men. During CSH, muscle mass and strength decreased and all measures of fat mass increased (all p < 0.001). The aBMD increased at the femoral neck, radius, lumbar spine, and total body; cortical and trabecular bone remained stable and bone turnover markers decreased (all p < 0.05). Although trans women, before CSH, have a lower aBMD and cortical bone size compared with control men, their skeletal status is well preserved during CSH treatment, despite of substantial muscle loss.

Calcium and bone metabolism during space flight

NASA Technical Reports Server (NTRS)

Smith, Scott M.; Heer, Martina

2002-01-01

Weightlessness induces bone loss. Understanding the nature of this loss and developing means to counteract it are significant challenges to potential human exploration missions. This article reviews the existing information from studies of bone and calcium metabolism conducted during space flight. It also highlights areas where nutrition may play a specific role in this bone loss, and where countermeasures may be developed to mitigate that loss.

Ready to Use Tissue Construct for Military Bone & Cartilage Trauma

DTIC Science & Technology

2015-12-01

loss, bone loss, cartilage loss, stiffness, limping, pain , arthritis, and permanent disability, often requiring multiple reconstructive surgeries and...immediate, short-term and long-term consequences such as acute limb loss, bone loss, cartilage loss, stiffness, limping, pain , arthritis, and permanent...blast-injury. Osteochondral injuries of any size require anatomically perfect reconstruction to prevent pain and post-traumatic arthritis. We

Contribution of mechanical unloading to trabecular bone loss following non-invasive knee injury in mice.

PubMed

Anderson, Matthew J; Diko, Sindi; Baehr, Leslie M; Baar, Keith; Bodine, Sue C; Christiansen, Blaine A

2016-10-01

Development of osteoarthritis commonly involves degeneration of epiphyseal trabecular bone. In previous studies, we observed 30-44% loss of epiphyseal trabecular bone (BV/TV) from the distal femur within 1 week following non-invasive knee injury in mice. Mechanical unloading (disuse) may contribute to this bone loss; however, it is unclear to what extent the injured limb is unloaded following injury, and whether disuse can fully account for the observed magnitude of bone loss. In this study, we investigated the contribution of mechanical unloading to trabecular bone changes observed following non-invasive knee injury in mice (female C57BL/6N). We investigated changes in gait during treadmill walking, and changes in voluntary activity level using Open Field analysis at 4, 14, 28, and 42 days post-injury. We also quantified epiphyseal trabecular bone using μCT and weighed lower-limb muscles to quantify atrophy following knee injury in both ground control and hindlimb unloaded (HLU) mice. Gait analysis revealed a slightly altered stride pattern in the injured limb, with a decreased stance phase and increased swing phase. However, Open Field analysis revealed no differences in voluntary movement between injured and sham mice at any time point. Both knee injury and HLU resulted in comparable magnitudes of trabecular bone loss; however, HLU resulted in considerably more muscle loss than knee injury, suggesting another mechanism contributing to bone loss following injury. Altogether, these data suggest that mechanical unloading likely contributes to trabecular bone loss following non-invasive knee injury, but the magnitude of this bone loss cannot be fully explained by disuse. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1680-1687, 2016. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Contribution of mechanical unloading to trabecular bone loss following non-invasive knee injury in mice

PubMed Central

Anderson, Matthew J.; Diko, Sindi; Baehr, Leslie M.; Baar, Keith; Bodine, Sue C.; Christiansen, Blaine A.

2016-01-01

Development of osteoarthritis commonly involves degeneration of epiphyseal trabecular bone. In previous studies, we observed 30–44% loss of epiphyseal trabecular bone (BV/TV) from the distal femur within one week following non-invasive knee injury in mice. Mechanical unloading (disuse) may contribute to this bone loss, however it is unclear to what extent the injured limb is unloaded following injury, and whether disuse can fully account for the observed magnitude of bone loss. In this study, we investigated the contribution of mechanical unloading to trabecular bone changes observed following non-invasive knee injury in mice (female C57BL/6N). We investigated changes in gait during treadmill walking, and changes in voluntary activity level using Open Field analysis at 4, 14, 28, and 42 days post-injury. We also quantified epiphyseal trabecular bone using μCT and weighed lower-limb muscles to quantify atrophy following knee injury in both ground control and hindlimb unloaded (HLU) mice. Gait analysis revealed a slightly altered stride pattern in the injured limb, with a decreased stance phase and increased swing phase. However, Open Field analysis revealed no differences in voluntary movement between injured and sham mice at any time point. Both knee injury and HLU resulted in comparable magnitudes of trabecular bone loss, however HLU resulted in considerably more muscle loss than knee injury, suggesting another mechanism contributing to bone loss following injury. Altogether, these data suggest that mechanical unloading likely contributes to trabecular bone loss following non-invasive knee injury, but the magnitude of this bone loss cannot be fully explained by disuse. PMID:26826014

Breast Cancer and Bone Loss

MedlinePlus

... Resource Find an Endocrinologist Search Breast Cancer and Bone Loss July 2010 Download PDFs English Espanol Editors ... What is the link between breast cancer and bone loss? Certain treatments for breast cancer can lead ...

Risedronate Prevents Early Radiation-Induced Osteoporosis in Mice at Multiple Skeletal Locations

PubMed Central

Willey, Jeffrey S.; Livingston, Eric W.; Robbins, Michael E.; Bourland, J. Daniel; Tirado-Lee, Leidamarie; Smith-Sielicki, Hope; Bateman, Ted A.

2009-01-01

Introduction Irradiation of normal, non-malignant bone during cancer therapy can lead to atrophy and increased risk of fracture at several skeletal sites, particularly the hip. This bone loss has been largely attributed to damaged osteoblasts. Little attention has been given to increased bone resorption as a contributor to radiation-induced osteoporosis. Our aims were to identify if radiation increases bone resorption resulting in acute bone loss, and if bone loss could be prevented by administering risedronate. Methods Twenty-week old female C57BL/6 mice were either: not irradiated and treated with placebo (NR+PL); whole-body irradiated with 2 Gy X-rays and treated with placebo (IR+PL); or irradiated and treated with risedronate (IR+RIS; 30μg/kg every other day). Calcein injections were administered 7 and 2 days before sacrifice. Bones were collected 1, 2, and 3 weeks after exposure. MicroCT analysis was performed at 3 sites: proximal tibial metaphysis; distal femoral metaphysis; and the body of the 5th lumbar vertebra (L5). Osteoclasts were identified from TRAP-stained histological sections. Dynamic histomorphometry of cortical and trabecular bone was performed. Circulating TRAP5b and osteocalcin concentrations were quantified. Results In animals receiving IR+PL, significant (P < 0.05) reduction in trabecular volume fraction relative to non-irradiated controls was observed at all three skeletal sites and time points. Likewise, radiation-induced loss of connectivity and trabecular number relative to NR+PL were observed at all skeletal sites throughout the study. Bone loss primarily occurred during the first week post-exposure. Trabecular and endocortical bone formation was not reduced until Week 2. Loss of bone volume was absent in animals receiving IR+RIS. Histology indicated greater osteoclast numbers at Week 1 within IR+PL mice. Serum TRAP5b concentration was increased in IR+PL mice only at Week 1 compared to NR+PL (P = 0.05). Risedronate treatment prevented the radiation-induced increase in osteoclast number, surface, and TRAP5b. Conclusion This study demonstrated a rapid loss of trabecular bone at several skeletal sites after whole-body irradiation. Changes were accompanied by an increase in osteoclast number and serum markers of bone loss. Risedronate entirely prevented bone loss, providing further evidence that an increase in bone resorption likely caused this radiation-induced bone loss. PMID:19747571

An individualised risk-adapted protocol of pre- and post transplant zoledronic acid reduces bone loss after allogeneic stem cell transplantation: results of a phase II prospective trial.

PubMed

Grigg, A; Butcher, B; Khodr, B; Bajel, A; Hertzberg, M; Patil, S; D'Souza, A B; Ganly, P; Ebeling, P; Wong, E

2017-09-01

Bone loss occurs frequently following allogeneic haematopoietic stem cell transplantation (alloSCT). The Australasian Leukaemia and Lymphoma Group conducted a prospective phase II study of pretransplant zoledronic acid (ZA) and individualised post-transplant ZA to prevent bone loss in alloSCT recipients. Patients received ZA 4 mg before conditioning. Administration of post-transplant ZA from days 100 to 365 post alloSCT was determined by a risk-adapted algorithm based on serial bone density assessments and glucocorticoid exposure. Of 82 patients enrolled, 70 were alive and without relapse at day 100. A single pretransplant dose of ZA prevented femoral neck bone loss at day 100 compared with baseline (mean change -2.6±4.6%). Using the risk-adapted protocol, 42 patients received ZA between days 100 and 365 post alloSCT, and this minimised bone loss at day 365 compared with pretransplant levels (mean change -2.9±5.3%). Femoral neck bone loss was significantly reduced in ZA-treated patients compared with historical untreated controls at days 100 and 365. This study demonstrates that a single dose of ZA pre-alloSCT prevents femoral neck bone loss at day 100 post alloSCT, and that a risk-adapted algorithm is able to guide ZA administration from days 100 to 365 post transplant and minimise further bone loss.

HIV-1 infection and antiretroviral therapies: risk factors for osteoporosis and bone fracture.

PubMed

Ofotokun, Ighovwerha; Weitzmann, M Neale

2010-12-01

Patients with HIV-1 infection/AIDS are living longer due to the success of highly active antiretroviral therapy (HAART). However, serious metabolic complications including bone loss and fractures are becoming common. Understanding the root causes of bone loss and its potential implications for aging AIDS patients will be critical to the design of effective interventions to stem a tidal wave of fractures in a population chronically exposed to HAART. Paradoxically, bone loss may occur not only due to HIV/AIDS but also as a consequence of HAART. The cause and mechanisms driving these distinct forms of bone loss, however, are complex and controversial. This review examines our current understanding of the underlying causes of HIV-1 and HAART-associated bone loss, and recent findings pertaining to the relevance of the immuno-skeletal interface in this process. It is projected that by 2015 more than half of the HIV/AIDS population in the USA will be over the age of 50 and the synergy between HIV and/or HAART-related bone loss with age-associated bone loss could lead to a significant health threat. Aggressive antiresorptive therapy may be warranted in high-risk patients.

Mineralization defects in cementum and craniofacial bone from loss of bone sialoprotein

PubMed Central

Foster, B.L.; Ao, M.; Willoughby, C.; Soenjaya, Y.; Holm, E.; Lukashova, L.; Tran, A. B.; Wimer, H.F.; Zerfas, P.M.; Nociti, F.H.; Kantovitz, K.R.; Quan, B.D.; Sone, E.D.; Goldberg, H.A.; Somerman, M.J.

2015-01-01

Bone sialoprotein (BSP) is a multifunctional extracellular matrix protein found in mineralized tissues, including bone, cartilage, tooth root cementum (both acellular and cellular types), and dentin. In order to define the role BSP plays in the process of biomineralization of these tissues, we analyzed cementogenesis, dentinogenesis, and osteogenesis (intramembranous and endochondral) in craniofacial bone in Bsp null mice and wild-type (WT) controls over a developmental period (1-60 days post natal; dpn) by histology, immunohistochemistry, undecalcified histochemistry, microcomputed tomography (microCT), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and quantitative PCR (qPCR). Regions of intramembranous ossification in the alveolus, mandible, and calvaria presented delayed mineralization and osteoid accumulation, assessed by von Kossa and Goldner's trichrome stains at 1 and 14 dpn. Moreover, Bsp−/− mice featured increased cranial suture size at the early time point, 1 dpn. Immunostaining and PCR demonstrated that osteoblast markers, osterix, alkaline phosphatase, and osteopontin were unchanged in Bsp null mandibles compared to WT. Bsp−/− mouse molars featured a lack of functional acellular cementum formation by histology, SEM, and TEM, and subsequent loss of Sharpey's collagen fiber insertion into the tooth root structure. Bsp−/− mouse alveolar and mandibular bone featured equivalent or fewer osteoclasts at early ages (1 and 14 dpn), however, increased RANKL immunostaining and mRNA, and significantly increased number of osteoclast-like cells (2-5 fold) were found at later ages (26 and 60 dpn), corresponding to periodontal breakdown and severe alveolar bone resorption observed following molar teeth entering occlusion. Dentin formation was unperturbed in Bsp−/− mouse molars, with no delay in mineralization, no alteration in dentin dimensions, and no differences in odontoblast markers analyzed. No defects were identified in endochondral ossification in the cranial base, and craniofacial morphology was unaffected in Bsp−/− mice. These analyses confirm a critical role for BSP in processes of cementogenesis and intramembranous ossification of craniofacial bone, whereas endochondral ossification in the cranial base was minimally affected and dentinogenesis was normal in Bsp−/− molar teeth. Dissimilar effects of loss of BSP on mineralization of dental and craniofacial tissues suggest local differences in the role of BSP and/or yet to be defined interactions with site-specific factors. PMID:25963390

[Quantitative data analysis for live imaging of bone.

PubMed

Seno, Shigeto

Bone tissue is a hard tissue, it was difficult to observe the interior of the bone tissue alive. With the progress of microscopic technology and fluorescent probe technology in recent years, it becomes possible to observe various activities of various cells forming bone society. On the other hand, the quantitative increase in data and the diversification and complexity of the images makes it difficult to perform quantitative analysis by visual inspection. It has been expected to develop a methodology for processing microscopic images and data analysis. In this article, we introduce the research field of bioimage informatics which is the boundary area of biology and information science, and then outline the basic image processing technology for quantitative analysis of live imaging data of bone.

Association between fat mass, lean mass, and bone loss: the Dubbo Osteoporosis Epidemiology Study.

PubMed

Yang, S; Center, J R; Eisman, J A; Nguyen, T V

2015-04-01

Lower body fat mass is a risk factor for bone loss at lumbar spine in postmenopausal women, but not in men. Body lean mass and fat mass were not associated with femoral neck bone loss in either gender. Bone density and body mass are closely associated. Whole body lean mass (LM) and fat mass (FM) together account for approximately 95 % of body mass. Bone loss is associated with loss of body mass but which of the components of body mass (FM or LM) is related to bone loss is not well understood. Therefore, in this study, we sought to assess whether baseline FM or LM has predictive value for future relative rate of bone mineral density (BMD) changes (%/year). The present population-based cohort study was part of the ongoing Dubbo Osteoporosis Epidemiology Study (DOES). BMD, FM, and LM were measured with dual energy X-ray absorptiometry (GE-LUNAR Corp, Madison, WI). BMD measurements were taken in approximately every 2 years between 2000 and 2010. We only included the participants with at least two BMD measurements at the femoral neck and lumbar spine. In total, 717 individuals (204 men and 513 women) aged 50 years or older were studied. Rate of bone loss at femoral neck and lumbar spine was faster in women than in men (all P < 0.01). In bivariable regression analysis, each 5 kg greater FM in women was associated with 0.4 %/year (P = 0.003) lower bone loss at lumbar spine. This magnitude of association remained virtually unchanged after adjusting for LM and/or other covariates (P = 0.03). After adjusting for covariates, variation of FM accounted for ∼1.5 % total variation in lumbar spine bone loss. However, there was no significant association between FM and change in femoral neck BMD in either men or women. Lower FM was an independent but modest risk factor for greater bone loss at the lumbar spine in women but not in men. If further studies confirm our findings, FM can help predict lumbar spine bone loss in women.

Predicting Bone Mechanical State During Recovery After Long-Duration Skeletal Unloading Using QCT and Finite Element Modeling

NASA Technical Reports Server (NTRS)

Chang, Katarina L.; Pennline, James A.

2013-01-01

During long-duration missions at the International Space Station, astronauts experience weightlessness leading to skeletal unloading. Unloading causes a lack of a mechanical stimulus that triggers bone cellular units to remove mass from the skeleton. A mathematical system of the cellular dynamics predicts theoretical changes to volume fractions and ash fraction in response to temporal variations in skeletal loading. No current model uses image technology to gather information about a skeletal site s initial properties to calculate bone remodeling changes and then to compare predicted bone strengths with the initial strength. The goal of this study is to use quantitative computed tomography (QCT) in conjunction with a computational model of the bone remodeling process to establish initial bone properties to predict changes in bone mechanics during bone loss and recovery with finite element (FE) modeling. Input parameters for the remodeling model include bone volume fraction and ash fraction, which are both computed from the QCT images. A non-destructive approach to measure ash fraction is also derived. Voxel-based finite element models (FEM) created from QCTs provide initial evaluation of bone strength. Bone volume fraction and ash fraction outputs from the computational model predict changes to the elastic modulus of bone via a two-parameter equation. The modulus captures the effect of bone remodeling and functions as the key to evaluate of changes in strength. Application of this time-dependent modulus to FEMs and composite beam theory enables an assessment of bone mechanics during recovery. Prediction of bone strength is not only important for astronauts, but is also pertinent to millions of patients with osteoporosis and low bone density.

In Vitro Evaluation of Nanoscale Hydroxyapatite-Based Bone Reconstructive Materials with Antimicrobial Properties.

PubMed

Ajduković, Zorica R; Mihajilov-Krstev, Tatjana M; Ignjatović, Nenad L; Stojanović, Zoran; Mladenović-Antić, Snezana B; Kocić, Branislava D; Najman, Stevo; Petrović, Nenad D; Uskoković, Dragan P

2016-02-01

In the field of oral implantology the loss of bone tissue prevents adequate patient care, and calls for the use of synthetic biomaterials with properties that resemble natural bone. Special attention is paid to the risk of infection after the implantation of these materials. Studies have suggested that some nanocontructs containing metal ions have antimicrobial properties. The aim of this study was to examine the antimicrobial and hemolytic activity of cobalt-substituted hydroxyapatite nanoparticles, compared to hydroxyapatite and hydroxyapatite/poly-lactide-co-glycolide. The antibacterial effects of these powders were tested against two pathogenic bacterial strains: Escherichia coi (ATCC 25922) and Staphylococcus aureus (ATCC 25923), using the disc diffusion method and the quantitative antimicrobial test in a liquid medium. The quantitative antimicrobial test showed that all of the tested biomaterials have some antibacterial properties. The effects of both tests were more prominent in case of S. aureus than in E coli. A higher percentage of cobalt in the crystal structure of cobalt-substituted hydroxyapatite nanoparticles led to an increased antimicrobial activity. All of the presented biomaterial samples were found to be non-hemolytic. Having in mind that the tested of cobalt-substituted hydroxyapatite (Ca/Co-HAp) material in given concentrations shows good hemocompatibility and antimicrobial effects, along with its previously studied biological properties, the conclusion can be reached that it is a potential candidate that could substitute calcium hydroxyapatite as the material of choice for use in bone tissue engineering and clinical practices in orthopedic, oral and maxillofacial surgery.

The estrogen-related receptors (ERRs): potential targets against bone loss.

PubMed

Zhang, Ling; Wong, Jiemin; Vanacker, Jean-Marc

2016-10-01

Bone loss and the resulting skeletal fragility is induced by several pathological or natural conditions, the most prominent of which being aging as well as the decreased levels of circulating estrogens in post-menopause females. To date, most treatments against bone loss aim at preventing excess bone resorption. We here summarize data indicating that the estrogen-related receptors (ERRs) α and γ prevent bone formation. Inhibiting these receptors may thus constitute an anabolic approach by increasing bone formation.

Ionizing Radiation Affects Gene Expression in Mouse Skin and Bone

NASA Technical Reports Server (NTRS)

Terada, Masahiro; Tahimic, Candice; Sowa, Marianne B.; Schreurs, Ann-Sofie; Shirazi-Fard, Yasaman; Alwood, Joshua; Globus, Ruth K.

2017-01-01

Future long-duration space exploration beyond low earth orbit will increase human exposure to space radiation and microgravity conditions as well as associated risks to skeletal health. In animal studies, radiation exposure (greater than 1 Gy) is associated with pathological changes in bone structure, enhanced bone resorption, reduced bone formation and decreased bone mineral density, which can lead to skeletal fragility. Definitive measurements and detection of bone loss typically require large and specialized equipment which can make their application to long duration space missions logistically challenging. Towards the goal of developing non-invasive and less complicated monitoring methods to predict astronauts' health during spaceflight, we examined whether radiation induced gene expression changes in skin may be predictive of the responses of skeletal tissue to radiation exposure. We examined oxidative stress and growth arrest pathways in mouse skin and long bones by measuring gene expression levels via quantitative polymerase chain reaction (qPCR) after exposure to total body irradiation (IR). To investigate the effects of irradiation on gene expression, we used skin and femora (cortical shaft) from the following treatment groups: control (normally loaded, sham-irradiated), and IR (0.5 Gy 56Fe 600 MeV/n and 0.5 Gy 1H 150 MeV/n), euthanized at one and 11 days post-irradiation (IR). To determine the extent of bone loss, tibiae were harvested and cancellous microarchitecture in the proximal tibia quantified ex vivo using microcomputed tomography (microCT). Statistical analysis was performed using Student's t-test. At one day post-IR, expression of FGF18 in skin was significantly greater (3.8X) than sham-irradiated controls, but did not differ at 11 days post IR. Expression levels of other genes associated with antioxidant response (Nfe2l2, FoxO3 and Sod1) and the cell cycle (Trp53, Cdkn1a, Gadd45g) did not significantly differ between the control and IR groups at either time point. Radiation exposure resulted in a 27.0% increase in FGF18-positive hair follicles at one day post-IR and returned to basal levels at 11 days post-IR. A similar trend was observed from FGF18 gene expression analysis of skin. In bone (femora), there was an increase in the expression of the pro-osteoclastogenic cytokine, MCP-1, one day after IR compared to non-irradiated controls. FGF18 expression in skin and MCP- 1 expression in bone were found to be positively correlated (P less than 0.002, r=0.8779). Further, microcomputed tomography analysis of tibia from these animals showed reduced cancellous bone volume (-9.9%) at 11 days post- IR. These results suggest that measurements of early radiation induced changes in FGF18 gene expression in skin may have value for predicting subsequent loss of cancellous bone mass. Further research may lead to the development of a relatively simple diagnostic tool for bone loss, with the advantage that hair follicles and skin are relatively easy to acquire from human subjects.

Modeling Calcium Loss from Bones During Space Flight

NASA Technical Reports Server (NTRS)

Wastney, Meryl E.; Morukov, Boris V.; Larina, Irina M.; Abrams, Steven A.; Nillen, Jeannie L.; Davis-Street, Janis E.; Lane, Helen W.; Smith, Scott M.; Paloski, W. H. (Technical Monitor)

1999-01-01

Calcium loss from bones during space flight creates a risk for astronauts who travel into space, and may prohibit space flights to other planets. The problem of calcium loss during space flight has been studied using animal models, bed rest (as a ground-based model), and humans in-flight. In-flight studies have typically documented bone loss by comparing bone mass before and after flight. To identify changes in metabolism leading to bone loss, we have performed kinetic studies using stable isotopes of calcium. Oral (Ca-43) and intravenous (Ca-46) tracers were administered to subjects (n=3), three-times before flight, once in-flight (after 110 days), and three times post-flight (on landing day, and 9 days and 3 months after flight). Samples of blood, saliva, urine, and feces were collected for up to 5 days after isotope administration, and were analyzed for tracer enrichment. Tracer data in tissues were analyzed using a compartmental model for calcium metabolism and the WinSAAM software. The model was used to: account for carryover of tracer between studies, fit data for all studies using the minimal number of changes between studies, and calculate calcium absorption, excretion, bone calcium deposition and bone calcium resorption. Results showed that fractional absorption decreased by 50% during flight and that bone resorption and urinary excretion increased by 50%. Results were supported by changes in biochemical markers of bone metabolism. Inflight bone loss of approximately 250 mg Ca/d resulted from decreased calcium absorption combined with increased bone resorption and excretion. Further studies will assess the time course of these changes during flight, and the effectiveness of countermeasures to mitigate flight-induced bone loss. The overall goal is to enable human travel beyond low-Earth orbit, and to allow for better understanding and treatment of bone diseases on Earth.

Biophotonics and Bone Biology

NASA Technical Reports Server (NTRS)

Zimmerli, Gregory; Fischer, David; Asipauskas, Marius; Chauhan, Chirag; Compitello, Nicole; Burke, Jamie; Tate, Melissa Knothe

2004-01-01

One of the more-serious side effects of extended space flight is an accelerated bone loss [Bioastronautics Critical Path Roadmap, http://research.hq.nasa.gov/code_u/bcpr/index.cfm]. Rates of bone loss are highest in the weight-bearing bones of the hip and spine regions, and the average rate of bone loss as measured by bone mineral density measurements is around 1.2% per month for persons in a microgravity environment. It shows that an extrapolation of the microgravity induced bone loss rates to longer time scales, such as a 2.5 year round-trip to Mars (6 months out at 0 g, 1.5 year stay on Mars at 0.38 g, 6 months back at 0 g), could severely compromise the skeletal system of such a person.

Preservation of bone structure and function by Lithothamnion sp. – derived minerals

PubMed Central

Aslam, Muhammad Nadeem; Bergin, Ingrid; Jepsen, Karl; Kreider, Jaclynn M.; Graf, Kristin H.; Naik, Madhav; Goldstein, Steven A.; Varani, James

2013-01-01

Progressive bone mineral loss and increasing bone fragility are hallmarks of osteoporosis. A combination of minerals isolated from the red marine algae, Lithothamnion sp. was examined for ability to inhibit bone mineral loss in female mice maintained on either a standard rodent chow (control) diet or a high-fat western diet (HFWD) for 5-, 12- and 18-months. At each time-point, femora were subjected to μ-CT analysis and biomechanical testing. A subset of caudal vertebrae was also analyzed. Following this, individual elements were assessed in bones. Serum levels of the 5b isoform of tartrate-resistant acid phosphatase (TRAP) and procollagen type I propeptide (P1NP) were also measured. Trabecular bone loss occurred in both diets (evident as early as 5-months). Cortical bone increased through month-5 and then declined. Cortical bone loss was primarily in mice on the HFWD. Inclusion of the minerals in the diet reduced bone mineral loss in both diets and improved bone strength. Bone mineral density (BMD) was also enhanced by these minerals. Of several cationic minerals known to be important to bone health, only strontium was significantly increased in bone tissue from animals fed the mineral diets, but the increase was large (5–10 fold). Serum levels of TRAP were consistently higher in mice receiving the minerals but levels of P1NP were not. These data suggest that trace minerals derived from marine red algae may be used to prevent progressive bone mineral loss in conjunction with calcium. Mineral supplementation could find use as part of an osteoporosis - prevention strategy. PMID:24096551

Preservation of bone structure and function by Lithothamnion sp. derived minerals.

PubMed

Aslam, Muhammad Nadeem; Bergin, Ingrid; Jepsen, Karl; Kreider, Jaclynn M; Graf, Kristin H; Naik, Madhav; Goldstein, Steven A; Varani, James

2013-12-01

Progressive bone mineral loss and increasing bone fragility are hallmarks of osteoporosis. A combination of minerals isolated from the red marine algae, Lithothamnion sp. was examined for ability to inhibit bone mineral loss in female mice maintained on either a standard rodent chow (control) diet or a high-fat western diet (HFWD) for 5, 12, and 18 months. At each time point, femora were subjected to μ-CT analysis and biomechanical testing. A subset of caudal vertebrae was also analyzed. Following this, individual elements were assessed in bones. Serum levels of the 5b isoform of tartrate-resistant acid phosphatase (TRAP) and procollagen type I propeptide (P1NP) were also measured. Trabecular bone loss occurred in both diets (evident as early as 5 months). Cortical bone increased through month 5 and then declined. Cortical bone loss was primarily in mice on the HFWD. Inclusion of the minerals in the diet reduced bone mineral loss in both diets and improved bone strength. Bone mineral density was also enhanced by these minerals. Of several cationic minerals known to be important to bone health, only strontium was significantly increased in bone tissue from animals fed the mineral diets, but the increase was large (5-10 fold). Serum levels of TRAP were consistently higher in mice receiving the minerals, but levels of P1NP were not. These data suggest that trace minerals derived from marine red algae may be used to prevent progressive bone mineral loss in conjunction with calcium. Mineral supplementation could find use as part of an osteoporosis-prevention strategy.

Chronic skin inflammation leads to bone loss by IL-17-mediated inhibition of Wnt signaling in osteoblasts.

PubMed

Uluçkan, Özge; Jimenez, Maria; Karbach, Susanne; Jeschke, Anke; Graña, Osvaldo; Keller, Johannes; Busse, Björn; Croxford, Andrew L; Finzel, Stephanie; Koenders, Marije; van den Berg, Wim; Schinke, Thorsten; Amling, Michael; Waisman, Ari; Schett, Georg; Wagner, Erwin F

2016-03-16

Inflammation has important roles in tissue regeneration, autoimmunity, and cancer. Different inflammatory stimuli can lead to bone loss by mechanisms that are not well understood. We show that skin inflammation induces bone loss in mice and humans. In psoriasis, one of the prototypic IL-17A-mediated inflammatory human skin diseases, low bone formation and bone loss correlated with increased serum IL-17A levels. Similarly, in two mouse models with chronic IL-17A-mediated skin inflammation,K14-IL17A(ind)andJunB(Δep), strong inhibition of bone formation was observed, different from classical inflammatory bone loss where osteoclast activation leads to bone degradation. We show that under inflammatory conditions, skin-resident cells such as keratinocytes, γδ T cells, and innate lymphoid cells were able to express IL-17A, which acted systemically to inhibit osteoblast and osteocyte function by a mechanism involving Wnt signaling. IL-17A led to decreased Wnt signaling in vitro, and importantly, pharmacological blockade of IL-17A rescued Wnt target gene expression and bone formation in vivo. These data provide a mechanism where IL-17A affects bone formation by regulating Wnt signaling in osteoblasts and osteocytes. This study suggests that using IL-17A blocking agents in psoriasis could be beneficial against bone loss in these patients. Copyright © 2016, American Association for the Advancement of Science.

BA321, a novel carborane analog that binds to androgen and estrogen receptors, acts as a new selective androgen receptor modulator of bone in male mice

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

Watanabe, Kenta; Cooperative Major in Advanced Health Science, Tokyo University of Agriculture and Technology, 2-24-16 Nakamachi, Koganei, Tokyo 184-8588; Hirata, Michiko

Carboranes are a class of carbon-containing polyhedral boron cluster compounds with globular geometry and hydrophobic surface that interact with hormone receptors such as estrogen receptor (ER) and androgen receptor (AR). We have synthesized BA321, a novel carborane compound, which binds to AR. We found here that it also binds to ERs, ERα and ERβ. In orchidectomized (ORX) mice, femoral bone mass was markedly reduced due to androgen deficiency and BA321 restored bone loss in the male, whilst the decreased weight of seminal vesicle in ORX mice was not recovered by administration of BA321. In female mice, BA321 acts as amore » pure estrogen agonist, and restored both the loss of bone mass and uterine atrophy due to estrogen deficiency in ovariectomized (OVX) mice. In bone tissues, the trabecular bone loss occurred in both ORX and OVX mice, and BA321 completely restored the trabecular bone loss in both sexes. Cortical bone loss occurred in ORX mice but not in OVX mice, and BA321 clearly restored cortical bone loss due to androgen deficiency in ORX mice. Therefore, BA321 is a novel selective androgen receptor modulator (SARM) that may offer a new therapy option for osteoporosis in the male. - Highlights: • A novel carborane compound BA321 binds to both AR and ERs, ERα and ERβ. • BA321 restores bone loss in orchidectomized mice without effects on sex organ. • BA321 acts as an estrogen agonist in bone and uterus in ovariectomized mice. • BA321 may be a new SARM to prevent the loss of musculoskeletal mass in elder men.« less

Management bone loss of the proximal femur in revision hip arthroplasty: Update on reconstructive options

PubMed Central

Sakellariou, Vasileios I; Babis, George C

2014-01-01

The number of revision total hip arthroplasties is expected to rise as the indications for arthroplasty will expand due to the aging population. The prevalence of extensive proximal femoral bone loss is expected to increase subsequently. The etiology of bone loss from the proximal femur after total hip arthroplasty is multifactorial. Stress shielding, massive osteolysis, extensive loosening and history of multiple surgeries consist the most common etiologies. Reconstruction of extensive bone loss of the proximal femur during a revision hip arthroplasty is a major challenge for even the most experienced orthopaedic surgeon. The amount of femoral bone loss and the bone quality of the remaining metaphyseal and diaphyseal bone dictate the selection of appropriate reconstructive option. These include the use of impaction allografting, distal press-fit fixation, allograft-prosthesis composites and tumor megaprostheses. This review article is a concise review of the current literature and provides an algorithmic approach for reconstruction of different types of proximal femoral bone defects. PMID:25405090

Bone formation is not impaired by hibernation (disuse) in black bears Ursus americanus

USGS Publications Warehouse

Donahue, S.W.; Vaughan, M.R.; Demers, L.M.; Donahue, H.J.

2003-01-01

Disuse by bed rest, limb immobilization or space flight causes rapid bone loss by arresting bone formation and accelerating bone resorption. This net bone loss increases the risk of fracture upon remobilization. Bone loss also occurs in hibernating ground squirrels, golden hamsters, and little brown bats by arresting bone formation and accelerating bone resorption. There is some histological evidence to suggest that black bears Ursus americanus do not lose bone mass during hibernation (i.e. disuse). There is also evidence suggesting that muscle mass and strength are preserved in black bears during hibernation. The question of whether bears can prevent bone loss during hibernation has not been conclusively answered. The goal of the current study was to further assess bone metabolism in hibernating black bears. Using the same serum markers of bone remodeling used to evaluate human patients with osteoporosis, we assayed serum from five black bears, collected every 10 days over a 196-day period, for bone resorption and formation markers. Here we show that bone resorption remains elevated over the entire hibernation period compared to the pre-hibernation period, but osteoblastic bone formation is not impaired by hibernation and is rapidly accelerated during remobilization following hibernation.

An Quantitative Analysis Method Of Trabecular Pattern In A Bone

NASA Astrophysics Data System (ADS)

Idesawa, Masanor; Yatagai, Toyohiko

1982-11-01

Orientation and density of trabecular pattern observed in a bone is closely related to its mechanical properties and deseases of a bone are appeared as changes of orientation and/or density distrbution of its trabecular patterns. They have been treated from a qualitative point of view so far because quantitative analysis method has not be established. In this paper, the authors proposed and investigated some quantitative analysis methods of density and orientation of trabecular patterns observed in a bone. These methods can give an index for evaluating orientation of trabecular pattern quantitatively and have been applied to analyze trabecular pattern observed in a head of femur and their availabilities are confirmed. Key Words: Index of pattern orientation, Trabecular pattern, Pattern density, Quantitative analysis

The impact of smoking on marginal bone loss in a 10-year prospective longitudinal study.

PubMed

Bahrami, Golnosh; Vaeth, Michael; Kirkevang, Lise-Lotte; Wenzel, Ann; Isidor, Flemming

2016-09-21

The aim of this epidemiologic study was to determine the impact of smoking on marginal bone loss in a subsample derived from an original randomly selected adult sample, after adjusting for oral and general factors. The number of participants at baseline in this 10-year longitudinal study was 616 (mean age: 42 years, range 21-63 years). The participants underwent a full-mouth radiographic survey. After recall in 2003, 473 (77%) of the participants accepted and completed an identical survey. In 2008, the survey was repeated, and 301 (48.9%) individuals were included in this study. The marginal bone level of each tooth was measured in mm. Age, gender, smoking habits, number of teeth, apical periodontitis, crowns and initial marginal bone level were also recorded for each individual. Only individuals who did not report a change in smoking habits during the 10-year period were included in the study. Multiple regression analyses were used to evaluate crude and adjusted associations between smoking and marginal bone loss. At the first, radiographic survey smokers had a statistically significantly more reduced marginal bone level (in average 0.9 mm) than nonsmokers. After 10 years, a progression of a mean marginal bone loss of > 2 mm was statistically significantly more common in smokers than in nonsmokers (7.1% and 0%, respectively). Furthermore, a marginal bone loss of 1-2 mm was observed in 29% of the smokers and 19% of the nonsmokers, and ≤ 1 mm marginal bone loss was found in 69% of smokers and 81% of nonsmokers. Even after adjusting for initial marginal bone level, gender, age, and also presence of apical periodontitis and crowns, the difference in progression of marginal bone loss was still statistically higher in smokers (on average 0.36 mm). The smokers started out with a more reduced marginal bone level than nonsmokers. However, even after adjusting for the initial marginal bone level, the progression of marginal bone loss in smokers was more pronounced than in nonsmokers. This shows that smoking is a factor with significant impact on the marginal bone level and can be assumed to be a true risk factor for marginal bone loss. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Feasibility and tolerability of whole‐body, low‐intensity vibration and its effects on muscle function and bone in patients with dystrophinopathies: a pilot study

PubMed Central

Polgreen, Lynda E.; Grames, Molly; Lowe, Dawn A.; Hodges, James S.; Karachunski, Peter

2017-01-01

ABSTRACT Introduction Dystrophinopathies are X‐linked muscle degenerative disorders that result in progressive muscle weakness complicated by bone loss. This study's goal was to evaluate feasibility and tolerability of whole‐body, low‐intensity vibration (WBLIV) and its potential effects on muscle and bone in patients with Duchenne or Becker muscular dystrophy. Methods This 12‐month pilot study included 5 patients (age 5.9–21.7 years) who used a low‐intensity Marodyne LivMD plate vibrating at 30–90 Hz for 10 min/day for the first 6 months. Timed motor function tests, myometry, and peripheral quantitative computed tomography were performed at baseline and at 6 and 12 months. Results Motor function and lower extremity muscle strength remained either unchanged or improved during the intervention phase, followed by deterioration after WBLIV discontinuation. Indices of bone density and geometry remained stable in the tibia. Conclusions WBLIV was well tolerated and appeared to have a stabilizing effect on lower extremity muscle function and bone measures. Muscle Nerve 55: 875–883, 2017 PMID:27718512

Fabric dependence of quasi-waves in anisotropic porous media

PubMed Central

Cardoso, Luis; Cowin, Stephen C.

2011-01-01

Assessment of bone loss and osteoporosis by ultrasound systems is based on the speed of sound and broadband ultrasound attenuation of a single wave. However, the existence of a second wave in cancellous bone has been reported and its existence is an unequivocal signature of poroelastic media. To account for the fact that ultrasound is sensitive to microarchitecture as well as bone mineral density (BMD), a fabric-dependent anisotropic poroelastic wave propagation theory was recently developed for pure wave modes propagating along a plane of symmetry in an anisotropic medium. Key to this development was the inclusion of the fabric tensor—a quantitative stereological measure of the degree of structural anisotropy of bone—into the linear poroelasticity theory. In the present study, this framework is extended to the propagation of mixed wave modes along an arbitrary direction in anisotropic porous media called quasi-waves. It was found that differences between phase and group velocities are due to the anisotropy of the bone microarchitecture, and that the experimental wave velocities are more accurately predicted by the poroelastic model when the fabric tensor variable is taken into account. This poroelastic wave propagation theory represents an alternative for bone quality assessment beyond BMD. PMID:21568431

Does the use of ACE inhibitors or angiotensin receptor blockers affect bone loss in older men?

PubMed Central

Leung, J.; Zhang, Y. F.; Bauer, D.; Ensrud, K. E.; Barrett-Connor, E.; Leung, P. C.

2013-01-01

Summary In a prospective cohort study of 5,995 older American men (MrOS), users of angiotensin-converting enzyme (ACE) inhibitors had a small but significant increase in bone loss at the hip over 4 years after adjustment for confounders. Use of angiotensin II AT1 receptor blockers (ARB) was not significantly associated with bone loss. Introduction Experimental evidence suggests that angiotensin II promotes bone loss by its effects on osteoblasts. It is therefore plausible that ACE inhibitor and ARB may reduce rates of bone loss. The objective of this study is to examine the independent effects of ACE inhibitor and ARB on bone loss in older men. Methods Out of 5,995 American men (87.2%) aged ≥65 years, 5,229 were followed up for an average of 4.6 years in a prospective six-center cohort study—The Osteoporotic Fractures in Men Study (MrOS). Bone mineral densities (BMD) at total hip, femoral neck, and trochanter were measured by Hologic densitometer (QDR 4500) at baseline and year 4. Results Out of 3,494 eligible subjects with complete data, 1,166 and 433 subjects reported use of ACE inhibitors and ARBs, respectively. When compared with nonusers, continuous use of ACE inhibitors was associated with a small (0.004 g/cm2) but significant increase in the average rate of BMD loss at total hip and trochanter over 4 years after adjustment for confounders. Use of ARB was not significantly associated with bone loss. Conclusion Use of ACE inhibitors but not ARB may marginally increase bone loss in older men. PMID:22080379

Quantitative analysis of rib movement based on dynamic chest bone images: preliminary results

NASA Astrophysics Data System (ADS)

Tanaka, R.; Sanada, S.; Oda, M.; Mitsutaka, M.; Suzuki, K.; Sakuta, K.; Kawashima, H.

2014-03-01

Rib movement during respiration is one of the diagnostic criteria in pulmonary impairments. In general, the rib movement is assessed in fluoroscopy. However, the shadows of lung vessels and bronchi overlapping ribs prevent accurate quantitative analysis of rib movement. Recently, an image-processing technique for separating bones from soft tissue in static chest radiographs, called "bone suppression technique", has been developed. Our purpose in this study was to evaluate the usefulness of dynamic bone images created by the bone suppression technique in quantitative analysis of rib movement. Dynamic chest radiographs of 10 patients were obtained using a dynamic flat-panel detector (FPD). Bone suppression technique based on a massive-training artificial neural network (MTANN) was applied to the dynamic chest images to create bone images. Velocity vectors were measured in local areas on the dynamic bone images, which formed a map. The velocity maps obtained with bone and original images for scoliosis and normal cases were compared to assess the advantages of bone images. With dynamic bone images, we were able to quantify and distinguish movements of ribs from those of other lung structures accurately. Limited rib movements of scoliosis patients appeared as reduced rib velocity vectors. Vector maps in all normal cases exhibited left-right symmetric distributions, whereas those in abnormal cases showed nonuniform distributions. In conclusion, dynamic bone images were useful for accurate quantitative analysis of rib movements: Limited rib movements were indicated as a reduction of rib movement and left-right asymmetric distribution on vector maps. Thus, dynamic bone images can be a new diagnostic tool for quantitative analysis of rib movements without additional radiation dose.

Diabetes mellitus related bone metabolism and periodontal disease

PubMed Central

Wu, Ying-Ying; Xiao, E; Graves, Dana T

2015-01-01

Diabetes mellitus and periodontal disease are chronic diseases affecting a large number of populations worldwide. Changed bone metabolism is one of the important long-term complications associated with diabetes mellitus. Alveolar bone loss is one of the main outcomes of periodontitis, and diabetes is among the primary risk factors for periodontal disease. In this review, we summarise the adverse effects of diabetes on the periodontium in periodontitis subjects, focusing on alveolar bone loss. Bone remodelling begins with osteoclasts resorbing bone, followed by new bone formation by osteoblasts in the resorption lacunae. Therefore, we discuss the potential mechanism of diabetes-enhanced bone loss in relation to osteoblasts and osteoclasts. PMID:25857702

Management of bone disease in women after breast cancer.

PubMed

Milat, F; Vincent, A J

2015-01-01

Breast cancer and osteoporosis are common conditions affecting women, particularly following menopause. With increasing breast cancer incidence, effects of therapies and decreasing mortality, issues relating to the preservation of bone health with breast cancer therapy have become a priority. Contributing factors to bone loss and fractures in women with breast cancer include tumor effects, estrogen deprivation secondary to breast cancer therapies (chemotherapy, ovarian ablation or aromatase inhibitors), natural menopause and secondary causes of bone loss, typically from concurrently prescribed medications. Management of osteoporosis and other survivorship care is complex, and a multi-disciplinary approach is recommended with assessment of risk factors for bone loss, optimization of bone health through lifestyle approaches and pharmacological interventions based on evidence-based algorithms. This review examines the pathophysiology of bone loss and gives guidelines for the management of bone disease in women with breast cancer.

S-Ketoprofen Inhibits Tenotomy-Induced Bone Loss and Dynamics in Weanling Rats

NASA Technical Reports Server (NTRS)

Zeng, Q. Q.; Jee, W. S. S.; Ke, H. Z.; Wechter, W. J.

1993-01-01

The objects of this study were to determine whether S-ketoprofen, a non-steroidal anti-inflammatory drug (NSAID), can prevent immobilization (tenotomy)-induced bone loss in weanling rats. Forty five 4 week-old Sprague-Dawley female rats were either sham-operated or subjected to knee tenotomy and treated simultaneously with 0, 0.02, 0.1, 0.5 or 2.5 mg of S-ketoprofen/kg per day for 21 days. We then studied double-fluorescent labeled proximal tibial longitudinal sections and tibial shaft cross sections using static and dynamic histomorphometry. Less cancellous bone mass in proximal tibial metaphyses was found in tenotomized controls than in basal (36%) and sham-operated (54%) controls. This was due to the inhibition of age-related bone gain and induced bone loss due to increased bone resorption and decreased bone formation. S-ketoprofen prevented both the inhibition of age-related bone gain and the stimulation of bone loss at the 2.5 mg/kg per day dose level, while it only prevented bone loss at the 0.5 mg/kg dose levels. In cancellous bone, dynamic histomorphometry showed that S-ketoprofen prevented the tenotomy induced decrease in bone formation and increase in bone resorption. In the tibial shaft, tenotomy inhibited the enlargement of total tissue area by depressing periosteal bone formation, and thus inhibited age-related cortical bone gain. S-ketoprofen treatment did not prevent this change at all dose levels, but reduced marrow cavity area to increase cortical bone area at the 0.1, 0.5 and 2.5 mg/kg per dose levels compared to tenotomy controls. However, the cortical bone area in the 0.1 and 0.5 mg dose-treated treated tenotomy rats was still lower than in the age-related controls. S-ketoprofen also prevented the increase in endocortical eroded perimeter induced by tenotomy. In summary, tenotomy inhibited age-related bone gain and stimulated bone loss in cancellous bone sites, and only inhibited age-related bone gain in cortical bone sites. S-ketoprofen treatment at the highest dose levels prevented the changes in cancellous bone, and reduced marrow area to increase cortical bone in the tibial shafts.

The Ovariectomized Rat as a Model for Studying Alveolar Bone Loss in Postmenopausal Women

PubMed Central

Johnston, Bryan D.; Ward, Wendy E.

2015-01-01

In postmenopausal women, reduced bone mineral density at the hip and spine is associated with an increased risk of tooth loss, possibly due to a loss of alveolar bone. In turn, having fewer natural teeth may lead to compromised food choices resulting in a poor diet that can contribute to chronic disease risk. The tight link between alveolar bone preservation, tooth retention, better nutritional status, and reduced risk of developing a chronic disease begins with the mitigation of postmenopausal bone loss. The ovariectomized rat, a widely used preclinical model for studying postmenopausal bone loss that mimics deterioration of bone tissue in the hip and spine, can also be used to study mineral and structural changes in alveolar bone to develop drug and/or dietary strategies aimed at tooth retention. This review discusses key findings from studies investigating mandible health and alveolar bone in the ovariectomized rat model. Considerations to maximize the benefits of this model are also included. These include the measurement techniques used, the age at ovariectomy, the duration that a rat is studied after ovariectomy and habitual diet consumed. PMID:26060817

Multiple fractures and impaired bone metabolism in Wolfram syndrome: a case report.

PubMed

Catalano, Antonino; Bellone, Federica; Cicala, Giuseppe; Giandalia, Annalisa; Morabito, Nunziata; Cucinotta, Domenico; Russo, Giuseppina Tiziana

2017-01-01

Wolfram Syndrome (WS) is a rare and lethal disease characterized by optic atrophy, diabetes mellitus, diabetes insipidus, and hearing loss. To date, osteoporotic related fractures have not been reported in affected patients. Here, we describe the case of a man affected by WS complicated by several bone fragility fractures. A 50-year-old Caucasian man was hospitalized because of tibia and fibula fractures. His clinical features included diabetes mellitus, diabetes insipidus, optic atrophy and deafness that were consistent with an unrecognized WS diagnosis, which was confirmed by the identification of a specific mutation in gene WFS1 encoding wolframin. Bone mineral density by phalangeal quantitative ultrasound demonstrated severe osteoporosis, with high serum levels of surrogate markers of bone turn-over. Previously unidentified rib fractures were also detected. To the best of our knowledge, this is the first report of osteoporotic related fractures in a patient affected by WS. Although no effective treatments are currently available to delay the progression of the disease, this case report suggests to evaluate fracture risk in the diagnostic work-up of WS.

Fluorosis increases the risk of postmenopausal osteoporosis by stimulating interferon γ.

PubMed

Lv, Yun-Gang; Kang, Li; Wu, Guangyao

2016-10-14

Estrogen deficiency in postmenopausal women frequently activates osteoclasts (OC), accelerates bone resorption, and leads to osteoporosis (OP). Previous studies have demonstrated that interferon γ (IFNγ) could increase bone resorption and may be involved in postmenopausal OP. Fluorosis also increased the risk of fractures and dental fluorosis, and fluoride may enhance osteoclast formation and induce osteoclastic bone destruction in postmenopausal women, but the underlying mechanisms are as yet unknown. Here, we show that serum fluoride and IFNγ levels are negatively correlated with bone mineral density (BMD) in postmenopausal women residing in a fluorotic area. Estrogen suppresses IFNγ, which is elevated by fluoride, playing a pivotal role in triggering bone loss in estrogen-deficient conditions. In vitro, IFNγ is inhibited by estrogen treatment and increased by fluoride in Raw264.7 cell, an osteoclast progenitor cell line. In ovariectomized (Ovx) mice, estrogen loss and IFNγ promote OC activation and subsequent bone loss in vivo. However, IFNγ deficiency prevents bone loss in Ovx mice even in fluoride conditions. Interestingly, fluoride fails to increase IFNγ expression in estrogen receptor α (ERα)-deficient conditions, but not in ERβ-deficient conditions. These findings demonstrate that fluorosis increases the bone loss in postmenopausal OP through an IFNγ-dependent mechanism. IFNγ signaling activates OC and aggravates estrogen deficiency inducing OP. Thus, stimulation of IFNγ production is a pivotal ''upstream'' mechanism by which fluoride promotes bone loss. Suppression of IFNγ levels may constitute a therapeutic approach for preventing bone loss. Copyright © 2016 Elsevier Inc. All rights reserved.

Estrogen-Related Receptors and the control of bone cell fate.

PubMed

Carnesecchi, Julie; Vanacker, Jean-Marc

2016-09-05

Bone loss is naturally occurring in aging males and females and exacerbated in the latter after menopause, altogether leading to cumulative skeleton fragility and increased fracture risk. Two types of therapeutic strategies can be envisioned to counteract age- or menopause-associated bone loss, aiming at either reducing bone resorption exerted by osteoclasts or, alternatively, promoting bone formation by osteoblasts. We here summarize data suggesting that inhibition of the Estrogen-Related Receptors α and/or γ could promote bone formation and compensate for bone loss induced by ageing or estrogen-deficiency. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Bone and Calcium Metabolism During Space Flight

NASA Technical Reports Server (NTRS)

Smith, Scott M.

2004-01-01

Understanding bone loss during space flight is one of the most critical challenges for maintaining astronaut health on space exploration missions. Flight and ground-based studies have been conducted to better understand the nature and mechanisms of weightlessness-induced bone loss, and to identify a means to counteract the loss. Maintenance of bone health requires a balance between bone formation and bone resorption. Early space research identified bone loss as a critical health issue, but could not provide a distinction between the bone formation and breakdown processes. The recent identification of collagen crosslinks as markers of bone resorption has made possible a clear understanding that a decrease in bone resorption is an important effect of space flight, with bone formation being unchanged or only slightly decreased. Calcium regulatory factors have also been studied, in an attempt to understand their role in bone loss. The lack of ultraviolet light exposure and insufficient dietary sources of vitamin D often lead to reduced vitamin D stores on long-duration flights. Serum parathyroid hormone (PTH) concentrations are decreased during flight compared to before flight, although small subject numbers often make this hard to document statistically. As expected, reduced PTH concentrations are accompanied by reduced 1,25-dihydroxyvitamin D concentrations. Calcium kinetic studies during space flight confirm and extend the information gained from biochemical markers of bone metabolism. Calcium kinetic studies demonstrate that bone resorption is increased, bone formation is unchanged or decreased, and dietary calcium absorption is reduced during space flight. Evaluations have also been conducted of countermeasures, including dietary, exercise, and pharmacological treatments. In recent studies, many potential countermeasures show promise at mitigating bone loss in ground-based analogs of weightlessness (e.g., bed rest), but require further ground and flight testing to ensure that the beneficial effects are seen in space flight. As we begin to plan for missions to go back to the Moon, and even off to Mars, many questions are yet to be answered. Maintaining bone is one of the greatest challenges, but with a better understanding of the mechanical processes of bone loss, countermeasures can be designed more efficiently, and the solution (or solutions) may be just over the horizon.

Loss of Cbl-PI3K interaction in mice prevents significant bone loss following ovariectomy

PubMed Central

Adapala, Naga Suresh; Holland, Danielle; Piccuillo, Vanessa; Barbe, Mary F.; Langdon, Wallace Y.; Tsygankov, Alexander Y.; Lorenzo, Joseph A.; Sanjay, Archana

2014-01-01

Cbl and Cbl-b are E3 ubiquitin ligases and adaptor proteins, which perform regulatory roles in bone remodeling. Cbl−/− mice have delayed bone development due to decreased osteoclast migration. Cbl-b−/− mice are osteopenic due to increased bone resorbing activity of osteoclasts. Unique to Cbl, but not present in Cbl-b, is tyrosine 737 in the YEAM motif, which upon phosphorylation provides a binding site for the regulatory p85 subunit of PI3K. Substitution of tyrosine 737 with phenylalanine (Y737F, CblYF/YF mice) prevents Y737 phosphorylation and abrogates the Cbl-PI3K interaction. We have previously reported that CblYF/YF mice had increased bone volume due to defective bone resorption and increased bone formation. Here we show that the lumbar vertebra from CblYF/YF mice did not have significant bone loss following ovariectomy. Our data also suggests that abrogation of Cbl-PI3K interaction in mice results in the loss of coupling between bone resorption and formation, since ovariectomized CblYF/YF mice did not show significant changes in serum levels of c-terminal telopeptide (CTX), whereas the serum levels of pro-collagen type-1 amino-terminal pro-peptide (P1NP) were decreased. In contrast, following ovariectomy, Cbl−/− and Cbl-b−/− mice showed significant bone loss in tibiae and L2 vertebrae, concomitant with increased serum CTX and P1NP levels. These data indicate that while lack of Cbl or Cbl-b distinctly affects bone remodeling, only the loss of Cbl-PI3K interaction protects mice from significant bone loss following ovariectomy. PMID:24994594

Loss of Cbl-PI3K interaction in mice prevents significant bone loss following ovariectomy.

PubMed

Adapala, Naga Suresh; Holland, Danielle; Scanlon, Vanessa; Barbe, Mary F; Langdon, Wallace Y; Tsygankov, Alexander Y; Lorenzo, Joseph A; Sanjay, Archana

2014-10-01

Cbl and Cbl-b are E3 ubiquitin ligases and adaptor proteins, which perform regulatory roles in bone remodeling. Cbl-/- mice have delayed bone development due to decreased osteoclast migration. Cbl-b-/- mice are osteopenic due to increased bone resorbing activity of osteoclasts. Unique to Cbl, but not present in Cbl-b, is tyrosine 737 in the YEAM motif, which upon phosphorylation provides a binding site for the regulatory p85 subunit of PI3K. Substitution of tyrosine 737 with phenylalanine (Y737F, CblYF/YF mice) prevents Y737 phosphorylation and abrogates the Cbl-PI3K interaction. We have previously reported that CblYF/YF mice had increased bone volume due to defective bone resorption and increased bone formation. Here we show that the lumbar vertebra from CblYF/YF mice did not have significant bone loss following ovariectomy. Our data also suggests that abrogation of Cbl-PI3K interaction in mice results in the loss of coupling between bone resorption and formation, since ovariectomized CblYF/YF mice did not show significant changes in serum levels of c-terminal telopeptide (CTX), whereas the serum levels of pro-collagen type-1 amino-terminal pro-peptide (P1NP) were decreased. In contrast, following ovariectomy, Cbl-/- and Cbl-b-/- mice showed significant bone loss in the tibiae and L2 vertebrae, concomitant with increased serum CTX and P1NP levels. These data indicate that while lack of Cbl or Cbl-b distinctly affects bone remodeling, only the loss of Cbl-PI3K interaction protects mice from significant bone loss following ovariectomy. Copyright © 2014 Elsevier Inc. All rights reserved.

Unloading-induced bone loss was suppressed in gold-thioglucose treated mice.

PubMed

Hino, K; Nifuji, A; Morinobu, M; Tsuji, K; Ezura, Y; Nakashima, K; Yamamoto, H; Noda, M

2006-10-15

Loss of mechanical stress causes bone loss. However, the mechanisms underlying the unloading-induced bone loss are largely unknown. Here, we examined the effects of gold-thioglucose (GTG) treatment, which destroys ventromedial hypothalamus (VMH), on unloading-induced bone loss. Unloading reduced bone volume in control (saline-treated) mice. Treatment with GTG-reduced bone mass and in these GTG-treated mice, unloading-induced reduction in bone mass levels was not observed. Unloading reduced the levels of bone formation rate (BFR) and mineral apposition rate (MAR). GTG treatment also reduced these parameters and under this condition, unloading did not further reduce the levels of BFR and MAR. Unloading increased the levels of osteoclast number (Oc.N/BS) and osteoclast surface (Oc.S/BS). GTG treatment did not alter the basal levels of these bone resorption parameters. In contrast to control, GTG treatment suppressed unloading-induced increase in the levels of Oc.N/BS and Oc.S/BS. Unloading reduced the levels of mRNA expression of the genes encoding osteocalcin, type I collagen and Cbfa1 in bone. In contrast, GTG treatment suppressed such unloading-induced reduction of mRNA expression. Unloading also enhanced the levels of fat mass in bone marrow and mRNA expression of the genes encoding PPARgamma2, C/EBPalpha, and C/EBPbeta in bone. In GTG-treated mice, unloading did not increase fat mass and the levels of fat-related mRNA expression. These results indicated that GTG treatment suppressed unloading-induced alteration in bone loss. 2006 Wiley-Liss, Inc.

Numeric simulation of bone remodelling patterns after implantation of a cementless straight stem.

PubMed

Lerch, Matthias; Windhagen, Henning; Stukenborg-Colsman, Christina M; Kurtz, Agnes; Behrens, Bernd A; Almohallami, Amer; Bouguecha, Anas

2013-12-01

For further development of better bone-preserving implants in total hip arthroplasty (THA), we need to look back and analyse established and clinically approved implants to find out what made them successful. Finite element analysis can help do this by simulating periprosthetic bone remodelling under different conditions. Our aim was thus to establish a numerical model of the cementless straight stem for which good long-term results have been obtained. We performed a numeric simulation of a cementless straight stem, which has been successfully used in its unaltered form since 1986/1987. We have 20 years of experience with this THA system and implanted it 555 times in 2012. We performed qualitative and quantitative validation using bone density data derived from a prospective dual-energy X-ray absorptiometry (DEXA) investigation. Bone mass loss converged to 9.25% for the entire femur. No change in bone density was calculated distal to the tip of the prosthesis. Bone mass decreased by 46.2% around the proximal half of the implant and by 7.6% in the diaphysis. The numeric model was in excellent agreement with DEXA data except for the calcar region, where deviation was 67.7%. The higher deviation in the calcar region is possibly a sign of the complex interactions between the titanium coating on the stem and the surrounding bone. We developed a validated numeric model to simulate bone remodelling for different stem-design modifications. We recommend that new THA implants undergo critical numeric simulation before clinical application.

Differences of bone mineral mass, volumetric bone mineral density, geometrical and structural parameters and derived strength of the tibia between premenopausal and postmenopausal women of different age groups: a peripheral Quantitative Computed Tomography (pQCT) study

PubMed Central

Stathopoulos, K.D.; Zoubos, A.B.; Papaioannou, N.A.; Mastrokalos, D.; Galanos, A.; Papagelopoulos, P.J.; Skarantavos, G.

2016-01-01

Menopause constitutes a significant cause of bone loss, and it is currently debated whether bone mass is preserved or begins to decline substantially before that time in women. We used pQCT of the tibia to estimate differences of bone mineral mass, bone geometry and derived strength between premenopausal and postmenopausal Caucasian women of different age-groups per decade of age (20-79y). For each individual, we assessed total, trabecular and cortical bone mineral content (BMC, mg) and volumetric bone mineral density (BMD, mg/cm3); total and cortical cross-sectional areas (CSA, mm2); periosteal circumference (PERI_C, mm); endosteal circumference (ENDO_C, mm); mean cortical thickness (CRT_THK, mm); and Stress-Strain Index (SSI). Comparisons were made both between premenopausal (N=84) and postmenopausal (N=231) women as distinct groups, and among women of the different age-groups. Our results indicated that premenopausal women had significantly higher trabecular and cortical BMC and vBMD, with higher cortical CSA, CRT_THK and SSI than postmenopausal women. Moreover, significant differences of trabecular but not cortical BMC, vBMD or SSI were found between women of the younger (<48y) age-groups. PERI_C, ENDO_C displayed lower values in the 20-29y group and higher values in the 70-79y group, denoting significant differences of bone geometry with aging. PMID:27282455

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

In vivo NMR microscopy allows short-term serial assessment of multiple skeletal implications of corticosteroid exposure

PubMed Central

Takahashi, Masaya; Wehrli, Felix W.; Hilaire, Luna; Zemel, Babette S.; Hwang, Scott N.

2002-01-01

Corticosteroids are in widespread clinical use but are known to have adverse skeletal side effects. Moreover, it is not known how soon these effects become apparent. Here, we describe a longitudinal approach to evaluate the short-term implications of excess corticosteroid exposure by quantitative in vivo magnetic resonance imaging and spectroscopy in conjunction with digital image processing and analysis in a rabbit model. Two-week treatment with dexamethasone induced a significant reduction in trabecular bone volume, which occurred at the expense of uniform trabecular thinning without affecting network architecture. Paralleling the loss in bone volume was conversion of hematopoietic to yellow marrow in the femoral metaphysis and atrophy of the femoral epiphyseal growth plate. This work demonstrates that detailed quantitative morphometric and physiological information can be obtained noninvasively at multiple skeletal locations. The method is likely to eventually replace invasive histomorphometry in that it obviates the need to sacrifice groups of animals at multiple time points. Finally, this work, which was performed on a clinical scanner, has implications for evaluating patients on high-dose steroid treatment. PMID:11904367

Retrospective clinical study of an implant with a sandblasted, large-grit, acid-etched surface and internal connection: analysis of short-term success rate and marginal bone loss.

PubMed

Lee, Jae-Wang; An, Jun Hyeong; Park, Sang-Hoon; Chong, Jong-Hyon; Kim, Gwang-Seok; Han, JeongJoon; Jung, Seunggon; Kook, Min-Suk; Oh, Hee-Kyun; Ryu, Sun-Youl; Park, Hong-Ju

2016-12-01

The purpose of this retrospective study was to evaluate the clinical utility of an implant with a sandblasted, large-grit, acid-etched (SLA) surface and internal connection. Six patients who received dental implants in the Department of Oral and Maxillofacial Surgery, Chonnam National University Dental Hospital, were analyzed by factors influencing the success rate and marginal bone loss. Factors included patient's age, sex, implant installation site, whether bone graft was done, type of bone graft materials, approaching method if sinus lift was done, and the size of the fixture. In addition, the marginal bone loss was analyzed by using a radiograph. All implants were successful, and the cumulative survival rate was 100 %. Average marginal bone loss of 6 months after the installation was 0.52 mm and 20 months after the functional loading was 1.06 mm. Total marginal bone resorption was 1.58 mm on average. There was no statistically significant difference in mesial and distal marginal bone loss. The short-term clinical success rate of the implant with an SLA surface and internal connection was satisfactory. Moreover, the marginal bone loss was also consistent with the implant success criteria.

The Use of Structural Allograft in Primary and Revision Knee Arthroplasty with Bone Loss

PubMed Central

Kuchinad, Raul A.; Garbedian, Shawn; Rogers, Benedict A.; Backstein, David; Safir, Oleg; Gross, Allan E.

2011-01-01

Bone loss around the knee in the setting of total knee arthroplasty remains a difficult and challenging problem for orthopaedic surgeons. There are a number of options for dealing with smaller and contained bone loss; however, massive segmental bone loss has fewer options. Small, contained defects can be treated with cement, morselized autograft/allograft or metal augments. Segmental bone loss cannot be dealt with through simple addition of cement, morselized autograft/allograft, or metal augments. For younger or higher demand patients, the use of allograft is a good option as it provides a durable construct with high rates of union while restoring bone stock for future revisions. Older patients, or those who are low demand, may be better candidates for a tumour prosthesis, which provides immediate ability to weight bear and mobilize. PMID:21991418

Prediction of risk of fracture in the tibia due to altered bone mineral density distribution resulting from disuse: a finite element study.

PubMed

Gislason, Magnus K; Coupaud, Sylvie; Sasagawa, Keisuke; Tanabe, Yuji; Purcell, Mariel; Allan, David B; Tanner, K Elizabeth

2014-02-01

The disuse-related bone loss that results from immobilisation following injury shares characteristics with osteoporosis in post-menopausal women and the aged, with decreases in bone mineral density leading to weakening of the bone and increased risk of fracture. The aim of this study was to use the finite element method to: (i) calculate the mechanical response of the tibia under mechanical load and (ii) estimate of the risk of fracture; comparing between two groups, an able-bodied group and spinal cord injury patients group suffering from varying degrees of bone loss. The tibiae of eight male subjects with chronic spinal cord injury and those of four able-bodied age-matched controls were scanned using multi-slice peripheral quantitative computed tomography. Images were used to develop full three-dimensional models of the tibiae in Mimics (Materialise) and exported into Abaqus (Simulia) for calculation of stress distribution and fracture risk in response to specified loading conditions - compression, bending and torsion. The percentage of elements that exceeded a calculated value of the ultimate stress provided an estimate of the risk of fracture for each subject, which differed between spinal cord injury subjects and their controls. The differences in bone mineral density distribution along the tibia in different subjects resulted in different regions of the bone being at high risk of fracture under set loading conditions, illustrating the benefit of creating individual material distribution models. A predictive tool can be developed based on these models, to enable clinicians to estimate the amount of loading that can be safely allowed onto the skeletal frame of individual patients who suffer from extensive musculoskeletal degeneration (including spinal cord injury, multiple sclerosis and the ageing population). The ultimate aim is to reduce fracture occurrence in these vulnerable groups.

Network Analysis Implicates Alpha-Synuclein (Snca) in the Regulation of Ovariectomy-Induced Bone Loss

PubMed Central

Calabrese, Gina; Mesner, Larry D.; Foley, Patricia L.; Rosen, Clifford J.; Farber, Charles R.

2016-01-01

The postmenopausal period in women is associated with decreased circulating estrogen levels, which accelerate bone loss and increase the risk of fracture. Here, we gained novel insight into the molecular mechanisms mediating bone loss in ovariectomized (OVX) mice, a model of human menopause, using co-expression network analysis. Specifically, we generated a co-expression network consisting of 53 gene modules using expression profiles from intact and OVX mice from a panel of inbred strains. The expression of four modules was altered by OVX, including module 23 whose expression was decreased by OVX across all strains. Module 23 was enriched for genes involved in the response to oxidative stress, a process known to be involved in OVX-induced bone loss. Additionally, module 23 homologs were co-expressed in human bone marrow. Alpha synuclein (Snca) was one of the most highly connected “hub” genes in module 23. We characterized mice deficient in Snca and observed a 40% reduction in OVX-induced bone loss. Furthermore, protection was associated with the altered expression of specific network modules, including module 23. In summary, the results of this study suggest that Snca regulates bone network homeostasis and ovariectomy-induced bone loss. PMID:27378017

Anti-osteoporotic activity of harpagide by regulation of bone formation in osteoblast cell culture and ovariectomy-induced bone loss mouse models.

PubMed

Chung, Hwa-Jin; Kyung Kim, Won; Joo Park, Hyen; Cho, Lan; Kim, Me-Riong; Kim, Min Jeong; Shin, Joon-Shik; Ho Lee, Jin; Ha, In-Hyuk; Kook Lee, Sang

2016-02-17

Harpagide, an iridoid glucoside, is a constituent of the root of Harpagophytum procumbens var. sublobatum (Engl.) Stapf, Devil's claw which has been used in patients with osteoarthritis (OA). In the present study, we investigated the anti-osteoporotic potential of harpagide and its underlying mechanism of action in in vitro cell culture and in vivo bone loss animal models. Harpagide was obtained from the alkalic hydrolysis of harpagoside, a major constituent of H. procumbens var. sublobatum Analysis of biomarkers for bone formation in osteoblastic MC3T3-E1 cells and bone resorption in osteoclast cells derived from mouse bone marrow cells was performed to evaluate the mechanism of action. The protective activity of harpagide against bone loss was also evaluated in ovariectomized (OVX) mouse model. Harpagide improved bone properties by stimulating the process of differentiation and maturation of osteoblast cells and suppressing the process of RANKL-induced differentiation of osteoclast cells. In OVX-induced bone loss mouse model, oral administration of harpagide significantly improved recovery of bone mineral density, trabecular bone volume, and trabecular number in the femur. Harpagide also prevented increase of trabecular separation and structure model index induced by OVX. Harpagide effectively inhibited the serum levels of biochemical markers of bone loss, including alkaline phosphatase, osteocalcin, C-terminal telopeptide, and tartrate-resistant acid phosphatase. Taken together, the present study demonstrates that harpagide has a potential for prevention of bone loss in OVX mice by regulating the stimulation of osteoblast differentiation and the suppression of osteoclast formation. Therefore, these findings suggest that harpagide might serve as a bioactive compound derived from H. procumbens var. sublobatum for improvement of age-dependent bone destruction disease. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Oral Steroids (Steroid Pills and Syrups)

MedlinePlus

... compressions, especially of the backbone and the hip Loss of blood supply to bones (aseptic necrosis) may cause severe bone pain and may require surgical correction Bones To prevent osteoporosis (loss of calcium in the bones), it is important ...

Hibernating little pocket mice show few seasonal changes in bone properties

Treesearch

Noellyn Pineda; Marjorie Owen; Claire Tucker; Samantha Wojda; Stanley Kitchen; Hal Black; Seth Donahue

2017-01-01

Periods of disuse or physical inactivity increases bone porosity and decreases bone mineral density, resulting in a loss of bone mechanical competence in many animals. Although large hibernators like bears and marmots prevent bone loss during hibernation, despite long periods of physical inactivity, some small hibernators do lose bone during hibernation. Little pocket...

Impaired extracellular matrix structure resulting from malnutrition in ovariectomized mature rats.

PubMed

El Khassawna, Thaqif; Böcker, Wolfgang; Brodsky, Katharina; Weisweiler, David; Govindarajan, Parameswari; Kampschulte, Marian; Thormann, Ulrich; Henss, Anja; Rohnke, Marcus; Bauer, Natali; Müller, Robert; Deutsch, Andreas; Ignatius, Anita; Dürselen, Lutz; Langheinrich, Alexander; Lips, Katrin S; Schnettler, Reinhard; Heiss, Christian

2015-11-01

Bone loss is a symptom related to disease and age, which reflects on bone cells and ECM. Discrepant regulation affects cell proliferation and ECM localization. Rat model of osteoporosis (OVX) was investigated against control rats (Sham) at young and old ages. Biophysical, histological and molecular techniques were implemented to examine the underlying cellular and extracellular matrix changes and to assess the mechanisms contributing to bone loss in the context of aging and the widely used osteoporotic models in rats. Bone loss exhibited a compromised function of bone cells and infiltration of adipocytes into bone marrow. However, the expression of genes regulating collagen catabolic process and adipogenesis was chronologically shifted in diseased bone in comparison with aged bone. The data showed the involvement of Wnt signaling inhibition in adipogenesis and bone loss due to over-expression of SOST in both diseased and aged bone. Further, in the OVX animals, an integrin-mediated ERK activation indicated the role of MAPK in osteoblastogenesis and adipogenesis. The increased PTH levels due to calcium and estrogen deficiency activated osteoblastogenesis. Thusly, RANKL-mediated osteoclastogenesis was initiated. Interestingly, the data show the role of MEPE regulating osteoclast-mediated resorption at late stages in osteoporotic bone. The interplay between ECM and bone cells change tissue microstructure and properties. The involvement of Wnt and MAPK pathways in activating cell proliferation has intriguing similarities to oncogenesis and myeloma. The study indicates the importance of targeting both pathways simultaneously to remedy metabolic bone diseases and age-related bone loss.

Nutritional interventions for optimizing healthy body composition in older adults in the community: an umbrella review of systematic reviews.

PubMed

Schultz, Timothy J; Roupas, Peter; Wiechula, Richard; Krause, Debra; Gravier, Susan; Tuckett, Anthony; Hines, Sonia; Kitson, Alison

2016-08-01

Optimizing body composition for healthy aging in the community is a significant challenge. There are a number of potential interventions available for older people to support both weight gain (for those who are underweight) and weight loss (for overweight or obese people). While the benefits of weight gain for underweight people are generally clearly defined, the value of weight loss in overweight or obese people is less clear, particularly for older people. This umbrella review aimed to measure the effectiveness of nutritional interventions for optimizing healthy body composition in older adults living in the community and to explore theirqualitative perceptions. The participants were older adults, 60 years of age or older, living in the community. The review examinedsix types of nutritional interventions: (i) dietary programs, (ii) nutritional supplements, (iii) meal replacements, (iv) food groups, (v) food delivery support and eating behavior, and (vi) nutritional counselling or education. This umbrella review considered any quantitative systematic reviews and meta-analyses of effectiveness, or qualitative systematic reviews, or a combination (i.e. comprehensive reviews). The quantitative outcome measures of body composition were: (i) nutritional status (e.g. proportion of overweight or underweight patients); (ii) fat mass (kg), (iii) lean mass or muscle mass (kg), (iv) weight (kg) or BMI (kg/m), (v) bone mass (kg) or bone measures such as bone mineral density, and (vi) hydration status. The phenomena of interestwere the qualitative perceptions and experiences of participants. We developed an iterative search strategy for nine bibliometric databases and gray literature. Critical appraisal of 13 studies was conducted independently in pairs using standard Joanna Briggs Institute tools. Six medium quality and seven high quality studies were identified. Data was extracted independently in pairs from all 13 included studies using the standard Joanna Briggs Institute data extraction tool. Only quantitative studies of effectiveness were included. The strength of evidence assessing the effectiveness of interventionswas graded using a traffic light system (green, amber, red). An overall assessment of the quality of the evidence for each comparison was undertaken. More systematic reviews investigating weight gain than those investigating weight loss were included. Studies onweight gain showed improved body composition for oral nutritional supplements on its own, for oral nutritional supplements in combination with resistance exercise training, and for oral nutritional supplements in combination with nutrition counselling. Studies on weight loss showed that diet in combination with exercise, diet in combination with exercise and nutrition counselling, and nutrition counselling on its own all can lead to reduced weight in older people. The outcomes of lean mass and weight/BMI were responsive to nutritional interventions, but fat mass did not vary. There were no qualitative reviews identified. Although effective interventions for weight gain and weight loss to optimize body composition of older people in the community were identified,making long term, clinically relevant changes in body composition is difficult. Multiple interventions are more effective than single interventions.

Naringin protects against bone loss in steroid-treated inflammatory bowel disease in a rat model.

PubMed

Li, Chengli; Zhang, Jun; Lv, Fang; Ge, Xingtao; Li, Gang

2018-07-15

We observed the effects of naringin on bone loss in glucocorticoid-treated inflammatory bowel disease (IBD) in a rat model. The IBD model was established in Sprague-Dawley rats by administering 5.0% dextran sodium sulfate. Dexamethasone (DEX) and naringin were given at the second week. Blood, colon and bone samples were collected for biomarker assay, histological analysis or microCT analysis. Superoxide dismutase, catalase and malonaldehyde were measured in bone. A significant decrease of procollagen type 1 N-terminal propeptide (P1NP) level was observed in DEX-treated IBD groups compared with the control (p < 0.05). P1NP levels were dose-dependently increased in the presence of naringin intervention. Bone loss and decreased bone biomechanical properties were observed in DEX-treated IBD rats compared with control rats (p < 0.01). Naringin intervention protected against bone loss and decreased bone biomechanical properties. Bone formation related gene mRNA expressions were significantly decreased in DEX-treated IBD rats compared with control rats. Naringin administration reversed the down-regulation of the expressions of those genes. Naringin treatment reduced the oxidative stress in bone from DEX-treated IBD rats. Our data indicated that naringin may have great potential for the treatment of bone loss in glucocorticoid-treated IBD patients via blocking oxidative stress and promoting bone formation. Copyright © 2018 Elsevier Inc. All rights reserved.

Quantitative imaging methods in osteoporosis.

PubMed

Oei, Ling; Koromani, Fjorda; Rivadeneira, Fernando; Zillikens, M Carola; Oei, Edwin H G

2016-12-01

Osteoporosis is characterized by a decreased bone mass and quality resulting in an increased fracture risk. Quantitative imaging methods are critical in the diagnosis and follow-up of treatment effects in osteoporosis. Prior radiographic vertebral fractures and bone mineral density (BMD) as a quantitative parameter derived from dual-energy X-ray absorptiometry (DXA) are among the strongest known predictors of future osteoporotic fractures. Therefore, current clinical decision making relies heavily on accurate assessment of these imaging features. Further, novel quantitative techniques are being developed to appraise additional characteristics of osteoporosis including three-dimensional bone architecture with quantitative computed tomography (QCT). Dedicated high-resolution (HR) CT equipment is available to enhance image quality. At the other end of the spectrum, by utilizing post-processing techniques such as the trabecular bone score (TBS) information on three-dimensional architecture can be derived from DXA images. Further developments in magnetic resonance imaging (MRI) seem promising to not only capture bone micro-architecture but also characterize processes at the molecular level. This review provides an overview of various quantitative imaging techniques based on different radiological modalities utilized in clinical osteoporosis care and research.

Managing peri-implant bone loss: current understanding.

PubMed

Aljateeli, Manar; Fu, Jia-Hui; Wang, Hom-Lay

2012-05-01

With the improved macro- and micro-designs, dental implants enjoy a high survival rate. However, peri-implant bone loss has recently emerged to be the focus of implant therapy. As such, researchers and clinicians are in need of finding predictable techniques to treat peri-implant bone loss and stop its progression. Literature search on the currently available treatment modalities was performed and a brief description of each modality was provided. Numerous techniques have been proposed and none has been shown to be superior and effective in managing peri-implant bone loss. This may be because of the complex of etiological factors acting on the implant-supported prosthesis hence the treatment approach has to be individually tailored. Due to the lack of high-level clinical evidence on the management of peri-implant bone loss, the authors, through a literature review, attempt to suggest a decision tree or guideline, based on sound periodontal surgical principles, to aid clinicians in managing peri-implantitis associated bone loss. © 2011 Wiley Periodicals, Inc.

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.

Bone effects of biologic drugs in rheumatoid arthritis.

PubMed

Corrado, Addolorata; Neve, Anna; Maruotti, Nicola; Cantatore, Francesco Paolo

2013-01-01

Biologic agents used in the treatment of rheumatoid arthritis (RA) are able to reduce both disease activity and radiographic progression of joint disease. These drugs are directed against several proinflammatory cytokines (TNF α , IL-6, and IL-1) which are involved both in the pathogenesis of chronic inflammation and progression of joint structural damage and in systemic and local bone loss typically observed in RA. However, the role of biologic drugs in preventing bone loss in clinical practice has not yet clearly assessed. Many clinical studies showed a trend to a positive effect of biologic agents in preventing systemic bone loss observed in RA. Although the suppression of inflammation is the main goal in the treatment of RA and the anti-inflammatory effects of biologic drugs exert a positive effect on bone metabolism, the exact relationship between the prevention of bone loss and control of inflammation has not been clearly established, and if the available biologic drugs against TNF α , IL-1, and IL-6 can exert their effect on systemic and local bone loss also through a direct mechanism on bone cell metabolism is still to be clearly defined.

Handheld Fluorescence Resonance Energy Transfer (FRET)-Aptamer Sensor for Bone Markers

NASA Technical Reports Server (NTRS)

Bruno, John G.

2015-01-01

Astronauts lose significant bone mass during lengthy space flights. NASA wishes to monitor this bone loss in order to develop nutritional and exercise countermeasures. Operational Technologies Corporation (OpTech) has developed a handheld device that quantifies bone loss in a spacecraft environment. The innovation works by adding fluorescent dyes and quenchers to aptamers to enable pushbutton, one-step bind-and-detect FRET assays that can be freeze-dried, rehydrated with body fluids, and used to quantify bone loss.

Prevent and cure disuse bone loss

NASA Technical Reports Server (NTRS)

Jee, Webster S. S.

1994-01-01

Anabolic agents like parathyroid hormone and postagladin E-like substances were studied in dogs and rats to determine their effectiveness in the prevention and cure of bone loss due to immobilization. It was determined that postagladin E2 administration prevented immobilization while at the same time it added extra bone in a dose responsive manner. Although bone mass returns, poor trabecular architecture remains after normal ambulation recovery from immobilization. Disuse related bone loss and poor trabecular architecture were cured by post-immobilization postagladin E2 treatment.

The effects of first gestation and lactation on bone metabolism in dairy goats and milk sheep.

PubMed

Liesegang, A; Risteli, J; Wanner, M

2006-06-01

The goal of the present study was to compare mobilization rate of calcium (Ca) from bone in pregnant and lactating goats and sheep. Blood samples were collected from goats and sheep monthly during pregnancy and at 1, 2, and 4 weeks postpartum (pp) and monthly during lactation until 6 months after parturition. Total bone mineral content (BMC) and total bone mineral density (BMD) were quantified using peripheral quantitative computed tomography at the same intervals as the blood was taken. Bone resorption was assessed by immunoassays quantitating two epitopes of the carboxyterminal telopeptide of type I collagen (ICTP, CTX). Bone formation was estimated by quantifying serum osteocalcin (OC) and bone-specific alkaline phosphatase (bAP). In addition, Ca and 1,25-dihydroxy vitamin D (1,25-VITD) concentrations were determined in serum. Mean ICTP and CTX concentrations of both animal species increased the first week after parturition. By the second week pp, the concentrations of both markers had decreased toward early gestation levels. In contrast, mean OC concentrations continually decreased until the 1st week pp. By the 2nd week pp, the mean concentrations of OC started to increase again. Mean bAP activities decreased during gestation and reached a nadir in the first week pp in goats and 4 weeks pp in sheep. Afterwards, mean bAP activities increased again in goats and sheep. 1,25-VITD concentrations peaked the first week pp and returned to early gestation values thereafter. Total BMC and BMD decreased from the 4th month of pregnancy until the 1st week pp in both species. Afterwards, BMC increased throughout the first month pp in goats and the first 3 months pp in sheep. BMD levels of sheep and goats returned to prepartum levels during lactation. The resorptive phase of bone remodeling is accelerated at parturition and in early lactation and is uncoupled from the process of bone formation. This allows the animal to achieve Ca homeostasis at the expense of bone. Increased bone remodeling during lactation may represent physiological mechanisms to help replace the maternal skeleton lost as the animal adapted to enormously increased Ca losses to the fetus and milk in late gestation and early lactation.

Marginal Bone Loss Around Early-Loaded SLA and SLActive Implants: Radiological Follow-Up Evaluation Up to 6.5 Years.

PubMed

Şener-Yamaner, Işil Damla; Yamaner, Gökhan; Sertgöz, Atilla; Çanakçi, Cenk Fatih; Özcan, Mutlu

2017-08-01

The aim of this study was to compare marginal bone loss around early-loaded SLA and SLActive tissue-level implants (Straumann Dental Implants; Institut Straumann AG, Basel, Switzerland) after a mean of 81-month follow-up period. One hundred seven SLA and 68 SLActive implants were placed in 55 patients and loaded with final restoration after 8 and 3 weeks of healing time, respectively. Marginal bone loss around implants was determined radiographically at initial and after a mean observation time ranging between 20 and 81 months. The effect of location (mandible vs maxilla), smoking habit, sex, implant length and diameter, and the type of prosthesis on the marginal bone loss was evaluated. The overall cumulative survival rate was 98.2% being 99% for SLA implants and 97% for SLActive implants. After 20-month follow-up period, mean marginal bone loss values for the SLA and SLActive implants were 0.24 and 0.17 mm, respectively. After 81 months, mean marginal bone loss for the SLA and SLActive implants reached 0.71 and 0.53 mm, respectively. Marginal bone loss was affected by the length and type of implant and patients' smoking habit after a mean observation time of 20 months. However, none of the parameters had any significant effect on the marginal bone loss after a follow-up period of 81 months. With both SLA and SLActive implants, successful clinical results could be achieved up to 6.5 years of follow-up period.

Bone mineral density changes during the menopause transition in a multiethnic cohort of women.

PubMed

Finkelstein, Joel S; Brockwell, Sarah E; Mehta, Vinay; Greendale, Gail A; Sowers, MaryFran R; Ettinger, Bruce; Lo, Joan C; Johnston, Janet M; Cauley, Jane A; Danielson, Michelle E; Neer, Robert M

2008-03-01

Rates of bone loss across the menopause transition and factors associated with variation in menopausal bone loss are poorly understood. Our objective was to assess rates of bone loss at each stage of the transition and examine major factors that modify those rates. We conducted a longitudinal cohort study of 1902 African-American, Caucasian, Chinese, or Japanese women participating in The Study of Women's Health Across the Nation. Women were pre- or early perimenopausal at baseline. We assessed bone mineral density (BMD) of the lumbar spine and total hip across a maximum of six annual visits. There was little change in BMD during the pre- or early perimenopause. BMD declined substantially in the late perimenopause, with an average loss of 0.018 and 0.010 g/cm2.yr from the spine and hip, respectively (P<0.001 for both). In the postmenopause, rates of loss from the spine and hip were 0.022 and 0.013 g/cm2.yr, respectively (P<0.001 for both). During the late peri- and postmenopause, bone loss was approximately 35-55% slower in women in the top vs. the bottom tertile of body weight. Apparent ethnic differences in rates of spine bone loss were largely explained by differences in body weight. Bone loss accelerates substantially in the late perimenopause and continues at a similar pace in the first postmenopausal years. Body weight is a major determinant of the rate of menopausal BMD loss, whereas ethnicity, per se, is not. Healthcare providers should consider this information when deciding when to screen women for osteoporosis.

Past and current weight change and forearm bone loss in middle-aged women: the Nord-Trøndelag Health Study, Norway.

PubMed

Forsmo, Siri; Langhammer, Arnulf; Schei, Berit

2009-01-01

The aim of this study was to investigate the association between bone loss and weight change before and concurrently to the assessment of forearm bone loss over 4.6 years in a population-based cohort of middle-aged women followed for more than 15 years. Among 8,856 women aged 45 to 60 years attending the first Nord-Trøndelag Health Study study, Norway (1984-1986), a 35% random sample was invited for forearm densitometry at Nord-Trøndelag Health Study 2 (1995-1997), and 2,188 women (78%) attended. After an average period of 4.6 years, they were subsequently invited for follow-up densitometry in 2001, and 1,421 women (67.8%) met. Weight and height were measured on all three occasions. During the total period of observation since baseline (15.5 y), the mean weight had increased by 3.4 kg, mostly in the youngest women. Weight loss had an accelerating and weight gain a decelerating effect on bone loss, and this was observed both for weight change occurring before the bone mineral density follow-up and for concurrent weight change. The relationship between prior weight gain or loss and bone loss seemed to persist, independent of the weight change observed during the period of bone loss assessment. Despite no mechanical impact of body weight on the forearm, weight loss in midlife women seems to be associated with a long-lasting negative effect on bone and vice versa for weight gain. This is presumably explained by humoral factors.

Serum markers of bone metabolism show bone loss in hibernating bears

USGS Publications Warehouse

Donahue, S.W.; Vaughan, M.R.; Demers, L.M.; Donahue, H.J.

2003-01-01

Disuse osteopenia was studied in hibernating black bears (Ursus americanus) using serum markers of bone metabolism. Blood samples were collected from male and female, wild black bears during winter denning and active summer periods. Radioimmunoassays were done to determine serum concentrations of cortisol, the carboxy-terminal cross-linked telopeptide, and the carboxy-terminal propeptide of Type I procollagen, which are markers of hone resorption and formation, respectively. The bone resorption marker was significantly higher during winter hibernation than it was in the active summer months, but the bone formation marker was unchanged, suggesting an imbalance in bone remodeling and a net bone loss during disuse. Serum cortisol was significantly correlated with the bone resorption marker, but not with the bone formation marker. The bone formation marker was four- to fivefold higher in an adolescent and a 17-year-old bear early in the remobilization period compared with the later summer months. These findings raise the possibility that hibernating black bears may minimize bone loss during disuse by maintaining osteoblastic function and have a more efficient compensatory mechanism for recovering immobilization-induced bone loss than that of humans or other animals.

HIV and Bone Metabolism

PubMed Central

Ofotokun, Ighovwerha; Weitzmann, M. Neale

2013-01-01

The skeleton is an organ whose integrity is maintained by constant lifelong renewal involving coordinated removal of worn bone by osteoclasts and resynthesis of new bone by osteoblasts. In young adult humans and animals this process is homeostatic with no net gain or loss of bone mass. With natural aging and exacerbated by numerous pathological conditions, bone removal exceeds bone formation, disrupting homeostasis and resulting in bone loss. Over time, skeletal decline reaches clinical significance with development of osteopenia and eventually osteoporosis, conditions that dramatically increase bone fragility and the risk of fracture. Bone fractures can be devastating with significant morbidity and mortality. Over the last decade, it has become clear that skeletal renewal is strongly influenced by the immune system, a consequence of deep integration and centralization of common cell types and cytokine mediators, which we have termed the “immuno-skeletal interface.” Consequently, dysregulated skeletal renewal and bone loss is a common feature of inflammatory conditions associated with immune activation. Interestingly, bone loss is also associated with conditions of immunodeficiency, including infection by the human immunodeficiency virus (HIV) that leads to acquired immunodeficiency syndrome (AIDS). Disruptions to the immuno-skeletal interface drive skeletal deterioration contributing to a high rate of bone fracture in HIV infection. This review examines current knowledge concerning the prevalence and etiology of skeletal complications in HIV infection, the effect of antiretroviral therapies (ART) on the skeleton, and how disruption of the immuno-skeletal interface may underlie bone loss in HIV infection and ART. PMID:21616037

Associations among endocrine, inflammatory, and bone markers, body composition and weight loss induced bone loss.

PubMed

Labouesse, Marie A; Gertz, Erik R; Piccolo, Brian D; Souza, Elaine C; Schuster, Gertrud U; Witbracht, Megan G; Woodhouse, Leslie R; Adams, Sean H; Keim, Nancy L; Van Loan, Marta D

2014-07-01

Weight loss reduces co-morbidities of obesity, but decreases bone mass. Our aims were to (1) determine if adequate dairy intake attenuates weight loss-induced bone loss; (2) evaluate the associations of endocrine, inflammatory and bone markers, anthropometric and other parameters to bone mineral density and content (BMD, BMC) pre- and post-weight loss; and (3) model the contribution of these variables to post weight-loss BMD and BMC. Overweight/obese women (BMI: 28-37 kg/m2) were enrolled in an energy reduced (-500 kcal/d; -2092 kJ/d) diet with adequate dairy (AD: 3-4 servings/d; n=25, 32.2±8.8 years) or low dairy (LD: ≤1 serving/d; n=26, 31.7±8.4 years). BMD, BMC and body composition were measured by DXA. Bone markers (CTX, PYD, BAP, OC), endocrine (PTH, vitamin D, leptin, adiponectin, ghrelin, amylin, insulin, GLP-1, PAI-1, HOMA) and inflammatory markers (CRP, IL1-β, IL-6, IL-8, TNF-α, cortisol) were measured in serum or plasma. PA was assessed by accelerometry. Following weight loss, AD intake resulted in significantly greater (p=0.004) lumbar spine BMD and serum osteocalcin (p=0.004) concentration compared to LD. Pre- and post-body fat was negatively associated with hip and lumbar spine BMC (r=-0.28, p=0.04 to -0.45, p=0.001). Of note were the significant negative associations among bone markers and IL-1β, TNFα and CRP ranging from r = -0.29 (p=0.04) to r = -0.34 (p=0.01); magnitude of associations did not change with weight loss. Adiponectin was negatively related to change in osteocalcin. Factor analysis resulted in 8 pre- and post-weight loss factors. Pre-weight loss factors accounted for 13.7% of the total variance in pre-weight loss hip BMD; post-weight loss factors explained 19.6% of the total variance in post-weight loss hip BMD. None of the factors contributed to the variance in lumbar spine BMD. AD during weight loss resulted in higher lumbar spine BMD and osteocalcin compared to LD. Significant negative associations were observed between bone and inflammatory markers suggesting that inflammation suppresses bone metabolism. Using factor analysis, 19.6% of total variance in post-weight loss hip BMD could be explained by endocrine, immune, and anthropometric variables, but not lumbar spine BMD. Published by Elsevier Inc.

Associations among Endocrine, Inflammatory, and Bone Markers, Body Composition and Physical Activity to Weight Loss Induced Bone Loss

PubMed Central

Labouesse, Marie A.; Gertz, Erik R.; Piccolo, Brian D.; Souza, Elaine C.; Schuster, Gertrud U.; Witbracht, Megan G.; Woodhouse, Leslie R.; Adams, Sean H.; Keim, Nancy L.; Van Loan, Marta D.

2015-01-01

INTRODUCTION Weight loss reduces co-morbidities of obesity, but decreases bone mass. PURPOSE Our aims were to 1) determine if adequate dairy intake attenuates weight loss-induced bone loss; 2) evaluate the associations of endocrine, inflammatory and bone markers, anthropometric and other parameters to bone mineral density and content (BMD, BMC) pre- and post-weight loss; 3) model the contribution of these variables to post weight-loss BMD and BMC METHODS Overweight/obese women (BMI: 28–37 kg/m2) were enrolled in an energy reduced (−500 kcal/d; −2092 kJ/d) diet with adequate dairy (AD: 3–4 servings/d; n=25, 32.2 ± 8.8y) or low dairy (LD: ≤ 1 serving/d; n=26, 31.7 ± 8.4 y). BMD, BMC and body composition were measured by DXA. Bone markers (CTX, PYD, BAP, OC), endocrine (PTH, vitamin D, leptin, adiponectin, ghrelin, amylin, insulin, GLP-1, PAI-1, HOMA) and inflammatory markers (CRP, IL1-β, IL-6, IL-8, TNF-α, cortisol) were measured in serum or plasma. PA was assessed by accelerometry. RESULTS Following weight loss, AD intake resulted in significantly greater (p= 0.004) lumbar spine BMD and serum osteocalcin (p=0.004) concentration compared to LD. Pre- and post- body fat were negatively associated with hip and lumbar spine BMC (r= −0.28, p=0.04 to −0.45, p=0.001). Of note were the significant negative associations among bone markers and IL-1β, TNFα and CRP ranging from r = −0.29 (p=0.04) to r = −0.34 (p=0.01); magnitude of associations did not change with weight loss. Adiponectin was negatively related to change in osteocalcin. Factor analysis resulted in 8 pre- and post-weight loss Factors. Pre-weight loss Factors accounted for 13.7% of the total variance in pre-weight loss hip BMD; post-weight loss Factors explained 19.6% of the total variance in post-weight loss hip BMD. None of the Factors contributed to the variance in lumbar spine BMD. CONCLUSION AD during weight loss resulted in higher lumbar spine BMD and osteocalcin compared to LD. Significant negative associations were observed between bone and inflammatory markers suggesting inflammation suppresses bone metabolism. Using Factor Analysis, 19.6% of total variance in post-weight loss hip BMD could be explained by endocrine, immune, and anthropometric variables, but not lumbar spine BMD. PMID:24709689

Novel Radiomitigator for Radiation-Induced Bone Loss

NASA Technical Reports Server (NTRS)

Schreurs, A-S; Shirazi-fard, Y.; Terada, M.; Alwood, J. S.; Steczina, S.; Medina, C.; Tahimic, C. G. T.; Globus, R. K.

2016-01-01

Radiation-induced bone loss can occur with radiotherapy patients, accidental radiation exposure and during long-term spaceflight. Bone loss due to radiation is due to an early increase in oxidative stress, inflammation and bone resorption, resulting in an imbalance in bone remodeling. Furthermore, exposure to high-Linear Energy Transfer (LET) radiation will impair the bone forming progenitors and reduce bone formation. Radiation can be classified as high-LET or low-LET based on the amount of energy released. Dried Plum (DP) diet prevents bone loss in mice exposed to total body irradiation with both low-LET and high-LET radiation. DP prevents the early radiation-induced bone resorption, but furthermore, we show that DP protects the bone forming osteoblast progenitors from high-LET radiation. These results provide insight that DP re-balances the bone remodeling by preventing resorption and protecting the bone formation capacity. This data is important considering that most of the current osteoporosis treatments only block the bone resorption but do not protect bone formation. In addition, DP seems to act on both the oxidative stress and inflammation pathways. Finally, we have preliminary data showing the potential of DP to be radio-protective at a systemic effect and could possible protect other tissues at risk of total body-irradiation such as skin, brain and heart.

Experimental Traumatic Brain Injury Induces Bone Loss in Rats.

PubMed

Brady, Rhys D; Shultz, Sandy R; Sun, Mujun; Romano, Tania; van der Poel, Chris; Wright, David K; Wark, John D; O'Brien, Terence J; Grills, Brian L; McDonald, Stuart J

2016-12-01

Few studies have investigated the influence of traumatic brain injury (TBI) on bone homeostasis; however, pathophysiological mechanisms involved in TBI have potential to be detrimental to bone. The current study assessed the effect of experimental TBI in rats on the quantity and quality of two different weight-bearing bones, the femur and humerus. Rats were randomly assigned into either sham or lateral fluid percussion injury (FPI) groups. Open-field testing to assess locomotion was conducted at 1, 4, and 12 weeks post-injury, with the rats killed at 1 and 12 weeks post-injury. Bones were analyzed using peripheral quantitative computed tomography (pQCT), histomorphometric analysis, and three-point bending. pQCT analysis revealed that at 1 and 12 weeks post-injury, the distal metaphyseal region of femora from FPI rats had reduced cortical content (10% decrease at 1 week, 8% decrease at 12 weeks; p < 0.01) and cortical thickness (10% decrease at 1 week, 11% decrease at 12 weeks p < 0.001). There was also a 23% reduction in trabecular bone volume ratio at 1 week post-injury and a 27% reduction at 12 weeks post-injury in FPI rats compared to sham (p < 0.001). There were no differences in bone quantity and mechanical properties of the femoral midshaft between sham and TBI animals. There were no differences in locomotor outcomes, which suggested that post-TBI changes in bone were not attributed to immobility. Taken together, these findings indicate that this rat model of TBI was detrimental to bone and suggests a link between TBI and altered bone remodeling.

The Influence of Reconstruction Kernel on Bone Mineral and Strength Estimates Using Quantitative Computed Tomography and Finite Element Analysis.

PubMed

Michalski, Andrew S; Edwards, W Brent; Boyd, Steven K

2017-10-17

Quantitative computed tomography has been posed as an alternative imaging modality to investigate osteoporosis. We examined the influence of computed tomography convolution back-projection reconstruction kernels on the analysis of bone quantity and estimated mechanical properties in the proximal femur. Eighteen computed tomography scans of the proximal femur were reconstructed using both a standard smoothing reconstruction kernel and a bone-sharpening reconstruction kernel. Following phantom-based density calibration, we calculated typical bone quantity outcomes of integral volumetric bone mineral density, bone volume, and bone mineral content. Additionally, we performed finite element analysis in a standard sideways fall on the hip loading configuration. Significant differences for all outcome measures, except integral bone volume, were observed between the 2 reconstruction kernels. Volumetric bone mineral density measured using images reconstructed by the standard kernel was significantly lower (6.7%, p < 0.001) when compared with images reconstructed using the bone-sharpening kernel. Furthermore, the whole-bone stiffness and the failure load measured in images reconstructed by the standard kernel were significantly lower (16.5%, p < 0.001, and 18.2%, p < 0.001, respectively) when compared with the image reconstructed by the bone-sharpening kernel. These data suggest that for future quantitative computed tomography studies, a standardized reconstruction kernel will maximize reproducibility, independent of the use of a quantitative calibration phantom. Copyright © 2017 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.

A correlative imaging based methodology for accurate quantitative assessment of bone formation in additive manufactured implants.

PubMed

Geng, Hua; Todd, Naomi M; Devlin-Mullin, Aine; Poologasundarampillai, Gowsihan; Kim, Taek Bo; Madi, Kamel; Cartmell, Sarah; Mitchell, Christopher A; Jones, Julian R; Lee, Peter D

2016-06-01

A correlative imaging methodology was developed to accurately quantify bone formation in the complex lattice structure of additive manufactured implants. Micro computed tomography (μCT) and histomorphometry were combined, integrating the best features from both, while demonstrating the limitations of each imaging modality. This semi-automatic methodology registered each modality using a coarse graining technique to speed the registration of 2D histology sections to high resolution 3D μCT datasets. Once registered, histomorphometric qualitative and quantitative bone descriptors were directly correlated to 3D quantitative bone descriptors, such as bone ingrowth and bone contact. The correlative imaging allowed the significant volumetric shrinkage of histology sections to be quantified for the first time (~15 %). This technique demonstrated the importance of location of the histological section, demonstrating that up to a 30 % offset can be introduced. The results were used to quantitatively demonstrate the effectiveness of 3D printed titanium lattice implants.

Targeted delivery of mesenchymal stem cells to the bone.

PubMed

Yao, Wei; Lane, Nancy E

2015-01-01

Osteoporosis is a disease of excess skeletal fragility that results from estrogen loss and aging. Age related bone loss has been attributed to both elevated bone resorption and insufficient bone formation. We developed a hybrid compound, LLP2A-Ale in which LLP2A has high affinity for the α4β1 integrin on mesenchymal stem cells (MSCs) and alendronate has high affinity for bone. When LLP2A-Ale was injected into mice, the compound directed MSCs to both trabecular and cortical bone surfaces and increased bone mass and bone strength. Additional studies are underway to further characterize this hybrid compound, LLP2A-Ale, and how it can be utilized for the treatment of bone loss resulting from hormone deficiency, aging, and inflammation and to augment bone fracture healing. This article is part of a Special Issue entitled "Stem Cells and Bone". Copyright © 2014 Elsevier Inc. All rights reserved.

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

Study of trabecular bone microstructure using spatial autocorrelation analysis

NASA Astrophysics Data System (ADS)

Wald, Michael J.; Vasilic, Branimir; Saha, Punam K.; Wehrli, Felix W.

2005-04-01

The spatial autocorrelation analysis method represents a powerful, new approach to quantitative characterization of structurally quasi-periodic anisotropic materials such as trabecular bone (TB). The method is applicable to grayscale images and thus does not require any preprocessing, such as segmentation which is difficult to achieve in the limited resolution regime of in vivo imaging. The 3D autocorrelation function (ACF) can be efficiently calculated using the Fourier transform. The resulting trabecular thickness and spacing measurements are robust to the presence of noise and produce values within the expected range as determined by other methods from μCT and μMRI datasets. TB features found from the ACF are shown to correlate well with those determined by the Fuzzy Distance transform (FDT) in the transverse plane, i.e. the plane orthogonal to bone"s major axis. The method is further shown to be applicable to in-vivo μMRI data. Using the ACF, we examine data acquired in a previous study aimed at evaluating the structural implications of male hypogonadism characterized by testosterone deficiency and reduced bone mass. Specifically, we consider the hypothesis that eugonadal and hypogonadal men differ in the anisotropy of their trabecular networks. The analysis indicates a significant difference in trabecular bone thickness and longitudinal spacing between the control group and the testosterone deficient group. We conclude that spatial autocorrelation analysis is able to characterize the 3D structure and anisotropy of trabecular bone and provides new insight into the structural changes associated with osteoporotic trabecular bone loss.

Magnetic resonance imaging can accurately assess the long-term progression of knee structural changes in experimental dog osteoarthritis.

PubMed

Boileau, C; Martel-Pelletier, J; Abram, F; Raynauld, J-P; Troncy, E; D'Anjou, M-A; Moreau, M; Pelletier, J-P

2008-07-01

Osteoarthritis (OA) structural changes take place over decades in humans. MRI can provide precise and reliable information on the joint structure and changes over time. In this study, we investigated the reliability of quantitative MRI in assessing knee OA structural changes in the experimental anterior cruciate ligament (ACL) dog model of OA. OA was surgically induced by transection of the ACL of the right knee in five dogs. High resolution three dimensional MRI using a 1.5 T magnet was performed at baseline, 4, 8 and 26 weeks post surgery. Cartilage volume/thickness, cartilage defects, trochlear osteophyte formation and subchondral bone lesion (hypersignal) were assessed on MRI images. Animals were killed 26 weeks post surgery and macroscopic evaluation was performed. There was a progressive and significant increase over time in the loss of knee cartilage volume, the cartilage defect and subchondral bone hypersignal. The trochlear osteophyte size also progressed over time. The greatest cartilage loss at 26 weeks was found on the tibial plateaus and in the medial compartment. There was a highly significant correlation between total knee cartilage volume loss or defect and subchondral bone hypersignal, and also a good correlation between the macroscopic and the MRI findings. This study demonstrated that MRI is a useful technology to provide a non-invasive and reliable assessment of the joint structural changes during the development of OA in the ACL dog model. The combination of this OA model with MRI evaluation provides a promising tool for the evaluation of new disease-modifying osteoarthritis drugs (DMOADs).

Trabecular bone class mapping across resolutions: translating methods from HR-pQCT to clinical CT

NASA Astrophysics Data System (ADS)

Valentinitsch, Alexander; Fischer, Lukas; Patsch, Janina M.; Bauer, Jan; Kainberger, Franz; Langs, Georg; DiFranco, Matthew

2015-03-01

Quantitative assessment of 3D bone microarchitecture in high-resolution peripheral quantitative computed tomography (HR-pQCT) has shown promise in fracture risk assessment and biomechanics, but is limited to the distal radius and tibia. Trabecular microarchitecture classes (TMACs), based on voxel-wise clustering texture and structure tensor features in HRpQCT, is extended in this paper to quantify trabecular bone classes in clinical multi-detector CT (MDCT) images. Our comparison of TMACs in 12 cadaver radii imaged using both HRpQCT and MDCT yields a mean Dice score of up to 0.717+/-0.40 and visually concordant bone quality maps. Further work to develop clinically viable bone quantitative imaging using HR-pQCT validation could have a significant impact on overall bone health assessment.

Simulated bone remodeling around two types of osseointegrated implants for direct fixation of upper-leg prostheses.

PubMed

Tomaszewski, P K; Verdonschot, N; Bulstra, S K; Rietman, J S; Verkerke, G J

2012-11-01

Direct attachment of an upper leg prosthesis to the skeletal system by a percutaneous implant is an alternative solution to the traditional socket fixation. In this study, we investigated long-term periprosthetic bone changes around two types of fixation implants using two different initial conditions, namely immediate post-amputation implantation and the conventional implantation after considerable time of socket prosthesis use. We questioned the difference in bone modeling response the implants provoked and if it could lead to premature bone fracture. Generic CT-based finite element models of an intact femoral bone and amputated bone implanted with models of two existing direct-fixation implants, the OPRA system (Integrum AB) and the ISP Endo/Exo prosthesis (ESKA Implants AG) were created for this study. Adaptive bone-remodeling simulations used the heel-strike and toe-off loads from a normal walking cycle. The bone loss caused by prolonged use of socket prosthesis had more severe effects on the ultimate bone quality than adaptation induced by the direct-fixation implants. Both implants showed considerable bone remodeling; the titanium screw implant (OPRA system) provoked more bone loss than the porous coated CoCrMo stem (ISP implant). The chance of the peri-prosthetic bone fracture remained higher for the post-socket case as compared to the direct amputation cases. In conclusion, both direct-fixation implants lead to considerable bone loss and bone loss is more severe after a prolonged period of post-socket use. Hence, from a biomechanical perspective it is better to limit the post-socket time and to re-design direct fixation devices to reduce bone loss and the probability of peri-prosthetic bone fractures. Copyright © 2012 Elsevier Ltd. All rights reserved.

Sheep model for osteoporosis: The effects of peripheral hormone therapy on centrally induced systemic bone loss in an osteoporotic sheep model.

PubMed

Oheim, Ralf; Simon, Maciej J K; Steiner, Malte; Vettorazzi, Eik; Barvencik, Florian; Ignatius, Anita; Amling, Michael; Clarke, Iain J; Pogoda, Pia; Beil, F Timo

2017-04-01

Hypothalamic-pituitary disconnection (HPD) leads to low bone turnover followed by bone loss and reduced biomechanical properties in sheep. To investigate the role of peripheral hormones in this centrally induced systemic bone loss model, we planned a hormone replacement experiment. Therefore, estrogen (OHE), thyroxin (OHT) or a combination of both (OHTE) was substituted in ovariectomized HPD sheep, as both hormones are decreased in HPD sheep and are known to have a significant but yet not fully understood impact on bone metabolism. Bone turnover and structural parameters were analyzed in comparison to different control groups - untreated sheep (C), ovariectomized (O) and ovariectomized+HPD sheep (OH). We performed histomorphometric and HR-pQCT analyses nine months after the HPD procedure, as well as biomechanical testing of all ewes studied. In HPD sheep (OH) the low bone turnover led to a significant bone loss. Treatment with thyroxin alone (OHT) mainly increased bone resorption, leading to a further reduction in bone volume. In contrast, the treatment with estrogen alone (OHE) and the combined treatment with estrogen and thyroxin (OHTE) prevented HPD-induced bone loss completely. In conclusion, peripheral hormone substitution was able to prevent HPD-induced low-turnover osteoporosis in sheep. But only the treatment with estrogen alone or in combination with thyroxin was able to completely preserve bone mass and structure. These findings demonstrate the importance of peripheral hormones for a balanced bone remodeling and a physiological bone turnover. Copyright © 2017 Elsevier Ltd. All rights reserved.

Limb salvage after infected knee arthroplasty with bone loss and extensor mechanism deficiency using a modular segmental replacement system.

PubMed

Namdari, Surena; Milby, Andrew H; Garino, Jonathan P

2011-09-01

Multiple total knee arthroplasty revisions pose significant surgical challenges, such as bone loss and soft tissue compromise. For patients with bone loss and extensor mechanism insufficiency after total knee arthroplasty, arthrodesis is a treatment option for the avoidance of amputation. However, arthrodesis is both difficult to achieve in situations with massive bone loss and potentially undesirable due to the dramatic shortening that follows. Although intramedullary nailing for knee arthrodesis has been widely reported, this technique has traditionally relied on the achievement of bony union. We report a case of a patient with massive segmental bone loss in which a modular intercalary prosthesis was used for arthrodesis to preserve limb length without bony union. Copyright © 2011 Elsevier Inc. All rights reserved.

Association Between Dietary Fiber Intake and Bone Loss in the Framingham Offspring Study.

PubMed

Dai, Zhaoli; Zhang, Yuqing; Lu, Na; Felson, David T; Kiel, Douglas P; Sahni, Shivani

2018-02-01

Dietary fiber may increase calcium absorption, but its role in bone mineralization is unclear. Furthermore, the health effect of dietary fiber may be different between sexes. We examined the association between dietary fiber (total fiber and fiber from cereal, fruits, vegetables, nuts, and legumes) and bone loss at the femoral neck, trochanter, and lumbar spine (L 2 to L 4 ) in older men and women. In the Framingham Offspring Study, at baseline (1996-2001), diet was assessed using the Willett food-frequency questionnaire, and bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry. Follow-up BMD was measured in 2001-2005 and 2005-2008 among 792 men (mean age 58.1 years; BMI 28.6 kg/m 2 ) and 1065 women (mean age 57.3 years; BMI 27.2 kg/m 2 ). We used sex-specific generalized estimating equations in multivariable regressions to estimate the difference (β) of annualized BMD change in percent (%ΔBMD) at each skeletal site per 5 g/d increase in dietary fiber. We further estimated the adjusted mean for bone loss (annualized %ΔBMD) among participants in each higher quartile (Q2, Q3, or Q4) compared with those in the lowest quartile (Q1) of fiber intake. Higher dietary total fiber (β = 0.06, p = 0.003) and fruit fiber (β = 0.10, p = 0.008) was protective against bone loss at the femoral neck in men but not in women. When examined in quartiles, men in Q2-Q4 of total fiber had significantly less bone loss at the femoral neck versus those in Q1 (all p < 0.04). For women, we did not observe associations with hip bone loss, although fiber from vegetables appeared to be protective against spine bone loss in women but not men. There were no associations with cereal fiber or nut and legume fiber and bone loss in men or women. Our findings suggest that higher dietary fiber may modestly reduce bone loss in men at the hip. © 2017 American Society for Bone and Mineral Research. © 2017 American Society for Bone and Mineral Research.

Effects of Spaceflight on Bone: The Rat as an Animal Model for Human Bone Loss

NASA Technical Reports Server (NTRS)

Halloran, B.; Weider, T.; Morey-Holton, E.

1999-01-01

The loss of weight bearing during spaceflight results in osteopenia in humans. Decrements in bone mineral reach 3-10% after as little as 75-184 days in space. Loss of bone mineral during flight decreases bone strength and increases fracture risk. The mechanisms responsible for, and the factors contributing to, the changes in bone induced by spaceflight are poorly understood. The rat has been widely used as an animal model for human bone loss during spaceflight. Despite its potential usefulness, the results of bone studies performed in the rat in space have been inconsistent. In some flights bone formation is decreased and cancellous bone volume reduced, while in others no significant changes in bone occur. In June of 1996 Drs. T. Wronski, S. Miller and myself participated in a flight experiment (STS 78) to examine the effects of glucocorticoids on bone during weightlessness. Technically the 17 day flight experiment was flawless. The results, however, were surprising. Cancellous bone volume and osteoblast surface in the proximal tibial metaphysis were the same in flight and ground-based control rats. Normal levels of cancellous bone mass and bone formation were also detected in the lumbar vertebrae and femoral neck of flight rats. Furthermore, periosteal bone formation rate was found to be identical in flight and ground-based control rats. Spaceflight had little or no effect on bone metabolism! These results prompted us to carefully review the changes in bone observed in, and the flight conditions of previous spaceflight missions.

Diagnostic accuracy of MRI in the measurement of glenoid bone loss.

PubMed

Gyftopoulos, Soterios; Hasan, Saqib; Bencardino, Jenny; Mayo, Jason; Nayyar, Samir; Babb, James; Jazrawi, Laith

2012-10-01

The purpose of this study is to assess the accuracy of MRI quantification of glenoid bone loss and to compare the diagnostic accuracy of MRI to CT in the measurement of glenoid bone loss. MRI, CT, and 3D CT examinations of 18 cadaveric glenoids were obtained after the creation of defects along the anterior and anteroinferior glenoid. The defects were measured by three readers separately and blindly using the circle method. These measurements were compared with measurements made on digital photographic images of the cadaveric glenoids. Paired sample Student t tests were used to compare the imaging modalities. Concordance correlation coefficients were also calculated to measure interobserver agreement. Our data show that MRI could be used to accurately measure glenoid bone loss with a small margin of error (mean, 3.44%; range, 2.06-5.94%) in estimated percentage loss. MRI accuracy was similar to that of both CT and 3D CT for glenoid loss measurements in our study for the readers familiar with the circle method, with 1.3% as the maximum expected difference in accuracy of the percentage bone loss between the different modalities (95% confidence). Glenoid bone loss can be accurately measured on MRI using the circle method. The MRI quantification of glenoid bone loss compares favorably to measurements obtained using 3D CT and CT. The accuracy of the measurements correlates with the level of training, and a learning curve is expected before mastering this technique.

Correlation of quantitative computed tomographic subchondral bone density and ash density in horses.

PubMed

Drum, M G; Les, C M; Park, R D; Norrdin, R W; McIlwraith, C W; Kawcak, C E

2009-02-01

The purpose of this study was to compare subchondral bone density obtained using quantitative computed tomography with ash density values from intact equine joints, and to determine if there are measurable anatomic variations in mean subchondral bone density. Five adult equine metacarpophalangeal joints were scanned with computed tomography (CT), disarticulated, and four 1-cm(3) regions of interest (ROI) cut from the distal third metacarpal bone. Bone cubes were ashed, and percent mineralization and ash density were recorded. Three-dimensional models were created of the distal third metacarpal bone from CT images. Four ROIs were measured on the distal aspect of the third metacarpal bone at axial and abaxial sites of the medial and lateral condyles for correlation with ash samples. Overall correlations of mean quantitative CT (QCT) density with ash density (r=0.82) and percent mineralization (r=0.93) were strong. There were significant differences between abaxial and axial ROIs for mean QCT density, percent bone mineralization and ash density (p<0.05). QCT appears to be a good measure of bone density in equine subchondral bone. Additionally, differences existed between axial and abaxial subchondral bone density in the equine distal third metacarpal bone.

Regulatory mechanism of food factors in bone metabolism and prevention of osteoporosis.

PubMed

Yamaguchi, Masayoshi

2006-11-01

Aging induces a decrease in bone mass, and osteoporosis with its accompanying decrease in bone mass is widely recognized as a major public health problem. Bone loss with increasing age may be due to decreased bone formation and increased bone resorption. Pharmacologic and nutritional factors may prevent bone loss with aging, although chemical compounds in food and plants which act on bone metabolism are poorly understood. We have found that isoflavones (including genistein and daidzein), which are contained in soybeans, have a stimulatory effect on osteoblastic bone formation and an inhibitory effect on osteoclastic bone resorption, thereby increasing bone mass. Menaquinone-7, an analogue of vitamin K(2) which is abundant in fermented soybeans, has been demonstrated to stimulate osteoblastic bone formation and to inhibit osteoclastic bone resorption. Of various carotenoids, beta-cryptoxanthin, which is abundant in Satsuma mandarin (Citrus unchiu MARC), has a stimulatory effect on osteoblastic bone formation and an inhibitory effect on osteoclastic bone resorption. The supplementation of these factors has a preventive effect on bone loss induced by ovariectomy in rats, which are an animal model of osteoporosis, and their intake has been shown to have a stimulatory effect on bone mass in humans. Factors with an anabolic effect on bone metabolism were found in extracts obtained from wasabi leafstalk (Wasabi japonica MATSUM), the marine alga Sargassum horneri, and bee pollen Cistus ladaniferus. Phytocomponent p-hydroxycinnamic acid was also found to have an anabolic effect on bone metabolism. Food chemical factors thus play a role in bone health and may be important in the prevention of bone loss with increasing age.

Anabolic steroids reduce spinal cord injury-related bone loss in rats associated with increased Wnt signaling

PubMed Central

Sun, Li; Pan, Jiangping; Peng, Yuanzhen; Wu, Yong; Li, Jianghua; Liu, Xuan; Qin, Yiwen; Bauman, William A.; Cardozo, Christopher; Zaidi, Mone; Qin, Weiping

2013-01-01

Background Spinal cord injury (SCI) causes severe bone loss. At present, there is no practical treatment to delay or prevent bone loss in individuals with motor-complete SCI. Hypogonadism is common in men after SCI and may exacerbate bone loss. The anabolic steroid nandrolone reduces bone loss due to microgravity or nerve transection. Objective To determine whether nandrolone reduced bone loss after SCI and, if so, to explore the mechanisms of nandrolone action. Methods Male rats with complete transection of the spinal cord were administered nandrolone combined with a physiological replacement dose of testosterone, or vehicle, beginning on day 29 after SCI and continued for 28 days. Results SCI reduced distal femoral and proximal tibial bone mineral density (BMD) by 25 and 16%, respectively, at 56 days. This bone loss was attenuated by nandrolone. In ex vivo osteoclasts cultures, SCI increased mRNA levels for tartrate-resistant acid phosphatase (TRAP) and calcitonin receptor; nandrolone-normalized expression levels of these transcripts. In ex vivo osteoblast cultures, SCI increased receptor activator of NF-kB ligand (RANKL) mRNA levels but did not alter osteoprotegerin (OPG) mRNA expression; nandrolone-increased expression of OPG and OPG/RANKL ratio. SCI reduced mRNA levels of Wnt signaling-related genes Wnt3a, low-density lipoprotein receptor-related protein 5 (LRP5), Fzd5, Tcf7, and ectodermal-neural cortex 1 (ENC1) in osteoblasts, whereas nandrolone increased expression of each of these genes. Conclusions The results demonstrate that nandrolone reduces bone loss after SCI. A potential mechanism is suggested by our findings wherein nandrolone modulates genes for differentiation and activity of osteoclasts and osteoblasts, at least in part, through the activation of Wnt signaling. PMID:24090150

Differential Bone Loss in Mouse Models of Colon Cancer Cachexia

PubMed Central

Bonetto, Andrea; Kays, Joshua K.; Parker, Valorie A.; Matthews, Ryan R.; Barreto, Rafael; Puppa, Melissa J.; Kang, Kyung S.; Carson, James A.; Guise, Theresa A.; Mohammad, Khalid S.; Robling, Alexander G.; Couch, Marion E.; Koniaris, Leonidas G.; Zimmers, Teresa A.

2017-01-01

Cachexia is a distinctive feature of colorectal cancer associated with body weight loss and progressive muscle wasting. Several mechanisms responsible for muscle and fat wasting have been identified, however it is not known whether the physiologic and molecular crosstalk between muscle and bone tissue may also contribute to the cachectic phenotype in cancer patients. The purpose of this study was to clarify whether tumor growth associates with bone loss using several experimental models of colorectal cancer cachexia, namely C26, HT-29, and ApcMin/+. The effects of cachexia on bone structure and strength were evaluated with dual energy X-ray absorptiometry (DXA), micro computed tomography (μCT), and three-point bending test. We found that all models showed tumor growth consistent with severe cachexia. While muscle wasting in C26 hosts was accompanied by moderate bone depletion, no loss of bone strength was observed. However, HT-29 tumor bearing mice showed bone abnormalities including significant reductions in whole-body bone mineral density (BMD), bone mineral content (BMC), femoral trabecular bone volume fraction (BV/TV), trabecular number (Tb.N), and trabecular thickness (Tb.Th), but no declines in strength. Similarly, cachexia in the ApcMin/+ mice was associated with significant decreases in BMD, BMC, BV/TV, Tb.N, and Tb.Th as well as decreased strength. Our data suggest that colorectal cancer is associated with muscle wasting and may be accompanied by bone loss dependent upon tumor type, burden, stage and duration of the disease. It is clear that preserving muscle mass promotes survival in cancer cachexia. Future studies will determine whether strategies aimed at preventing bone loss can also improve outcomes and survival in colorectal cancer cachexia. PMID:28123369

Differential Bone Loss in Mouse Models of Colon Cancer Cachexia.

PubMed

Bonetto, Andrea; Kays, Joshua K; Parker, Valorie A; Matthews, Ryan R; Barreto, Rafael; Puppa, Melissa J; Kang, Kyung S; Carson, James A; Guise, Theresa A; Mohammad, Khalid S; Robling, Alexander G; Couch, Marion E; Koniaris, Leonidas G; Zimmers, Teresa A

2016-01-01

Cachexia is a distinctive feature of colorectal cancer associated with body weight loss and progressive muscle wasting. Several mechanisms responsible for muscle and fat wasting have been identified, however it is not known whether the physiologic and molecular crosstalk between muscle and bone tissue may also contribute to the cachectic phenotype in cancer patients. The purpose of this study was to clarify whether tumor growth associates with bone loss using several experimental models of colorectal cancer cachexia, namely C26, HT-29, and Apc Min/+ . The effects of cachexia on bone structure and strength were evaluated with dual energy X-ray absorptiometry (DXA), micro computed tomography (μCT), and three-point bending test. We found that all models showed tumor growth consistent with severe cachexia. While muscle wasting in C26 hosts was accompanied by moderate bone depletion, no loss of bone strength was observed. However, HT-29 tumor bearing mice showed bone abnormalities including significant reductions in whole-body bone mineral density (BMD), bone mineral content (BMC), femoral trabecular bone volume fraction (BV/TV), trabecular number (Tb.N), and trabecular thickness (Tb.Th), but no declines in strength. Similarly, cachexia in the Apc Min/+ mice was associated with significant decreases in BMD, BMC, BV/TV, Tb.N, and Tb.Th as well as decreased strength. Our data suggest that colorectal cancer is associated with muscle wasting and may be accompanied by bone loss dependent upon tumor type, burden, stage and duration of the disease. It is clear that preserving muscle mass promotes survival in cancer cachexia. Future studies will determine whether strategies aimed at preventing bone loss can also improve outcomes and survival in colorectal cancer cachexia.

Glucocorticoid: A potential role in microgravity-induced bone loss

NASA Astrophysics Data System (ADS)

Yang, Jiancheng; Yang, Zhouqi; Li, Wenbin; Xue, Yanru; Xu, Huiyun; Li, Jingbao; Shang, Peng

2017-11-01

Exposure of animals and humans to conditions of microgravity, including actual spaceflight and simulated microgravity, results in numerous negative alterations to bone structure and mechanical properties. Although there are abundant researches on bone loss in microgravity, the explicit mechanism is not completely understood. At present, it is widely accepted that the absence of mechanical stimulus plays a predominant role in bone homeostasis disorders in conditions of weightlessness. However, aside from mechanical unloading, nonmechanical factors such as various hormones, cytokines, dietary nutrition, etc. are important as well in microgravity induced bone loss. The stress-induced increase in endogenous glucocorticoid (GC) levels is inevitable in microgravity environments. Moreover, it is well known that GCs have a detrimental effect to bone health at excess concentrations. Therefore, GC plays a potential role in microgravity-induced bone loss. This review summarizeds several studies and their prospective solutions to this hypothesis.

The Relevance of Mouse Models for Investigating Age-Related Bone Loss in Humans

PubMed Central

2013-01-01

Mice are increasingly used for investigation of the pathophysiology of osteoporosis because their genome is easily manipulated, and their skeleton is similar to that of humans. Unlike the human skeleton, however, the murine skeleton continues to grow slowly after puberty and lacks osteonal remodeling of cortical bone. Yet, like humans, mice exhibit loss of cancellous bone, thinning of cortical bone, and increased cortical porosity with advancing age. Histologic evidence in mice and humans alike indicates that inadequate osteoblast-mediated refilling of resorption cavities created during bone remodeling is responsible. Mouse models of progeria also show bone loss and skeletal defects associated with senescence of early osteoblast progenitors. Additionally, mouse models of atherosclerosis, which often occurs in osteoporotic participants, also suffer bone loss, suggesting that common diseases of aging share pathophysiological pathways. Knowledge of the causes of skeletal fragility in mice should therefore be applicable to humans if inherent limitations are recognized. PMID:23689830

[Ethnic origin and alveolar bone loss in Israeli adults].

PubMed

Zadik, Y; Bechor, R; Shochat, Z; Galor, S

2008-04-01

The aim of this study was to evaluate the association of alveolar bone loss and ethnic origin among Israeli adults. The study population consisted of 815 male military personnel, aged 25 to 60 years (average 38.1 +/- 7.0 yr), who arrived at a military dental clinic for routine dental examination during 2004-5. The distance between CEJ and alveolar bone crest was measure on pair of standardized posterior bitewing radiographs. Associations between the periodontal score and place of birth, the father ethnic origin and the mother ethnic origin were evaluated using the chi2-test. The individual's place of birth had no influence on the radiographic alveolar bone loss. Father of Yemenite-, North-African- or Mediterranean-origin, and mother of Yemenite-, North-African- or Asian-origin have associated to the occurrence and severity of alveolar bone loss, whereas sons to father or mother from Israeli or European descent were found to have less bone loss (p < 0.001). Ethnic origin has an influence on the alveolar bone loss in Israeli adults. However, more research is needed on the role of the potentially confounders in the association between origin and periodontal health.

Building better bone: The weaving of biologic and engineering strategies for managing bone loss.

PubMed

Schwartz, Andrew M; Schenker, Mara L; Ahn, Jaimo; Willett, Nick J

2017-09-01

Segmental bone loss remains a challenging clinical problem for orthopaedic trauma surgeons. In addition to the missing bone itself, the local tissues (soft tissue, vascular) are often highly traumatized as well, resulting in a less than ideal environment for bone regeneration. As a result, attempts at limb salvage become a highly expensive endeavor, often requiring multiple operations and necessitating the use of every available strategy (autograft, allograft, bone graft substitution, Masquelet, bone transport, etc.) to achieve bony union. A cost-sensitive, functionally appropriate, and volumetrically adequate engineered substitute would be practice-changing for orthopaedic trauma surgeons and these patients with difficult clinical problems. In tissue engineering and bone regeneration fields, numerous research efforts continue to make progress toward new therapeutic interventions for segmental bone loss, including novel biomaterial development as well as cell-based strategies. Despite an ever-evolving literature base of these new therapeutic and engineered options, there remains a disconnect with the clinical practice, with very few translating into clinical use. A symposium entitled "Building better bone: The weaving of biologic and engineering strategies for managing bone loss," was presented at the 2016 Orthopaedic Research Society Conference to further explore this engineering-clinical disconnect, by surveying basic, translational, and clinical researchers along with orthopaedic surgeons and proposing ideas for pushing the bar forward in the field of segmental bone loss. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1855-1864, 2017. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Osteocyte-derived RANKL is a critical mediator of the increased bone resorption caused by dietary calcium deficiency

PubMed Central

Xiong, Jinhu; Piemontese, Marilina; Thostenson, Jeff D.; Weinstein, Robert S.; Manolagas, Stavros C.; O’Brien, Charles A.

2014-01-01

Parathyroid hormone (PTH) excess stimulates bone resorption. This effect is associated with increased expression of the osteoclastogenic cytokine receptor activator of nuclear factor кB ligand (RANKL) in bone. However, several different cell types, including bone marrow stromal cells, osteocytes, and T lymphocytes, express both RANKL and the PTH receptor and it is unclear whether RANKL expression by any of these cell types is required for PTH-induced bone loss. Here we have used mice lacking the RANKL gene in osteocytes to determine whether RANKL produced by this cell type is required for the bone loss caused by secondary hyperparathyroidism induced by dietary calcium deficiency in adult mice. Thirty days of dietary calcium deficiency caused bone loss in control mice, but this effect was blunted in mice lacking RANKL in osteocytes. The increase in RANKL expression in bone and the increase in osteoclast number caused by dietary calcium deficiency were also blunted in mice lacking RANKL in osteocytes. These results demonstrate that RANKL produced by osteocytes contributes to the increased bone resorption and the bone loss caused by secondary hyperparathyroidism, strengthening the evidence that osteocytes are an important target cell for hormonal control of bone remodeling. PMID:24933342

Role of Oxidative Damage in Radiation-Induced Bone Loss

NASA Technical Reports Server (NTRS)

Schreurs, Ann-Sofie; Alwood, Joshua S.; Limoli, Charles L.; Globus, Ruth K.

2014-01-01

During prolonged spaceflight, astronauts are exposed to both microgravity and space radiation, and are at risk for increased skeletal fragility due to bone loss. Evidence from rodent experiments demonstrates that both microgravity and ionizing radiation can cause bone loss due to increased bone-resorbing osteoclasts and decreased bone-forming osteoblasts, although the underlying molecular mechanisms for these changes are not fully understood. We hypothesized that excess reactive oxidative species (ROS), produced by conditions that simulate spaceflight, alter the tight balance between osteoclast and osteoblast activities, leading to accelerated skeletal remodeling and culminating in bone loss. To test this, we used the MCAT mouse model; these transgenic mice over-express the human catalase gene targeted to mitochondria, the major organelle contributing free radicals. Catalase is an anti-oxidant that converts reactive species, hydrogen peroxide into water and oxygen. This animal model was selected as it displays extended lifespan, reduced cardiovascular disease and reduced central nervous system radio-sensitivity, consistent with elevated anti-oxidant activity conferred by the transgene. We reasoned that mice overexpressing catalase in mitochondria of osteoblast and osteoclast lineage cells would be protected from the bone loss caused by simulated spaceflight. Over-expression of human catalase localized to mitochondria caused various skeletal phenotypic changes compared to WT mice; this includes greater bone length, decreased cortical bone area and moment of inertia, and indications of altered microarchitecture. These findings indicate mitochondrial ROS are important for normal bone-remodeling and skeletal integrity. Catalase over-expression did not fully protect skeletal tissue from structural decrements caused by simulated spaceflight; however there was significant protection in terms of cellular oxidative damage (MDA levels) to the skeletal tissue. Furthermore, we used an array of countermeasures (Antioxidant diets and injections) to prevent the radiation-induced bone loss, although these did not prevent bone loss, analysis is ongoing to determine if these countermeasure protected radiation-induced damage to other tissues.

Genetic influences on bone loss in the San Antonio Family Osteoporosis Study

PubMed Central

Shaffer, John R.; Kammerer, Candace M.; Bruder, Jan M.; Cole, Shelley A.; Dyer, Thomas D.; Almasy, Laura; MacCluer, Jean W.; Blangero, John; Bauer, Richard L.; Mitchell, Braxton D.

2009-01-01

Summary The genetic contribution to age-related bone loss is not well understood. We estimated that genes accounted for 25–45% of variation in 5-year change in bone mineral density in men and women. An autosome-wide linkage scan yielded no significant evidence for chromosal regions implicated in bone loss. Introduction The contribution of genetics to acquisition of peak bone mass is well documented, but little is know about the influence of genes on subsequent bone loss with age. We therefore measured 5-year change in bone mineral density (BMD) in 300 Mexican Americans (>45 years of age) from the San Antonio Family Osteoporosis Study to identify genetic factors influencing bone loss. Methods Annualized change in BMD was calculated from measurements taken 5.5 years apart. Heritability (h2) of BMD change was estimated using variance components methods and autosome-wide linkage analysis was carried out using 460 microsatellite markers at a mean 7.6 cM interval density. Results Rate of BMD change was heritable at the forearm (h2=0.31, p=0.021), hip (h2 =0.44, p=0.017), spine (h2=0.42, p=0.005), but not whole body (h2=0.18, p=0.123). Covariates associated with rapid bone loss (advanced age, baseline BMD, female sex, low baseline weight, postmenopausal status, and interim weight loss) accounted for 10% to 28% of trait variation. No significant evidence of linkage was observed at any skeletal site. Conclusions This is one of the first studies to report significant heritability of BMD change for weight-bearing and non-weight-bearing bones in an unselected population and the first linkage scan for change in BMD. PMID:18414963

A novel role for dopamine signaling in the pathogenesis of bone loss from the atypical antipsychotic drug risperidone in female mice.

PubMed

Motyl, Katherine J; Beauchemin, Megan; Barlow, Deborah; Le, Phuong T; Nagano, Kenichi; Treyball, Annika; Contractor, Anisha; Baron, Roland; Rosen, Clifford J; Houseknecht, Karen L

2017-10-01

Atypical antipsychotic (AA) drugs, including risperidone (RIS), are used to treat schizophrenia, bipolar disorder, and autism, and are prescribed off-label for other mental health issues. AA drugs are associated with severe metabolic side effects of obesity and type 2 diabetes. Cross-sectional and longitudinal data also show that risperidone causes bone loss and increases fracture risk in both men and women. There are several potential mechanisms of bone loss from RIS. One is hypogonadism due to hyperprolactinemia from dopamine receptor antagonism. However, many patients have normal prolactin levels; moreover we demonstrated that bone loss from RIS in mice can be blocked by inhibition of β-adrenergic receptor activation with propranolol, suggesting the sympathetic nervous system (SNS) plays a pathological role. Further, when, we treated ovariectomized (OVX) and sham operated mice daily for 8weeks with RIS or vehicle we demonstrated that RIS causes significant trabecular bone loss in both sham operated and OVX mice. RIS directly suppressed osteoblast number in both sham and OVX mice, but increased osteoclast number and surface in OVX mice alone, potentially accounting for the augmented bone loss. Thus, hypogonadism alone cannot explain RIS induced bone loss. In the current study, we show that dopamine and RIS are present in the bone marrow compartment and that RIS can exert its effects directly on bone cells via dopamine receptors. Our findings of both direct and indirect effects of AA drugs on bone are relevant for current and future clinical and translational studies investigating the mechanism of skeletal changes from AA drugs. Copyright © 2017 Elsevier Inc. All rights reserved.

Non-canonical Wnt4 prevents skeletal aging and inflammation by inhibiting NF-κB

PubMed Central

Yu, Bo; Chang, Jia; Liu, Yunsong; Li, Jiong; Kevork, Kareena; Al-Hezaimi, Khalid; Graves, Dana T; Park, No-Hee; Wang, Cun-Yu

2014-01-01

Aging-related bone loss and osteoporosis affect millions of patients worldwide. Chronic inflammation associated with aging and arthritis promotes bone resorption and impairs bone formation. Here we show that Wnt4 attenuated bone loss in osteoporosis and skeletal aging by inhibiting nuclear factor-kappa B (NF-κB) via non-canonical Wnt signaling. Transgenic mice expressing Wnt4 from osteoblasts were significantly protected from bone loss and chronic inflammation induced by ovariectomy, tumor necrosis factor or natural aging. In addition to promoting bone formation, Wnt4 could inhibit osteoclast formation and bone resorption. Mechanistically, Wnt4 inhibited transforming growth factor beta-activated kinase 1-mediated NF-κB activation in macrophages and osteoclast precursors independent of β-catenin. Moreover, recombinant Wnt4 proteins were able to alleviate osteoporotic bone loss and inflammation by inhibiting NF-κB in vivo. Taken together, our results suggest that Wnt4 might be used as a therapeutic agent for treating osteoporosis by attenuating NF-κB. PMID:25108526

Sex steroids, bone mass, and bone loss. A prospective study of pre-, peri-, and postmenopausal women.

PubMed

Slemenda, C; Longcope, C; Peacock, M; Hui, S; Johnston, C C

1996-01-01

Although bone loss around the time of menopause is driven by estrogen deficiency, the roles of estrogens and androgens in the preservation of skeletal mass at other stages of life are less well understood. To address this issue we studied 231 women between the ages of 32 and 77 with multiple measurements of sex steroids and bone mass over a period of 2-8 yr. In all women bone mass was negatively associated with concentrations of sex-hormone binding globulin, and positively associated with weight. Bone loss occurred from all skeletal sites in peri- and postmenopausal women, but premenopausal women lost bone only from the hip (-0.3%/yr) and had positive rates of change in the radius and spine. Bone loss was significantly associated with lower androgen concentrations in premenopausal women, and with lower estrogens and androgens in peri- and postmenopausal women. Sex steroids are important for the maintenance of skeletal integrity before menopause, and for as long as 20-25 yr afterwards.

Epidemiologic Analyses of Risk Factors for Bone Loss and Recovery Related to Long-Duration Space Flight

NASA Technical Reports Server (NTRS)

Sibonga, Jean; Amin, Shreyasee

2010-01-01

AIM 1: To investigate the risk of microgravity exposure on long-term changes in bone health and fracture risk. compare data from crew members ("observed") with what would be "expected" from Rochester Bone Health Study. AIM 2: To provide a summary of current evidence available on potential risk factors for bone loss, recovery & fracture following long-duration space flight. integrative review of all data pre, in-, and post-flight across disciplines (cardiovascular, nutrition, muscle, etc.) and their relation to bone loss and recovery

Blueberry consumption prevents loss of collagen in bone matrix and inhibits senescence pathways in osteoblastic cells

USDA-ARS?s Scientific Manuscript database

Ovariectomy (OVX)-induced bone loss has been linked to increased bone turnover and higher bone matrix collagen degradation as the result of osteoclast activation. However, the role of degraded collagen matrix in the fate of resident bone-forming cells is unclear. In this report, we show that OVX-i...

Bone Quest - A Space-Based Science and Health Education Unit

NASA Technical Reports Server (NTRS)

Smith, Scott M.; David-Street, Janis E.; Abrams, Steve A.

2000-01-01

This proposal addresses the need for effective and innovative science and health education materials that focus on space bone biology and its implications for bone health on Earth. The focus of these materials, bone biology and health, will increase science knowledge as well as health awareness. Current investigations of the bone loss observed after long-duration space missions provide a link between studies of bone health in space, and studies of osteoporosis, a disease characterized by bone loss and progressive skeletal weakness. The overall goal of this project is to design and develop web-based and print-based materials for high school science students, that will address the following: a) knowledge of normal bone biology and bone biology in a microgravity environment; b) knowledge of osteoporosis; c) knowledge of treatment modalities for space- and Earth-based bone loss; and d} bone-related nutrition knowledge and behavior. To this end, we propose to design and develop a Bone Biology Tutorial which will instruct students about normal bone biology, bone biology in a microgravity environment, osteoporosis - its definition, detection, risk factors, and prevention, treatment modalities for space- and Earth-based bone loss, and the importance of nutrition in bone health. Particular emphasis will be placed on current trends in . adolescent nutrition, and their relationships to bone health. Additionally, we propose to design and develop two interactive nutrition/health ' education activities that will allow students to apply the information provided in the Bone Biology Tutorial. In the first, students will apply constructs provided in the Bone Biology Tutorial to design "Bone Health Plans" for space travelers.

The Lyme Disease Pathogen Borrelia burgdorferi Infects Murine Bone and Induces Trabecular Bone Loss.

PubMed

Tang, Tian Tian; Zhang, Lucia; Bansal, Anil; Grynpas, Marc; Moriarty, Tara J

2017-02-01

Lyme disease is caused by members of the Borrelia burgdorferi sensu lato species complex. Arthritis is a well-known late-stage pathology of Lyme disease, but the effects of B. burgdorferi infection on bone at sites other than articular surfaces are largely unknown. In this study, we investigated whether B. burgdorferi infection affects bone health in mice. In mice inoculated with B. burgdorferi or vehicle (mock infection), we measured the presence of B. burgdorferi DNA in bones, bone mineral density (BMD), bone formation rates, biomechanical properties, cellular composition, and two- and three-dimensional features of bone microarchitecture. B. burgdorferi DNA was detected in bone. In the long bones, increasing B. burgdorferi DNA copy number correlated with reductions in areal and trabecular volumetric BMDs. Trabecular regions of femora exhibited significant, copy number-correlated microarchitectural disruption, but BMD, microarchitectural, and biomechanical properties of cortical bone were not affected. Bone loss in tibiae was not due to increased osteoclast numbers or bone-resorbing surface area, but it was associated with reduced osteoblast numbers, implying that bone loss in long bones was due to impaired bone building. Osteoid-producing and mineralization activities of existing osteoblasts were unaffected by infection. Therefore, deterioration of trabecular bone was not dependent on inhibition of osteoblast function but was more likely caused by blockade of osteoblastogenesis, reduced osteoblast survival, and/or induction of osteoblast death. Together, these data represent the first evidence that B. burgdorferi infection induces bone loss in mice and suggest that this phenotype results from inhibition of bone building rather than increased bone resorption. Copyright © 2017 Tang et al.

Implant and root supported overdentures - a literature review and some data on bone loss in edentulous jaws.

PubMed

Carlsson, Gunnar E

2014-08-01

To present a literature review on implant overdentures after a brief survey of bone loss after extraction of all teeth. Papers on alveolar bone loss and implant overdentures have been studied for a narrative review. Bone loss of the alveolar process after tooth extraction occurs with great individual variation, impossible to predict at the time of extraction. The simplest way to prevent bone loss is to avoid extraction of all teeth. To keep a few teeth and use them or their roots for a tooth or root-supported overdenture substantially reduces bone loss. Jaws with implant-supported prostheses show less bone loss than jaws with conventional dentures. Mandibular 2-implant overdentures provide patients with better outcomes than do conventional dentures, regarding satisfaction, chewing ability and oral-health-related quality of life. There is no strong evidence for the superiority of one overdenture retention-system over the others regarding patient satisfaction, survival, peri-implant bone loss and relevant clinical factors. Mandibular single midline implant overdentures have shown promising results but long-term results are not yet available. For a maxillary overdenture 4 to 6 implants splinted with a bar provide high survival both for implants and overdenture. In edentulous mandibles, 2-implant overdentures provide excellent long-term success and survival, including patient satisfaction and improved oral functions. To further reduce the costs a single midline implant overdenture can be a promising option. In the maxilla, overdentures supported on 4 to 6 implants splinted with a bar have demonstrated good functional results.

Implant and root supported overdentures - a literature review and some data on bone loss in edentulous jaws

PubMed Central

2014-01-01

PURPOSE To present a literature review on implant overdentures after a brief survey of bone loss after extraction of all teeth. MATERIALS AND METHODS Papers on alveolar bone loss and implant overdentures have been studied for a narrative review. RESULTS Bone loss of the alveolar process after tooth extraction occurs with great individual variation, impossible to predict at the time of extraction. The simplest way to prevent bone loss is to avoid extraction of all teeth. To keep a few teeth and use them or their roots for a tooth or root-supported overdenture substantially reduces bone loss. Jaws with implant-supported prostheses show less bone loss than jaws with conventional dentures. Mandibular 2-implant overdentures provide patients with better outcomes than do conventional dentures, regarding satisfaction, chewing ability and oral-health-related quality of life. There is no strong evidence for the superiority of one overdenture retention-system over the others regarding patient satisfaction, survival, peri-implant bone loss and relevant clinical factors. Mandibular single midline implant overdentures have shown promising results but long-term results are not yet available. For a maxillary overdenture 4 to 6 implants splinted with a bar provide high survival both for implants and overdenture. CONCLUSION In edentulous mandibles, 2-implant overdentures provide excellent long-term success and survival, including patient satisfaction and improved oral functions. To further reduce the costs a single midline implant overdenture can be a promising option. In the maxilla, overdentures supported on 4 to 6 implants splinted with a bar have demonstrated good functional results. PMID:25177466

[Remodeling simulation of human femur under bed rest and spaceflight circumstances based on three dimensional finite element analysis].

PubMed

Yang, Wenting; Wang, Dongmei; Lei, Zhoujixin; Wang, Chunhui; Chen, Shanguang

2017-12-01

Astronauts who are exposed to weightless environment in long-term spaceflight might encounter bone density and mass loss for the mechanical stimulus is smaller than normal value. This study built a three dimensional model of human femur to simulate the remodeling process of human femur during bed rest experiment based on finite element analysis (FEA). The remodeling parameters of this finite element model was validated after comparing experimental and numerical results. Then, the remodeling process of human femur in weightless environment was simulated, and the remodeling function of time was derived. The loading magnitude and loading cycle on human femur during weightless environment were increased to simulate the exercise against bone loss. Simulation results showed that increasing loading magnitude is more effective in diminishing bone loss than increasing loading cycles, which demonstrated that exercise of certain intensity could help resist bone loss during long-term spaceflight. At the end, this study simulated the bone recovery process after spaceflight. It was found that the bone absorption rate is larger than bone formation rate. We advise that astronauts should take exercise during spaceflight to resist bone loss.

Dihydroartemisinin attenuates lipopolysaccharide-induced osteoclastogenesis and bone loss via the mitochondria-dependent apoptosis pathway

PubMed Central

Dou, C; Ding, N; Xing, J; Zhao, C; Kang, F; Hou, T; Quan, H; Chen, Y; Dai, Q; Luo, F; Xu, J; Dong, S

2016-01-01

Dihydroartemisinin (DHA) is a widely used antimalarial drug isolated from the plant Artemisia annua. Recent studies suggested that DHA has antitumor effects utilizing its reactive oxygen species (ROS) yielding mechanism. Here, we reported that DHA is inhibitory on lipopolysaccharide (LPS)-induced osteoclast (OC) differentiation, fusion and bone-resorption activity in vitro. Intracellular ROS detection revealed that DHA could remarkably increase ROS accumulation during LPS-induced osteoclastogenesis. Moreover, cell apoptosis was also increased by DHA treatment. We found that DHA-activated caspase-3 increased Bax/Bcl-2 ratio during LPS-induced osteoclastogenesis. Meanwhile, the translocation of apoptotic inducing factor (AIF) and the release of cytochrome c from the mitochondria into the cytosol were observed, indicating that ROS-mediated mitochondrial dysfunction is crucial in DHA-induced apoptosis during LPS-induced osteoclastogenesis. In vivo study showed that DHA treatment decreased OC number, prevents bone loss, rescues bone microarchitecture and restores bone strength in LPS-induced bone-loss mouse model. Together, our findings indicate that DHA is protective against LPS-induced bone loss through apoptosis induction of osteoclasts via ROS accumulation and the mitochondria-dependent apoptosis pathway. Therefore, DHA may be considered as a new therapeutic candidate for treating inflammatory bone loss. PMID:27031959

Quantitative 3D analysis of bone in hip osteoarthritis using clinical computed tomography.

PubMed

Turmezei, Tom D; Treece, Graham M; Gee, Andrew H; Fotiadou, Anastasia F; Poole, Kenneth E S

2016-07-01

To assess the relationship between proximal femoral cortical bone thickness and radiological hip osteoarthritis using quantitative 3D analysis of clinical computed tomography (CT) data. Image analysis was performed on clinical CT imaging data from 203 female volunteers with a technique called cortical bone mapping (CBM). Colour thickness maps were created for each proximal femur. Statistical parametric mapping was performed to identify statistically significant differences in cortical bone thickness that corresponded with the severity of radiological hip osteoarthritis. Kellgren and Lawrence (K&L) grade, minimum joint space width (JSW) and a novel CT-based osteophyte score were also blindly assessed from the CT data. For each increase in K&L grade, cortical thickness increased by up to 25 % in distinct areas of the superolateral femoral head-neck junction and superior subchondral bone plate. For increasing severity of CT osteophytes, the increase in cortical thickness was more circumferential, involving a wider portion of the head-neck junction, with up to a 7 % increase in cortical thickness per increment in score. Results were not significant for minimum JSW. These findings indicate that quantitative 3D analysis of the proximal femur can identify changes in cortical bone thickness relevant to structural hip osteoarthritis. • CT is being increasingly used to assess bony involvement in osteoarthritis • CBM provides accurate and reliable quantitative analysis of cortical bone thickness • Cortical bone is thicker at the superior femoral head-neck with worse osteoarthritis • Regions of increased thickness co-locate with impingement and osteophyte formation • Quantitative 3D bone analysis could enable clinical disease prediction and therapy development.

Is multidetector CT-based bone mineral density and quantitative bone microstructure assessment at the spine still feasible using ultra-low tube current and sparse sampling?

PubMed

Mei, Kai; Kopp, Felix K; Bippus, Rolf; Köhler, Thomas; Schwaiger, Benedikt J; Gersing, Alexandra S; Fehringer, Andreas; Sauter, Andreas; Münzel, Daniela; Pfeiffer, Franz; Rummeny, Ernst J; Kirschke, Jan S; Noël, Peter B; Baum, Thomas

2017-12-01

Osteoporosis diagnosis using multidetector CT (MDCT) is limited to relatively high radiation exposure. We investigated the effect of simulated ultra-low-dose protocols on in-vivo bone mineral density (BMD) and quantitative trabecular bone assessment. Institutional review board approval was obtained. Twelve subjects with osteoporotic vertebral fractures and 12 age- and gender-matched controls undergoing routine thoracic and abdominal MDCT were included (average effective dose: 10 mSv). Ultra-low radiation examinations were achieved by simulating lower tube currents and sparse samplings at 50%, 25% and 10% of the original dose. BMD and trabecular bone parameters were extracted in T10-L5. Except for BMD measurements in sparse sampling data, absolute values of all parameters derived from ultra-low-dose data were significantly different from those derived from original dose images (p<0.05). BMD, apparent bone fraction and trabecular thickness were still consistently lower in subjects with than in those without fractures (p<0.05). In ultra-low-dose scans, BMD and microstructure parameters were able to differentiate subjects with and without vertebral fractures, suggesting osteoporosis diagnosis is feasible. However, absolute values differed from original values. BMD from sparse sampling appeared to be more robust. This dose-dependency of parameters should be considered for future clinical use. • BMD and quantitative bone parameters are assessable in ultra-low-dose in vivo MDCT scans. • Bone mineral density does not change significantly when sparse sampling is applied. • Quantitative trabecular bone microstructure measurements are sensitive to dose reduction. • Osteoporosis subjects could be differentiated even at 10% of original dose. • Radiation exposure should be considered when comparing quantitative bone parameters.

IFN-γ stimulates osteoclast formation and bone loss in vivo via antigen-driven T cell activation

PubMed Central

Gao, Yuhao; Grassi, Francesco; Ryan, Michaela Robbie; Terauchi, Masakazu; Page, Karen; Yang, Xiaoying; Weitzmann, M. Neale; Pacifici, Roberto

2006-01-01

T cell–produced cytokines play a pivotal role in the bone loss caused by inflammation, infection, and estrogen deficiency. IFN-γ is a major product of activated T helper cells that can function as a pro- or antiresorptive cytokine, but the reason why IFN-γ has variable effects in bone is unknown. Here we show that IFN-γ blunts osteoclast formation through direct targeting of osteoclast precursors but indirectly stimulates osteoclast formation and promotes bone resorption by stimulating antigen-dependent T cell activation and T cell secretion of the osteoclastogenic factors RANKL and TNF-α. Analysis of the in vivo effects of IFN-γ in 3 mouse models of bone loss — ovariectomy, LPS injection, and inflammation via silencing of TGF-β signaling in T cells — reveals that the net effect of IFN-γ in these conditions is that of stimulating bone resorption and bone loss. In summary, IFN-γ has both direct anti-osteoclastogenic and indirect pro-osteoclastogenic properties in vivo. Under conditions of estrogen deficiency, infection, and inflammation, the net balance of these 2 opposing forces is biased toward bone resorption. Inhibition of IFN-γ signaling may thus represent a novel strategy to simultaneously reduce inflammation and bone loss in common forms of osteoporosis. PMID:17173138

Clinical Impact and Cellular Mechanisms of Iron Overload-Associated Bone Loss

PubMed Central

Jeney, Viktória

2017-01-01

Diseases/conditions with diverse etiology, such as hemoglobinopathies, hereditary hemochromatosis and menopause, could lead to chronic iron accumulation. This condition is frequently associated with a bone phenotype; characterized by low bone mass, osteoporosis/osteopenia, altered microarchitecture and biomechanics, and increased incidence of fractures. Osteoporotic bone phenotype constitutes a major complication in patients with iron overload. The purpose of this review is to summarize what we have learnt about iron overload-associated bone loss from clinical studies and animal models. Bone is a metabolically active tissue that undergoes continuous remodeling with the involvement of osteoclasts that resorb mineralized bone, and osteoblasts that form new bone. Growing evidence suggests that both increased bone resorption and decreased bone formation are involved in the pathological bone-loss in iron overload conditions. We will discuss the cellular and molecular mechanisms that are involved in this detrimental process. Fuller understanding of this complex mechanism may lead to the development of improved therapeutics meant to interrupt the pathologic effects of excess iron on bone. PMID:28270766

Utilizing time-lapse micro-CT-correlated bisphosphonate binding kinetics and soft tissue-derived input functions to differentiate site-specific changes in bone metabolism in vivo.

PubMed

Tower, R J; Campbell, G M; Müller, M; Glüer, C C; Tiwari, S

2015-05-01

The turnover of bone is a tightly regulated process between bone formation and resorption to ensure skeletal homeostasis. This process differs between bone types, with trabecular bone often associated with higher turnover than cortical bone. Analyses of bone by micro-computed tomography (micro-CT) reveal changes in structure and mineral content, but are limited in the study of metabolic activity at a single time point, while analyses of serum markers can reveal changes in bone metabolism, but cannot delineate the origin of any aberrant findings. To obtain a site-specific assessment of bone metabolic status, bisphosphonate binding kinetics were utilized. Using a fluorescently-labeled bisphosphonate, we show that early binding kinetics monitored in vivo using fluorescent molecular tomography (FMT) can monitor changes in bone metabolism in response to bone loss, stimulated by ovariectomy (OVX), or bone gain, resulting from treatment with the anabolic bone agent parathyroid hormone (PTH), and is capable of distinguishing different, metabolically distinct skeletal sites. Using time-lapse micro-CT, longitudinal bone turnover was quantified. The spine showed a significantly greater percent resorbing volume and surface in response to OVX, while mice treated with PTH showed significantly greater resorbing volume per bone surface in the spine and significantly greater forming surfaces in the knee. Correlation studies between binding kinetics and micro-CT suggest that forming surfaces, as assessed by time-lapse micro-CT, are preferentially reflected in the rate constant values while forming and resorbing bone volumes primarily affect plateau values. Additionally, we developed a blood pool correction method which now allows for quantitative multi-compartment analyses to be conducted using FMT. These results further expand our understanding of bisphosphonate binding and the use of bisphosphonate binding kinetics as a tool to monitor site-specific changes in bone metabolism in vivo. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Mammary tumorigenesis causes bone loss and dietary selenium supplementation does not affect such bone loss in male MMTV-PyMT mice

USDA-ARS?s Scientific Manuscript database

Cancer progression is accompanied by wasting that eventually results in cachexia characterized by significant weight loss and multi-organ functional failures. Limited clinical trials indicate that bone is adversely affected by cancer-associated wasting. To determine the effects of breast cancer on...

Vitamin K supplementation does not prevent bone loss in ovariectomized Norway rats

USDA-ARS?s Scientific Manuscript database

Despite plausible biological mechanisms, the differential abilities of phylloquinone (PK) and menaquinones (MKn) to prevent bone loss remain controversial. The objective of the current study was to compare the effects of PK, menaquinone-4 (MK-4) and menaquinone-7(MK-7) on the rate of bone loss in o...

Effect of an estrogen-deficient state and alendronate therapy on bone loss resulting from experimental periapical lesions in rats.

PubMed

Xiong, Haofei; Peng, Bin; Wei, Lili; Zhang, Xiaolei; Wang, Li

2007-11-01

The aim of the research was to evaluate the impact of an estrogen-deficient state and alendronate (ALD) therapy on bone loss resulting from experimental periapical lesions in rats. Periapical lesions were induced on ovariectomized (OVX) and sham-ovariectomized (Sham) rats. After sample preparation, histologic and radiographic examination for periapical bone loss area and an enzyme histochemical test for tartrate-resistant acid phosphatase (TRAP) were performed. The results showed that OVX significantly increased bone loss resulting from periradicular lesions. After daily subcutaneous injection of ALD, the bone loss area and the number of TRAP-positive cells (osteoclasts) were reduced. These findings suggested that alendronate may protect against increased bone loss from experimental periapical lesions in estrogen-deficient rats. Given recent recognition of adverse effects of bisphosphonates, including an increased risk for osteonecrosis, the findings from this study should not be interpreted as a new indication for ALD treatment. However, they may offer insight into understanding and predicting outcomes in female postmenopausal patients already on ALD therapy for medical indications.

Use of ossein-hydroxyapatite complex in the prevention of bone loss: a review.

PubMed

Castelo-Branco, C; Dávila Guardia, J

2015-02-01

The ossein-hydroxyapatite complex (OHC) is a microcrystalline form of calcium which provides a number of additional minerals (magnesium, phosphorus, potassium, zinc), and proteins (osteocalcin, type I collagen, type I insulin growth factor I and II, transforming growth factor beta) associated with bone metabolism. The objective of this review is to examine the role of OHC in preventing bone loss in different conditions. A review of clinical trials assessing the relationship between OHC and bone loss was made using the following data sources: Medline (from 1966 to December 2013), the Cochrane Controlled Clinical Trials Register, Embase (up to December 2013), contact with companies marketing the supplements studied, and reference lists. Different randomized, clinical trials and meta-analysis suggest that OHC is more effective than calcium supplements in maintaining bone mass in postmenopausal women and in different conditions related to bone loss. In addition, OHC improves pain symptoms and accelerates fracture consolidation in patients with osteopenia or osteoporosis. The ossein-hydroxyapatite complex is significantly more effective in preventing bone loss than calcium carbonate.

Tibial Tray Thickness Significantly Increases Medial Tibial Bone Resorption in Cobalt-Chromium Total Knee Arthroplasty Implants.

PubMed

Martin, J Ryan; Watts, Chad D; Levy, Daniel L; Miner, Todd M; Springer, Bryan D; Kim, Raymond H

2017-01-01

Stress shielding is an uncommon complication associated with primary total knee arthroplasty. Patients are frequently identified radiographically with minimal clinical symptoms. Very few studies have evaluated risk factors for postoperative medial tibial bone loss. We hypothesized that thicker cobalt-chromium tibial trays are associated with increased bone loss. We performed a retrospective review of 100 posterior stabilized, fixed-bearing total knee arthroplasty where 50 patients had a 4-mm-thick tibial tray (thick tray cohort) and 50 patients had a 2.7-mm-thick tibial tray (thin tray cohort). A clinical evaluation and a radiographic assessment of medial tibial bone loss were performed on both cohorts at a minimum of 2 years postoperatively. Mean medial tibial bone loss was significantly higher in the thick tray cohort (1.07 vs 0.16 mm; P = .0001). In addition, there were significantly more patients with medial tibial bone loss in the thick tray group compared with the thin tray group (44% vs 10%, P = .0002). Despite these differences, there were no statistically significant differences in range of motion, knee society score, complications, or revision surgeries performed. A thicker cobalt-chromium tray was associated with significantly more medial tibial bone loss. Despite these radiographic findings, we found no discernable differences in clinical outcomes in our patient cohort. Further study and longer follow-up are needed to understand the effects and clinical significance of medial tibial bone loss. Copyright © 2016 Elsevier Inc. All rights reserved.

Low serum vitamin D is associated with higher cortical porosity in elderly men.

PubMed

Sundh, D; Mellström, D; Ljunggren, Ö; Karlsson, M K; Ohlsson, C; Nilsson, M; Nilsson, A G; Lorentzon, M

2016-11-01

Bone loss at peripheral sites in the elderly is mainly cortical and involves increased cortical porosity. However, an association between bone loss at these sites and 25-hydroxyvitamin D has not been reported. To investigate the association between serum levels of 25-hydroxyvitamin D, bone microstructure and areal bone mineral density (BMD) in elderly men. A population-based cohort of 444 elderly men (mean ± SD age 80.2 ± 3.5 years) was investigated. Bone microstructure was measured by high-resolution peripheral quantitative computed tomography, areal BMD by dual-energy X-ray absorptiometry and serum 25-hydroxyvitamin D and parathyroid hormone levels by immunoassay. Mean cortical porosity at the distal tibia was 14.7% higher (12.5 ± 4.3% vs. 10.9 ± 4.1%, P < 0.05) whilst cortical volumetric BMD, area, trabecular bone volume fraction and femoral neck areal BMD were lower in men in the lowest quartile of vitamin D levels compared to the highest. In men with vitamin D deficiency (<25 nmol L -1 ) or insufficiency [25-49 nmol L -1 , in combination with an elevated serum level of parathyroid hormone (>6.8 pmol L -1 )], cortical porosity was 17.2% higher than in vitamin D-sufficient men (P < 0.01). A linear regression model including age, weight, height, daily calcium intake, physical activity, smoking vitamin D supplementation and parathyroid hormone showed that 25-hydroxyvitamin D independently predicted cortical porosity (standardized β = -0.110, R 2 = 1.1%, P = 0.024), area (β = 0.123, R 2 = 1.4%, P = 0.007) and cortical volumetric BMD (β = 0.125, R 2 = 1.4%, P = 0.007) of the tibia as well as areal BMD of the femoral neck (β = 0.102, R 2 = 0.9%, P = 0.04). Serum vitamin D is associated with cortical porosity, area and density, indicating that bone fragility as a result of low vitamin D could be due to changes in cortical bone microstructure and geometry. © 2016 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.

Bone microarchitecture of the tibial plateau in skeletal health and osteoporosis.

PubMed

Krause, Matthias; Hubert, Jan; Deymann, Simon; Hapfelmeier, Alexander; Wulff, Birgit; Petersik, Andreas; Püschel, Klaus; Amling, Michael; Hawellek, Thelonius; Frosch, Karl-Heinz

2018-05-07

Impaired bone structure poses a challenge for the treatment of osteoporotic tibial plateau fractures. As knowledge of region-specific structural bone alterations is a prerequisite to achieving successful long-term fixation, the aim of the current study was to characterize tibial plateau bone structure in patients with osteoporosis and the elderly. Histomorphometric parameters were assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT) in 21 proximal tibiae from females with postmenopausal osteoporosis (mean age: 84.3 ± 4.9 years) and eight female healthy controls (45.5 ± 6.9 years). To visualize region-specific structural bony alterations with age, the bone mineral density (Hounsfield units) was additionally analyzed in 168 human proximal tibiae. Statistical analysis was based on evolutionary learning using globally optimal regression trees. Bone structure deterioration of the tibial plateau due to osteoporosis was region-specific. Compared to healthy controls (20.5 ± 4.7%) the greatest decrease in bone volume fraction was found in the medio-medial segments (9.2 ± 3.5%, p < 0.001). The lowest bone volume was found in central segments (tibial spine). Trabecular connectivity was severely reduced. Importantly, in the anterior and posterior 25% of the lateral and medial tibial plateaux, trabecular support and subchondral cortical bone thickness itself were also reduced. Thinning of subchondral cortical bone and marked bone loss in the anterior and posterior 25% of the tibial plateau should require special attention when osteoporotic patients require fracture fixation of the posterior segments. This knowledge may help to improve the long-term, fracture-specific fixation of complex tibial plateau fractures in osteoporosis. Copyright © 2018 Elsevier B.V. All rights reserved.

Effects of Ibuprofen and Resistance Training on Bone and Muscle: A Randomized Controlled Trial in Older Women.

PubMed

Duff, Whitney R D; Chilibeck, Philip D; Candow, Darren G; Gordon, Julianne J; Mason, Riley S; Taylor-Gjevre, Regina; Nair, Bindu; Szafron, Michael; Baxter-Jones, Adam; Zello, Gordon A; Kontulainen, Saija A

2017-04-01

Resistance training with ibuprofen supplementation may improve musculoskeletal health in postmenopausal women. The study purpose was to determine the efficacy of resistance training and ibuprofen supplementation on bone and muscle properties in postmenopausal women. Participants (n = 90, 65.3 ± 4.9 yr) were randomly assigned to: supervised resistance training or stretching (placebo-exercise) with postexercise ibuprofen (400 mg) or placebo supplementation for 3 d·wk (9 months). Baseline and postintervention measurements included distal and shaft scans of the forearm and lower leg using peripheral quantitative computed tomography. Distal site outcomes included cross-sectional area, content, and density for total and trabecular bone, as well as estimated bone strength in compression. Shaft site outcomes included total bone area; cortical bone area, content, and density; estimated bone strength in torsion; and muscle area and density. Exercise-supplement-time interactions for total bone content at the distal radius (P = 0.009) and cortical density at the radius shaft (P = 0.038) were significant. Resistance training with ibuprofen decreased total bone content (-1.5%) at the distal radius in comparison to the resistance training (0.6%; P = 0.032) and ibuprofen alone (0.5%; P = 0.050). Change in cortical density at the radius shaft differed between the stretching with placebo and ibuprofen supplementation groups (-1.8% vs 1.1%; P = 0.050). Resistance training preserved muscle density in the lower leg more so than stretching (-3.1% vs -5.4%; P = 0.015). Ibuprofen consumed immediately after resistance training had a deleterious effect on bone mineral content at the distal radius, whereas resistance training or ibuprofen supplementation individually prevented bone loss. Resistance training prevented muscle density decline in the lower leg.

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

Can the adult skeleton recover lost bone?

NASA Technical Reports Server (NTRS)

Leblanc, Adrian; Schneider, Victor

1991-01-01

The loss of bone mineral with aging and subsequent development of osteoporosis is a common problem in elderly women, and as life expectancy increases, in elderly men as well. Space flight also causes bone loss and could be a limiting factor for long duration missions, such as, a Mars expedition or extended occupation of a Space Station. Before effective countermeasures can be devised, a thorough knowledge of the extent, location, and rate of bone loss during weightlessness is needed from actual space flight data or ground-based disuse models. In addition, the rate and extent that these losses are reversed after return from space flight are of primary importance. Although the mechanisms are not likely to be the same in aging and space flight, there are common elements. For example, strategies developed to prevent disuse bone loss or to enhance the rate of recovery following space flight might have direct applicability to clinical medicine. For various reasons, little attention has been given to recovery of bone mass following space flight. As a prelude to the design of strategies to enhance recovery of bone, this paper reviews published literature related to bone recovery in the adult. We conclude that recovery can be expected, but the rate and extent will be individual and bone site dependent. The development of strategies to encourage or enhance bone formation following space flight may be as important as implementing countermeasures during flight.

Treatment of Radix Dipsaci extract prevents long bone loss induced by modeled microgravity in hindlimb unloading rats.

PubMed

Niu, Yinbo; Li, Chenrui; Pan, Yalei; Li, Yuhua; Kong, Xianghe; Wang, Shuo; Zhai, YuanKun; Wu, Xianglong; Fan, Wutu; Mei, Qibing

2015-01-01

Radix Dipsaci is a kidney tonifying herbal medicine with a long history of safe use for treatment of bone fractures and joint diseases in China. Previous studies have shown that Radix Dipsaci extract (RDE) could prevent bone loss in ovariectomized rats. This study investigates the effect of RDE against bone loss induced by simulated microgravity. A hindlimb unloading rat model was established to determine the effect of RDE on bone mineral density and bone microarchitecture. Twenty-four male Sprague-Dawley rats were divided into four groups (n = 6 per group): control (CON), hindlimb unloading with vehicle (HLU), hindlimb unloading treated with alendronate (HLU-ALN, 2.0 mg/kg/d), and hindlimb unloading treated with RDE (HLU-RDE, 500 mg/kg/d). RDE or ALN was administrated orally for 4 weeks. Treatment with RDE had a positive effect on mechanical strength, BMD, BMC, bone turnover markers, and the changes in urinary calcium and phosphorus excretion. MicroCT analysis showed that RDE significantly prevented the reduction of the bone volume fraction, connectivity density, trabecular number, thickness, tissue mineral density, and tissue mineral content as well as improved the trabecular separation and structure model index. RDE was demonstrated to prevent the loss of bone mass induced by HLU treatment, which suggests the potential application of RDE in the treatment of microgravity-induced bone loss.

Association of Circulating Renin and Aldosterone With Osteocalcin and Bone Mineral Density in African Ancestry Families.

PubMed

Kuipers, Allison L; Kammerer, Candace M; Pratt, J Howard; Bunker, Clareann H; Wheeler, Victor W; Patrick, Alan L; Zmuda, Joseph M

2016-05-01

Hypertension is associated with accelerated bone loss, and the renin-angiotensin-aldosterone system is a key regulator of blood pressure. Although components of this system are expressed in human bone cells, studies in humans are sparse. Thus, we studied the association of circulating renin and aldosterone with osteocalcin and bone mineral density. We recruited 373 African ancestry family members without regard to health status from 6 probands (mean family size: 62 and relative pairs: 1687). Participants underwent a clinical examination, dual-energy x-ray absorptiometry, and quantitative computed tomographic scans. Renin activity, aldosterone concentration, and osteocalcin were measured in fasting blood samples. Aldosterone/renin ratio was calculated as aldosterone concentration/renin activity. All models were analyzed using pedigree-based variance components methods. Full models included adjustment for age, sex, body composition, comorbidities, lifestyle factors, blood pressure, and antihypertensive medication. Higher renin activity was significantly associated with lower total osteocalcin and with higher trabecular bone mineral density (both P<0.01). There were also significant genetic correlations between renin activity and whole-body bone mineral density. There were no associations with aldosterone concentration in any model and results for aldosterone/renin ratio were similar to those for renin activity. This is the first study to report a significant association between renin activity and a marker of bone turnover and bone mineral density in generally healthy individuals. Also, there is evidence for significant genetic pleiotropy and, thus, there may be a shared biological mechanism underlying both the renin-angiotensin-aldosterone system and bone metabolism that is independent of hypertension. © 2016 American Heart Association, Inc.

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.

ASSOCIATION OF CIRCULATING RENIN AND ALDOSTERONE WITH OSTEOCALCIN AND BONE MINERAL DENSITY IN AFRICAN ANCESTRY FAMILIES

PubMed Central

Kuipers, Allison L; Kammerer, Candace M; Howard Pratt, J; Bunker, Clareann H; Wheeler, Victor W; Patrick, Alan L; Zmuda, Joseph M

2016-01-01

Hypertension is associated with accelerated bone loss and the renin-angiotensin-aldosterone system is a key regulator of blood pressure. Although components of this system are expressed in human bone cells, studies in humans are sparse. Thus, we studied the association of circulating renin and aldosterone with osteocalcin and bone mineral density. We recruited 373 African ancestry family members without regard to health status from 6 probands (mean family size: 62; relative pairs: 1687). Participants underwent a clinical exam, dual energy x-ray absorptiometry, and quantitative computed tomography scans. Renin activity, aldosterone concentration, and osteocalcin were measured in fasting blood samples. Aldosterone to renin ratio was calculated as aldosterone concentration/renin activity. All models were analyzed using pedigree-based variance components methods. Full models included adjustment for age, sex, body composition, co-morbidities, lifestyle factors, blood pressure, and antihypertensive medication. Higher renin activity was significantly associated with lower total osteocalcin and with higher trabecular bone mineral density (both p<0.01). There were also significant genetic correlations between renin activity and whole body bone mineral density. There were no associations with aldosterone concentration in any model and results for aldosterone to renin ratio were similar to those for renin activity. This is the first study to report a significant association between renin activity and a marker of bone turnover and bone mineral density in generally healthy individuals. Also, there is evidence for significant genetic pleiotropy and, thus, there may be a shared biologic mechanism underlying both the renin-angiotensin-aldosterone system and bone metabolism that is independent of hypertension. PMID:26975710

The effects of thyrotropin-suppressing therapy on bone metabolism in patients with well-differentiated thyroid carcinoma.

PubMed

Kim, Mee Kyoung; Yun, Kyung-Jin; Kim, Min-Hee; Lim, Dong-Jun; Kwon, Hyuk-Sang; Song, Ki-Ho; Kang, Moo-Il; Baek, Ki Hyun

2015-02-01

Studies on the effects of levothyroxine (LT4) therapy on bone and bone metabolism have yielded conflicting results. This 1-year prospective study examined whether LT4 in patients with well-differentiated thyroid carcinoma (DTC) is a risk factor for bone mass loss and the subsequent development of osteoporosis. We examined 93 patients with DTC over 12months after initiating LT4 therapy (early postoperative period). We examined another 33 patients on long-term LT4 therapy for DTC (late postoperative period). Dual energy X-ray absorptiometry was performed at baseline and after 1year. The mean bone losses during the early postoperative period in the lumbar spine, femoral neck, and total hip, calculated as the percentage change between levels at baseline and 12months, were -0.88, -1.3 and -0.81%, respectively. Bone loss was more evident in postmenopausal women (lumbar spine -2.1%, femoral neck -2.2%, and hip -2.1%; all P<0.05). We compared the changes in annual bone mineral density (BMD) in postmenopausal women according to calcium/vitamin D supplementation. Bone loss tended to be higher in the postmenopausal women receiving no supplementation. There was no decrease in BMD among patients during the late postoperative period. The mean bone loss was generally greater in the early than in the late postoperative group, and this was significant at the lumbar spine (P=0.041) and femoral neck (P=0.010). TSH-suppressive levothyroxine therapy accelerates bone loss, predominantly in postmenopausal women and exclusively during the early post-thyroidectomy period. Copyright © 2014 Elsevier Inc. All rights reserved.

Bone density in limb-immobilized beagles: An animal model for bone loss in weightlessness

NASA Technical Reports Server (NTRS)

Wolinsky, Ira

1987-01-01

Prolonged weightlessness is man in space flight results in a slow progressive demineralization of bone accompanied by an increased calcium output in the urine resulting in negative calcium balances. This possibly irreversible bone loss may constitute a serious limiting factor to long duration manned space flight. In order to seek and test preventative measures an appropriate ground based animal model simulating weightlessness is necessary. Use of the mature Beagle in limb immobilization has been documented as an excellent model for orthopedic research since this animal most closely simulates the phenomenom of bone loss with regards to growth, remodeling, structure, chemistry and mineralization. The purpose of this project is to develop a research protocol for the study of bone loss in Beagles during and after cast immobilization of a hindleg; research will then be initiated.

Sodium selenate treatment mitigates reduction of bone volume following traumatic brain injury in rats.

PubMed

Brady, R D; Grills, B L; Romano, T; Wark, J D; O'Brien, T J; Shultz, S R; McDonald, S J

2016-12-14

Administration of sodium selenate to rats given traumatic brain injury (TBI) attenuates brain damage and improves long-term behavioural outcomes. We have previously provided evidence that TBI causes bone loss in rats, however the effect of sodium selenate treatment on bone quantity following TBI is unknown. Rats were randomly assigned into sham injury or fluid percussion injury (FPI) groups and administered saline or sodium selenate for 12 weeks post-injury. Femora were analysed using histomorphometry, peripheral quantitative computed tomography (pQCT) and biomechanical testing. Distal metaphyseal trabecular bone volume fraction of FPI-selenate rats was higher than FPI-vehicle rats (41.8%; p<0.01), however, femora from selenate-treated groups were shorter in length (4.3%; p<0.01) and had increased growth plate width (22.1%; p<0.01), indicating that selenate impaired long bone growth. pQCT analysis demonstrated that distal metaphyseal cortical thickness was decreased in TBI rats compared to shams (11.7%; p<0.05), however selenate treatment to TBI animals offset this reduction (p<0.05). At the midshaft we observed no differences in biomechanical measures. These are the first findings to indicate that mitigating TBI-induced neuropathology may have the added benefit of preventing osteoporosis and associated fracture risk following TBI.

Loss of trabeculae by mechano-biological means may explain rapid bone loss in osteoporosis.

PubMed

Mulvihill, Brianne M; McNamara, Laoise M; Prendergast, Patrick J

2008-10-06

Osteoporosis is characterized by rapid and irreversible loss of trabecular bone tissue leading to increased bone fragility. In this study, we hypothesize two causes for rapid loss of bone trabeculae; firstly, the perforation of trabeculae is caused by osteoclasts resorbing a cavity so deep that it cannot be refilled and, secondly, the increases in bone tissue elastic modulus lead to increased propensity for trabecular perforation. These hypotheses were tested using an algorithm that was based on two premises: (i) bone remodelling is a turnover process that repairs damaged bone tissue by resorbing and returning it to a homeostatic strain level and (ii) osteoblast attachment is under biochemical control. It was found that a mechano-biological algorithm based on these premises can simulate the remodelling cycle in a trabecular strut where damaged bone is resorbed to form a pit that is subsequently refilled with new bone. Furthermore, the simulation predicts that there is a depth of resorption cavity deeper than which refilling of the resorption pits is impossible and perforation inevitably occurs. However, perforation does not occur by a single fracture event but by continual removal of microdamage after it forms beneath the resorption pit. The simulation also predicts that perforations would occur more easily in trabeculae that are more highly mineralized (stiffer). Since both increased osteoclast activation rates and increased mineralization have been measured in osteoporotic bone, either or both may contribute to the rapid loss of trabecular bone mass observed in osteoporotic patients.

Bone marrow oxytocin mediates the anabolic action of estrogen on the skeleton

USDA-ARS?s Scientific Manuscript database

Estrogen withdrawal in women due to natural or artificial menopause is followed by rapid bone loss, osteoporosis, and a high fracture risk. Replacement with estrogen prevents this bone loss and reduces the risk of fracture. Estrogen uses two mechanisms to exert this effect: it inhibits bone resorpti...

Cobalt Alloy Implant Debris Induces Inflammation and Bone Loss Primarily through Danger Signaling, Not TLR4 Activation: Implications for DAMP-ening Implant Related Inflammation

PubMed Central

Samelko, Lauryn; Landgraeber, Stefan; McAllister, Kyron; Jacobs, Joshua; Hallab, Nadim James

2016-01-01

Cobalt alloy debris has been implicated as causative in the early failure of some designs of current total joint implants. The ability of implant debris to cause excessive inflammation via danger signaling (NLRP3 inflammasome) vs. pathogen associated pattern recognition receptors (e.g. Toll-like receptors; TLRs) remains controversial. Recently, specific non-conserved histidines on human TLR4 have been shown activated by cobalt and nickel ions in solution. However, whether this TLR activation is directly or indirectly an effect of metals or secondary endogenous alarmins (danger-associated molecular patterns, DAMPs) elicited by danger signaling, remains unknown and contentious. Our study indicates that in both a human macrophage cell line (THP-1) and primary human macrophages, as well as an in vivo murine model of inflammatory osteolysis, that Cobalt-alloy particle induced NLRP3 inflammasome danger signaling inflammatory responses were highly dominant relative to TLR4 activation, as measured respectively by IL-1β or TNF-α, IL-6, IL-10, tissue histology and quantitative bone loss measurement. Despite the lack of metal binding histidines H456 and H458 in murine TLR4, murine calvaria challenge with Cobalt alloy particles induced significant macrophage driven in vivo inflammation and bone loss inflammatory osteolysis, whereas LPS calvaria challenge alone did not. Additionally, no significant increase (p<0.05) in inflammation and inflammatory bone loss by LPS co-challenge with Cobalt vs. Cobalt alone was evident, even at high levels of LPS (i.e. levels commiserate with hematogenous levels in fatal sepsis, >500pg/mL). Therefore, not only do the results of this investigation support Cobalt alloy danger signaling induced inflammation, but under normal homeostasis low levels of hematogenous PAMPs (<2pg/mL) from Gram-negative bacteria, seem to have negligible contribution to the danger signaling responses elicited by Cobalt alloy metal implant debris. This suggests the unique nature of Cobalt alloy particle bioreactivity is strong enough to illicit danger signaling that secondarily activate concomitant TLR activation, and may in part explain Cobalt particulate associated inflammatory and toxicity-like reactions of specific orthopedic implants. PMID:27467577

Evaluation of Treadmill Exercise in a Lower Body Negative Pressure Chamber as a Countermeasure for Weightlessness-Induced Bone Loss: a Bed Rest Study with Identical Twins

NASA Technical Reports Server (NTRS)

Smith, Scott M.; Davis-Street, Janis E.; Fesperman, J. Vernell; Calkins, D. S.; Bawa, Maneesh; Macias, Brandon R.; Meyer, R. Scott; Hargens, Alan R.

2003-01-01

Counteracting bone loss is required for future space exploration. We evaluated the ability of treadmill exercise in a LBNP chamber to counteract bone loss in a 30-day bed rest study. Eight pairs of identical twins were randomly assigned to sedentary control or exercise groups. Exercise within LBNP decreased the bone resorption caused by bed rest and may provide a countermeasure for spaceflight. INTRODUCTION: Bone loss is one of the greatest physiological challenges for extended-duration space missions. The ability of exercise to counteract weightlessness-induced bone loss has been studied extensively, but to date, it has proven ineffective. We evaluated the effectiveness of a combination of two countermeasures-treadmill exercise while inside a lower body negative pressure (LBNP) chamber-on bone loss during a 30-day bed rest study. MATERIALS AND METHODS: Eight pairs of identical twins were randomized into sedentary (SED) or exercise/LBNP (EX/LBNP) groups. Blood and urine samples were collected before, several times during, and after the 30-day bed rest period. These samples were analyzed for markers of bone and calcium metabolism. Repeated measures ANOVA was used to determine statistical significance. Because identical twins were used, both time and group were treated as repeated variables. RESULTS: Markers of bone resorption were increased during bed rest in samples from sedentary subjects, including the collagen cross-links and serum and urinary calcium concentrations. For N-telopeptide and deoxypyridinoline, there were significant (p < 0.05) interactions between group (SED versus EX/LBNP) and phase of the study (sample collection point). Pyridinium cross-links were increased above pre-bed rest levels in both groups, but the EX/LBNP group had a smaller increase than the SED group. Markers of bone formation were unchanged by bed rest in both groups. CONCLUSIONS: These data show that this weight-bearing exercise combined with LBNP ameliorates some of the negative effects of simulated weightlessness on bone metabolism. This protocol may pave the way to counteracting bone loss during spaceflight and may provide valuable information about normal and abnormal bone physiology here on Earth.

Soy Isoflavones and Osteoporotic Bone Loss: A Review with an Emphasis on Modulation of Bone Remodeling

PubMed Central

Zheng, Xi; Lee, Sun-Kyeong

2016-01-01

Abstract Osteoporosis is an age-related disorder that affects both women and men, although estrogen deficiency induced by menopause accelerates bone loss in older women. As the demographic shifts to a more aged population, a growing number of men and women will be afflicted with osteoporosis. Since the current drug therapies available have multiple side effects, including increased risk of developing certain types of cancer or complications, a search for potential nonpharmacologic alternative therapies for osteoporosis is of prime interest. Soy isoflavones (SI) have demonstrated potential bone-specific effects in a number of studies. This article provides a systematic review of studies on osteoporotic bone loss in relation to SI intake from diet or supplements to comprehensively explain how SI affect the modulation of bone remodeling. Evidence from epidemiologic studies supports that dietary SI attenuate menopause-induced osteoporotic bone loss by decreasing bone resorption and stimulating bone formation. Other studies have also illustrated that bone site-specific trophic and synergistic effects combined with exercise intervention might contribute to improve the bioavailability of SI or strengthen the bone-specific effects. To date, however, the effects of dietary SI on osteoporotic bone loss remain inconclusive, and study results vary from study to study. The current review will discuss the potential factors that result in the conflicting outcomes of these studies, including dosages, intervention materials, study duration, race, and genetic differences. Further well-designed studies are needed to fully understand the underlying mechanism and evaluate the effects of SI on osteoporosis in humans. PMID:26670451

Breastfeeding and postmenopausal osteoporosis.

PubMed

Grimes, Julia P; Wimalawansa, Sunil J

2003-06-01

Bone loss associated with osteoporosis occurs with high frequency among the elderly and often results in debilitating fractures. A combination of lifestyle behaviors, genetic predisposition, and disease processes contributes to bone metabolism. Therefore, any discussion regarding bone health must address these factors. The impact of menopause on bone turnover has been generally well studied and characterized. Breastfeeding places significant stress on calcium metabolism and, as a consequence, directly influences bone metabolism. The most significant factors affecting bone mineral density (BMD) and bone metabolism are the duration and frequency of lactation, the return of menses, and pre-pregnancy weight. Although transient, lactation is associated with bone loss. As clinical guidelines and public health policies are being formulated, there is a compelling need for further investigation into the relationship of lactation, BMD, and subsequent risk of osteoporosis. Better understanding of this relationship will provide new opportunities for early intervention and ultimately help in the prevention of bone loss in postmenopausal women.

Medicines and Bone Loss

MedlinePlus

... The doses of thyroid hormone used to treat hypothyroidism (underactive thyroid) don’t harm bone and shouldn’t be cause for concern. Only high doses, used for thyroid cancer treatment, can cause bone loss. High doses or long- ...

Green tea polyphenols mitigate bone loss of female rats in a chronic inflammation-induced bone loss model

USDA-ARS?s Scientific Manuscript database

The purpose of this study was to explore bioavailability, efficacy, and molecular mechanisms of green tea polyphenols (GTP) related to preventing bone loss in rats with chronic inflammation. A 2 (placebo vs. lipopolysaccharide, LPS) × 2 (no GTP vs. 0.5% GTP in drinking water) factorial design using ...

Radiographic evidence of disuse osteoporosis in the monkey /M. nemestrina/

NASA Technical Reports Server (NTRS)

Young, D. R.; Schneider, V. S.

1981-01-01

Radiological techniques were utilized for monitoring progressive changes in compact bone in the tibia of monkeys during experimentally induced osteopenia. Bone mass loss in the tibia during restraint was evaluated from radiographs, from bone mineral analysis, and from images reconstructed from gamma ray computerized tomography. The losses during 6 months of restraint tended to occur predominantly in the proximal tibia and were characterized by subperiosteal bone loss, intracortical striations, and scalloped endosteal surfaces. Bone mineral content in the cross section of the tibia declined 17-21%. In 6 months of recovery, the mineral content of the proximal tibia remained depressed.

Skeletal unloading inhibits the in vitro proliferation and differentiation of rat osteoprogenitor cells

NASA Technical Reports Server (NTRS)

Kostenuik, P. J.; Halloran, B. P.; Morey-Holton, E. R.; Bikle, D. D.

1997-01-01

Loss of weight bearing in the growing rat decreases bone formation, osteoblast numbers, and bone maturation in unloaded bones. These responses suggest an impairment of osteoblast proliferation and differentiation. To test this assumption, we assessed the effects of skeletal unloading using an in vitro model of osteoprogenitor cell differentiation. Rats were hindlimb elevated for 0 (control), 2, or 5 days, after which their tibial bone marrow stromal cells (BMSCs) were harvested and cultured. Five days of hindlimb elevation led to significant decreases in proliferation, alkaline phosphatase (AP) enzyme activity, and mineralization of BMSC cultures. Differentiation of BMSCs was analyzed by quantitative competitive polymerase chain reaction of cDNA after 10, 15, 20, and 28 days of culture. cDNA pools were analyzed for the expression of c-fos (an index of proliferation), AP (an index of early osteoblast differentiation), and osteocalcin (a marker of late differentiation). BMSCs from 5-day unloaded rats expressed 50% less c-fos, 61% more AP, and 35% less osteocalcin mRNA compared with controls. These data demonstrate that cultured osteoprogenitor cells retain a memory of their in vivo loading history and indicate that skeletal unloading inhibits proliferation and differentiation of osteoprogenitor cells in vitro.

Vitamin D threshold to prevent aromatase inhibitor-related bone loss: the B-ABLE prospective cohort study.

PubMed

Prieto-Alhambra, Daniel; Servitja, Sonia; Javaid, M Kassim; Garrigós, Laia; Arden, Nigel K; Cooper, Cyrus; Albanell, Joan; Tusquets, Ignasi; Diez-Perez, Adolfo; Nogues, Xavier

2012-06-01

Aromatase inhibitor (AI)-related bone loss is associated with increased fracture rates. Vitamin D might play a role in minimising this effect. We hypothesised that 25-hydroxy-vitamin D concentrations [25(OH)D] after 3 months supplementation might relate to bone loss after 1 year on AI therapy. We conducted a prospective cohort study from January 2006 to December 2011 of a consecutive sample of women initiating AI for early breast cancer who were ineligible for bisphosphonate therapy and stayed on treatment for 1 year (N = 232). Serum 25(OH)D was measured at baseline and 3 months, and lumbar spine (LS) bone mineral density at baseline and 1 year. Subjects were supplemented with daily calcium (1 g) and vitamin D(3) (800 IU) and additional oral 16,000 IU every 2 weeks if baseline 25(OH)D was <30 ng/ml. Linear regression models were fitted to adjust for potential confounders. After 1 year on AI therapy, 232 participants experienced a significant 1.68 % [95 % CI 1.15-2.20 %] bone loss at LS (0.017 g/cm(2) [0.012-0.024], P < 0.0001). Higher 25(OH)D at 3 months protected against LS bone loss (-0.5 % per 10 ng/ml [95 % CI -0.7 to -0.3 %], adjusted P = 0.0001), and those who reached levels ≥40 ng/ml had reduced bone loss by 1.70 % [95 % CI 0.4-3.0 %; adjusted P = 0.005] compared to those with low 25(OH)D levels (<30 ng/ml). We conclude that improved vitamin D status using supplementation is associated with attenuation of AI-associated bone loss. For this population, the current Institute of Medicine target recommendation of 20 ng/ml might be too low to ensure good bone health.

Peri-Implant Distribution of Polyethylene Debris in Postmortem-Retrieved Knee Arthroplasties: Can Polyethylene Debris Explain Loss of Cement-Bone Interlock in Successful Total Knee Arthroplasties?

PubMed

Cyndari, Karen I; Goodheart, Jacklyn R; Miller, Mark A; Oest, Megan E; Damron, Timothy A; Mann, Kenneth A

2017-07-01

Loss of mechanical interlock between cement and bone with in vivo service has been recently quantified for functioning, nonrevised, cemented total knee arthroplasties (TKAs). The cause of interlocking trabecular resorption is not known. The goal of this study is to quantify the distribution of PE debris at the cement-bone interface and determine if polyethylene (PE) debris is locally associated with loss of interlock. Fresh, nonrevised, postmortem-retrieved TKAs (n = 8) were obtained en bloc. Laboratory-prepared constructs (n = 2) served as negative controls. The intact cement-bone interface of each proximal tibia was embedded in Spurr's resin, sectioned, and imaged under polarized light to identify birefringent PE particles. PE wear particle number density was quantified at the cement-bone interface and distal to the interface, and then compared with local loss of cement-bone interlock. The average PE particle number density for postmortem-retrieved TKAs ranged from 8.6 (1.3) to 24.9 (3.1) particles/mm 2 (standard error) but was weakly correlated with years in service. The average particle number density was twice as high as distal (>5mm) to the interface compared to at the interface. The local loss of interlock at the interface was not related to the presence, absence, or particle density of PE. PE debris can migrate extensively along the cement-bone interface of well-fixed tibial components. However, the amount of local bone loss at the cement-bone interface was not correlated with the amount of PE debris at the interface, suggesting that the observed loss of trabecular interlock in these well-fixed TKAs may be due to alternative factors. Copyright © 2017 Elsevier Inc. All rights reserved.

Low Magnitude, High Frequency Signals Could Reduce Bone Loss During Spaceflight

NASA Astrophysics Data System (ADS)

Hawkey, A.

The removal of gravitational loading results in a loss of homeostasis of the skeleton. This leads to significant losses of bone mass during long-duration missions in space. Conventional exercise countermeasures, such as running and resistance training, have only limited effectiveness in reducing the rate at which bone is demineralised in microgravity. Bone loss, therefore, remains a major concern and if not annulled could be so severe as to jeopardise an extended human presence in space. In addition, current exercise regimes occupy valuable crew time, and astronauts often find the equipment cumbersome and uncomfortable to use. Recent studies suggest that exposing the body to short periods (<20mins) of low magnitude (<1g), high frequency (15-35Hz) signals (vibration) everyday could reduce, even prevent, bone loss during conditions such as osteoporo- sis on earth. The new vibration therapy treatment could also have several advantages over existing exercise countermeasures used in spaceflight due to it being very simple to operate, relatively inexpensive, and requiring only short periods of time `training', unlike the complicated, expensive and time-consuming devices currently used. This review highlights the detrimen- tal effects that microgravity has on the strength and integrity of bone, how current countermeasures are ineffective at stemming this level of deterioration, and how new vibration techniques could significantly reduce space-induced bone loss.

Aging and bone loss: new insights for the clinician

PubMed Central

Demontiero, Oddom; Vidal, Christopher

2012-01-01

It is well known that the underlying mechanisms of osteoporosis in older adults are different than those associated with estrogen deprivation. Age-related bone loss involves a gradual and progressive decline, which is also seen in men. Markedly increased bone resorption leads to the initial fall in bone mineral density. With increasing age, there is also a significant reduction in bone formation. This is mostly due to a shift from osteoblastogenesis to predominant adipogenesis in the bone marrow, which also has a lipotoxic effect that affects matrix formation and mineralization. We review new evidence on the pathophysiology of age-related bone loss with emphasis upon the mechanism of action of current osteoporosis treatments. New potential treatments are also considered, including therapeutic approaches to osteoporosis in the elderly that focus on the pathophysiology and potential reversal of adipogenic shift in bone. PMID:22870496

Sexual Dimorphism in Periapical Inflammation and Bone Loss from MAP Kinase Phosphatase-1 Deficient Mice

PubMed Central

McAbee, Justin; Li, Qiyan; Yu, Hong; Kirkwood, Keith L.

2012-01-01

Introduction Mitogen Activating Protein (MAPK) kinase phosphatase-1 (MKP-1) has been shown to be a key negative regulator of the MAP kinase pathways of the innate immune system. The impact of MKP-1 in an endodontic model has yet to be studied. Thus, the purpose of this study was to determine the role of MKP-1 in a bacterial-driven model of pathological endodontic bone loss. Methods Pulps were exposed in both lower 1st molars of 10-week old mkp-1+/+ and mkp-1−/− mice and left open to the oral environment for either 3 or 8 weeks. At sacrifice, mandibles were harvested and scanned by microcomputed tomography (μCT) to determine periapical bone loss. Histopathological scoring was then performed on the samples to determine the amount of inflammatory infiltrate within the periapical microenvironment. Results Significant bone loss and inflammatory infiltrate were found in all experimental groups when compared to control. No statistical difference was found between mkp-1+/+ and mkp-1−/− at either time point with respect to bone loss or inflammatory infiltrate. At 8 weeks, male mkp-1−/− mice were found to have significantly more bone loss and inflammatory infiltrate when compared to female mkp-1−/− mice. There was also a significant correlation between an increase in bone loss and increase in inflammatory infiltrate. Conclusions A sexual dimorphism exists in the periapical inflammatory process, where male mkp-1−/− mice have more inflammation than female mkp-1−/− mice. The increase in inflammatory infiltrate correlates to more bone loss in the male mice. PMID:22794213

Does bone loss begin after weight loss ends? Results 2 years after weight loss or regain in postmenopausal women.

PubMed

Von Thun, Nancy L; Sukumar, Deeptha; Heymsfield, Steven B; Shapses, Sue A

2014-05-01

Short-term weight loss is accompanied by bone loss in postmenopausal women. The longer-term impact of weight loss on bone in reduced overweight/obese women compared with women who regained their weight was examined in this study using a case-control design. Postmenopausal women (N = 42; mean [SD] body mass index, 28.3 [2.8] kg/m; mean [SD] age, 60.7 [5.5] y) were recruited 2 years after the start of a 6-month weight loss trial; those who maintained their weight (weight loss maintainer [WL-M] group) were matched to a cohort of women who regained their weight (weight loss regainer [WL-R] group). Serum hormones and bone markers were measured in a subset. Bone mineral density (BMD) at the femoral neck, trochanter, spine, radius, and total body, and soft-tissue composition were taken at baseline, 0.5 years, and 2 years. During weight loss, both groups lost 9.3% (3.4%) of body weight, with no significant difference between the groups. After weight loss, weight change was -0.1% (2.7%) and 6.0% (3.3%) in the WL-M (n = 22) and WL-R (n = 20) groups, respectively. After 2 years, both groups lost BMD at the femoral neck and trochanter (P ≤ 0.01), whereas only the WL-M group reduced BMD at the 1/3 radius (P < 0.001). There was greater BMD loss at the trochanter (-6.8% [5.7%]) and 1/3 radius (-4.5% [3.3%]) in the WL-M group compared with the WL-R group after 2 years. Multiple linear regression showed that change in leg fat mass (but not trunk fat) contributed to trochanter BMD loss (P < 0.05). After 2 years, there is no BMD recovery of weight reduction-induced bone loss, irrespective of weight regain. These data suggest that the period after weight loss may be an important point in time to prevent bone loss for those who maintain weight and those who regain weight.

Yeast-incorporated gallium attenuates glucocorticoid-induced bone loss in rats by inhibition of bone resorption.

PubMed

Ren, Zhaozhou; Yang, Liqing; Xue, Feng; Meng, Qingjie; Wang, Kejia; Wu, Xian; Ji, Chao; Jiang, Teng; Liu, Da; Zhou, Long; Zhang, Jing; Fu, Qin

2013-06-01

Glucocorticoids (GC) are potent anti-inflammatory agents and widely used for the treatment of many immune-mediated and inflammatory diseases, whereas GC-induced osteoporosis (GIOP) is the most common cause of secondary osteoporosis and significantly increases the patients' morbidity and mortality. GIOP is characterized as diminished osteogenesis and accelerated bone resorption. Yeast-incorporated gallium (YG) as an organic compound not only reduces elements-associated toxicity, but also maintains its therapeutic effect on improving bone loss or promoting fracture healing in ovariectomized female rats. The aim of this study was to examine whether YG could prevent GC-induced bone loss. Five-month-old male Sprague-Dawley rats were randomly divided into three groups (n = 6): two groups were administered dexamethasone (0.1 mg/kg/day) or vehicle (PBS) subcutaneously for 5 weeks; one other group was received dexamethasone subcutaneously and YG (120 μg/kg/day) orally. Trabecular bone microarchitectural parameters, bone mineral density (BMD), bone strength, body weight, and serum biochemical markers of bone resorption and formation were examined. Compared to the GC alone group, treatment with YG not only prevented microarchitectural deterioration of trabecular bone volume relative to tissue volume, trabecular number, and trabecular separation, but also significantly improved BMD, mechanical strength, and body weight in GC-treated rats. Moreover, YG decreased tartrate-resistant acid phosphatase 5b level but failed to change alkaline phosphatase level in GC-treated rats. This is the first study to show that YG prominently attenuates bone loss and microarchitectural deterioration and inhibits the increased bone resorption in GIOP. It implies that YG might be an alternative therapy for prevention of GC-induced bone loss in humans.

Platinum nanoparticles reduce ovariectomy-induced bone loss by decreasing osteoclastogenesis

PubMed Central

Kim, Woon-Ki; Kim, Jin-Chun; Park, Hyun-Jung; Sul, Ok-Joo; Lee, Mi-Hyun; Kim, Ji-Soon

2012-01-01

Platinum nanoparticles (PtNP) exhibit remarkable antioxidant activity. There is growing evidence concerning a positive relationship between oxidative stress and bone loss, suggesting that PtNP could protect against bone loss by modulating oxidative stress. Intragastric administration of PtNP reduced ovariectomy (OVX)-induced bone loss with a decreased level of activity and number of osteoclast (OC) in vivo. PtNP inhibited OC formation by impairing the receptor activator of nuclear factor-κB ligand (RANKL) signaling. This impairment was due to a decreased activation of nuclear factor-κB and a reduced level of nuclear factor in activated T-cells, cytoplasmic 1 (NFAT2). PtNP lowered RANKL-induced long lasting reactive oxygen species as well as intracellular concentrations of Ca2+ oscillation. Our data clearly highlight the potential of PtNP for the amelioration of bone loss after estrogen deficiency by attenuated OC formation. PMID:22525805

[Hearing and balance in metabolic bone diseases].

PubMed

Zatoński, Tomasz; Temporale, Hanna; Krecicki, Tomasz

2012-03-01

There are reports that hearing loss is one of the clinical manifestations of metabolic bone diseases. Demineralization can lead to a reduction in ossicular mass. Paget's disease can reveal loss of mineral density of the cochlear bone. Ear bone remodeling in osteoporosis is similar to the changes in otosclerosis. Moreover, osteoporosis, osteogenesis imperfecta and otosclerosis have a similar genetic mechanism. According to some researchers osteopenia and osteoporosis may well be associated with idiopathic benign positional vertigo (BPV). Dysfunction of the organ of hearing and balance in patients with renal insufficiency may be due to disturbances in calcium phosphate balance and renal osteodystrophy in the course of the disease. Proving the presence of hearing loss in patients with metabolic bone diseases may lead to determining the new indications for bone densitometry in some patients with hearing impairment. Furthermore, audiological examination in patients with osteoporosis may be important because of the impact of hearing loss on prognosis for patients with metabolic bone diseases.

Repression of osteoblast maturation by ERRα accounts for bone loss induced by estrogen deficiency.

PubMed

Gallet, Marlène; Saïdi, Soraya; Haÿ, Eric; Photsavang, Johann; Marty, Caroline; Sailland, Juliette; Carnesecchi, Julie; Tribollet, Violaine; Barenton, Bruno; Forcet, Christelle; Birling, Marie-Christine; Sorg, Tania; Chassande, Olivier; Cohen-Solal, Martine; Vanacker, Jean-Marc

2013-01-01

ERRα is an orphan member of the nuclear receptor family, the complete inactivation of which confers resistance to bone loss induced by ageing and estrogen withdrawal to female mice in correlation with increased bone formation in vivo. Furthermore ERRα negatively regulates the commitment of mesenchymal cells to the osteoblast lineage ex vivo as well as later steps of osteoblast maturation. We searched to determine whether the activities of ERRα on osteoblast maturation are responsible for one or both types of in vivo induced bone loss. To this end we have generated conditional knock out mice in which the receptor is normally present during early osteoblast differentiation but inactivated upon osteoblast maturation. Bone ageing in these animals was similar to that observed for control animals. In contrast conditional ERRαKO mice were completely resistant to bone loss induced by ovariectomy. We conclude that the late (maturation), but not early (commitment), negative effects of ERRα on the osteoblast lineage contribute to the reduced bone mineral density observed upon estrogen deficiency.

Analysis of glycerophosphocholine molecular species as derivatives of 7-[(chlorocarbonyl)-methoxy]-4-methylcoumarin.

PubMed

Wheelan, P; Zirrolli, J A; Clay, K L

1992-01-01

A method has been developed for the analysis of derivatized diradylglycerols obtained from glycerophosphocholine (GPC) of transformed murine bone marrow-derived mast cells that provided high performance liquid chromatography (HPLC) separation of GPC subclasses and molecular species separation with on-line quantitation using UV detection. In addition, the derivatized diradylglycerol species were unequivocably identified by continuous flow fast-atom bombardment mass spectrometry. GPC was initially isolated by thin-layer chromatography (TLC), the phosphocholine group was hydrolyzed, and the resultant diradylglycerol was derivatized with 7-[(chlorocarbonyl)-methoxy]-4-methylcoumarin (CMMC). After separation of the derivatized subclasses by normal phase HPLC, the individual molecular species of the alkylacyl and diacyl subclasses were quantitated and collected during a subsequent reverse phase HPLC step. With an extinction coefficient of 14,700 l mol-1 cm-1 at a wavelength detection of 320 nm, the CMMC derivatives afforded sensitive UV detection (100 pmol) and quantitation of the molecular species. Continuous flow fast-atom bombardment mass spectrometry of the alkylacyl CMMC derivatives yielded abundant [MH]+ ions and a single fragment ion formed by loss of alkylketene from the sn-2 acyl group, [MH-(R = C = O)]+. No fragmentation of the sn-1 alkyl chain was observed. Diacyl derivatives also produced abundant [MH]+ ions plus two fragment ions arising from loss of RCOOH from each of the acyl substituents and two fragment ions from the loss of alkyketene from each acyl group. Individual molecular species substituents were assigned from these ions.

Targeting sphingosine-1-phosphate lyase as an anabolic therapy for bone loss.

PubMed

Weske, Sarah; Vaidya, Mithila; Reese, Alina; von Wnuck Lipinski, Karin; Keul, Petra; Bayer, Julia K; Fischer, Jens W; Flögel, Ulrich; Nelsen, Jens; Epple, Matthias; Scatena, Marta; Schwedhelm, Edzard; Dörr, Marcus; Völzke, Henry; Moritz, Eileen; Hannemann, Anke; Rauch, Bernhard H; Gräler, Markus H; Heusch, Gerd; Levkau, Bodo

2018-05-01

Sphingosine-1-phosphate (S1P) signaling influences bone metabolism, but its therapeutic potential in bone disorders has remained unexplored. We show that raising S1P levels in adult mice through conditionally deleting or pharmacologically inhibiting S1P lyase, the sole enzyme responsible for irreversibly degrading S1P, markedly increased bone formation, mass and strength and substantially decreased white adipose tissue. S1P signaling through S1P 2 potently stimulated osteoblastogenesis at the expense of adipogenesis by inversely regulating osterix and PPAR-γ, and it simultaneously inhibited osteoclastogenesis by inducing osteoprotegerin through newly discovered p38-GSK3β-β-catenin and WNT5A-LRP5 pathways. Accordingly, S1P 2 -deficient mice were osteopenic and obese. In ovariectomy-induced osteopenia, S1P lyase inhibition was as effective as intermittent parathyroid hormone (iPTH) treatment in increasing bone mass and was superior to iPTH in enhancing bone strength. Furthermore, lyase inhibition in mice successfully corrected severe genetic osteoporosis caused by osteoprotegerin deficiency. Human data from 4,091 participants of the SHIP-Trend population-based study revealed a positive association between serum levels of S1P and bone formation markers, but not resorption markers. Furthermore, serum S1P levels were positively associated with serum calcium , negatively with PTH , and curvilinearly with body mass index. Bone stiffness, as determined through quantitative ultrasound, was inversely related to levels of both S1P and the bone formation marker PINP, suggesting that S1P stimulates osteoanabolic activity to counteract decreasing bone quality. S1P-based drugs should be considered as a promising therapeutic avenue for the treatment of osteoporotic diseases.

Association with replication between estrogen-related receptor gamma (ESRRgamma) polymorphisms and bone phenotypes in women of European ancestry.

PubMed

Elfassihi, Latifa; Giroux, Sylvie; Bureau, Alexandre; Laflamme, Nathalie; Cole, David Ec; Rousseau, François

2010-04-01

Osteoporosis is a bone disease characterized by low bone mineral density (BMD), a highly heritable polygenic trait. Women are more prone than men to develop osteoporosis owing to a lower peak bone mass and accelerated bone loss at menopause. Lack of estrogen thus is a major risk factor for osteoporosis. In addition to having strong similarity to the estrogen receptor 1 (ESR1), the orphan nuclear estrogen-related receptor gamma (ESRRgamma) is widely expressed and shows overlap with ESR1 expression in tissues where estrogen has important physiologic functions. For these reasons, we have undertaken a study of ESRRgamma sequence variants in association with bone measurements [heel quantitative ultrasound (QUS) by measurements of broadband ultrasound attenuation (BUA), speed of sound (SOS), and stiffness index (SI) and dual-energy X-ray absorptiometry (DXA) at the femoral neck (FN) and lumbar spine (LS)]. A silent variant was found to be associated with multiple bone measurements (LS, BUA, SOS, and SI), the p values ranging from .006 to .04 in a sample of 5144 Quebec women. The region of this variant was analyzed using the HapMap database and the Gabriel method to define a block of 20 kb. Using the Tagger method, eight TagSNPs were identified and genotyped in a sample of 1335 women. Four of these SNPs capture the five major block haplotypes. One SNP (rs2818964) and one haplotype were significantly associated with multiple bone measures. All SNPs involved in the associations were analyzed in two other sample sets with significant results in the same direction. These results suggest involvement of ESRRgamma in the determination of bone density in women. Copyright 2010 American Society for Bone and Mineral Research.

Histological and compositional responses of bone to immobilization and other experimental conditions

NASA Technical Reports Server (NTRS)

Brown, R. J.; Niklowitz, W. J.

1985-01-01

Histological techniques were utilized for evaluating progressive changes in tibial compact bone in adult male monkeys during chronic studies of immobilization-associated osteopenia. The animals were restrained in a semirecumbent position which reduces normally occurring stresses in the lower extremities and results in bone mass loss. The longest immobilization studies were of seven months duration. Losses of haversian bone tended to occur predominatly in the proximal tibia and were characterized by increased activation with excessive depth of penetration of osteoclastic activity. There was no apparent regulation of the size and orientation of resorption cavities. Rapid bone loss seen during 10 weeks of immobilization appeared to be due to unrestrained osteoclastic activity without controls and regulation which are characteristic of adaptive systems. The general pattern of loss persisted throughout 7 months of immobilization. Clear cut evidence of a formation phase in haversian bone was seen only after two months of reambulation.

New management options for osteoporosis with emphasis on SERMs.

PubMed

McClung, M R

2015-01-01

Albright was the first of many to show that loss of bone mass due to estrogen deficiency is an important part of the pathogenesis of postmenopausal osteoporosis. This led to the use of estrogen therapy which was shown to prevent bone loss at menopause and to reduce the risk of important fragility fractures. Selective estrogen receptor modulators (SERMs), with salutary estrogen-like skeletal effects and with protection from breast cancer, have important roles in the management of young postmenopausal women. New members of the SERM family may approach the effectiveness of estrogen in preventing bone loss and reducing fracture risk. When combined with estrogen, new SERMs prevent endometrial hyperplasia, and that combination reduces menopausal symptoms and prevents bone loss. Drugs that reduce bone turnover or stimulate bone formation by non-estrogen pathways have also been developed to treat osteoporosis. Emerging therapies, with unique mechanisms of action, may provide improved efficacy in treating women who already have osteoporosis.

Exercise training in obese older adults prevents increase in bone turnover and attenuates decrease in hip BMD induced by weight loss despite decline in bone-active hormones*

PubMed Central

Shah, Krupa; Armamento-Villareal, Reina; Parimi, Nehu; Chode, Suresh; Sinacore, David R.; Hilton, Tiffany N.; Napoli, Nicola; Qualls, Clifford; Villareal, Dennis T.

2011-01-01

Weight-loss therapy to improve health in obese older adults is controversial because it causes further bone loss. Therefore, it is recommended that weight-loss therapy should include an intervention to minimize bone loss such as exercise training (ET). The purpose of this study was to determine the independent and combined effects of weight loss and ET on bone metabolism in relation to bone mineral density (BMD) in obese older adults. One-hundred-seven older (age >65 yrs) obese (BMI ≥30 kg/m2) adults were randomly assigned to a control group, diet group, exercise group, and diet-exercise group for 1 year. Body weight decreased in the diet (−9.6%) and diet-exercise (−9.4%) groups, not in the exercise (−1%) and control (−0.2%) groups (between-group P<.001). However, despite comparable weight loss, bone loss at the total hip was relatively less in the diet-exercise group (−1.1%) than in the diet group (−2.6%), whereas BMD increased in the exercise group (1.5%) (between-group P<.001) Serum C-terminal telopeptide (CTX) and osteocalcin concentrations increased in the diet group (31% and 24%) while they decreased in the exercise group (−13% and −15%) (between-group P<.001). In contrast, similar to the control group, serum CTX and osteocalcin concentrations did not change in the diet-exercise group. Serum procollagen propeptide concentrations decreased in the exercise group (−15%) compared with the diet group (9%) (P=.04). Serum leptin and estradiol concentrations decreased in the diet (−25% and −15%) and diet-exercise (−38% and −13%) groups, not in the exercise and control groups (between-group P=.001). Multivariate analyses revealed that changes in lean body mass (β=.33), serum osteocalcin (β= −.24), and 1-RM strength (β=.23) were independent predictors of changes in hip BMD (all P<.05). In conclusion, the addition of ET to weight-loss therapy among obese older adults prevents weight-loss-induced increase in bone turnover and attenuates weight-loss-induced reduction in hip BMD despite weight-loss-induced decrease in bone-active hormones. PMID:21786319

Osteoporosis in Rheumatic Diseases: Anti-rheumatic Drugs and the Skeleton.

PubMed

Dubrovsky, Alanna M; Lim, Mie Jin; Lane, Nancy E

2018-05-01

Osteoporosis in rheumatic diseases is a very well-known complication. Systemic inflammation results in both generalized and localized bone loss and erosions. Recently, increased knowledge of inflammatory process in rheumatic diseases has resulted in the development of potent inhibitors of the cytokines, the biologic DMARDs. These treatments reduce systemic inflammation and have some effect on the generalized and localized bone loss. Progression of bone erosion was slowed by TNF, IL-6 and IL-1 inhibitors, a JAK inhibitor, a CTLA4 agonist, and rituximab. Effects on bone mineral density varied between the biological DMARDs. Medications that are approved for the treatment of osteoporosis have been evaluated to prevent bone loss in rheumatic disease patients, including denosumab, cathepsin K, bisphosphonates, anti-sclerostin antibodies and parathyroid hormone (hPTH 1-34), and have some efficacy in both the prevention of systemic bone loss and reducing localized bone erosions. This article reviews the effects of biologic DMARDs on bone mass and erosions in patients with rheumatic diseases and trials of anti-osteoporotic medications in animal models and patients with rheumatic diseases.

Increasing dietary nitrate has no effect on cancellous bone loss or fecal microbiome in ovariectomized rats.

PubMed

Conley, Melissa N; Roberts, Cooper; Sharpton, Thomas J; Iwaniec, Urszula T; Hord, Norman G

2017-05-01

Studies suggest diets rich in fruit and vegetables reduce bone loss, although the specific compounds responsible are unknown. Substrates for endogenous nitric oxide (NO) production, including organic nitrates and dietary nitrate, may support NO production in age-related conditions, including osteoporosis. We investigated the capability of dietary nitrate to improve NO bioavailability, reduce bone turnover and loss. Six-month-old Sprague Dawley rats [30 ovariectomized (OVX) and 10 sham-operated (sham)] were randomized into three groups: (i) vehicle (water) control, (ii) low-dose nitrate (LDN, 0.1 mmol nitrate/kg bw/day), or (iii) high-dose nitrate (HDN, 1.0 mmol nitrate/kg bw/day) for three weeks. The sham received vehicle. Serum bone turnover markers; bone mass, mineral density, and quality; histomorphometric parameters; and fecal microbiome were examined. Three weeks of LDN or HDN improved NO bioavailability in a dose-dependent manner. OVX resulted in cancellous bone loss, increased bone turnover, and fecal microbiome changes. OVX increased relative abundances of Firmicutes and decreased Bacteroideceae and Alcaligenaceae. Nitrate did not affect the skeleton or fecal microbiome. These data indicate that OVX affects the fecal microbiome and that the gut microbiome is associated with bone mass. Three weeks of nitrate supplementation does not slow bone loss or alter the fecal microbiome in OVX. © 2017 The Authors. Molecular Nutrition & Food Research published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Increasing dietary nitrate has no effect on cancellous bone loss or fecal microbiome in ovariectomized rats

PubMed Central

Conley, Melissa N.; Roberts, Cooper; Sharpton, Thomas J.; Iwaniec, Urszula T.

2017-01-01

Scope Studies suggest diets rich in fruit and vegetables reduce bone loss, although the specific compounds responsible are unknown. Substrates for endogenous nitric oxide (NO) production, including organic nitrates and dietary nitrate, may support NO production in age‐related conditions, including osteoporosis. We investigated the capability of dietary nitrate to improve NO bioavailability, reduce bone turnover and loss. Methods and results Six‐month‐old Sprague Dawley rats [30 ovariectomized (OVX) and 10 sham‐operated (sham)] were randomized into three groups: (i) vehicle (water) control, (ii) low‐dose nitrate (LDN, 0.1 mmol nitrate/kg bw/day), or (iii) high‐dose nitrate (HDN, 1.0 mmol nitrate/kg bw/day) for three weeks. The sham received vehicle. Serum bone turnover markers; bone mass, mineral density, and quality; histomorphometric parameters; and fecal microbiome were examined. Three weeks of LDN or HDN improved NO bioavailability in a dose‐dependent manner. OVX resulted in cancellous bone loss, increased bone turnover, and fecal microbiome changes. OVX increased relative abundances of Firmicutes and decreased Bacteroideceae and Alcaligenaceae. Nitrate did not affect the skeleton or fecal microbiome. Conclusion These data indicate that OVX affects the fecal microbiome and that the gut microbiome is associated with bone mass. Three weeks of nitrate supplementation does not slow bone loss or alter the fecal microbiome in OVX. PMID:28087899

Dietary Intake Can Predict and Protect Against Changes in Bone Metabolism during Spaceflight and Recovery (Pro K)

NASA Technical Reports Server (NTRS)

Smith, Scott M.; Zwart, S. R.; Shackelford, L.; Heer, M.

2009-01-01

Bone loss is not only a well-documented effect of spaceflight on astronauts, but also a condition that affects millions of men and women on Earth each year. Many countermeasures aimed at preventing bone loss during spaceflight have been proposed, and many have been evaluated to some degree. To date, those showing potential have focused on either exercise or pharmacological interventions, but none have targeted dietary intake alone as a factor to predict or minimize bone loss during spaceflight. The "Dietary Intake Can Predict and Protect against Changes in Bone Metabolism during Spaceflight and Recovery" investigation ("Pro K") is one of the first inflight evaluations of a dietary countermeasure to lessen bone loss of astronauts. This protocol will test the hypothesis that the ratio of acid precursors to base precursors (specifically animal protein to potassium) in the diet can predict directional changes in bone mineral during spaceflight and recovery. The ratio of animal protein to potassium in the diet will be controlled for multiple short (4-day) periods before and during flight. Based on multiple sets of bed rest data, we hypothesize that a higher ratio of the intake of animal protein to the intake of potassium will yield higher concentrations of markers of bone resorption and urinary calcium excretion during flight and during recovery from bone mineral loss after long-duration spaceflight.

Bone remodeling and calcium homeostasis in patients with spinal cord injury: a review.

PubMed

Maïmoun, Laurent; Fattal, Charles; Sultan, Charles

2011-12-01

Patients with spinal cord injury exhibit early and acute bone loss with the major functional consequence being a high incidence of pathological fractures. The bone status of these patients is generally investigated by dual-energy x-ray absorptiometry, but this technique does not reveal the pathophysiological mechanism underlying the bone loss. Bone cell activity can be indirectly evaluated by noninvasive techniques, including measurement of specific biochemical markers of bone formation (such as osteocalcin or bone-alkaline phosphatase) and resorption (such as procollagen type I N- or C-terminal propeptide). The bone loss in spinal cord injury is clearly due to an uncoupling of bone remodeling in favor of bone resorption, which starts just after the injury and peaks at about 1 to 4 months. Beyond 6 months, bone resorption activity decreases progressively but remains elevated for many years after injury. Conversely, bone formation is less affected. Antiresorptive treatment induces an early and acute reduction in bone resorption markers. Level of injury and health-related complications do not seem to be implicated in the intensity of bone resorption. During the acute phase, the hypercalcemic status is associated with the suppression of parathyroid hormone and vitamin D metabolites. The high sensitivity of these markers after treatment suggests that they can be used for monitoring treatment efficacy and patient compliance. The concomitant use of bone markers and dual-energy x-ray absorptiometry may improve the physician's ability to detect patients at risk of severe bone loss and subsequent fractures. Copyright © 2011 Elsevier Inc. All rights reserved.

Immediate fall of bone formation and transient increase of bone resorption in the course of high-dose, short-term glucocorticoid therapy in young patients with multiple sclerosis.

PubMed

Dovio, Andrea; Perazzolo, Laura; Osella, Giangiacomo; Ventura, Massimo; Termine, Angela; Milano, Eva; Bertolotto, Antonio; Angeli, Alberto

2004-10-01

Glucocorticoid (GC)-induced osteoporosis is the leading form of secondary osteoporosis. Bone loss can be rapid. However, longitudinal studies at the very beginning of treatment are scarce. Patients relapsing from multiple sclerosis are treated with high-dose, short-term iv GCs. A number of them are young, without concomitant disease affecting bone and with no substantial impairment of mobility. Such patients were selected for the present study. Thirteen patients suffering from multiple sclerosis [11 females, two males; age 32 +/- 2 yr (mean +/- se)] and receiving iv methylprednisolone 15 mg/kg daily for 10 d completed the study. We measured serum osteocalcin (OC), aminoterminal propeptide of type I collagen (PINP), bone isoform of alkaline phosphatase (bALP), carboxyterminal telopeptide of type I collagen (CTX), and urinary calcium/creatinine ratio (uCa/Cr) during the 10-d cycle and 3 months later. Dual-energy x-ray absorptiometry and calcaneal quantitative ultrasonometry were performed before and 6 months after therapy. We found an immediate, impressive fall of OC and PINP (-80 +/- 3 and -54 +/- 5% at d 2, respectively), which persisted throughout the whole treatment period (P < 0.0001 for both markers). bALP levels showed only a modest decrease at d 6 (-19 +/- 7%, P < 0.05), with subsequent return to baseline in d 7-10. After 3 months, OC, PINP, and bALP levels rose to +51 +/- 22, +37 +/- 16 (not significant), and +61 +/- 17% (P < 0.01) with respect to baseline, respectively. uCa/Cr and CTX showed a progressive, marked increase during treatment, peaking at d 7-9 (+92 +/- 44 and +149 +/- 63%, respectively), with subsequent decrement at d 10 (P < 0.01 and P < 0.05, respectively) despite continuing GC administration. After 3 months, uCa/Cr and CTX levels were also higher than baseline. No change in quantitative ultrasonometry parameters and bone mineral density was observed 6 months after therapy. In conclusion, high-dose, short-term iv GC regimens cause an immediate and persistent decrease in bone formation and a rapid and transient increase of bone resorption. Our data also support the concept that discontinuation of such regimens is followed by a high bone turnover phase.

MicroRNA-188 regulates age-related switch between osteoblast and adipocyte differentiation.

PubMed

Li, Chang-Jun; Cheng, Peng; Liang, Meng-Ke; Chen, Yu-Si; Lu, Qiong; Wang, Jin-Yu; Xia, Zhu-Ying; Zhou, Hou-De; Cao, Xu; Xie, Hui; Liao, Er-Yuan; Luo, Xiang-Hang

2015-04-01

Bone marrow mesenchymal stem cells (BMSCs) exhibit an age-dependent reduction in osteogenesis that is accompanied by an increased propensity toward adipocyte differentiation. This switch increases adipocyte numbers and decreases the number of osteoblasts, contributing to age-related bone loss. Here, we found that the level of microRNA-188 (miR-188) is markedly higher in BMSCs from aged compared with young mice and humans. Compared with control mice, animals lacking miR-188 showed a substantial reduction of age-associated bone loss and fat accumulation in bone marrow. Conversely, mice with transgenic overexpression of miR-188 in osterix+ osteoprogenitors had greater age-associated bone loss and fat accumulation in bone marrow relative to WT mice. Moreover, using an aptamer delivery system, we found that BMSC-specific overexpression of miR-188 in mice reduced bone formation and increased bone marrow fat accumulation. We identified histone deacetylase 9 (HDAC9) and RPTOR-independent companion of MTOR complex 2 (RICTOR) as the direct targets of miR-188. Notably, BMSC-specific inhibition of miR-188 by intra-bone marrow injection of aptamer-antagomiR-188 increased bone formation and decreased bone marrow fat accumulation in aged mice. Together, our results indicate that miR-188 is a key regulator of the age-related switch between osteogenesis and adipogenesis of BMSCs and may represent a potential therapeutic target for age-related bone loss.

Zoledronate prevents lactation induced bone loss and results in additional post-lactation bone mass in mice.

PubMed

Wendelboe, Mette Høegh; Thomsen, Jesper Skovhus; Henriksen, Kim; Vegger, Jens Bay; Brüel, Annemarie

2016-06-01

In rodents, lactation is associated with a considerable and very rapid bone loss, which almost completely recovers after weaning. The aim of the present study was to investigate whether the bisphosphonate Zoledronate (Zln) can inhibit lactation induced bone loss, and if Zln interferes with recovery of bone mass after lactation has ceased. Seventy-six 10-weeks-old NMRI mice were divided into the following groups: Baseline, Pregnant, Lactation, Lactation+Zln, Recovery, Recovery+Zln, and Virgin Control (age-matched). The lactation period was 12days, then the pups were removed, and thereafter recovery took place for 28days. Zln, 100μg/kg, was given s.c. on the day of delivery, and again 4 and 8days later. Mechanical testing, μCT, and dynamic histomorphometry were performed. At L4, lactation resulted in a substantial loss of bone strength (-55% vs. Pregnant, p<0.01), BV/TV (-40% vs. Pregnant, p<0.01), and trabecular thickness (Tb.Th) (-29% vs. Pregnant, p<0.001). Treatment with Zln completely prevented lactation induced loss of bone strength, BV/TV, and Tb.Th at L4. Full recovery of micro-architectural and mechanical properties was found 28days after weaning in vehicle-treated mice. Interestingly, the recovery group treated with Zln during the lactation period had higher BV/TV (+45%, p<0.01) and Tb.Th (+16%, p<0.05) compared with virgin controls. Similar results were found at the proximal tibia and femur. This indicates that Zln did not interfere with the bone formation taking place after weaning. On this background, we conclude that post-lactation bone formation is not dependent on a preceding lactation induced bone loss. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

Biophotonics and Bone Biology

NASA Technical Reports Server (NTRS)

Zimmerli, Gregory; Fischer, David; Asipauskas, Marius; Chauhan, Chirag; Compitello, Nicole; Burke, Jamie; Tate, Melissa Knothe

2004-01-01

One of the more serious side effects of extended space flight is an accelerated bone loss. Rates of bone loss are highest in the weight-bearing bones of the hip and spine regions, and the average rate of bone loss as measured by bone mineral density measurements is around 1.2% per month for persons in a microgravity environment. It is well known that bone remodeling responds to mechanical forces. We are developing two-photon microscopy techniques to study bone tissue and bone cell cultures to better understand the fundamental response mechanism in bone remodeling. Osteoblast and osteoclast cell cultures are being studied, and the goal is to use molecular biology techniques in conjunction with Fluorescence Lifetime Imaging Microscopy (FLIM) to study the physiology of in-vitro cell cultures in response to various stimuli, such as fluid flow induced shear stress and mechanical stress. We have constructed a two-photon fluorescence microscope for these studies, and are currently incorporating FLIM detection. Current progress will be reviewed. This work is supported by the NASA John Glenn Biomedical Engineering Consortium.

[Characteristics of local human skeleton reactions to microgravity and drug treatment of osteoporosis in clinic].

PubMed

Oganov, V S; Skripnikova, I A; Novikov, V E; Bakulin, A V; Kabitskaia, O E; Murashko, L M

2011-01-01

Analysis of the results of long-term investigations of bones in cosmonauts flown on the orbital station MIR and International space station (n = 80) was performed. Theoretically predicted (evolutionary predefined) change in mass of different skeleton bones was found to correlate (r = 0.904) with position relatively the Earth's gravity vector. Vector dependence of bone loss ensues from local specificity of expression of bone metabolism genes which reflects mechanic prehistory of skeleton structures in the evolution of Homo erectus. Genetic polymorphism is accountable for high individual variability of bone loss attested by the dependence of bone loss rate on polymorphism of certain bone metabolism markers. Parameters of one and the other orbital vehicle did not modulate individual-specific stability of the bone loss ratio in different segments of the skeleton. This fact is considered as a phenotype fingerprint of local metabolism in the form of a locus-unique spatial structure of distribution of noncollagenous proteins responsible for position regulation of endosteal metabolism. Drug treatment of osteoporosis (n = 107) evidences that recovery rate depends on bone location; the most likely reason is different effectiveness of local osteotrophic intervention into areas of bustling resorption.

Synergistic effects of green tea polyphenols and alphacalcidol on chronic inflammation-induced bone loss in female rats

PubMed Central

Yeh, J. K.; Cao, J. J.; Tatum, O. L.; Dagda, R. Y.; Wang, J.-S.

2010-01-01

Summary Studies suggest that green tea polyphenols (GTP) or alphacalcidol is promising agent for preventing bone loss. Findings that GTP supplementation plus alphacalcidol administration increased bone mass via a decrease of oxidative stress and inflammation suggest a significant role of GTP plus alphacalcidol in bone health of patients with chronic inflammation. Introduction Studies have suggested that green tea polyphenols (GTP) or alphacalcidol are promising dietary supplements for preventing bone loss in women. However, the mechanism(s) related to the possible osteo-protective role of GTP plus D3 in chronic inflammation-induced bone loss is not well understood. Methods This study evaluated bioavailability, efficacy, and related mechanisms of GTP in combination with alphacalcidol in conserving bone loss in rats with chronic inflammation. A 12-week study of 2 (no GTP vs. 0.5% GTP in drinking water) × 2 (no alphacalcidol vs. 0.05 μg/kg alphacalcidol, 5×/week) factorial design in lipopolysaccharide-administered female rats was performed. In addition, a group receiving placebo administration was used to compare with a group receiving lipopolysaccharide administration only to evaluate the effect of lipopolysaccharide. Results Lipopolysaccharide administration resulted in lower values for bone mass, but higher values for serum tartrate-resistant acid phosphatase (TRAP), urinary 8-hydroxy-2′-deoxyguanosine, and mRNA expression of tumor necrosis factor-α and cyclooxygenase-2 in spleen. GTP supplementation increased urinary epigallocatechin and epicatechin concentrations. Both GTP supplementation and alphacalcidol administration resulted in a significant increase in bone mass, but a significant decrease in serum TRAP levels, urinary 8-hydroxydeoxyguanosine levels, and mRNA expression of tumor necrosis factor-α and cyclooxygenase-2 in spleen. A synergistic effect of GTP and alphacalcidol was observed in these parameters. Neither GTP nor alphacalcidol affected femoral bone area or serum osteocalcin. Conclusion We conclude that a bone-protective role of GTP plus alphacalcidol during chronic inflammation bone loss may be due to a reduction of oxidative stress damage and inflammation. PMID:20069278

Comparison of marginal bone loss and implant success between axial and tilted implants in maxillary All-on-4 treatment concept rehabilitations after 5 years of follow-up.

PubMed

Hopp, Milena; de Araújo Nobre, Miguel; Maló, Paulo

2017-10-01

There is need for more scientific and clinical information on longer-term outcomes of tilted implants compared to implants inserted in an axial position. Comparison of marginal bone loss and implant success after a 5-year follow-up between axial and tilted implants inserted for full-arch maxillary rehabilitation. The retrospective clinical study included 891 patients with 3564 maxillary implants rehabilitated according to the All-on-4 treatment concept. The follow-up time was 5 years. Linear mixed-effect models were performed to analyze the influence of implant orientation (axial/tilted) on marginal bone loss and binary logistic regression to assess the effect of patient characteristics on occurrence of marginal bone loss >2.8 mm. Only those patients with measurements of at least one axial and one tilted implant available were analyzed. This resulted in a data set of 2379 implants (1201 axial, 1178 tilted) in 626 patients (=reduced data set). Axial and tilted implants showed comparable mean marginal bone losses of 1.14 ± 0.71 and 1.19 ± 0.82 mm, respectively. Mixed model analysis indicated that marginal bone loss levels at 5 years follow up was not significantly affected by the orientation (axial/tilted) of the implants in the maxillary bone. Smoking and female gender were associated with marginal bone loss >2.8 mm in a logistic regression analysis. Five-year implant success rates were 96%. The occurrence of implant failure showed to be statistically independent from orientation. Within the limitations of this study and considering a follow-up time of 5 years, it can be concluded that tilted implants behave similarly with regards to marginal bone loss and implant success in comparison to axial implants in full-arch rehabilitation of the maxilla. Longer-term outcomes (10 years +) are needed to verify this result. © 2017 Wiley Periodicals, Inc.

The impact of microgravity on bone metabolism in vitro and in vivo.

PubMed

Loomer, P M

2001-01-01

Exposure to microgravity has been associated with several physiological changes in astronauts and cosmonauts, including an osteoporosis-like loss of bone mass. In-flight measures used to counteract this, including intensive daily exercise regimens, have been only partially successful in reducing the bone loss and in the process have consumed valuable work time. If this bone loss is to be minimized or, preferably, prevented, more effective treatment strategies are required. This, however, requires a greater understanding of the mechanisms through which bone metabolism is affected by microgravity. Various research strategies have been used to examine this problem, including in vitro studies using bone cells and in vivo studies on humans and rats. These have been conducted both in flight and on the ground, by strategies that produce weightlessness to mimic the effects of microgravity. Overall, the majority of the studies have found that marked decreases in gravitation loading result in the loss of bone mass. The processes of bone formation and bone resorption become uncoupled, with an initial transitory increase in resorption accompanied by a prolonged decrease in formation. Loss of bone mass is not uniform throughout the skeleton, but varies at different sites depending on the type of bone and on the mechanical load received. It appears that the skeletal response is a physiologic adaptation to the space environment which, after long space flights or repeated shorter ones, could eventually lead to significant reductions in the ability of the skeletal tissues to withstand the forces of gravity and increased susceptibility to fracture.

Anatomic and Quantitative Temporal Bone CT for Preoperative Assessment of Branchio-Oto-Renal Syndrome.

PubMed

Ginat, D T; Ferro, L; Gluth, M B

2016-12-01

We describe the temporal bone computed tomography (CT) findings of an unusual case of branchio-oto-renal syndrome with ectopic ossicles that are partially located in the middle cranial fossa. We also describe quantitative temporal bone CT assessment pertaining to cochlear implantation in the setting of anomalous cochlear anatomy associated with this syndrome.

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.

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

FES-Rowing versus Zoledronic Acid to Improve BoneHealth in SCI

DTIC Science & Technology

2016-12-01

SUPPLEMENTARY NOTES 14. ABSTRACT There is no established treatment to prevent bone loss or to induce new bone formation following SCI, although the... no established treatment to prevent bone loss or to induce new bone formation following SCI. The goal of this clinical trial -- FES-Rowing versus...Army position, policy or decision unless so designated by other documentation. REPORT DOCUMENTATION PAGE Form Approved OMB No . 0704-0188 Public

Extending Rest between Unloading Cycles Does Not Enhance Bone's Long-Term Recovery.

PubMed

Manske, Sarah L; Vijayaraghavan, Surabhi; Tuthill, Alyssa; Brutus, Olivier; Yang, Jie; Gupta, Shikha; Judex, Stefan

2015-10-01

Multiple exposures to unloading are overall more deleterious to the skeleton than is single exposure, although the rate of bone loss may diminish during multiple exposures. Here, we determined whether extending the reambulation (RA) period from 3 wk to 9 wk will mitigate bone loss during three distinct 3-wk hindlimb unloading (HLU) periods and enhance long-term recovery in skeletally mature, genetically heterogeneous mice. Female adult mice (4 months old) were subjected to three cycles of 3-wk unloading with 3-wk or 9-wk RA periods in between. Mice were terminated 46 wk after initiation of the study. Outcome measures for the distal femur were determined from multiple in vivo micro-computed tomography scans and finite-element modeling. Tripling RA duration enhanced trabecular bone recovery in between HLU periods but also increased the rate of loss of bone volume fraction (bone volume/tissue volume) and metaphyseal stiffness during subsequent HLU periods. With shorter RA periods, the magnitude of bone loss decreased by the second HLU period, whereas this decrease was delayed with longer RA periods. RA duration did not affect long-term recovery 46 wk after the start of the experimental protocol, as both HLU groups had similar levels of bone volume/tissue volume, cortical area, and stiffness. Individual cage activity levels were unrelated to the magnitude of bone loss during HLU or bone recovery during RA. These data suggest that extending recovery duration between periods of unloading may provide temporary benefits but is an ineffective long-term strategy for combating the devastation of trabecular morphology and mechanics, as temporarily enhanced recovery is largely cancelled out by greater susceptibility to unloading. They also emphasize that cortical bone is more amenable to long-term recovery than is trabecular bone.

Abutment Disconnection/Reconnection Affects Peri-implant Marginal Bone Levels: A Meta-Analysis.

PubMed

Koutouzis, Theofilos; Gholami, Fatemeh; Reynolds, John; Lundgren, Tord; Kotsakis, Georgios A

Preclinical and clinical studies have shown that marginal bone loss can be secondary to repeated disconnection and reconnection of abutments that affect the peri-implant mucosal seal. The aim of this systematic review and meta-analysis was to evaluate the impact of abutment disconnections/reconnections on peri-implant marginal bone level changes. To address this question, two reviewers independently performed an electronic search of three major databases up to October 2015 complemented by manual searches. Eligible articles were selected on the basis of prespecified inclusion and exclusion criteria after a two-phase search strategy and assessed for risk of bias. A random-effects meta-analysis was performed for marginal bone loss. The authors initially identified 392 titles and abstracts. After evaluation, seven controlled clinical studies were included. Qualitative assessment of the articles revealed a trend toward protective marginal bone level preservation for implants with final abutment placement (FAP) at the time of implant placement compared with implants for which there were multiple abutment placements (MAP). The FAP group exhibited a marginal bone level change ranging from 0.08 to 0.34 mm, whereas the MAP group exhibited a marginal bone level change ranging from 0.09 to 0.55 mm. Meta-analysis of the seven studies reporting on 396 implants showed significantly greater bone loss in cases of multiple abutment disconnections/reconnections. The weighted mean difference in marginal bone loss was 0.19 mm (95% confidence interval, 0.06-0.32 mm), favoring bone preservation in the FAP group. Within the limitations of this meta-analysis, abutment disconnection and reconnection significantly affected peri-implant marginal bone levels. These findings pave the way for revisiting current restorative protocols at the restorative treatment planning stage to prevent incipient marginal bone loss.

ZIP4 silencing improves bone loss in pancreatic cancer

PubMed Central

Yang, Jingxuan; Ding, Hao; LeBrun, Drake; Ding, Kai; Houchen, Courtney W.; Postier, Russell G.; Ambrose, Catherine G.; Li, Zhaoshen; Bi, Xiaohong; Li, Min

2015-01-01

Metabolic bone disorders are associated with several types of human cancers. Pancreatic cancer patients usually suffer from severe nutrition deficiency, muscle wasting, and loss of bone mass. We have previously found that silencing of a zinc transporter ZIP4 prolongs the survival and reduces the severity of the cachexia in vivo. However, the role of ZIP4 in the pancreatic cancer related bone loss remains unknown. In this study we investigated the effect of ZIP4 knockdown on the bone structure, composition and mechanical properties of femurs in an orthotopic xenograft mouse model. Our data showed that silencing of ZIP4 resulted in increased bone tissue mineral density, decreased bone crystallinity and restoration of bone strength through the RANK/RANKL pathway. The results further support the impact of ZIP4 on the progression of pancreatic cancer, and suggest its potential significance as a therapeutic target for treating patients with such devastating disease and cancer related disorders. PMID:26305676

Diagnosis and treatment of common metabolic spinal disorders in the geriatric population.

PubMed

Eck, J C; Humphreys, S C

1998-12-01

Bone is constantly resorbed and remodeled throughout life. After approximately age 30, there is a net loss of bone mass. This places the geriatric population at an increased risk of pathologic bone disorders that can lead to fractures and deformity. In this paper, we review bone metabolism and remodeling and introduce the proper diagnostic techniques. The most common pathologic spinal disorders are introduced, with emphasis on presentation and treatment options. To prevent excessive bone loss, patients should be educated on proper nutrition (calcium and vitamin D requirements) and lifestyle (avoiding alcohol and cigarette smoking). Sex hormone and drug therapies are available to reduce bone loss. New bisphosphonates such as alendronate sodium (Fosamax) have been effective in increasing bone mass. Early diagnosis and proper treatment of pathologic bone disorders can reduce the incidence of fracture and allow the patient a more productive and comfortable life.

Predicting Bone Mechanical Properties of Cancellous Bone from DXA, MRI, and Fractal Dimensional Measurements

NASA Technical Reports Server (NTRS)

Harrigan, Timothy P.; Ambrose, Catherine G.; Hogan, Harry A.; Shackleford, Linda; Webster, Laurie; LeBlanc, Adrian; Lin, Chen; Evans, Harlan

1997-01-01

This project was aimed at making predictions of bone mechanical properties from non-invasive DXA and MRI measurements. Given the bone mechanical properties, stress calculations can be made to compare normal bone stresses to the stresses developed in exercise countermeasures against bone loss during space flight. These calculations in turn will be used to assess whether mechanical factors can explain bone loss in space. In this study we assessed the use of T2(sup *) MRI imaging, DXA, and fractal dimensional analysis to predict strength and stiffness in cancellous bone.

Association between alveolar bone loss and serum C-reactive protein levels in aggressive and chronic periodontitis patients

PubMed Central

Chopra, Rahul; Patil, Sudhir R.; Kalburgi, Nagaraj B.; Mathur, Shivani

2012-01-01

Background: C-reactive protein (CRP) is an acute phase reactant that is produced in response to diverse inflammatory stimuli, and is known predictor of cardiovascular disease risk. Aggressive and chronic periodontitis are two main forms of periodontal disease, which differ mainly in the method of disease progression. This study aims at determining and comparing the relative levels of serum CRP and alveolar bone loss in aggressive and chronic periodontitis patients. Materials and Methods: A total of 45 subjects, which were divided into 3 groups diagnosed as having generalized aggressive periodontitis (GAP), chronic generalized periodontitis (CGP) and non-periodontitis controls (NP), were selected for the study. Venous blood samples were collected for quantitative CRP analysis using Turbidimetric immunoassay. Alveolar bone loss (ABL) was measured at proximal sites of posterior teeth on a panoramic radiograph. The relationship between the mean ratio of ABL to root length and serum CRP levels was statistically analyzed using Student unpaired t-test, analysis of variance (ANOVA) and Pearson's correlation coefficient. Results: Mean CRP levels were significantly greater in both GAP (7.49±2.31 mg/l) and CGP (4.88±1.80 mg/l) groups as compared to NP (0.68±0.23 mg/l) with P value <0.0001. The mean value of ABL (%) was 31.58 in CGP group and 36.77 in the GAP group, the difference being statistically significant (P=0.0079). Correlation coefficient between CRP and ABL is 0.9310 in CGP, and 0.9252 in GAP, which indicates a positive correlation between both variables. Conclusion: Both forms of periodontitis are associated with increased systemic inflammatory response with aggressiveness of disease progression determining the degree of response. PMID:22628959

Association between alveolar bone loss and serum C-reactive protein levels in aggressive and chronic periodontitis patients.

PubMed

Chopra, Rahul; Patil, Sudhir R; Kalburgi, Nagaraj B; Mathur, Shivani

2012-01-01

C-reactive protein (CRP) is an acute phase reactant that is produced in response to diverse inflammatory stimuli, and is known predictor of cardiovascular disease risk. Aggressive and chronic periodontitis are two main forms of periodontal disease, which differ mainly in the method of disease progression. This study aims at determining and comparing the relative levels of serum CRP and alveolar bone loss in aggressive and chronic periodontitis patients. A total of 45 subjects, which were divided into 3 groups diagnosed as having generalized aggressive periodontitis (GAP), chronic generalized periodontitis (CGP) and non-periodontitis controls (NP), were selected for the study. Venous blood samples were collected for quantitative CRP analysis using Turbidimetric immunoassay. Alveolar bone loss (ABL) was measured at proximal sites of posterior teeth on a panoramic radiograph. The relationship between the mean ratio of ABL to root length and serum CRP levels was statistically analyzed using Student unpaired t-test, analysis of variance (ANOVA) and Pearson's correlation coefficient. Mean CRP levels were significantly greater in both GAP (7.49±2.31 mg/l) and CGP (4.88±1.80 mg/l) groups as compared to NP (0.68±0.23 mg/l) with P value <0.0001. The mean value of ABL (%) was 31.58 in CGP group and 36.77 in the GAP group, the difference being statistically significant (P=0.0079). Correlation coefficient between CRP and ABL is 0.9310 in CGP, and 0.9252 in GAP, which indicates a positive correlation between both variables. Both forms of periodontitis are associated with increased systemic inflammatory response with aggressiveness of disease progression determining the degree of response.

Correlation between clinical parameters characterising peri-implant and periodontal health: A practice-based research in Spain in a series of patients with implants installed 4-5 years ago

PubMed Central

Lopez-Piriz, Roberto; Giménez, Maria J.; Bowen, Antonio; Carroquino, Rafael; Aguilar, Lorenzo; Corral, Ignacio; del Val, Cora; González, Inmaculada; Ilzarbe, Luis M.; Maestre, Juan R.; Padullés, Esteban; Torres-Lear, Francisco; Granizo, Juan J.; San-Román, Fide; Hernández, Sofía; Prieto, José

2012-01-01

Objectives: To explore periimplant health (and relation with periodontal status) 4-5 years after implant insertion. Study Design: A practice-based dental research network multicentre study was performed in 11 Spanish centres. The first patient/month with implant insertion in 2004 was considered. Per patient four teeth (one per quadrant) showing the highest bone loss in the 2004 panoramic X-ray were selected for periodontal status assessment. Bone losses in implants were calculated as the differences between 2004 and 2009 bone levels in radiographs. Results: A total of 117 patients were included. Of the 408 teeth considered, 73 (17.9%) were lost in 2009 (losing risk: >50% for bone losses ≥7mm). A total of 295 implants were reviewed. Eight of 117 (6.8%) patients had lost implants (13 of 295 implants installed; 4.4%). Implant loss rate (quadrant status) was 1.4% (edentulous), 3.6% (preserved teeth), and 11.1% (lost teeth) (p=0.037). The percentage of implant loss significantly (p<0.001) increased when the medial/distal bone loss was ≥3 mm. The highest (p≤0.001) pocket depths were found in teeth with ≥5mm and implants with ≥3mm bone losses, with similar mean values (≥4mm), associated with higher rates of plaque index and bleeding by probing. Conclusions: The significant bi-directional relation between plaque and bone loss, and between each of these two parameters/signs and pocket depths or bleeding (both in teeth and implants, and between them) together with the higher percentage of implants lost when the bone loss of the associated teeth was ≥3 mm suggest that the patient’s periodontal status is a critical issue in predicting implant health/lesion. Key words:Implants, periimplantitis, periodontitis, oral health, practice-based research PMID:22549681

Supportive periodontal therapy and periodontal biotype as prognostic factors in implants placed in patients with a history of periodontitis.

PubMed

Aguirre-Zorzano, Luis-Antonio; Vallejo-Aisa, Francisco-Javier; Estefanía-Fresco, Ruth

2013-09-01

To evaluate bone loss around implants placed in patients with a history of treated chronic periodontitis and who did or did not attend supportive periodontal therapy, after one year in function. Furthermore, the influence of periodontal biotype and level of plaque was also evaluated. Forty-nine patients participated voluntarily in the study. All subjects had a history of chronic periodontitis, which had been previously treated. After the active treatment, 27 patients attended supportive periodontal therapy (SPT) and the rest did not (No SPT). The O'Leary plaque index and periodontal biotype were recorded for each subject and 246 Astra Tech® OsseospeedTM implants were radiographically analysed (123 placed in SPT patients and 123 in No SPT patients) at the time of loading and one year later, measuring marginal bone loss with the program Dental Studio NX 6.0®. The statistical analysis was performed with Windows SPSS, applying Pearson's correlation index and the Kruskal-Wallis and U-Mann Whitney non-parametric tests. Six patients were found to have periimplantitis and sixteen mucositis. The survival rate was 99.59% (100% SPT and 99.18% No SPT). Mean bone loss was 0.39 mm (range [-0.71 - 8.05]). Among SPT patients, 95% of the implants had losses less than or equal to the mean (mean bone loss of 0.16 mm) compared to 53.7% for the No SPT group (mean bone loss of 0.62 mm). A statistically significant relationship was demonstrated between bone loss around the implant and the patient's periodontal biotype and plaque index. The marginal bone loss around implants in patients with treated chronic periodontitis is minimal if they are in a controlled SPT programme and there is individual control of plaque index. Moreover, the presence of a thin periodontal biotype represents a risk factor for additional bone loss.

Mechanical Loading Attenuates Radiation-Induced Bone Loss in Bone Marrow Transplanted Mice.

PubMed

Govey, Peter M; Zhang, Yue; Donahue, Henry J

2016-01-01

Exposure of bone to ionizing radiation, as occurs during radiotherapy for some localized malignancies and blood or bone marrow cancers, as well as during space travel, incites dose-dependent bone morbidity and increased fracture risk. Rapid trabecular and endosteal bone loss reflects acutely increased osteoclastic resorption as well as decreased bone formation due to depletion of osteoprogenitors. Because of this dysregulation of bone turnover, bone's capacity to respond to a mechanical loading stimulus in the aftermath of irradiation is unknown. We employed a mouse model of total body irradiation and bone marrow transplantation simulating treatment of hematologic cancers, hypothesizing that compression loading would attenuate bone loss. Furthermore, we hypothesized that loading would upregulate donor cell presence in loaded tibias due to increased engraftment and proliferation. We lethally irradiated 16 female C57Bl/6J mice at age 16 wks with 10.75 Gy, then IV-injected 20 million GFP(+) total bone marrow cells. That same day, we initiated 3 wks compression loading (1200 cycles 5x/wk, 10 N) in the right tibia of 10 of these mice while 6 mice were irradiated, non-mechanically-loaded controls. As anticipated, before-and-after microCT scans demonstrated loss of trabecular bone (-48.2% Tb.BV/TV) and cortical thickness (-8.3%) at 3 wks following irradiation. However, loaded bones lost 31% less Tb.BV/TV and 8% less cortical thickness (both p<0.001). Loaded bones also had significant increases in trabecular thickness and tissue mineral densities from baseline. Mechanical loading did not affect donor cell engraftment. Importantly, these results demonstrate that both cortical and trabecular bone exposed to high-dose therapeutic radiation remain capable of an anabolic response to mechanical loading. These findings inform our management of bone health in cases of radiation exposure.

Evolutionary medicine and bone loss in chronic inflammatory diseases--A theory of inflammation-related osteopenia.

PubMed

Straub, Rainer H; Cutolo, Maurizio; Pacifici, Roberto

2015-10-01

Bone loss is typical in chronic inflammatory diseases such as rheumatoid arthritis, psoriasis, ankylosing spondylitis, systemic lupus erythematosus, multiple sclerosis, inflammatory bowel diseases, pemphigus vulgaris, and others. It is also typical in transplantation-related inflammation and during the process of aging. While we recognized that bone loss is tightly linked to immune system activation or inflamm-aging in the form of acute, chronic active, or chronic smoldering inflammation, bone loss is typically discussed to be an "accident of inflammation." Extensive literature search in PubMed central. Using elements of evolutionary medicine, energy regulation, and neuroendocrine regulation of homeostasis and immune function, we work out that bone waste is an adaptive, evolutionarily positively selected program that is absolutely necessary during acute inflammation. However, when acute inflammation enters a chronic state due to the inability to terminate inflammation (e.g., in autoimmunity or in continuous immunity against microbes), the acute program of bone loss is a misguided adaptive program. The article highlights the complexity of interwoven pathways of osteopenia. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Evolutionary medicine and bone loss in chronic inflammatory diseases – a theory of inflammation-related osteopenia

PubMed Central

Straub, Rainer H.; Cutolo, Maurizio; Pacifici, Roberto

2015-01-01

Objective Bone loss is typical in chronic inflammatory diseases such as rheumatoid arthritis, psoriasis, ankylosing spondylitis, systemic lupus erythematosus, multiple sclerosis, inflammatory bowel diseases, pemphigus vulgaris, and others. It is also typical in transplantation-related inflammation and during the process of aging. While we recognized that bone loss is tightly linked to immune system activation or inflammaging in the form of acute, chronic active, or chronic smoldering inflammation, bone loss is typically discussed to be an “accident of inflammation”. Methods Extensive literature search in PubMed central. Results Using elements of evolutionary medicine, energy regulation, and neuroendocrine regulation of homeostasis and immune function, we work out that bone waste is an adaptive, evolutionarily positively selected program that is absolutely necessary during acute inflammation. However, when acute inflammation enters a chronic state due to the inability to terminate inflammation (e.g., in autoimmunity or in continuous immunity against microbes), the acute program of bone loss is a misguided adaptive program. Conclusions The article highlights the complexity of interwoven pathways of osteopenia. PMID:26044543

iss051e034105

NASA Image and Video Library

2017-05-02

iss051e034105 (May 2, 2017) --- Commander Peggy Whitson is working on the OsteoOmics bone cell study that utilizes the Microgravity Science Glovebox inside the U.S. Destiny laboratory. OsteoOmics investigates the molecular mechanisms that dictate bone loss in microgravity by examining osteoblasts, which form bone, and osteoclasts, which dissolves bone. This leads to better preventative care or therapeutic treatments for people suffering bone loss as a result of bone diseases like osteopenia and osteoporosis, or for patients on prolonged bed rest.

Spaceflight-induced Bone Loss: Is there a Risk for Accelerated Osteoporosis after Return?

NASA Technical Reports Server (NTRS)

Sibonga, Jean

2008-01-01

The evidence-to to-date suggests that the rapid rate of site-specific bone loss in space, due to the unbalanced stimulation of bone resorption, may predispose crew members to irreversible changes in bone structure and microarchitecture. No analyses conducted in the postflight period to assess microarchitectural changes. There is no complete analysis of skeletal recovery in the postflight period to evaluate the structural changes that accompany increases in DXA aBMD. Postflight analyses based upon QCT scans performed on limited crew members indicate reductions in hip bone strength and incomplete recovery at 1 year. No recovery of trabecular vBMD after 1 year return (HRP IWG). Time course of bone loss in space unknown.

Internal bone transport using a cannulated screw as a mounting device in the treatment of a post-infective ulnar defect.

PubMed

Tsitskaris, Konstantinos; Havard, Heledd; Bijlsma, Paulien; Hill, Robert A

2016-04-01

Bone transport techniques can be used to address the segmental bone loss occurring after debridement for infection. Secure fixation of the bone transport construct to the bone transport segment can be challenging, particularly if the bone is small and osteopenic. We report a case of a segmental ulnar bone defect in a young child treated with internal bone transport using a cannulated screw as the mounting device. We found this technique particularly useful in the treatment of bone loss secondary to infection, where previous treatment and prolonged immobilisation had led to osteopenia. This technique has not been previously reported.

Qualitative and quantitative evaluation of avian demineralized bone matrix in heterotopic beds.

PubMed

Reza Sanaei, M; Abu, Jalila; Nazari, Mojgan; A B, Mohd Zuki; Allaudin, Zeenathul N

2013-11-01

To evaluate the osteogenic potential of avian demineralized bone matrix (DBM) in the context of implant geometry. Experimental. Rock pigeons (n = 24). Tubular and chipped forms of DBM were prepared by acid demineralization of long bones from healthy allogeneic donors and implanted bilaterally into the pectoral region of 24 pigeons. After euthanasia at 1, 4, 6, 8, 10, and 12 weeks, explants were evaluated histologically and compared by means of quantitative (bone area) and semi quantitative measures (scores). All explants had new bone at retrieval with the exception of tubular implants at the end of week 1. The most reactive part in both implants was the interior region between the periosteal and endosteal surfaces followed by the area at the implant-muscle interface. Quantitative measurements demonstrated a significantly (P = .012) greater percentage of new bone formation induced by tubular implants (80.28 ± 8.94) compared with chip implants (57.64 ± 3.12). There was minimal inflammation. Avian DBM initiates heterotopic bone formation in allogeneic recipients with low grades of immunogenicity. Implant geometry affects this phenomenon as osteoconduction appeared to augment the magnitude of the effects in larger tubular implants. © Copyright 2013 by The American College of Veterinary Surgeons.

Effect of avocado/soybean unsaponifiables on ligature-induced bone loss and bone repair after ligature removal in rats.

PubMed

Oliveira, G J P L; Paula, L G F; Souza, J A C; Spin-Neto, R; Stavropoulos, A; Marcantonio, R A C

2016-06-01

The aim of this study was to evaluate the effects of administration of avocado/soybean unsaponifiable (ASU), a drug that is commonly used in the treatment of rheumatoid arthritis, on ligature-induced bone loss and bone repair after ligature removal in rats. Eighty-four rats were randomly assigned to four groups of equal size and received a daily gavage of either sterile saline [control (CTR)] or ASU (0.6 mg/kg), starting 7 d before (ASU/-7), on the day of (ASU/0) or 7 d after (ASU/+7) periodontitis induction. Periodontitis was induced by placing silk ligatures into the gingival sulcus of the second maxillary molars for 7 d; after 7 d, the ligatures were removed. Seven rats from each group were sacrificed, 7, 15 or 30 d after ligature removal. Bone resorption was evaluated by histomorphometry and micro-computed tomography (micro-CT). Immunohistochemistry was used to evaluate the expression of TRAP, RANKL and alkaline phosphatase (ALP), and quantitative PCR (qPCR) was used to evaluate the levels of interleukin-1beta (Il1β), tumor necrosis factor alpha (Tnfα), interleukin-6 (Il-6), Rankl and Alp. Statistical analysis was performed using the Shapiro-Wilk test, ANOVA and Tukey's test for normal data, and using the Kruskall-Wallis and Dunnet's tests for non-normal data (p < 0.05). Histomorphometry and micro-CT analysis showed greater bone resorption in the CTR group than in the ASU/0 (15 d) and ASU/+7 (7 and 15 d) groups. The CTR group also presented with a higher expression of TRAP (15 and 30 d) and RANKL (7 and 15 d) compared with ASU/0 and ASU/+7 groups. Similarly, qPCR analysis showed higher levels of Rankl and Il1β mRNAs, and lower levels of Alp mRNA, in the CTR group compared with all other groups (for all periods). ASU exhibited a positive effect on bone repair following ligature-induced periodontitis in rats. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Bisphosphonate ISS Flight Experiment

NASA Technical Reports Server (NTRS)

LeBlanc, Adrian; Matsumoto, Toshio; Jones, Jeffrey; Shapiro, Jay; Lang, Thomas; Shackleford, Linda; Smith, Scott M.; Evans, Harlan; Spector, Elizabeth; Ploutz-Snyder, Robert;

Aging of marrow stromal (skeletal) stem cells and their contribution to age-related bone loss.

PubMed

Bellantuono, Ilaria; Aldahmash, Abdullah; Kassem, Moustapha

2009-04-01

Marrow stromal cells (MSC) are thought to be stem cells with osteogenic potential and therefore responsible for the repair and maintenance of the skeleton. Age related bone loss is one of the most prevalent diseases in the elder population. It is controversial whether MSC undergo a process of aging in vivo, leading to decreased ability to form and maintain bone homeostasis with age. In this review we summarize evidence of MSC involvement in age related bone loss and suggest new emerging targets for intervention.

Recommendations for the standardization of bone marrow disease assessment and reporting in children with neuroblastoma on behalf of the International Neuroblastoma Response Criteria Bone Marrow Working Group.

PubMed

Burchill, Susan A; Beiske, Klaus; Shimada, Hiroyuki; Ambros, Peter F; Seeger, Robert; Tytgat, Godelieve A M; Brock, Penelope R; Haber, Michelle; Park, Julie R; Berthold, Frank

2017-04-01

The current study was conducted to expedite international standardized reporting of bone marrow disease in children with neuroblastoma and to improve equivalence of care. A multidisciplinary International Neuroblastoma Response Criteria Bone Marrow Working Group was convened by the US National Cancer Institute in January 2012 with representation from Europe, North America, and Australia. Practical transferable recommendations to standardize the reporting of bone marrow disease were developed. To the authors' knowledge, the current study is the first to comprehensively present consensus criteria for the collection, analysis, and reporting of the percentage area of bone marrow parenchyma occupied by tumor cells in trephine-biopsies. The quantitative analysis of neuroblastoma content in bone marrow aspirates by immunocytology and reverse transcriptase-quantitative polymerase chain reaction are revised. The inclusion of paired-like homeobox 2b (PHOX2B) for immunohistochemistry and reverse transcriptase-quantitative polymerase chain reaction is recommended. Recommendations for recording bone marrow response are provided. The authors endorse the quantitative assessment of neuroblastoma cell content in bilateral core needle biopsies-trephines and aspirates in all children with neuroblastoma, with the exception of infants, in whom the evaluation of aspirates alone is advised. It is interesting to note that 5% disease is accepted as an internationally achievable level for disease assessment. The quantitative assessment of neuroblastoma cells is recommended to provide data from which evidence-based numerical criteria for the reporting of bone marrow response can be realized. This is particularly important in the minimal disease setting and when neuroblastoma detection in bone marrow is intermittent, where clinical impact has yet to be validated. The wide adoption of these harmonized criteria will enhance the ability to compare outcomes from different trials and facilitate collaborative trial design. Cancer 2017;123:1095-1105. © 2016 American Cancer Society. © 2016 American Cancer Society.

Inhibition of bone loss with surface-modulated, drug-loaded nanoparticles in an intraosseous model of prostate cancer.

PubMed

Adjei, Isaac M; Sharma, Blanka; Peetla, Chiranjeevi; Labhasetwar, Vinod

2016-06-28

Advanced-stage prostate cancer usually metastasizes to bone and is untreatable due to poor biodistribution of intravenously administered anticancer drugs to bone. In this study, we modulated the surface charge/composition of biodegradable nanoparticles (NPs) to sustain their blood circulation time and made them small enough to extravasate through the openings of the bone's sinusoidal capillaries and thus localize into marrow. NPs with a neutral surface charge, achieved by modulating the NP surface-associated emulsifier composition, were more effective at localizing to bone marrow than NPs with a cationic or anionic surface charge. These small neutral NPs (~150nm vs. the more usual ~320nm) were also ~7-fold more effective in localizing in bone marrow than large NPs. We hypothesized that NPs that effectively localize to marrow could improve NP-mediated anticancer drug delivery to sites of bone metastasis, thereby inhibiting cancer progression and preventing bone loss. In a PC-3M-luc cell-induced osteolytic intraosseous model of prostate cancer, these small neutral NPs demonstrated greater accumulation in bone within metastatic sites than in normal contralateral bone as well as co-localization with the tumor mass in marrow. Significantly, a single-dose intravenous administration of these small neutral NPs loaded with paclitaxel (PTX-NPs), but not anionic PTX-NPs, slowed the progression of bone metastasis. In addition, neutral PTX-NPs prevented bone loss, whereas animals treated with the rapid-release drug formulation Cremophor EL (PTX-CrEL) or saline (control) showed >50% bone loss. Neutral PTX-NPs did not cause acute toxicity, whereas animals treated with PTX-CrEL experienced weight loss. These results indicate that NPs with appropriate physical and sustained drug-release characteristics could be explored to treat bone metastasis, a significant clinical issue in prostate and other cancers. Copyright © 2016 Elsevier B.V. All rights reserved.

Probiotics Protect Mice from Ovariectomy-Induced Cortical Bone Loss

PubMed Central

Ohlsson, Claes; Engdahl, Cecilia; Fåk, Frida; Andersson, Annica; Windahl, Sara H.; Farman, Helen H.; Movérare-Skrtic, Sofia; Islander, Ulrika; Sjögren, Klara

2014-01-01

The gut microbiota (GM) modulates the hosts metabolism and immune system. Probiotic bacteria are defined as live microorganisms which when administered in adequate amounts confer a health benefit on the host and can alter the composition of the GM. Germ-free mice have increased bone mass associated with reduced bone resorption indicating that the GM also regulates bone mass. Ovariectomy (ovx) results in bone loss associated with altered immune status. The purpose of this study was to determine if probiotic treatment protects mice from ovx-induced bone loss. Mice were treated with either a single Lactobacillus (L) strain, L. paracasei DSM13434 (L. para) or a mixture of three strains, L. paracasei DSM13434, L. plantarum DSM 15312 and DSM 15313 (L. mix) given in the drinking water during 6 weeks, starting two weeks before ovx. Both the L. para and the L. mix treatment protected mice from ovx-induced cortical bone loss and bone resorption. Cortical bone mineral content was higher in both L. para and L. mix treated ovx mice compared to vehicle (veh) treated ovx mice. Serum levels of the resorption marker C-terminal telopeptides and the urinary fractional excretion of calcium were increased by ovx in the veh treated but not in the L. para or the L. mix treated mice. Probiotic treatment reduced the expression of the two inflammatory cytokines, TNFα and IL-1β, and increased the expression of OPG, a potent inhibitor of osteoclastogenesis, in cortical bone of ovx mice. In addition, ovx decreased the frequency of regulatory T cells in bone marrow of veh treated but not probiotic treated mice. In conclusion, treatment with L. para or the L. mix prevents ovx-induced cortical bone loss. Our findings indicate that these probiotic treatments alter the immune status in bone resulting in attenuated bone resorption in ovx mice. PMID:24637895

Probiotics protect mice from ovariectomy-induced cortical bone loss.

PubMed

Ohlsson, Claes; Engdahl, Cecilia; Fåk, Frida; Andersson, Annica; Windahl, Sara H; Farman, Helen H; Movérare-Skrtic, Sofia; Islander, Ulrika; Sjögren, Klara

2014-01-01

The gut microbiota (GM) modulates the hosts metabolism and immune system. Probiotic bacteria are defined as live microorganisms which when administered in adequate amounts confer a health benefit on the host and can alter the composition of the GM. Germ-free mice have increased bone mass associated with reduced bone resorption indicating that the GM also regulates bone mass. Ovariectomy (ovx) results in bone loss associated with altered immune status. The purpose of this study was to determine if probiotic treatment protects mice from ovx-induced bone loss. Mice were treated with either a single Lactobacillus (L) strain, L. paracasei DSM13434 (L. para) or a mixture of three strains, L. paracasei DSM13434, L. plantarum DSM 15312 and DSM 15313 (L. mix) given in the drinking water during 6 weeks, starting two weeks before ovx. Both the L. para and the L. mix treatment protected mice from ovx-induced cortical bone loss and bone resorption. Cortical bone mineral content was higher in both L. para and L. mix treated ovx mice compared to vehicle (veh) treated ovx mice. Serum levels of the resorption marker C-terminal telopeptides and the urinary fractional excretion of calcium were increased by ovx in the veh treated but not in the L. para or the L. mix treated mice. Probiotic treatment reduced the expression of the two inflammatory cytokines, TNFα and IL-1β, and increased the expression of OPG, a potent inhibitor of osteoclastogenesis, in cortical bone of ovx mice. In addition, ovx decreased the frequency of regulatory T cells in bone marrow of veh treated but not probiotic treated mice. In conclusion, treatment with L. para or the L. mix prevents ovx-induced cortical bone loss. Our findings indicate that these probiotic treatments alter the immune status in bone resulting in attenuated bone resorption in ovx mice.

Mechanical Loading Attenuates Radiation-Induced Bone Loss in Bone Marrow Transplanted Mice

PubMed Central

Govey, Peter M.; Zhang, Yue; Donahue, Henry J.

2016-01-01

Exposure of bone to ionizing radiation, as occurs during radiotherapy for some localized malignancies and blood or bone marrow cancers, as well as during space travel, incites dose-dependent bone morbidity and increased fracture risk. Rapid trabecular and endosteal bone loss reflects acutely increased osteoclastic resorption as well as decreased bone formation due to depletion of osteoprogenitors. Because of this dysregulation of bone turnover, bone’s capacity to respond to a mechanical loading stimulus in the aftermath of irradiation is unknown. We employed a mouse model of total body irradiation and bone marrow transplantation simulating treatment of hematologic cancers, hypothesizing that compression loading would attenuate bone loss. Furthermore, we hypothesized that loading would upregulate donor cell presence in loaded tibias due to increased engraftment and proliferation. We lethally irradiated 16 female C57Bl/6J mice at age 16 wks with 10.75 Gy, then IV-injected 20 million GFP(+) total bone marrow cells. That same day, we initiated 3 wks compression loading (1200 cycles 5x/wk, 10 N) in the right tibia of 10 of these mice while 6 mice were irradiated, non-mechanically-loaded controls. As anticipated, before-and-after microCT scans demonstrated loss of trabecular bone (-48.2% Tb.BV/TV) and cortical thickness (-8.3%) at 3 wks following irradiation. However, loaded bones lost 31% less Tb.BV/TV and 8% less cortical thickness (both p<0.001). Loaded bones also had significant increases in trabecular thickness and tissue mineral densities from baseline. Mechanical loading did not affect donor cell engraftment. Importantly, these results demonstrate that both cortical and trabecular bone exposed to high-dose therapeutic radiation remain capable of an anabolic response to mechanical loading. These findings inform our management of bone health in cases of radiation exposure. PMID:27936104

NADPH oxidase 4 limits bone mass by promoting osteoclastogenesis

PubMed Central

Goettsch, Claudia; Babelova, Andrea; Trummer, Olivia; Erben, Reinhold G.; Rauner, Martina; Rammelt, Stefan; Weissmann, Norbert; Weinberger, Valeska; Benkhoff, Sebastian; Kampschulte, Marian; Obermayer-Pietsch, Barbara; Hofbauer, Lorenz C.; Brandes, Ralf P.; Schröder, Katrin

2013-01-01

ROS are implicated in bone diseases. NADPH oxidase 4 (NOX4), a constitutively active enzymatic source of ROS, may contribute to the development of such disorders. Therefore, we studied the role of NOX4 in bone homeostasis. Nox4–/– mice displayed higher bone density and reduced numbers and markers of osteoclasts. Ex vivo, differentiation of monocytes into osteoclasts with RANKL and M-CSF induced Nox4 expression. Loss of NOX4 activity attenuated osteoclastogenesis, which was accompanied by impaired activation of RANKL-induced NFATc1 and c-JUN. In an in vivo model of murine ovariectomy–induced osteoporosis, pharmacological inhibition or acute genetic knockdown of Nox4 mitigated loss of trabecular bone. Human bone obtained from patients with increased osteoclast activity exhibited increased NOX4 expression. Moreover, a SNP of NOX4 was associated with elevated circulating markers of bone turnover and reduced bone density in women. Thus, NOX4 is involved in bone loss and represents a potential therapeutic target for the treatment of osteoporosis. PMID:24216508

Radiographic evaluation of marginal bone level around implants with different neck designs after 1 year.

PubMed

Shin, Young-Kyu; Han, Chong-Hyun; Heo, Seong-Joo; Kim, Sunjai; Chun, Heoung-Jae

2006-01-01

To evaluate the influence of macro- and microstructure of the implant surface at the marginal bone level after functional loading. Sixty-eight patients were randomly assigned to 1 of 3 groups. The first group received 35 implants with a machined neck (Ankylos); the second group, 34 implants with a rough-surfaced neck (Stage 1); and the third, 38 implants with a rough-surfaced neck with microthreads (Oneplant). Clinical and radiographic examinations were conducted at baseline (implant loading) and 3, 6, and 12 months postloading. Two-way repeated analysis of variance (ANOVA) was used to test the significance of marginal bone change of each tested group at baseline, 3, 6, and 12 month follow-ups and 1-way ANOVA was also used to compare the bone loss of each time interval within the same implant group (P < .05). At 12 months, significant differences were noted in the amount of alveolar bone loss recorded for the 3 groups (P < .05). The group with the rough-surfaced microthreaded neck had a mean crestal bone loss of 0.18 +/- 0.16 mm; the group with the rough-surfaced neck, 0.76 +/- 0.21 mm; and the group with the machined neck, 1.32 +/- 0.27 mm. In the rough-surfaced group and the rough-surfaced microthreaded group, no statistically significant changes were observed after 3 months, whereas the machined-surface group showed significant bone loss for every interval (P < .05). To minimize marginal bone loss, in addition to the use of a rough surface at the marginal bone level, a macroscopic modification such as the addition of microthreads could be recommended. A rough surface and microthreads at the implant neck not only reduce crestal bone loss but also help with early biomechanical adaptation against loading in comparison to the machined neck design. A rough surface with microthreads at the implant neck was the most effective design to maintain the marginal bone level against functional loading.

Differences in bone structure between rheumatoid arthritis and psoriatic arthritis patients relative to autoantibody positivity.

PubMed

Kocijan, Roland; Finzel, Stephanie; Englbrecht, Matthias; Engelke, Klaus; Rech, Juergen; Schett, Georg

2014-11-01

To investigate whether trabecular and cortical bone structure differ between patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA). So far, no study has performed a detailed comparative analysis of bone structure in patients with RA and PsA. 110 patients (60 RA, 50 PsA) received high-resolution peripheral quantitative CT of the distal radius. Demographic and disease-specific parameters including anti-rheumatic treatment, bone erosion status and previous fractures were recorded. RA and PsA patients were comparable in age, gender, body mass index, disease duration, disease activity, functional status, antirheumatic treatment and bone erosion status. No significant differences were found for volumetric bone mineral density (BMD), including total BMD (300±77 vs 316±62 mgHA/cm(3)), trabecular BMD (152±46 vs 165±40 mgHA/cm(3)) and cortical BMD (787±113 vs 818±76 mgHA/cm(3)) when comparing RA patients to PsA patients, respectively. However, in contrast to seronegative RA, seropositive RA showed significantly reduced trabecular BMD (p=0.007), bone volume per tissue volume (p=0.007) and trabecular number (p=0.044), as well as a strong trend towards higher trabecular inhomogeneity compared to PsA patients. In the regression analysis, higher age, female gender and presence of autoantibodies were independently associated with trabecular bone loss. Seropositive RA exhibits more profound changes in trabecular bone architecture than seronegative RA or PsA. The data support the concept that seropositive RA is a disease entity that is distinct from seronegative RA and PsA. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Bone matrix, cellularity, and structural changes in a rat model with high-turnover osteoporosis induced by combined ovariectomy and a multiple-deficient diet.

PubMed

Govindarajan, Parameswari; Böcker, Wolfgang; El Khassawna, Thaqif; Kampschulte, Marian; Schlewitz, Gudrun; Huerter, Britta; Sommer, Ursula; Dürselen, Lutz; Ignatius, Anita; Bauer, Natali; Szalay, Gabor; Wenisch, Sabine; Lips, Katrin S; Schnettler, Reinhard; Langheinrich, Alexander; Heiss, Christian

2014-03-01

In estrogen-deficient, postmenopausal women, vitamin D and calcium deficiency increase osteoporotic fracture risk. Therefore, a new rat model of combined ovariectomy and multiple-deficient diet was established to mimic human postmenopausal osteoporotic conditions under nutrient deficiency. Sprague-Dawley rats were untreated (control), laparatomized (sham), or ovariectomized and received a deficient diet (OVX-Diet). Multiple analyses involving structure (micro-computed tomography and biomechanics), cellularity (osteoblasts and osteoclasts), bone matrix (mRNA expression and IHC), and mineralization were investigated for a detailed characterization of osteoporosis. The study involved long-term observation up to 14 months (M14) after laparotomy or after OVX-Diet, with intermediate time points at M3 and M12. OVX-Diet rats showed enhanced osteoblastogenesis and osteoclastogenesis. Bone matrix markers (biglycan, COL1A1, tenascin C, and fibronectin) and low-density lipoprotein-5 (bone mass marker) were down-regulated at M12 in OVX-Diet rats. However, up-regulation of matrix markers and existence of unmineralized osteoid were seen at M3 and M14. Osteoclast markers (matrix metallopeptidase 9 and cathepsin K) were up-regulated at M14. Micro-computed tomography and biomechanics confirmed bone fragility of OVX-Diet rats, and quantitative RT-PCR revealed a higher turnover rate in the humerus than in lumbar vertebrae, suggesting enhanced bone formation and resorption in OVX-Diet rats. Such bone remodeling caused disturbed bone mineralization and severe bone loss, as reported in patients with high-turnover, postmenopausal osteoporosis. Therefore, this rat model may serve as a suitable tool to evaluate osteoporotic drugs and new biomaterials or fracture implants. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Proandrogenic and Antiandrogenic Progestins in Transgender Youth: Differential Effects on Body Composition and Bone Metabolism.

PubMed

Tack, Lloyd J W; Craen, Margarita; Lapauw, Bruno; Goemaere, Stefan; Toye, Kaatje; Kaufman, Jean-Marc; Vandewalle, Sara; T'Sjoen, Guy; Zmierczak, Hans-Georg; Cools, Martine

2018-06-01

Progestins can be used to attenuate endogenous hormonal effects in late-pubertal transgender (trans) adolescents (Tanner stage B4/5 and G4/5). Currently, no data are available on the effects of progestins on the development of bone mass or body composition in trans youth. To study prospectively the evolution of body composition and bone mass in late-pubertal trans adolescents using the proandrogenic or antiandrogenic progestins lynestrenol (L) and cyproterone acetate (CA), respectively. Forty-four trans boys (Tanner B4/5) and 21 trans girls (Tanner G4/5) were treated with L or CA for 11.6 (4 to 40) and 10.6 (5 to 31) months, respectively. Anthropometry, grip strength, body composition, and bone mass, size, and density were determined by dual-energy X-ray absorptiometry and peripheral quantitative computed tomography before the start of progestin and before addition of cross-sex hormones. Using L, lean mass [+3.2 kg (8.6%)] and grip strength [+3 kg (10.6%)] significantly increased, which coincided with a more masculine body shape in trans boys. Trans girls showed loss of lean mass [-2.2 kg (4.7%)], gain of fat mass [+1.5 kg (9.4%)], and decreased grip strength Z scores. CA limited normal bone expansion and impeded pubertal bone mass accrual, mostly at the lumbar spine [Z score: -0.765 to -1.145 (P = 0.002)]. L did not affect physiological bone development. Proandrogenic and antiandrogenic progestins induce body composition changes in line with the desired appearance within 1 year of treatment. Bone health, especially at the lumbar spine, is of concern in trans girls, as bone mass accrual is severely affected by androgen suppressive therapy.

Hypochlorhydria-induced calcium malabsorption does not affect fracture healing but increases post-traumatic bone loss in the intact skeleton.

PubMed

Haffner-Luntzer, Melanie; Heilmann, Aline; Heidler, Verena; Liedert, Astrid; Schinke, Thorsten; Amling, Michael; Yorgan, Timur Alexander; Vom Scheidt, Annika; Ignatius, Anita

2016-11-01

Efficient calcium absorption is essential for skeletal health. Patients with impaired gastric acidification display low bone mass and increased fracture risk because calcium absorption is dependent on gastric pH. We investigated fracture healing and post-traumatic bone turnover in mice deficient in Cckbr, encoding a gastrin receptor that affects acid secretion by parietal cells. Cckbr-/- mice display hypochlorhydria, calcium malabsorption, and osteopenia. Cckbr-/- and wildtype (WT) mice received a femur osteotomy and were fed either a standard or calcium-enriched diet. Healed and intact bones were assessed by biomechanical testing, histomorphometry, micro-computed tomography, and quantitative backscattering. Parathyroid hormone (PTH) serum levels were determined by enzyme-linked immunosorbent assay. Fracture healing was unaffected in Cckbr-/- mice. However, Cckbr-/- mice displayed increased calcium mobilization from the intact skeleton during bone healing, confirmed by significantly elevated PTH levels and osteoclast numbers compared to WT mice. Calcium supplementation significantly reduced secondary hyperparathyroidism and bone resorption in the intact skeleton in both genotypes, but more efficiently in WT mice. Furthermore, calcium administration improved bone healing in WT mice, indicated by significantly increased mechanical properties and bone mineral density of the fracture callus, whereas it had no significant effect in Cckbr-/- mice. Therefore, under conditions of hypochlorhydria-induced calcium malabsorption, calcium, which is essential for callus mineralization, appears to be increasingly mobilized from the intact skeleton in favor of fracture healing. Calcium supplementation during fracture healing prevented systemic calcium mobilization, thereby maintaining bone mass and improving fracture healing in healthy individuals whereas the effect was limited by gastric hypochlorhydria. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1914-1921, 2016. © 2016 The Authors. Journal of Orthopaedic Research Published by by Wiley Periodicals, Inc.

Feasibility of Quantitative Ultrasound Measurement of the Heel Bone in People with Intellectual Disabilities

ERIC Educational Resources Information Center

Mergler, S.; Lobker, B.; Evenhuis, H. M.; Penning, C.

2010-01-01

Low bone mineral density (BMD) and fractures are common in people with intellectual disabilities (ID). Reduced mobility in case of motor impairment and the use of anti-epileptic drugs contribute to the development of low BMD. Quantitative ultrasound (QUS) measurement of the heel bone is a non-invasive and radiation-free method for measuring bone…

Bisphosphonates as a Countermeasure to Space Flight Induced Bone Loss

NASA Technical Reports Server (NTRS)

LeBlanc, Adrian; Matsumoto, Toshio; Jones, Jeffrey A.; Shapiro, Jay; Lang, Thomas F.; Smith, Scott M.; Shackelford, Linda C.; Sibonga, Jean; Evans, Harlan; Spector, Elisabeth;

Alendronate increases skeletal mass of growing rats during unloading by inhibiting resorption of calcified cartilage

NASA Technical Reports Server (NTRS)

Bikle, D. D.; Morey-Holton, E. R.; Doty, S. B.; Currier, P. A.; Tanner, S. J.; Halloran, B. P.

1994-01-01

Loss of bone mass during periods of skeletal unloading remains an important clinical problem. To determine the extent to which resorption contributes to the relative loss of bone during skeletal unloading of the growing rat and to explore potential means of preventing such bone loss, 0.1 mg P/kg alendronate was administered to rats before unloading of the hindquarters. Skeletal unloading markedly reduced the normal increase in tibial mass and calcium content during the 9 day period of observation, primarily by decreasing bone formation, although bone resorption was also modestly stimulated. Alendronate not only prevented the relative loss of skeletal mass during unloading but led to a dramatic increase in calcified tissue in the proximal tibia compared with the vehicle-treated unloaded or normally loaded controls. Bone formation, however, assessed both by tetracycline labeling and by [3H]proline and 45Ca incorporation, was suppressed by alendronate treatment and further decreased by skeletal unloading. Total osteoclast number increased in alendronate-treated animals, but values were similar to those in controls when corrected for the increased bone area. However, the osteoclasts had poorly developed brush borders and appeared not to engage the bone surface when examined at the ultrastructural level. We conclude that alendronate prevents the relative loss of mineralized tissue in growing rats subjected to skeletal unloading, but it does so primarily by inhibiting the resorption of the primary and secondary spongiosa, leading to altered bone modeling in the metaphysis.

Identification of Hip BMD Loss and Fracture Risk Markers Through Population-Based Serum Proteomics: HIP BMD LOSS & FRACTURE RISK MARKERS BY POPULATION-BASED SERUM PROTEOMICS

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

Nielson, Carrie M.; Wiedrick, Jack; Shen, Jian

Accelerated bone loss significantly increases the risk of osteoporosis and fracture. The mechanisms underlying bone loss remain incompletely understood, and there are few available biomarkers. We utilized a novel proteomics approach to identify serum peptides and proteins associated with bone loss in 1967 older men who were randomly chosen from the Osteoporotic Fracture in Men Study (MrOS study) (age ≥ 65 yrs). Men had 2-3 measures of femoral neck BMD over an average follow-up of 4.6 years. Change in BMD was estimated and then categorized into three groups: maintained BMD (n=453), expected loss (n=1185) and accelerated loss (n=237). A liquidmore » chromatography–ion mobility separation-mass spectrometry (LC-IMS-MS) proteomics platform was used to identify and quantify peptides from serum proteins. The whole cohort was randomly divided into discovery (N= 960) and validation (N= 915) sub-cohorts. Linear regression models and a random forest approach were used to discover differentially abundant individual peptides and a proteomic signature that distinguished individuals with accelerated bone loss from those who maintained BMD. Network analyses were performed using the MetaCore knowledgebase. We identified 12 peptides that were associated with BMD loss in both discovery (P< 0.1 FDR) and replication sub-cohorts (P<0.05). Those 12 peptides mapped to the following proteins: ALS, LYVE1, RNAS1, C2, ICOSL, C163A, C7, HEMO, CD14, CERU, CRAC1 and CD59. Meta-analysis of peptidesassociated with bone loss identified 6 additional proteins including GRP78, IGF-2, SHBG, ENPP2, IBP2 and IBP6. We also identified a proteomic signature that was predictive of BMD loss with a discriminative value similar to serum bone marker carboxy-terminal collagen crosslink peptide (CTX). Interestingly, combining the proteomic signature with CTX significantly improved the ability to discriminate men with accelerated loss. In summary, we have identified potential new biomarkers for bone loss that provide a more in depth understanding of its pathophysiology.« less

Cancer treatment-induced bone loss in premenopausal women: a need for therapeutic intervention?

PubMed

Hadji, P; Gnant, M; Body, J J; Bundred, N J; Brufsky, A; Coleman, R E; Guise, T A; Lipton, A; Aapro, M S

2012-10-01

Current clinical treatment guidelines recommend cytotoxic chemotherapy, endocrine therapy, or both (with targeted therapy if indicated) for premenopausal women with early-stage breast cancer, depending on the biologic characteristics of the primary tumor. Some of these therapies can induce premature menopause or are specifically designed to suppress ovarian function and reduce circulating estrogen levels. In addition to bone loss associated with low estrogen levels, cytotoxic chemotherapy may have a direct negative effect on bone metabolism. As a result, cancer treatment-induced bone loss poses a significant threat to bone health in premenopausal women with breast cancer. Clinical trials of antiresorptive therapies, such as bisphosphonates, have demonstrated the ability to slow or prevent bone loss in this setting. Current fracture risk assessment tools are based on data from healthy postmenopausal women and do not adequately address the risks associated with breast cancer therapy, especially in younger premenopausal women. We therefore recommend that all premenopausal women with breast cancer be informed about the potential risk of bone loss prior to beginning anticancer therapy. Women who experience amenorrhea should have bone mineral density assessed by dual-energy X-ray absorptiometry and receive regular follow-up to monitor bone health. Regular exercise and daily calcium and vitamin D supplementation are recommended. Women with a Z-score <-2.0 or Z-score ≤-1.0 and/or a 5-10% annual decrease in bone mineral density should be considered for bisphosphonate therapy in addition to calcium and vitamin D supplements. Copyright © 2012 Elsevier Ltd. All rights reserved.

Transplantation of Hepatocyte Growth Factor-Modified Dental Pulp Stem Cells Prevents Bone Loss in the Early Phase of Ovariectomy-Induced Osteoporosis.

PubMed

Kong, Fanxuan; Shi, Xuefeng; Xiao, Fengjun; Yang, Yuefeng; Zhang, Xiaoyan; Wang, Li-Sheng; Wu, Chu-Tse; Wang, Hua

2018-02-01

Investigations based on mesenchymal stem cells (MSCs) for osteoporosis have attracted attention recently. MSCs can be derived from various tissues, such as bone marrow, adipose, umbilical cord, placenta, and dental pulp. Among these, dental pulp-derived MSCs (DPSCs) and hepatocyte growth factor (HGF)-modified DPSCs (DPSCs-HGF) highly express osteogenic-related genes and have stronger osteogenic differentiation capacities. DPSCs have more benefits in treating osteoporosis. The purpose of this study was to investigate the roles of HGF gene-modified DPSCs in bone regeneration using a mouse model of ovariectomy (OVX)-induced bone loss. The HGF and luciferase genes were transferred into human DPSCs using recombinant adenovirus. These transduced cells were assayed for distribution or bone regeneration assay by transplantation into an OVX-induced osteoporosis model. By using bioluminogenic imaging, it was determined that some DPSCs could survive for >1 month in vivo. The DPSCs were mainly distributed to the lung in the early stage and to the liver in the late stage of OVX osteoporosis after administration, but they were scarcely distributed to the bone. The homing efficiency of DPSCs is higher when administrated in the early stage of a mouse OVX model. Micro-computed tomography indicated that DPSCs-Null or DPSCs-HGF transplantation significantly reduces OVX-induced bone loss in the trabecular bone of the distal femur metaphysis, and DPSCs-HGF show a stronger capacity to reduce bone loss. The data suggest that systemic infusion of DPSCs-HGF is a potential therapeutic approach for OVX-induced bone loss, which might be mediated by paracrine mechanisms.

MicroRNA-188 regulates age-related switch between osteoblast and adipocyte differentiation

PubMed Central

Li, Chang-Jun; Cheng, Peng; Liang, Meng-Ke; Chen, Yu-Si; Lu, Qiong; Wang, Jin-Yu; Xia, Zhu-Ying; Zhou, Hou-De; Cao, Xu; Xie, Hui; Liao, Er-Yuan; Luo, Xiang-Hang

2015-01-01

Bone marrow mesenchymal stem cells (BMSCs) exhibit an age-dependent reduction in osteogenesis that is accompanied by an increased propensity toward adipocyte differentiation. This switch increases adipocyte numbers and decreases the number of osteoblasts, contributing to age-related bone loss. Here, we found that the level of microRNA-188 (miR-188) is markedly higher in BMSCs from aged compared with young mice and humans. Compared with control mice, animals lacking miR-188 showed a substantial reduction of age-associated bone loss and fat accumulation in bone marrow. Conversely, mice with transgenic overexpression of miR-188 in osterix+ osteoprogenitors had greater age-associated bone loss and fat accumulation in bone marrow relative to WT mice. Moreover, using an aptamer delivery system, we found that BMSC-specific overexpression of miR-188 in mice reduced bone formation and increased bone marrow fat accumulation. We identified histone deacetylase 9 (HDAC9) and RPTOR-independent companion of MTOR complex 2 (RICTOR) as the direct targets of miR-188. Notably, BMSC-specific inhibition of miR-188 by intra–bone marrow injection of aptamer-antagomiR-188 increased bone formation and decreased bone marrow fat accumulation in aged mice. Together, our results indicate that miR-188 is a key regulator of the age-related switch between osteogenesis and adipogenesis of BMSCs and may represent a potential therapeutic target for age-related bone loss. PMID:25751060

Physical activity effects on bone metabolism.

PubMed

Smith, E L; Gilligan, C

1991-01-01

The incidence of osteoporotic fractures rises exponentially with age and is increasing faster than the demographic increase in the aging population. Physical activity has great potential to reduce the risk for osteoporotic fractures. Three independent but interactive factors contribute to the risk of fractures: bone strength, the risk of falling, and the effectiveness of neuromuscular response that protects the skeleton from injury. Exercise can reduce fracture risk not only by preventing bone loss, but by decreasing the risk of falling and the force of impact by improving strength, flexibility, balance, and reaction time. Extreme inactivity causes rapid bone loss of up to 40%, while athletic activity results in bone hypertrophy of up to 40%. Exercise intervention programs have reduced bone loss or increased bone mass in both men and women of various ages and initial bone status. These benefits have been shown for arm bone mineral content, total body calcium, spine, calcium bone index, tibia, and calcaneus. In both middle-aged and elderly women, physical activity intervention reduced bone loss or increased bone mass. The mechanisms for maintenance of skeletal integrity rely on a cellular response to hormonal and mechanical load stimuli. Studies in animal models show that training affects cellular activity. In osteoporotics, cellular erosion is increased and mineral apposition rate (MAR) decreased compared with normal age-matched controls. In contrast to this, sows trained on a treadmill 20 min per day for 20 weeks had greater active periosteal surface, periosteal MAR, and osteonal MAR than untrained sows.

Indication for Computed Tomography Scan in Shoulder Instability: Sensitivity and Specificity of Standard Radiographs to Predict Bone Defects After Traumatic Anterior Glenohumeral Instability.

PubMed

Delage Royle, Audrey; Balg, Frédéric; Bouliane, Martin J; Canet-Silvestri, Fanny; Garant-Saine, Laurianne; Sheps, David M; Lapner, Peter; Rouleau, Dominique M

2017-10-01

Quantifying glenohumeral bone loss is key in preoperative surgical planning for a successful Bankart repair. Simple radiographs can accurately measure bone defects in cases of recurrent shoulder instability. Cohort study (diagnosis); Level of evidence, 2. A true anteroposterior (AP) view, alone and in combination with an axillary view, was used to evaluate the diagnostic properties of radiographs compared with computed tomography (CT) scan, the current gold standard, to predict significant bone defects in 70 patients. Sensitivity, specificity, and positive and negative predictive values were evaluated and compared. Detection of glenoid bone loss on plain film radiographs, with and without axillary view, had a sensitivity of 86% for both views and a specificity of 73% and 64% with and without the axillary view, respectively. For detection of humeral bone loss, the sensitivity was 8% and 17% and the specificity was 98% and 91% with and without the axillary view, respectively. Regular radiographs would have missed 1 instance of significant bone loss on the glenoid side and 20 on the humeral side. Interobserver reliabilities were moderate for glenoid detection (κ = 0.473-0.503) and poor for the humeral side (κ = 0.278-0.336). Regular radiographs showed suboptimal sensitivity, specificity, and reliability. Therefore, CT scan should be considered in the treatment algorithm for accurate quantification of bone loss to prevent high rates of recurrent instability.

iNOS-Derived Nitric Oxide Stimulates Osteoclast Activity and Alveolar Bone Loss in Ligature-Induced Periodontitis in Rats

PubMed Central

Herrera, Bruno S.; Martins-Porto, Rodrigo; Maia-Dantas, Aline; Campi, Paula; Spolidorio, Luis C.; Costa, Soraia K.P.; Van Dyke, Thomas E.; Gyurko, Robert; Muscara, Marcelo N.

2012-01-01

Background Inflammatory stimuli activate inducible nitric oxide synthase (iNOS) in a variety of cell types, including osteoclasts (OC) and osteoblasts, resulting in sustained NO production. In this study, we evaluate the alveolar bone loss in rats with periodontitis under long-term iNOS inhibition, and the differentiation and activity of OC from iNOS-knockout (KO) mice in vitro. Methods Oral aminoguanidine (an iNOS inhibitor) or water treatment was started 2 weeks before induction of periodontitis. Rats were sacrificed 3, 7, or 14 days after ligature placement, and alveolar bone loss was evaluated. In vitro OC culture experiments were also performed to study the differentiation of freshly isolated bone marrow cells from both iNOS KO and wild-type C57BL/6 mice. OC were counted 6 days later after tartrate-resistant acid phosphatase staining (a marker of osteoclast identity), and bone resorption activity was assessed by counting the number of resorption pits on dentin disks. Results Rats with ligature showed progressive and significant alveolar bone loss compared to sham animals, and aminoguanidine treatment significantly inhibited ligature-induced bone loss at 7 and 14 days after the induction. In comparison to bone marrow cells from wild-type mice, cells from iNOS KO mice showed decreased OC growth and the resulting OC covered a smaller culture dish area and generated fewer resorption pit counts. Conclusion Our results demonstrate that iNOS inhibition prevents alveolar bone loss in a rat model of ligature-induced periodontitis, thus confirming that iNOS-derived NO plays a crucial role in the pathogenesis of periodontitis, probably by stimulating OC differentiation and activity. PMID:21417589

Electrical stimulation at the dorsal root ganglion preserves trabecular bone mass and microarchitecture of the tibia in hindlimb-unloaded rats.

PubMed

Lau, Y-C; Qian, X; Po, K-T; Li, L-M; Guo, X

2015-02-01

This study seeks to investigate the effect of electrical stimulation (ES) at dorsal root ganglion (DRG) on disuse bone loss in a rat model. Hindlimb unloading for 14 days resulted in significant bone loss in rat tibia while rats with ES at DRG showed a significant reduced bone loss Mechanical unloading induces osteoporosis in both human and animals. Previous studies demonstrated that electrical stimulation (ES) to dorsal root ganglion (DRG) could trigger secretion of calcitonin gene-related peptide (CGRP) which plays an important role in bone modeling and remodeling. This study seeks to investigate the effect of ES to DRG on disuse bone loss in a rat model. Twenty-four rats were randomly assigned in three experimental groups: cage control (CC), hindlimb unloading (HU), and hindlimb unloading with ES (HUES). ES was applied via implantable micro-electrical stimulators (IMES) to right DRGs at vertebral levels L4-L6 in HUES group. Hindlimb unloading for 14 days resulted in 25.9% decrease in total bone mineral content (BMC), 29.2% decrease in trabecular BMD and trabecular microarchitecture and connectivity were significantly deteriorated in the proximal tibia metaphysis in HU group, while rats with ES at DRG showed significant reduced bone loss that there was 3.8% increase in total BMC, 2.3% decrease in trabecular BMD, and significant improvement in trabecular microarchitecture. There was a concurrent enhancement of expression of CGRP in stimulated DRGs. The results confirm the effect of ES at DRG on enhancing CGRP expression and suggest potential applications of IMES for the prevention and treatment of disuse bone loss.

Repression of Osteoblast Maturation by ERRα Accounts for Bone Loss Induced by Estrogen Deficiency

PubMed Central

Gallet, Marlène; Saïdi, Soraya; Haÿ, Eric; Photsavang, Johann; Marty, Caroline; Sailland, Juliette; Carnesecchi, Julie; Tribollet, Violaine; Barenton, Bruno; Forcet, Christelle; Birling, Marie-Christine; Sorg, Tania; Chassande, Olivier; Cohen-Solal, Martine; Vanacker, Jean-Marc

2013-01-01

ERRα is an orphan member of the nuclear receptor family, the complete inactivation of which confers resistance to bone loss induced by ageing and estrogen withdrawal to female mice in correlation with increased bone formation in vivo. Furthermore ERRα negatively regulates the commitment of mesenchymal cells to the osteoblast lineage ex vivo as well as later steps of osteoblast maturation. We searched to determine whether the activities of ERRα on osteoblast maturation are responsible for one or both types of in vivo induced bone loss. To this end we have generated conditional knock out mice in which the receptor is normally present during early osteoblast differentiation but inactivated upon osteoblast maturation. Bone ageing in these animals was similar to that observed for control animals. In contrast conditional ERRαKO mice were completely resistant to bone loss induced by ovariectomy. We conclude that the late (maturation), but not early (commitment), negative effects of ERRα on the osteoblast lineage contribute to the reduced bone mineral density observed upon estrogen deficiency. PMID:23359549

Bone loss in Crohn's disease: exercise as a potential countermeasure.

PubMed

Lee, Naomi; Radford-Smith, Graham; Taaffe, Dennis R

2005-12-01

Crohn's disease (CD) is associated with a number of secondary conditions including osteoporosis, which increases the risk of bone fracture. The cause of metabolic bone disease in this population is believed to be multifactorial and may include the disease itself and associated inflammation, high-dose corticosteroid use, weight loss and malabsorption, a lack of exercise and physical activity, and an underlying genetic predisposition to bone loss. Reduced bone mineral density has been reported in between 5% to 80% of CD sufferers, although it is generally believed that approximately 40% of patients suffer from osteopenia and 15% from osteoporosis. Recent studies suggest a small but significantly increased risk of fracture compared with healthy controls and, perhaps, sufferers of other gastrointestinal disorders such as ulcerative colitis. The role of physical activity and exercise in the prevention and treatment of CD-related bone loss has received little attention, despite the benefits of specific exercises being well documented in healthy populations. This article reviews the prevalence of and risk factors for low bone mass in CD patients and examines various treatments for osteoporosis in these patients, with a particular focus on physical activity.

Cadmium accelerates bone loss in ovariectomized mice and fetal rat limb bones in culture.

PubMed Central

Bhattacharyya, M H; Whelton, B D; Stern, P H; Peterson, D P

1988-01-01

Loss of bone mineral after ovariectomy was studied in mice exposed to dietary cadmium at 0.25, 5, or 50 ppm. Results show that dietary cadmium at 50 ppm increased bone mineral loss to a significantly greater extent in ovariectomized mice than in sham-operated controls. These results were obtained from two studies, one in which skeletal calcium content was determined 6 months after ovariectomy and a second in which 45Ca release from 45Ca-prelabeled bones was measured immediately after the start of dietary cadmium exposure. Furthermore, experiments with 45Ca-prelabeled fetal rat limb bones in culture demonstrated that Cd at 10 nM in the medium, a concentration estimated to be in the plasma of mice exposed to 50 ppm dietary Cd, strikingly increased bone resorption, from 27 +/- 2% (mean +/- SEM) 45Ca release in cultures with no added cadmium to 68 +/- 6% release in cultures containing cadmium (n = 4). These in vitro results indicate that cadmium may enhance bone mineral loss by a direct action on bone. Results of the in vivo studies are consistent with a significant role of cadmium in the etiology of Itai-Itai disease among postmenopausal women in Japan and may in part explain the increased risk of postmenopausal osteoporosis among women who smoke. Images PMID:3186759

Quantitation of calcium metabolism in postmenopausal osteoporosis and in scoliosis

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

Bronner, F.; Richelle, L. J.; Saville, P. D.

1963-06-01

By a combination of balance and isotope techniques, the following parameters of Ca metabolism were measured: pool size, rate of loss from pool, urinary excretion, fecal excretion, intake, endogenous fecal Ca, absorption, balance, bone formation, and bone resorption. The subjects were two normal women and five women with postmenopausal osteoporosis, aged 41 to 74 years, and four patients with scoliosis, aged 12 to 22 years. The latter were studied before, shortly after, and many months after immobilization in plaster casts. On the basis of observed relationships, it appeared that the negative Ca balance observed in the older women was duemore » to the low intensity of the various vectors of Ca metabolism, without clearcut distinction between the subjects with and without osteoporosis. Conversely, in the young patients with scoliosis, the negative balance incident to treatment by immobilization was associated with vectors of relatively high intensity whose relationships were altered temporarily.« less

Polymethoxy flavonoids, nobiletin and tangeretin, prevent lipopolysaccharide-induced inflammatory bone loss in an experimental model for periodontitis.

PubMed

Tominari, Tsukasa; Hirata, Michiko; Matsumoto, Chiho; Inada, Masaki; Miyaura, Chisato

2012-01-01

Nobiletin, a polymethoxy flavonoid (PMF), inhibits systemic bone resorption and maintains bone mass in estrogen-deficient ovariectomized mice. This study examined the anti-inflammatory effects of PMFs, nobiletin, and tangeretin on lipopolysaccharide (LPS)-induced bone resorption. Nobiletin and tangeretin suppressed LPS-induced osteoclast formation and bone resorption and suppressed the receptor activator of NFκB ligand-induced osteoclastogenesis in RAW264.7 macrophages. Nobiletin clearly restored the alveolar bone mass in a mouse experimental model for periodontitis by inhibiting LPS-induced bone resorption. PMFs may therefore provide a new therapeutic approach for periodontal bone loss.

A cannabinoid 2 receptor agonist attenuates bone cancer-induced pain and bone loss

PubMed Central

Lozano, Alysia; Wright, Courtney; Vardanyan, Anna; King, Tamara; Largent-Milnes, Tally M.; Nelson, Mark; Jimenez-Andrade, Juan Miguel; Mantyh, Patrick W; Vanderah, Todd W.

2010-01-01

Aims Cannabinoid CB2 agonists have been shown to alleviate behavioral signs of inflammatory and neuropathic pain in animal models. AM1241, a CB2 agonist, does not demonstrate central nervous system side-effects seen with CB1 agonists such as hypothermia and catalepsy. Metastatic bone cancer causes severe pain in patients and is treated with analgesics such as opiates. Recent reports suggest that sustained opiates can produce paradoxical hyperalgesic actions and enhance bone destruction in a murine model of bone cancer. In contrast, CB2 selective agonists have been shown to reduce bone loss associated with a model of osteoporosis. Here we tested whether a CB2 agonist administered over a 7 day period inhibits bone cancer-induced pain as well as attenuates cancer-induced bone degradation. Main Methods A murine bone cancer model was used in which osteolytic sarcoma cells were injected into the intramedullary space of the distal end of the femur. Behavioral and radiographic image analysis was performed at days 7, 10 and 14 after injection of tumor cells into the femur. Key Findings Osteolytic sarcoma within the femur produced spontaneous and touch evoked behavioral signs of pain within the tumor-bearing limb. The systemic administration of AM1241 acutely or for 7 days significantly attenuated spontaneous and evoked pain in the inoculated limb. Sustained AM1241 significantly reduced bone loss and decreased the incidence of cancer-induced bone fractures. Significance These findings suggest a novel therapy for cancer-induced bone pain, bone loss and bone fracture while lacking many unwanted side effects seen with current treatments for bone cancer pain. PMID:20176037

Bisphosphonates as a Countermeasure to Space Flight Induced Bone Loss

NASA Technical Reports Server (NTRS)

LeBlanc, A.; Matsumoto, T.; Jones, J.; Shapiro, J.; Lang, T.; Shackelford, L.; Smith, S.; Evans, H.; Spector, E.; Ploutz-Snyder, R.;

Radiation activated CHK1/MEPE pathway may contribute to microgravity-induced bone density loss

NASA Astrophysics Data System (ADS)

Zhang, Xiangming; Wang, Ping; Wang, Ya

2015-11-01

Bone density loss in astronauts on long-term space missions is a chief medical concern. Microgravity in space is the major cause of bone density loss (osteopenia), and it is believed that high linear energy transfer (LET) radiation in space exacerbates microgravity-induced bone density loss; however, the mechanism remains unclear. It is known that acidic serine- and aspartate-rich motif (ASARM) as a small peptide released by matrix extracellular phosphoglycoprotein (MEPE) promotes osteopenia. We previously discovered that MEPE interacted with checkpoint kinase 1 (CHK1) to protect CHK1 from ionizing radiation promoted degradation. In this study, we addressed whether the CHK1-MEPE pathway activated by radiation contributes to the effects of microgravity on bone density loss. We examined the CHK1, MEPE and secreted MEPE/ASARM levels in irradiated (1 Gy of X-ray) and rotated cultured human osteoblast cells. The results showed that radiation activated CHK1, decreased the levels of CHK1 and MEPE in human osteoblast cells and increased the release of MEPE/ASARM. These results suggest that the radiation-activated CHK1/MEPE pathway exacerbates the effects of microgravity on bone density loss, which may provide a novel targeting factor/pathway for a future countermeasure design that could contribute to reducing osteopenia in astronauts.

Dietary Sodium Effects on Bone Loss and Calcium Metabolism During Bed Rest

NASA Technical Reports Server (NTRS)

Smith, Scott M.; Arnaud, Sara B.; Abrams, Steven A.; Paloski, W. H. (Technical Monitor)

2000-01-01

The acceleration of age-related bone loss is one of the most detrimental effects of space flight. The ability to understand and counteract this loss will be critical for crew health and safety during and after long-duration missions. Studies in healthy ambulatory individuals have linked high salt (sodium) diets, hypercalciuria, and increased renal stone risk. Dietary salt may modulate bone loss through changes in calcium metabolism and the calcium endocrine system. The research proposed here will determine the role of dietary salt in the loss of bone during simulated space flight. Calcium metabolism will be determined through calcium kinetics studies, endocrine and biochemical measurements; and estimates of the mass, distribution and mechanical properties of bone, in subjects fed low (100 mmol sodium/day) or high (250 mmol sodium/day) levels of dietary salt during 28 days of headdown tilt bedrest. This research addresses the role of dietary salt in the loss of bone and calcium in space flight, and integrates the changes in calcium metabolism with those occurring in other physiologic systems. These data will be critical for both countermeasure development, and in determination of nutritional requirements for extended-duration space flight. The potential countermeasures resulting from this research will reduce health risks due to acceleration of age-related osteoporosis and increased risk of renal stone formation..

Alendronate as an Effective Countermeasure to Disuse Induced Bone loss

NASA Technical Reports Server (NTRS)

LeBlanc, Adrian D.; Driscol, Theda B.; Shackelford, Linda C.; Evans, Harlan J.; Rianon, Nahid J.; Smith, Scott M.; Lai, Dejian

2002-01-01

Microgravity, similar to diuse immobilization on earth, causes rapid bone loss. This loss is believed to be an adaptive response to the reduced musculoskelatal forces in space and occurs gradually enough that changes occurring during short duration space flight are not a concern. Bone loss, however, will be a major impediment for long duration missions if effective countermeasures are not developed and implemented. Bed rest is used to simulate the reduced mechanical forces in humans and was used to test the hypothesis that oral alendronate would reduce the effects of long duration (17 weeks) inactivity on bone. Eight male subjects were given daily oral doses of alendronate during 17 weeks of horizontal bed rest and compared with 13 male control subjects not given the drug. Efficacy was evaluated based on measurements of bone markers, calcium balance and bone density performed before, during and after the bed rest. The results show that oral alendronate attenuates most of the characteristic changes associated with long duration bed rest and presumably space flight.

Modeling corticosteroid effects in a rat model of rheumatoid arthritis II: mechanistic pharmacodynamic model for dexamethasone effects in Lewis rats with collagen-induced arthritis.

PubMed

Earp, Justin C; Dubois, Debra C; Molano, Diana S; Pyszczynski, Nancy A; Almon, Richard R; Jusko, William J

2008-08-01

A mechanism-based model for pharmacodynamic effects of dexamethasone (DEX) was incorporated into our model for arthritis disease progression in the rat to aid in identification of the primary factors responsible for edema and bone loss. Collagen-induced arthritis was produced in male Lewis rats after injection of type II porcine collagen. DEX was given subcutaneously in single doses of 0.225 or 2.25 mg/kg or 7-day multiple doses of 0.045 or 0.225 mg/kg at 21 days postdisease induction. Effects on disease progression were measured by paw swelling, bone mineral density (BMD), body weights, plasma corticosterone (CST), and tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, and glucocorticoid receptor (GR) mRNA expression in paw tissue. Lumbar and femur BMD was determined by PIXImus II dual-energy X-ray absorptiometry. Plasma CST was assayed by high-performance liquid chromatography. Cytokine and GR mRNA were assayed by quantitative real-time polymerase chain reaction. Indirect response models, drug interaction models, transduction processes, and the fifth-generation model of corticosteroid dynamics were integrated and applied using S-ADAPT software to describe how dexamethasone binding to GR can regulate diverse processes. Cytokine mRNA, GR mRNA, plasma CST, and paw edema were suppressed after DEX administration. TNF-alpha mRNA expression and BMD seemed to increase immediately after dosing but were ultimately reduced. Model parameters indicated that IL-6 and IL-1beta were most sensitive to inhibition by DEX. TNF-alpha seemed to primarily influence edema, whereas IL-6 contributed the most to bone loss. Lower doses of corticosteroids may be sufficient to suppress the cytokines most relevant to bone erosion.

Streptozocin-induced type-1 diabetes mellitus results in decreased density of CGRP sensory and TH sympathetic nerve fibers that are positively correlated with bone loss at the mouse femoral neck.

PubMed

Enríquez-Pérez, Iris A; Galindo-Ordoñez, Karla E; Pantoja-Ortíz, Christian E; Martínez-Martínez, Arisaí; Acosta-González, Rosa I; Muñoz-Islas, Enriqueta; Jiménez-Andrade, Juan M

2017-08-10

Type-1 diabetes mellitus (T1DM) results in loss of innervation in some tissues including epidermis and retina; however, the effect on bone innervation is unknown. Likewise, T1DM results in pathological bone loss and increased risk of fracture. Thus, we quantified the density of calcitonin gene-related peptide (CGRP + ) sensory and tyrosine hydroxylase (TH + ) sympathetic nerve fibers and determined the association between the innervation density and microarchitecture of trabecular bone at the mouse femoral neck. Ten weeks-old female mice received 5 daily administrations of streptozocin (i.p. 50mg/kg) or citrate (control group). Twenty weeks later, femurs were analyzed by microCT and processed for immunohistochemistry. Confocal microscopy analysis revealed that mice with T1DM had a significant loss of both CGRP + and TH + nerve fibers in the bone marrow at the femoral neck. Likewise, microCT analysis revealed a significant decrease in the trabecular bone mineral density (tBMD), bone volume/total volume ratio (BV/TB), trabecular thickness (Tb.Th), trabecular number (Tb.N) and trabecular separation (Tb.Sp) in mice with T1DM as compared to control mice. Analysis of correlation revealed a positive and significant association between density of CGRP + or TH + nerve fibers with tBMD, BV/TV, Tb.Th and Tb.Sp, but not with trabecular number (there was a positive association only for CGRP + ) and degree of anisotropy (DA). This study suggests an interaction between sensory and sympathetic nervous system and T1DM-induced bone loss. Identification of the factors involved in the loss of CGRP + sensory and TH + sympathetic fibers and how they regulate bone loss may result in new avenues to treat T1DM-related osteoporosis. Copyright © 2017 Elsevier B.V. All rights reserved.

Bone mineral density before and after OLT: long-term follow-up and predictive factors.

PubMed

Guichelaar, Maureen M J; Kendall, Rebecca; Malinchoc, Michael; Hay, J Eileen

2006-09-01

Fracturing after liver transplantation (OLT) occurs due to the combination of preexisting low bone mineral density (BMD) and early posttransplant bone loss, the risk factors for which are poorly defined. The prevalence and predictive factors for hepatic osteopenia and osteoporosis, posttransplant bone loss, and subsequent bone gain were studied by the long-term posttransplant follow-up of 360 consecutive adult patients with end-stage primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). Only 20% of patients with advanced PBC or PSC have normal bone mass. Risk factors for low spinal BMD are low body mass index, older age, postmenopausal status, muscle wasting, high alkaline phosphatase and low serum albumin. A high rate of spinal bone loss occurred in the first 4 posttransplant months (annual rate of 16%) especially in those with younger age, PSC, higher pretransplant bone density, no inflammatory bowel disease, shorter duration of liver disease, current smoking, and ongoing cholestasis at 4 months. Factors favoring spinal bone gain from 4 to 24 months after transplantation were lower baseline and/or 4-month bone density, premenopausal status, lower cumulative glucocorticoids, no ongoing cholestasis, and higher levels of vitamin D and parathyroid hormone. Bone mass therefore improves most in patients with lowest pretransplant BMD who undergo successful transplantation with normal hepatic function and improved gonadal and nutritional status. Patients transplanted most recently have improved bone mass before OLT, and although bone loss still occurs early after OLT, these patients also have a greater recovery in BMD over the years following OLT.

Muscle changes can account for bone loss after botulinum toxin injection.

PubMed

Manske, Sarah L; Boyd, Steven K; Zernicke, Ronald F

2010-12-01

Studies to date have assumed that botulinum toxin type A (BTX) affects bone indirectly, through its action on muscle. We hypothesized that BTX has no discernable effect on bone morphometry, independent of its effect on muscle. Therefore, we investigated whether BTX had an additional effect on bone when combined with tenotomy compared to tenotomy in isolation. Female BALB/c mice (n = 73) underwent one of the following procedures in the left leg: BTX injection and Achilles tenotomy (BTX-TEN), BTX injection and sham surgery (BTX-sham), Achilles tenotomy (TEN), or sham surgery (sham). BTX groups were injected with 20 μL of BTX (1 U/100 g) in the posterior lower hindlimb. At 4 weeks, muscle cross-sectional area (MCSA) and tibial bone morphometry were assessed using micro-CT. Each treatment, other than sham, resulted in significant muscle and bone loss (P < 0.05). BTX-TEN experienced the greatest muscle loss (23-45% lower than other groups) and bone loss (20-30% lower bone volume fraction than other groups). BTX-sham had significantly lower MCSA and bone volume fraction than TEN and sham. After adjusting for differences in MCSA, there were no significant between-group differences in bone properties. We found that BTX injection resulted in more adverse muscle and bone effects than tenotomy and that effects were amplified when the procedures were combined. However, between-group differences in bone could be accounted for by MCSA. We conclude that any independent effect of BTX on bone morphometry is likely small or negligible compared with the effect on muscle.

Novel use of an ultrasonic bone-cutting device for endoscopic-assisted craniosynostosis surgery.

PubMed

Chaichana, Kaisorn L; Jallo, George I; Dorafshar, Amir H; Ahn, Edward S

2013-07-01

Endoscopic-assisted craniosynostosis surgery is associated with less blood loss and shorter operative times as compared to open surgery. However, in infants who have low circulating blood volumes, the endoscopic approach is still associated with significant blood loss. A major source of blood loss is the bone that is cut during surgery. We discuss the novel use of an ultrasonic bone-cutting device for craniosynostosis surgery, which decreases bone bleeding. This device, which has primarily only been used for spine and skull base surgery, may help reduce blood loss in these infants. All patients with single suture craniosynostosis who were operated on with the use of an ultrasonic bone-cutting device were identified. The information retrospectively recorded from patient charts included patient age, suture involved, blood loss, operative times, complications, preoperative hemoglobin, postoperative hemoglobin, length of hospital stay, and follow-up times. Thirteen patients (12 males, 1 female) underwent surgery with an ultrasonic bone-cutting device during the reviewed period. The average age (±standard deviation) of the patients was 11.8 (±1.6) weeks. Four patients had metopic synostosis and nine patients had sagittal synostosis. The average surgery time was 84 (±13) min. The median (interquartile range) blood loss was 20 (10-70) cc. No patients required blood transfusions. Three patients had dural tears. We demonstrate the novel use of an ultrasonic bone-cutting device for endoscopic-assisted craniosynostosis surgery. This device limited blood loss while maintaining short operative times for infants with low circulating blood volumes.

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.

Dynamic Simulation of Three Dimensional Architectural and Mechanical Alterations in Human Trabecular Bone during Menopause

PubMed Central

Liu, X. Sherry; Huang, Angela H.; Zhang, X. Henry; Sajda, Paul; Ji, Baohua; Guo, X. Edward

2008-01-01

A three dimensional (3D) computational simulation of dynamic process of trabecular bone remodeling was developed with all the parameters derived from physiological and clinical data. Contributions of the microstructural bone formation deficits: trabecular plate perforations, trabecular rod breakages, and isolated bone fragments, to the rapid bone loss and disruption of trabecular microarchitecture during menopause were studied. Eighteen human trabecular bone samples from femoral neck (FN) and spine were scanned using a micro computed tomography (μCT) system. Bone resorption and formation were simulated as a computational cycle corresponding to 40-day resorption/160-day formation. Resorption cavities were randomly created over the bone surface according to the activation frequency, which was strictly based on clinical data. Every resorption cavity was refilled during formation unless it caused trabecular plate perforation, trabecular rod breakage or isolated fragments. A 20-year-period starting 5 years before and ending 15 years after menopause was simulated for each specimen. Elastic moduli, standard and individual trabeculae segmentation (ITS)-based morphological parameters were evaluated for each simulated 3D image. For both spine and FN groups, the time courses of predicted bone loss pattern by microstructural bone formation deficits were fairly consistent with the clinical measurements. The percentage of bone loss due to trabecular plate perforation, trabecular rod breakage, and isolated bone fragments were 73.2%, 18.9% and 7.9% at the simulated 15 years after menopause. The ITS-based plate fraction (pBV/BV), mean plate surface area (pTb.S), plate number density (pTb.N), and mean rod thickness (rTb.Th) decreased while rod fraction (rBV/BV) and rod number density (rTb.N) increased after the simulated menopause. The dynamic bone remodeling simulation based on microstructural bone formation deficits predicted the time course of menopausal bone loss pattern of spine and FN. Microstructural plate perforation could be the primary cause of menopausal trabecular bone loss. The combined effect of trabeculae perforation, breakage, and isolated fragments resulted in fewer and smaller trabecular plates and more but thinner trabecular rods. PMID:18550463

Microtomographic imaging in the process of bone modeling and simulation

NASA Astrophysics Data System (ADS)

Mueller, Ralph

1999-09-01

Micro-computed tomography ((mu) CT) is an emerging technique to nondestructively image and quantify trabecular bone in three dimensions. Where the early implementations of (mu) CT focused more on technical aspects of the systems and required equipment not normally available to the general public, a more recent development emphasized practical aspects of micro- tomographic imaging. That system is based on a compact fan- beam type of tomograph, also referred to as desktop (mu) CT. Desk-top (mu) CT has been used extensively for the investigation of osteoporosis related health problems gaining new insight into the organization of trabecular bone and the influence of osteoporotic bone loss on bone architecture and the competence of bone. Osteoporosis is a condition characterized by excessive bone loss and deterioration in bone architecture. The reduced quality of bone increases the risk of fracture. Current imaging technologies do not allow accurate in vivo measurements of bone structure over several decades or the investigation of the local remodeling stimuli at the tissue level. Therefore, computer simulations and new experimental modeling procedures are necessary for determining the long-term effects of age, menopause, and osteoporosis on bone. Microstructural bone models allow us to study not only the effects of osteoporosis on the skeleton but also to assess and monitor the effectiveness of new treatment regimens. The basis for such approaches are realistic models of bone and a sound understanding of the underlying biological and mechanical processes in bone physiology. In this article, strategies for new approaches to bone modeling and simulation in the study and treatment of osteoporosis and age-related bone loss are presented. The focus is on the bioengineering and imaging aspects of osteoporosis research. With the introduction of desk-top (mu) CT, a new generation of imaging instruments has entered the arena allowing easy and relatively inexpensive access to the three-dimensional microstructure of bone, thereby giving bone researchers a powerful tool for the exploration of age-related bone loss and osteoporosis.

Quantifying glenoid bone loss in anterior shoulder instability: reliability and accuracy of 2-dimensional and 3-dimensional computed tomography measurement techniques.

PubMed

Bois, Aaron J; Fening, Stephen D; Polster, Josh; Jones, Morgan H; Miniaci, Anthony

2012-11-01

Glenoid support is critical for stability of the glenohumeral joint. An accepted noninvasive method of quantifying glenoid bone loss does not exist. To perform independent evaluations of the reliability and accuracy of standard 2-dimensional (2-D) and 3-dimensional (3-D) computed tomography (CT) measurements of glenoid bone deficiency. Descriptive laboratory study. Two sawbone models were used; one served as a model for 2 anterior glenoid defects and the other for 2 anteroinferior defects. For each scapular model, predefect and defect data were collected for a total of 6 data sets. Each sample underwent 3-D laser scanning followed by CT scanning. Six physicians measured linear indicators of bone loss (defect length and width-to-length ratio) on both 2-D and 3-D CT and quantified bone loss using the glenoid index method on 2-D CT and using the glenoid index, ratio, and Pico methods on 3-D CT. The intraclass correlation coefficient (ICC) was used to assess agreement, and percentage error was used to compare radiographic and true measurements. With use of 2-D CT, the glenoid index and defect length measurements had the least percentage error (-4.13% and 7.68%, respectively); agreement was very good (ICC, .81) for defect length only. With use of 3-D CT, defect length (0.29%) and the Pico(1) method (4.93%) had the least percentage error. Agreement was very good for all linear indicators of bone loss (range, .85-.90) and for the ratio linear and Pico surface area methods used to quantify bone loss (range, .84-.98). Overall, 3-D CT results demonstrated better agreement and accuracy compared to 2-D CT. None of the methods assessed in this study using 2-D CT was found to be valid, and therefore, 2-D CT is not recommended for these methods. However, the length of glenoid defects can be reliably and accurately measured on 3-D CT. The Pico and ratio techniques are most reliable; however, the Pico(1) method accurately quantifies glenoid bone loss in both the anterior and anteroinferior locations. Future work is required to implement valid imaging techniques of glenoid bone loss into clinical practice. This is one of the only studies to date that has investigated both the reliability and accuracy of multiple indicators and quantification methods that evaluate glenoid bone loss in anterior glenohumeral instability. These data are critical to ensure valid methods are used for preoperative assessment and to determine when a glenoid bone augmentation procedure is indicated.

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.

The effects of tumour necrosis factor-α on bone cells involved in periodontal alveolar bone loss; osteoclasts, osteoblasts and osteocytes.

PubMed

Algate, K; Haynes, D R; Bartold, P M; Crotti, T N; Cantley, M D

2016-10-01

Periodontitis is the most common bone loss pathology in adults and if left untreated is responsible for premature tooth loss. Cytokines, such as tumour necrosis factor-α (TNFα), involved in the chronic inflammatory response within the periodontal gingiva, significantly influence the normal bone remodelling processes. In this review, the effects of TNFα on bone metabolism in periodontitis are evaluated in relation to its direct and indirect actions on bone cells including osteoclasts, osteoblasts and osteocytes. Evidence published to date suggests a potent catabolic role for TNFα through the stimulation of osteoclastic bone resorption as well as the suppression of osteoblastic bone formation and osteocytic survival. However, the extent and timing of TNFα exposure in vitro and in vivo greatly influences its effect on skeletal cells, with contradictory anabolic activity observed with TNFα in a number of studies. None the less, it is evident that managing the chronic inflammatory response in addition to the deregulated bone metabolism is required to improve periodontal and inflammatory bone loss treatments‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effect of methylprednisolone on bone mineral density in rats with ovariectomy-induced bone loss and suppressed endogenous adrenaline levels by metyrosine

PubMed Central

Yilmaz, Mehmet; Isaoglu, Unal; Uslu, Turan; Yildirim, Kadir; Seven, Bedri; Akcay, Fatih; Hacimuftuoglu, Ahmet

2013-01-01

Objectives: In this study, effect of methylprednisolone on bone mineral density (BMD) was investigated in rats with overiectomy induced bone lose and suppressed endogenous adrenalin levels, and compared to alendronate. Materials and Methods: Severity of bone loss in the examined material (femur bones) was evaluated by BMD measurement. Results: The group with the highest BMD value was metyrosinemetyrosine + methylprednisolone combination (0.151 g/cm2), while that with the lowest BMD was methylprednisolone (0.123 g/cm2). Alendronate was effective only when used alone in ovariectomized rats (0.144 g/cm2), but not when used in combination with methylprednisolone (0.124 g/cm2). In the ovariectomized rat group which received only metyrosine, BMD value was statistically indifferent from ovariectomized control group. Conclusions: Methylprednisolone protected bone loss in rats with suppressed adrenaline levels because of metyrosinemetyrosine. PMID:24014908

Bone Remodeling Monitor

NASA Technical Reports Server (NTRS)

Foucar, Charlie; Goldberg, Leslie; Hon, Bodin; Moore, Shannon; Williams, Evan

2009-01-01

The impact of bone loss due to different mechanical loadings in microgravity is a major concern for astronauts upon reintroduction to gravitational forces in exploration missions to the Moon and Mars. it has been shown that astronauts not only lose bone at differing rates, with levels up to 2% per month, but each astronaut will respond to bone loss treatments differently. Pre- and post-flight imaging techniques and frozen urine samples for post-flight laboratory immunoassays To develop a novel, non-invasive, highly . sensitive, portable, intuitive, and low-powered device to measure bone resorption levels in 'real time' to provide rapid and Individualized feedback to maximize the efficacy of bone loss countermeasures 1. Collect urine specimen and analyze the level of bone resorption marker, DPD (deoxypridinoline) excreted. 2. Antibodies specific to DPD conjugated with nanoshells and mixed with specimen, the change in absorbance from agglutination is measured by an optical device. 3. The concentration of DPD is displayed and recorded on a PDA

Quantitative trait loci for energy balance traits in an advanced intercross line derived from mice divergently selected for heat loss

PubMed Central

Nielsen, Merlyn K.; Thorn, Stephanie R.; Valdar, William; Pomp, Daniel

2014-01-01

Obesity in human populations, currently a serious health concern, is considered to be the consequence of an energy imbalance in which more energy in calories is consumed than is expended. We used interval mapping techniques to investigate the genetic basis of a number of energy balance traits in an F11 advanced intercross population of mice created from an original intercross of lines selected for increased and decreased heat loss. We uncovered a total of 137 quantitative trait loci (QTLs) for these traits at 41 unique sites on 18 of the 20 chromosomes in the mouse genome, with X-linked QTLs being most prevalent. Two QTLs were found for the selection target of heat loss, one on distal chromosome 1 and another on proximal chromosome 2. The number of QTLs affecting the various traits generally was consistent with previous estimates of heritabilities in the same population, with the most found for two bone mineral traits and the least for feed intake and several body composition traits. QTLs were generally additive in their effects, and some, especially those affecting the body weight traits, were sex-specific. Pleiotropy was extensive within trait groups (body weights, adiposity and organ weight traits, bone traits) and especially between body composition traits adjusted and not adjusted for body weight at sacrifice. Nine QTLs were found for one or more of the adiposity traits, five of which appeared to be unique. The confidence intervals among all QTLs averaged 13.3 Mb, much smaller than usually observed in an F2 cross, and in some cases this allowed us to make reasonable inferences about candidate genes underlying these QTLs. This study combined QTL mapping with genetic parameter analysis in a large segregating population, and has advanced our understanding of the genetic architecture of complex traits related to obesity. PMID:24918027

Is there a relation between local bone quality as assessed on panoramic radiographs and alveolar bone level?

PubMed

Nackaerts, Olivia; Gijbels, Frieda; Sanna, Anna-Maria; Jacobs, Reinhilde

2008-03-01

The aim was to explore the relation between radiographic bone quality on panoramic radiographs and relative alveolar bone level. Digital panoramic radiographs of 94 female patients were analysed (mean age, 44.5; range, 35-74). Radiographic density of the alveolar bone in the premolar region was determined using Agfa Musica software. Alveolar bone level and bone quality index (BQI) were also assessed. Relationships between bone density and BQI on one hand and the relative loss of alveolar bone level on the other were assessed. Mandibular bone density and loss of alveolar bone level were weakly but significantly negatively correlated for the lower premolar area (r = -.27). The BQI did not show a statistically significant relation to alveolar bone level. Radiographic mandibular bone density on panoramic radiographs shows a weak but significant relation to alveolar bone level, with more periodontal breakdown for less dense alveolar bone.

Does bone loss begin after weight loss ends? Results two years after weight loss or regain in postmenopausal women

PubMed Central

Von Thun, Nancy L.; Sukumar, Deeptha; Heymsfield, Steven B.; Shapses, Sue A.

2016-01-01

Objective Short-term weight loss is accompanied by bone loss in postmenopausal women. The longer-term impact on bone in the reduced overweight/obese woman compared to those who regain their weight was examined in this study using a case-control design. Methods Postmenopausal women (n = 42, body mass index of 28.3 ± 2.8 kg/m2; 60.7 ± 5.5 y) were recruited 2 years after the start of a 6 month weight loss trial and those who maintained their weight (WL-M) were matched to a cohort who regained weight (WL-R). Serum hormones and bone markers were measured in a subset. Bone mineral density (BMD) at the femoral neck (FN), trochanter, spine, radius, and total body and soft tissue composition were taken at baseline, 0.5 and 2 years. Results During WL, both groups lost 9.3 ± 3.4% body weight with no significant difference between groups. After weight loss, weight change was −0.1 ± 2.7 % and 6.0 ± 3.3% in the WL-M (n=22) and WL-R (n=20) groups, respectively. After 2 years, both groups lost BMD at the FN and trochanter (p ≤ 0.01), whereas only the WL-M group reduced BMD at the 1/3 radius (p < 0.001). There was a greater BMD loss at the trochanter (−6.8 ± 5.7%) and the 1/3 radius (−4.5 ± 3.3%) in the WL-M compared to the WL-R group after 2 years. Multiple linear regression showed that change in leg fat mass (but not trunk fat) contributed to trochanter BMD loss (p <0.05). Conclusions After 2 years, there is no BMD recovery of weight reduction-induced bone loss, irrespective of weight-regain. These data suggest that the period after weight loss may be an important point in time to prevent bone loss for both those who maintain or regain weight. PMID:24149920

Warped frequency transform analysis of ultrasonic guided waves in long bones

NASA Astrophysics Data System (ADS)

De Marchi, L.; Baravelli, E.; Xu, K.; Ta, D.; Speciale, N.; Marzani, A.; Viola, E.

2010-03-01

Long bones can be seen as irregular hollow tubes, in which, for a given excitation frequency, many ultrasonic Guided Waves (GWs) can propagate. The analysis of GWs is potential to reflect more information on both geometry and material properties of the bone than any other method (such as dual-energy X-ray absorptiometry, or quantitative computed tomography), and can be used in the assessment of osteoporosis and in the evaluation of fracture healing. In this study, time frequency representations (TFRs) were used to gain insights into the expected behavior of GWs in bones. To this aim, we implemented a dedicated Warped Frequency Transform (WFT) which decomposes the spectrotemporal components of the different propagating modes by selecting an appropriate warping map to reshape the frequency axis. The map can be designed once the GWs group velocity dispersion curves can be predicted. To this purpose, the bone is considered as a hollow cylinder with inner and outer diameter of 16.6 and 24.7 mm, respectively, and linear poroelastic material properties in agreement with the low level of stresses induced by the waves. Timetransient events obtained experimentally, via a piezoelectric ultrasonic set-up applied to bovine tibiae, are analyzed. The results show that WFT limits interference patterns which appear with others TFRs (such as scalograms or warpograms) and produces a sparse representation suitable for characterization purposes. In particular, the mode-frequency combinations propagating with minimal losses are identified.

Non-ototoxic local delivery of bisphosphonate to the mammalian cochlea

PubMed Central

Kang, Woo Seok; Sun, Shuting; Nguyen, Kim; Kashemirov, Boris; McKenna, Charles E.; Hacking, S. Adam; Quesnel, Alicia M.; Sewell, William F.; McKenna, Michael J.; Jung, David H.

2015-01-01

Hypothesis Local delivery of bisphosphonates results in superior localization of these compounds for the treatment of cochlear otosclerosis, without ototoxicity. Background Otosclerosis is a common disorder of abnormal bone remodeling within the human otic capsule. It is a frequent cause of conductive hearing loss from stapes fixation. Large lesions that penetrate the cochlear endosteum and injure the spiral ligament result in sensorineural hearing loss. Nitrogen-containing bisphosphonates (e.g., zoledronate) are potent inhibitors of bone remodeling with proven efficacy in the treatment of metabolic bone diseases, including otosclerosis. Local delivery to the cochlea may allow for improved drug targeting, higher local concentrations, and the avoidance of systemic complications. In this study, we utilize a fluorescently labeled bisphosphonate compound (6-FAM-ZOL) to determine drug localization and concentration within the otic capsule. Various methods for delivery are compared. Ototoxicity is evaluated by ABR and DPOAEs. Methods 6-FAM-ZOL was administered to guinea pigs via intraperitoneal injection, placement of alginate beads onto the round window membrane (RWM), or microfluidic pump infusion via a cochleostomy. Hearing was evaluated. Specimens were embedded into resin blocks, ground to a mid-modiolar section, and quantitatively imaged using fluorescence microscopy. Results There was a dose-dependent increase in fluorescent signal following systemic 6-FAM-ZOL treatment. Local delivery via the RWM or a cochleostomy increased delivery efficiency. No significant ototoxicity was observed following either systemic or local 6-FAM-ZOL delivery. Conclusions These findings establish important pre-clinical parameters for the treatment of cochlear otosclerosis in humans. PMID:25996080

The 18 kDa Translocator Protein (Peripheral Benzodiazepine Receptor) Expression in the Bone of Normal, Osteoprotegerin or Low Calcium Diet Treated Mice

PubMed Central

Kam, Winnie Wai-Ying; Meikle, Steven R.; Dunstan, Colin R.; Banati, Richard B.

2012-01-01

The presence of the translocator protein (TSPO), previously named as the mitochondrial or peripheral benzodiazepine receptor, in bone cells was studied in vitro and in situ using RT-qPCR, and receptor autoradiography using the selective TSPO ligand PK11195. In vitro, the TSPO is highly expressed in osteoblastic and osteoclastic cells. In situ, constitutive expression of TSPO is found in bone marrow and trabecular bone, e.g., spongiosa. Mice with a reduction of bone turnover induced by a 4-day treatment of osteoprotegerin reduces [3H]PK11195 binding in the spongiosa (320±128 Bq.mg−1, 499±106 Bq.mg−1 in saline-treated controls). In contrast, mice with an increase in bone turnover caused by a 4-day low calcium diet increases [3H]PK11195 binding in the spongiosa (615±90 Bq.mg−1). Further, our study includes technical feasibility data on [18F]fluoride microPET imaging of rodent bone with altered turnover. Despite [18F]fluoride having high uptake, the in vivo signal differences were small. Using a phantom model, we describe the spillover effect and partial volume loss that affect the quantitative microPET imaging of the small bone structures in experimental mouse models. In summary, we demonstrate the expression of TSPO in small rodent bone tissues, including osteoblasts and osteoclasts. A trend increase in TSPO expression was observed in the spongiosa from low to high bone turnover conditions. However, despite the potential utility of TSPO expression as an in vivo biomarker of bone turnover in experimental rodent models, our small animal PET imaging data using [18F]fluoride show that even under the condition of a good biological signal-to-noise ratio and high tracer uptake, the currently achievable instrument sensitivity and spatial resolution is unlikely to be sufficient to detect subtle differences in small structures, such as mouse bone. PMID:22295097

Glycemic control and alveolar bone loss progression in type 2 diabetes.

PubMed

Taylor, G W; Burt, B A; Becker, M P; Genco, R J; Shlossman, M

1998-07-01

This study tested the hypothesis that the risk for alveolar bone loss is greater, and bone loss progression more severe, for subjects with poorly controlled (PC) type 2 diabetes mellitus (type 2 DM) compared to those without type 2 DM or with better controlled (BC) type 2 DM. The PC group had glycosylated hemoglobin (HbA1) > or = 9%; the BC group had HbA1 < 9%. Data from the longitudinal study of the oral health of residents of the Gila River Indian Community were analyzed. Of the 359 subjects, aged 15 to 57 with less than 25% radiographic bone loss at baseline, 338 did not have type 2 DM, 14 were BC, and 7 were PC. Panoramic radiographs were used to assess interproximal bone level. Bone scores (scale 0-4) corresponding to bone loss of 0%, 1% to 24%, 25% to 49%, 50% to 74%, or > or = 75% were used to identify the worst bone score (WBS) in the dentition. Change in worst bone score at follow-up, the outcome, was specified on a 4-category ordinal scale as no change, or a 1-, 2-, 3-, or 4-category increase over baseline WBS (WBS1). Poorly controlled diabetes, age, calculus, time to follow-up examination, and WBS1 were statistically significant explanatory variables in ordinal logistic regression models. Poorly controlled type 2 DM was positively associated with greater risk for a change in bone score (compared to subjects without type 2 DM) when the covariates were included in the model. The cumulative odds ratio (COR) at each threshold of the ordered response was 11.4 (95% CI = 2.5, 53.3). When contrasted with subjects with BC type 2 DM, the COR for those in the PC group was 5.3 (95% CI = 0.8, 53.3). The COR for subjects with BC type 2 DM was 2.2 (95% CI = 0.7, 6.5), when contrasted to those without type 2 DM. These results suggest that poorer glycemic control leads to both an increased risk for alveolar bone loss and more severe progression over those without type 2 DM, and that there may be a gradient, with the risk for bone loss progression for those with better controlled type 2 DM intermediate to the other 2 groups.

Research Advances: Onions Battle Osteoporosis

ERIC Educational Resources Information Center

King, Angela G.

2005-01-01

Researchers at the University of Bern in Switzerland have identified a compound in the popular vegetable that appears to decrease bone loss in laboratory studies using rat bone cells. It is suggested that eating onions might help prevent bone loss and osteoporosis, a disease, which predominantly affects older women.

Alpha-1 antitrypsin gene therapy prevented bone loss in ovariectomy induced osteoporosis mouse model

USDA-ARS?s Scientific Manuscript database

Osteoporosis is a major healthcare burden affecting mostly postmenopausal women characterized by compromised bone strength and increased risk of fragility fracture. Although pathogenesis of this disease is complex, elevated proinflammatory cytokine production is clearly involved in bone loss at meno...

Mechanical Signaling for Bone Modeling and Remodeling

PubMed Central

Robling, Alexander G.; Turner, Charles H.

2012-01-01

Proper development of the skeleton in utero and during growth requires mechanical stimulation. Loading results in adaptive changes in bone that strengthen bone structure. Bone’s adaptive response is regulated by the ability of resident bone cells to perceive and translate mechanical energy into a cascade of structural and biochemical changes within the cells — a process known as mechanotransduction. Mechanotransduction pathways are among the most anabolic in bone, and consequently, there is great interest in elucidating how mechanical loading produces its observed effects, including increased bone formation, reduced bone loss, changes in bone cell differentiation and lifespan, among others. A molecular understanding of these processes is developing, and with it comes a profound new insight into the biology of bone. In this article, we review the nature of the physical stimulus to which bone cells mount an adaptive response, including the identity of the sensor cells, their attributes and physical environment, and putative mechanoreceptors they express. Particular attention is allotted to the focal adhesion and Wnt signaling, in light of their emerging role in bone mechanotransduction. The cellular mechanisms for increased bone loss during disuse, and reduced bone loss during loading are considered. Finally, we summarize the published data on bone cell accommodation, whereby bone cells stop responding to mechanical signaling events. Collectively, these data highlight the complex yet finely orchestrated process of mechanically regulated bone homeostasis. PMID:19817708

Accelerated bone mass senescence after hematopoietic stem cell transplantation.

PubMed

Serio, B; Pezzullo, L; Fontana, R; Annunziata, S; Rosamilio, R; Sessa, M; Giudice, V; Ferrara, I; Rocco, M; De Rosa, G; Ricci, P; Tauchmanovà, L; Montuori, N; Selleri, C

2013-01-01

Osteoporosis and avascular necrosis (AVN) are long-lasting and debilitating complications of hematopoietic stem cell transplantation (HSCT). We describe the magnitude of bone loss, AVN and impairment in osteogenic cell compartment following autologous (auto) and allogeneic (allo) HSCT, through the retrospective bone damage revaluation of 100 (50 auto- and 50 allo-HSCT) long-term survivors up to 15 years after transplant. Current treatment options for the management of these complications are also outlined. We found that auto- and allo-HSCT recipients show accelerated bone mineral loss and micro-architectural deterioration during the first years after transplant. Bone mass density (BMD) at the lumbar spine, but not at the femur neck, may improve in some patients after HSCT, suggesting more prolonged bone damage in cortical bone. Phalangeal BMD values remained low for even more years, suggesting persistent bone micro-architectural alterations after transplant. The incidence of AVN was higher in allo-HSCT recipients compared to auto-HSCT recipients. Steroid treatment length, but not its cumulative dose was associated with a higher incidence of bone loss. Allo-HSCT recipients affected by chronic graft versus host disease seem to be at greater risk of continuous bone loss and AVN development. Reduced BMD and higher incidence of AVN was partly related to a reduced regenerating capacity of the normal marrow osteogenic cell compartment. Our results suggest that all patients after auto-HSCT and allo-HSCT should be evaluated for their bone status and treated with anti-resorptive therapy as soon as abnormalities are detected.

Quantitative evaluation of bone resorption activity of osteoclast-like cells by measuring calcium phosphate resorbing area using incubator-facilitated and video-enhanced microscopy.

PubMed

Morimoto, Yoshitaka; Hoshino, Hironobu; Sakurai, Takashi; Terakawa, Susumu; Nagano, Akira

2009-04-01

Quantitative evaluation of the ability of bone resorption activity in live osteoclast-like cells (OCLs) has not yet been reported on. In this study, we observed the sequential morphological change of OCLs and measured the resorbing calcium phosphate (CP) area made by OCLs alone and with the addition of elcatonin utilizing incubator facilitated video-enhanced microscopy. OCLs, which were obtained from a coculture of ddy-mouse osteoblastic cells and bone marrow cells, were cultured on CP-coated quartz cover slips. The CP-free area increased constantly in the OCLs alone, whereas it did not increase after the addition of elcatonin. This study showed that analysis of the resorbed areas under the OCL body using this method enables the sequential quantitative evaluation of the bone resorption activity and the effect of several therapeutic agents on bone resorption in vitro.

Load-adaptive bone remodeling simulations reveal osteoporotic microstructural and mechanical changes in whole human vertebrae.

PubMed

Badilatti, Sandro D; Christen, Patrik; Parkinson, Ian; Müller, Ralph

2016-12-08

Osteoporosis is a major medical burden and its impact is expected to increase in our aging society. It is associated with low bone density and microstructural deterioration. Treatments are available, but the critical factor is to define individuals at risk from osteoporotic fractures. Computational simulations investigating not only changes in net bone tissue volume, but also changes in its microstructure where osteoporotic deterioration occur might help to better predict the risk of fractures. In this study, bone remodeling simulations with a mechanical feedback loop were used to predict microstructural changes due to osteoporosis and their impact on bone fragility from 50 to 80 years of age. Starting from homeostatic bone remodeling of a group of seven, mixed sex whole vertebrae, five mechanostat models mimicking different biological alterations associated with osteoporosis were developed, leading to imbalanced bone formation and resorption with a total net loss of bone tissue. A model with reduced bone formation rate and cell sensitivity led to the best match of morphometric indices compared to literature data and was chosen to predict postmenopausal osteoporotic bone loss in the whole group. Thirty years of osteoporotic bone loss were predicted with changes in morphometric indices in agreement with experimental measurements, and only showing major deviations in trabecular number and trabecular separation. In particular, although being optimized to match to the morphometric indices alone, the predicted bone loss revealed realistic changes on the organ level and on biomechanical competence. While the osteoporotic bone was able to maintain the mechanical stability to a great extent, higher fragility towards error loads was found for the osteoporotic bones. Copyright © 2016 Elsevier Ltd. All rights reserved.

Comparison of bone density in amenorrheic women due to athletics, weight loss, and premature menopause.

PubMed

Jones, K P; Ravnikar, V A; Tulchinsky, D; Schiff, I

1985-07-01

Studied was the peripheral bone density of 39 women (ages 18 to 43) with the diagnosis of secondary amenorrhea in an effort to define the population of amenorrheic women at risk for osteoporosis. Eight women had exercise-induced amenorrhea (athletes), 20 women had amenorrhea associated with weight loss, and 11 women had premature menopause. These diagnoses were made on the basis of history, physical examination, and luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin levels, and failure to have withdrawal bleeding after the administration of progestin. Twenty-five nonathletic, normally menstruating women served as control subjects. The peripheral bone density of the amenorrheic athletes (0.738 g/cm2 +/- 0.047) was not significantly different from that of the controls (0.726 g/cm2 +/- 0.044). The average bone density of the group with weight loss-associated amenorrhea (0.672 g/cm2 +/- 0.066) was significantly less than controls (P less than .005) as was that of the women with premature menopause (0.616 g/cm2 +/- 0.048, P less than .001). There was a significant correlation between months of amenorrhea and decrease in bone density (r = 0.506, P less than .001). From this study it was concluded that women with exercise-associated amenorrhea are not at significant risk for cortical bone loss as measured by direct photon absorptiometry. Women with weight loss-associated amenorrhea and women with premature menopause are at significant risk for bone loss when compared with normal controls.

Osteoporosis and Periodontitis.

PubMed

Wang, Chin-Wei Jeff; McCauley, Laurie K

2016-12-01

Osteoporosis and periodontitis are both diseases characterized by bone resorption. Osteoporosis features systemic degenerative bone loss that leads to loss of skeletal cancellous microstructure and subsequent fracture, whereas periodontitis involves local inflammatory bone loss, following an infectious breach of the alveolar cortical bone, and it may result in tooth loss. Most cross-sectional studies have confirmed the association of osteoporosis and periodontitis primarily on radiographic measurements and to a lesser degree on clinical parameters. Multiple shared risk factors include age, genetics, hormonal change, smoking, as well as calcium and vitamin D deficiency. Both diseases could also be risk factors for each other and have a mutual impact that requires concomitant management. Suggested mechanisms underlying the linkage are disruption of the homeostasis concerning bone remodeling, hormonal balance, and inflammation resolution. A mutual interventional approach is emerging with complex treatment interactions. Prevention and management of both diseases require interdisciplinary approaches and warrants future well-controlled longitudinal and interventional studies for evidence-based clinical guidelines.

Radiographic sclerotic contour loss in the identification of glenoid bone loss.

PubMed

Bornes, Troy D; Jaremko, Jacob L; Beaupre, Lauren A; Bouliane, Martin J

2016-07-01

Quantification of glenoid bone loss guides surgical management in the setting of anterior shoulder instability. Glenoid defects resulting in ≥20 % articular area loss require bony reconstruction. The objective of this study was to evaluate the utility of sclerotic glenoid contour loss on true anteroposterior radiography in the detection of varying quantities of simulated glenoid bone loss using a cadaveric model. Eight cadaveric scapulae with full radiographic sclerotic contour were osteotomized to produce glenoid surface area reductions of 10-50 %. Radiography was performed initially and following each osteotomy, and assessed by an orthopedic surgeon and radiologist twice. Quantity of glenoid loss was compared using Fisher's exact test. Sensitivity, specificity, and reliability analyses were performed. On the first radiographic review, sclerotic contour loss was detected in 6 out of 8 scapulae with 50 % area loss, but only 1 out of 8 scapulae with 20 % area loss. There was a significantly higher proportion of radiographs containing sclerotic contour loss for defects with 50 % area loss compared to those with 0-25 % loss (p ≤ 0.02). In the detection of ≥20 % area loss, sclerotic contour loss had a sensitivity of 33-43 % and specificity of 88-100 %. Moderate inter-observer reliability (Cohen's kappa value of 0.42-0.53) and intra-observer reliability (kappa value of 0.46-0.58) were found. Radiographic sclerotic contour loss is commonly observed in radiographs of scapulae with 40-50 % glenoid area loss and less often with smaller lesions. However, this finding lacks utility in discerning specific quantifications of glenoid bone loss. In a clinical setting, sclerotic contour loss suggests the presence of a large glenoid defect that may require bony reconstruction. However, an intact sclerotic contour does not rule out significant bone loss.

[Oral Anatomy.

PubMed

Abe, Shinichi

With regard to oral cavity, it is known that jaw bone morphology greatly changes with tooth loss. Therefore, it is necessary to consider the muscles attached to the jaw bone and the surrounding vessels and nerves, in connection with the jaw bone morphology after tooth loss. As an example, the height of the mandibular bone decreases to the position of the mylohyoid line after tooth loss. By this marked morphological change in the alveolar area, the lingual nerve and the lingual artery branches running in the sublingual area on the mandibular inner surface becomes located in the area almost the same as the alveolar crest.

Dried Plum Protects From Radiation-Induced Bone Loss by Attenuating Pro-Osteoclastic and Oxidative Stress Responses

NASA Technical Reports Server (NTRS)

Globus, Ruth

2015-01-01

Future space explorations beyond the earths magnetosphere will increase human exposure to space radiation and associated risks to skeletal health. We hypothesize that oxidative stress resulting from radiation exposure plays a major role in progressive bone loss and dysfunction in associated tissue. In animal studies, increased free radical formation is associated with pathological changes in bone structure, enhanced bone resorption, reduced bone formation and decreased bone mineral density, which can lead to skeletal fragility. Our long-term goals are to define the mechanisms and risk of bone loss in the spaceflight environment and to facilitate the development of effective countermeasures. We had previously reported that exposure to low or high-LET radiation correlates with an acute increase in the expression of pro-osteoclastic and oxidative stress genes in bone during the early response to radiation followed by pathological changes in skeletal structure. We then conducted systematic screening for potential countermeasures against bone loss where we tested the ability of various antioxidants to mitigate the radiation-induced increase in expression of these markers. For the screen, 16-week old C57Bl6J mice were treated with a dietary antioxidant cocktail, injectable DHLA or a dried plum-enriched diet (DP). Mice were then exposed to 2Gy 137Cs radiation and one day later, marrow cells were collected and the relevant genes analyzed for expression levels. Among the candidate countermeasures tested, DP was most effective in reducing the expression of genes associated with bone loss. Furthermore, analysis of skeletal structure by microcomputed tomography (microCT) revealed that DP also prevents the radiation-induced deterioration in skeletal microarchitecture as indicated by parameters such as percent bone volume (BVTV), trabecular spacing and trabecular number. We also found that DP has similar protective effects on skeletal structure in a follow-up study using 1 Gy of sequential proton and iron, radiation species relevant to spaceflight. When cultured ex vivo under osteogenic conditions, bone marrow-derived cells from DP-fed animals exhibited increased colony numbers compared to control diet-fed animals. These findings suggest that DP exerts pro-osteogenic effects apart from its previously demonstrated anti-resorptive action, which may be one of the mechanisms underlying its radioprotective effect on bone. In conclusion, a diet enriched in certain types of antioxidants may be useful as an intervention for radiation-induced bone loss.

Composite Bone and Soft Tissue Loss Treated with Distraction Histiogenesis

DTIC Science & Technology

2010-01-01

their frames removed had healed docking sites, and the fourth whose frame remained in place had a healing fracture without evidence of delayed union ...interventions (3–8). The goals of limb salvage surgery in this setting are to restore length and alignment, regenerate bone loss, obtain fracture union ...angulation to manage composite bone and soft tissue loss associated with combat-related type IIIB open tibia fractures . Four patients underwent placement

Targeting skeletal endothelium to ameliorate bone loss.

PubMed

Xu, Ren; Yallowitz, Alisha; Qin, An; Wu, Zhuhao; Shin, Dong Yeon; Kim, Jung-Min; Debnath, Shawon; Ji, Gang; Bostrom, Mathias P; Yang, Xu; Zhang, Chao; Dong, Han; Kermani, Pouneh; Lalani, Sarfaraz; Li, Na; Liu, Yifang; Poulos, Michael G; Wach, Amanda; Zhang, Yi; Inoue, Kazuki; Di Lorenzo, Annarita; Zhao, Baohong; Butler, Jason M; Shim, Jae-Hyuck; Glimcher, Laurie H; Greenblatt, Matthew B

2018-06-01

Recent studies have identified a specialized subset of CD31 hi endomucin hi (CD31 hi EMCN hi ) vascular endothelium that positively regulates bone formation. However, it remains unclear how CD31 hi EMCN hi endothelium levels are coupled to anabolic bone formation. Mice with an osteoblast-specific deletion of Shn3, which have markedly elevated bone formation, demonstrated an increase in CD31 hi EMCN hi endothelium. Transcriptomic analysis identified SLIT3 as an osteoblast-derived, SHN3-regulated proangiogenic factor. Genetic deletion of Slit3 reduced skeletal CD31 hi EMCN hi endothelium, resulted in low bone mass because of impaired bone formation and partially reversed the high bone mass phenotype of Shn3 -/- mice. This coupling between osteoblasts and CD31 hi EMCN hi endothelium is essential for bone healing, as shown by defective fracture repair in SLIT3-mutant mice and enhanced fracture repair in SHN3-mutant mice. Finally, administration of recombinant SLIT3 both enhanced bone fracture healing and counteracted bone loss in a mouse model of postmenopausal osteoporosis. Thus, drugs that target the SLIT3 pathway may represent a new approach for vascular-targeted osteoanabolic therapy to treat bone loss.

A Flexible Method for Producing F.E.M. Analysis of Bone Using Open-Source Software

NASA Technical Reports Server (NTRS)

Boppana, Abhishektha; Sefcik, Ryan; Myers, Jerry G.; Lewandowski, Beth

2016-01-01

Individuals who experience decreases in load-bearing bone densities can be subject to a higher risk of bone fracture during daily activity. Astronauts may lose up to nine percent of their load-bearing bone density for every month they spend in space [1]. Because of this, specialized countermeasures reduce percent loss in bone density and reduce fracture risk upon returning to Earth. Astronauts will typically not be at risk for fracture during spaceflight, because of the lesser loads experienced in microgravity conditions. However, once back on Earth, astronauts have an increased risk for bone fracture as a result of weakened bone and return to 1G conditions [2]. It is therefore important to understand the significance of any bone density loss in addition to developing exercises in an attempt to limit losses in bone strength. NASA seeks to develop a deeper understanding of fracture risk through the development of a computational bone strength model to assess the bone fracture risk of astronauts pre-flight and post-flight. This study addresses the several key processes needed to develop such strength analyses using medical image processing and finite element modeling.

Osteoprotective effects of osthole in a mouse model of 5/6 nephrectomy through inhibiting osteoclast formation.

PubMed

Li, Xiaofeng; Xue, Chunchun; Wang, Libo; Tang, Dezhi; Huang, Jian; Zhao, Yongjian; Chen, Yan; Zhao, Dongfeng; Shi, Qi; Wang, Yongjun; Shu, Bing

2016-10-01

The present study aimed to investigate the effects of osthole on osteoclast formation and bone loss in a mouse model of 5/6 nephrectomy. The mice in control and osthole groups were treated 1 month following 5/6 nephrectomy with either a placebo or osthole, respectively. At 2 months post‑nephrectomy, the L4 vertebrae were harvested. The bone mineral density (BMD) of cancellous bone was measured using micro‑CT and tartrate‑resistant acid phosphatase (TRAP) staining was performed to evaluate osteoclast formation. Immunohistochemistry staining and reverse transcription‑quantitative polymerase chain reaction were performed to detect the expression of nuclear factor of activated T‑cells, cytoplasmic‑1 (NFATc‑1), c‑Fos, cathepsin K, Trap, matrix metalloproteinase 9 (Mmp9), osteoprotegerin (Opg) and receptor activator for nuclear factor‑κB ligand (Rankl). Bone marrow cells were cultured with osthole, and osteoclast formation was shown by TRAP staining. Primary calvaria osteoblasts were cultured with osthole, and expression levels of Opg and Rankl were detected. Compared with the sham group, the BMD of mice in model group was significantly reduced. The numbers of osteoclasts and the expression levels of NFATc‑1, c‑Fos, cathepsin K and Mmp9 were significantly increased. Compared with the control group, the mice in the osthole group exhibited increased BMD of the L4 vertebrae, a reduction in osteoclast numbers and decreased expression levels of NFATc‑1, c‑Fos, cathepsin K and Mmp9. In vitro experiments also showed that osteoclast formation was decreased following treatment with osthole. Osteoprotegerin (Opg)/receptor activator for nuclear factor‑κB ligand (Rankl) was upregulated by osthole treatment in the L4 vertebrae and in primary cultures of calvarial osteoblasts. Osthole inhibited osteoclast formation and partially reversed the bone loss induced by 5/6 nephrectomy in mice through the upregulation of OPG/RANKL.

Increased activity of osteocyte autophagy in ovariectomized rats and its correlation with oxidative stress status and bone loss

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

Yang, Yuehua, E-mail: yuesjtu@126.com; Zheng, Xinfeng, E-mail: zxf272@126.com; Li, Bo, E-mail: libo@126.com

Highlights: • Examine autophagy level in the proximal tibia of ovariectomized rats. • Investigate whether autophagy level is associated with bone loss. • Investigate whether autophagy level is associated with oxidative stress status. - Abstract: Objectives: The objectives of the present study were to investigate ovariectomy on autophagy level in the bone and to examine whether autophagy level is associated with bone loss and oxidative stress status. Methods: 36 female Sprague–Dawley rats were randomly divided into sham-operated (Sham), and ovariectomized (OVX) rats treated either with vehicle or 17-β-estradiol. At the end of the six-week treatment, bone mineral density (BMD) andmore » bone micro-architecture in proximal tibias were assessed by micro-CT. Serum 17β-estradiol (E2) level were measured. Total antioxidant capacity (T-AOC), superoxide dismutase (SOD) activity, catalase (CAT) activity in proximal tibia was also determined. The osteocyte autophagy in proximal tibias was detected respectively by Transmission Electron Microscopy (TEM), immunofluorescent histochemistry (IH), realtime-PCR and Western blot. In addition, the spearman correlation between bone mass, oxidative stress status, serum E2 and autophagy were analyzed. Results: Ovariectomy increased Atg5, LC3, and Beclin1 mRNA and proteins expressions while decreased p62 expression. Ovariectomy also declined the activities of T-AOC, CAT, and SOD. Treatment with E2 prevented the reduction in bone mass as well as restored the autophagy level. Furthermore, LC3-II expression was inversely correlated with T-AOC, CAT, and SOD activities. A significant inverse correlation between LC3-II expression and BV/TV, Tb.N, BMD in proximal tibias was found. Conclusions: Ovariectomy induced oxidative stress, autophagy and bone loss. Autophagy of osteocyte was inversely correlated with oxidative stress status and bone loss.« less

A Radiographic Comparison of Progressive and Conventional Loading on Crestal Bone Loss and Density in Single Dental Implants: A Randomized Controlled Trial Study

PubMed Central

Ghoveizi, Rahab; Alikhasi, Marzieh; Siadat, Mohammad-Reza; Siadat, Hakimeh; Sorouri, Majid

2013-01-01

Objective: Crestal bone loss is a biological complication in implant dentistry. The aim of this study was to compare the effect of progressive and conventional loading on crestal bone height and bone density around single osseointegrated implants in the posterior maxilla by a longitudinal radiographic assessment technique. Materials and Methods: Twenty micro thread implants were placed in 10 patients (two implants per patient). One of the two implants in each patient was assigned to progressive and the other to conventional loading groups. Eight weeks after surgery, conventional implants were restored with a metal ceramic crown and the progressive group underwent a progressive loading protocol. The progressive loading group took different temporary acrylic crowns at 2, 4 and 6 months. After eight months, acrylic crowns were replaced with a metal ceramic crown. Computer radiography of both progressive and conventional implants was taken at 2, 4, 6, and 12 months. Image analysis was performed to measure the height of crestal bone loss and bone density. Results: The mean values of crestal bone loss at month 12 were 0.11 (0.19) mm for progressively and 0.36 (0.36) mm for conventionally loaded implants, with a statistically significant difference (P < 0.05) using Wilcoxon sign rank. Progressively loaded group showed a trend for higher bone density gain compared to the conventionally loaded group, but when tested with repeated measure ANOVA, the differences were not statistically significant (P > 0.05). Conclusion: The progressive group showed less crestal bone loss in single osseointegrated implant than the conventional group. Bone density around progressively loaded implants showed increase in crestal, middle and apical areas. PMID:23724215

Bone-Protective Effects of Dried Plum in Postmenopausal Women: Efficacy and Possible Mechanisms

PubMed Central

Arjmandi, Bahram H.; Johnson, Sarah A.; Pourafshar, Shirin; Navaei, Negin; George, Kelli S.; Hooshmand, Shirin; Chai, Sheau C.; Akhavan, Neda S.

2017-01-01

Osteoporosis is an age-related chronic disease characterized by a loss of bone mass and quality, and is associated with an increased risk of fragility fractures. Postmenopausal women are at the greatest risk of developing osteoporosis due to the cessation in ovarian hormone production, which causes accelerated bone loss. As the demographic shifts to a more aged population, a growing number of postmenopausal women will be afflicted with osteoporosis. Certain lifestyle factors, including nutrition and exercise, are known to reduce the risk of developing osteoporosis and therefore play an important role in bone health. In terms of nutrition, accumulating evidence suggests that dried plum (Prunus domestica L.) is potentially an efficacious intervention for preventing and reversing bone mass and structural loss in an ovariectomized rat model of osteoporosis, as well as in osteopenic postmenopausal women. Here, we provide evidence supporting the efficacy of dried plum in preventing and reversing bone loss associated with ovarian hormone deficiency in rodent models and in humans. We end with the results of a recent follow-up study demonstrating that postmenopausal women who previously consumed 100 g dried plum per day during our one-year clinical trial conducted five years earlier retained bone mineral density to a greater extent than those receiving a comparative control. Additionally, we highlight the possible mechanisms of action by which bioactive compounds in dried plum exert bone-protective effects. Overall, the findings of our studies and others strongly suggest that dried plum in its whole form is a promising and efficacious functional food therapy for preventing bone loss in postmenopausal women, with the potential for long-lasting bone-protective effects. PMID:28505102

Vitamin K’s role in age-related bone loss: A critical review

USDA-ARS?s Scientific Manuscript database

The protective role of vitamin K in age-related bone loss continues to be controversial. The results of observational analyses are inconsistent with respect to associations between vitamin K status and bone, which arguably may be related to the limitations of observational study designs and analyt...

Effects of endocrine and inflammatory changes on markers of bone turnover following Roux-en-Y gastric bypass surgery

USDA-ARS?s Scientific Manuscript database

Bariatric surgery is associated with increased bone turnover. The mechanisms involved are unclear but may involve nutrition, mechanical unloading, altered secretion of gastrointestinal and adipose hormones and changes in inflammatory status leading to weight loss induced bone loss. We assessed marke...

Synergistic effects of green tea polyphenols and alphacalcidol on chronic inflammation-induced bone loss in female rats

USDA-ARS?s Scientific Manuscript database

Summary: Studies suggest that green tea polyphenols (GTP) or alphacalcidol is promising agent for preventing bone loss. Findings that GTP supplementation in the drinking water plus alphacalcidol administration resulted in increased bone mass via a decrease of oxidative stress and inflammation sugges...

Transplantation of osteoporotic bone marrow stromal cells rejuvenated by the overexpression of SATB2 prevents alveolar bone loss in ovariectomized rats.

PubMed

Xu, Rongyao; Fu, Zongyun; Liu, Xue; Xiao, Tao; Zhang, Ping; Du, Yifei; Yuan, Hua; Cheng, Jie; Jiang, Hongbing

2016-11-01

Estrogen-deficient osteoporosis is an aging-related disease with high morbidity that not only significantly increases a woman's risk of fragility fracture but is also associated with tooth and bone loss in the supporting alveolar bone of the jaw. Emerging evidence suggests that the aging of bone marrow stromal cells (BMSCs) contributes to the development of osteoporosis. In this study, we aimed to investigate the role of the special AT-rich sequence-binding protein 2 (SATB2), a stemness and senescence regulator of craniofacial BMSCs, in rat ovariectomy-induced alveolar osteoporosis. We also sought to determine whether transplantation of SATB2-modified BMSCs could ameliorate estrogen deficient alveolar bone loss. Our data revealed that BMSCs from ovariectomy-induced alveolar bone exhibited typical senescence phenotypes such as diminished stemness and osteogenic capacity, increased expression of senescence or osteoclastic markers and enhanced adipogenic potential. These phenotypic changes are a result of SATB2-mediated senescence dysregulation as evidenced by nuclear γH2AX foci formation. Moreover, overexpression of SATB2 significantly alleviated the senescence of osteoporotic BMSCs in vitro. Importantly, transplantation of SATB2-modified BMSCs significantly attenuated ovariectomy-induced alveolar bone loss in vivo. Together, our results revealed that SATB2 is a critical regulator of alveolar BMSC senescence, and its overexpression decreases these senescent changes both in vitro and in vivo. SATB2-modified BMSC delivery could be a viable and promising therapeutic strategy for alveolar bone loss induced by estrogen-deficient osteoporosis. Copyright © 2016 Elsevier Inc. All rights reserved.

Superolateral Hoffa's fat pad (SHFP) oedema and patellar cartilage volume loss: quantitative analysis using longitudinal data from the Foundation for the National Institute of Health (FNIH) Osteoarthritis Biomarkers Consortium.

PubMed

Haj-Mirzaian, Arya; Guermazi, Ali; Hafezi-Nejad, Nima; Sereni, Christopher; Hakky, Michael; Hunter, David J; Zikria, Bashir; Roemer, Frank W; Demehri, Shadpour

2018-04-12

To determine the association of superolateral Hoffa's fat pad (SHFP) oedema and patellofemoral joint structural damage in participants of Foundation for the National Institute of Health Osteoarthritis Biomarkers Consortium study. Baseline and 24-month MRIs of 600 subjects were assessed. The presence of SHFP oedema (using 0-3 grading scale) and patellar morphology metrics were determined using baseline MRI. Quantitative patellar cartilage volume and semi-quantitative MRI osteoarthritis knee score (MOAKS) variables were extracted. The associations between SHFP oedema and patellar cartilage damage, bone marrow lesion (BML), osteophyte and morphology were evaluated in cross-sectional model. In longitudinal analysis, the associations between oedema and cartilage volume loss (defined using reliable change index) and MOAKS worsening were evaluated. In cross-sectional evaluations, the presence of SHFP oedema was associated with simultaneous lateral patellar cartilage/BML defects and inferior-medial patellar osteophyte size. A significant positive correlation between the degree of patella alta and SHFP oedema was detected (r = 0.259, p < 0.001). The presence of oedema was associated with 24-month cartilage volume loss (odds ratio (OR) 2.11, 95% confidence interval 1.46-3.06) and medial patellar BML size (OR 1.92 (1.15-3.21)) and number (OR 2.50 (1.29-4.88)) worsening. The optimal cut-off value for the grade of baseline SHFP oedema regarding both presence and worsening of patellar structural damage was ≥ 1 (presence of any SHFP hyperintensity). The presence of SHFP oedema could be considered as a predictor of future patellar cartilage loss and BML worsening, and an indicator of simultaneous cartilage, BML and osteophyte defects. • SHFP oedema was associated with simultaneous lateral patellar OA-related structural damage. • SHFP oedema was associated with longitudinal patellar cartilage loss over 24 months. • SHFP oedema could be considered as indicator and predictor of patellar OA.

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.

Effect of 1 year of an intentional weight loss intervention on bone mineral density in type 2 diabetes: results from the Look AHEAD randomized trial.

PubMed

Schwartz, Ann V; Johnson, Karen C; Kahn, Steven E; Shepherd, John A; Nevitt, Michael C; Peters, Anne L; Walkup, Michael P; Hodges, Amelia; Williams, Carrie C; Bray, George A

2012-03-01

Intentional weight loss is an important component of treatment for overweight patients with type 2 diabetes, but the effects on bone density are not known. We used data from the Look AHEAD trial to determine the impact of an intensive lifestyle weight loss intervention (ILI) compared with diabetes support and education (DSE) on changes in bone mineral density (BMD) over 12 months. Overweight and obese adults with type 2 diabetes were randomly assigned to ILI or DSE. In a substudy of BMD conducted at 5 of 16 clinical centers, hip, spine, and whole body dual X-ray absorptiometry scans were obtained at baseline and 1-year later on 642 of 739 ILI and 632 of 740 DSE participants. At baseline, mean age was 58.4 years, and average body mass index was 35.2 kg/m(2). Total hip BMD T-score was <-2.5 in 1% and <-1.0 in 8%. At 1 year, weight loss was greater in ILI than DSE (-8.6% versus -0.7%), and glycemic control and fitness were also improved. Bone loss over 1 year was greater in ILI at the total hip (-1.4% versus -0.4%; p < 0.001) and femoral neck (-1.5% versus -0.8%; p = 0.009), but change in BMD for the lumbar spine and whole body did not differ between groups. In ILI, bone loss at the total hip was independently associated with weight loss in men and women and with poorer glycemic control in men, but was not associated with changes in fitness. One year of an intensive lifestyle intervention in adults with type 2 diabetes, resulting in weight loss, was associated with a modest increase in hip bone loss despite improved fitness and glycemic control. Copyright © 2012 American Society for Bone and Mineral Research.

Insights from the conduct of a device trial in older persons: Low Magnitude Mechanical Stimulation for Musculoskeletal Health

PubMed Central

Kiel, Douglas P.; Hannan, Marian T.; Barton, Bruce A.; Bouxsein, Mary L.; Lang, Thomas. F.; Brown, Kathleen M.; Shane, Elizabeth; Magaziner, Jay; Zimmerman, Sheryl; Rubin, Clinton T.

2011-01-01

Background Osteoporosis is a common complication of aging. Alternatives to pharmacologic treatment are needed for older adults. Non-pharmacologic treatment with low magnitude, high frequency mechanical stimulation has been shown to prevent bone loss in animal and human studies. Methods The VIBES (Vibration to Improve Bone Density in Elderly Subjects) study is a randomized, double-blind, sham-controlled trial of the efficacy of low magnitude, high frequency mechanical stimulation in 200 men and women aged 60 years and older with bone mineral density T-scores by dual-x-ray absorptiometry between –1 and –2.5 at entry. Participants are healthy, cognitively intact residents of independent living communities in the Boston area who receive free calcium and Vitamin D supplements. They are randomly assigned to active or sham treatment and stand on their assigned platform once daily for 10 minutes. All platforms have adherence data collection software downloadable to a laptop computer. Adverse events are closely monitored. 174 participants were randomized and will be followed for two years. Almost all active subjects have attained one year of follow-up. Bone mineral density is measured by both dual x-ray absorptiometry and quantitative computed tomography at baseline and annually. The main analysis will compare mean changes from baseline in volumetric bone density by quantitative computed tomography in active and sham groups. Adherence and treatment effect magnitude will also be evaluated. Secondary analyses will compare changes in three biochemical markers of bone turnover as well as longitudinal comparisons of muscle and balance endpoints. Results The VIBES trial has completed its first year of data collection and encountered multiple challenges leading to valuable lessons learned about the areas of recruitment from independent living communities, deployment of multi-user mechanical devices using radio frequency identification cards and electronic adherence monitoring, organization of transportation for imaging at a central site, and the expansion of study aims to include additional musculoskeletal outcomes. Conclusions These lessons will guide future investigations in studies of individuals of advanced age. PMID:20571129

Calcium Kinetics During Space Flight

NASA Technical Reports Server (NTRS)

Smith, Scott M.; OBrien, K. O.; Abrams, S. A.; Wastney, M. E.

2005-01-01

Bone loss during space flight is one of the most critical challenges to astronaut health on space exploration missions. Defining the time course and mechanism of these changes will aid in developing means to counteract bone loss during space flight, and will have relevance for other clinical situations that impair weight-bearing activity. Bone health is a product of the balance between bone formation and bone resorption. Early space research could not clearly identify which of these was the main process altered in bone loss, but identification of the collagen crosslinks in the 1990s made possible a clear understanding that the impact of space flight was greater on bone resorption, with bone formation being unchanged or only slightly decreased. Calcium kinetics data showed that bone resorption was greater during flight than before flight (668 plus or minus 130 vs. 427 plus or minus 153 mg/d, p less than 0.001), and clearly documented that true intestinal calcium absorption was lower during flight than before flight (233 plus or minus 87 vs. 460 plus or minus 47 mg/d, p less than 0.01). Weightlessness had a detrimental effect on the balance in bone turnover: the difference between daily calcium balance during flight (-234 plus or minus 102 mg/d) and calcium balance before flight (63 plus or minus 75 mg/d) approached 300 mg/d (p less than 0.01). These data demonstrate that the bone loss that occurs during space flight is a consequence of increased bone resorption and decreased intestinal calcium absorption. Examining the changes in bone and calcium homeostasis in the initial days and weeks of space flight, as well as at later times on missions longer than 6 months, is critical to understanding the nature of bone adaptation to weightlessness. To increase knowledge of these changes, we studied bone adaptation to space flight on the 16-day Space Shuttle Columbia (STS-107) mission. When the brave and talented crew of Columbia were lost during reentry on the tragic morning of February 1, 2003, in a much smaller matter, the scientific products of this experiment, successfully obtained on orbit, were lost as well. As we begin to plan for missions back to the Moon, and even off to Mars, many questions remain to be answered. Counteracting bone loss is one of the greatest challenges. Calcium kinetics studies provide a valuable tool for assessing this loss, and evaluating countermeasures.

Gene Expression in Bone

NASA Astrophysics Data System (ADS)

D'Ambrogio, A.

Skeletal system has two main functions, to provide mechanical integrity for both locomotion and protection and to play an important role in mineral homeostasis. There is extensive evidence showing loss of bone mass during long-term Space-Flights. The loss is due to a break in the equilibrium between the activity of osteoblasts (the cells that forms bone) and the activity of osteoclasts (the cells that resorbs bone). Surprisingly, there is scanty information about the possible altered gene expression occurring in cells that form bone in microgravity.(Just 69 articles result from a "gene expression in microgravity" MedLine query.) Gene-chip or microarray technology allows to screen thousands of genes at the same time: the use of this technology on samples coming from cells exposed to microgravity could provide us with many important informations. For example, the identification of the molecules or structures which are the first sensors of the mechanical stress derived from lack of gravity, could help in understanding which is the first event leading to bone loss due to long-term exposure to microgravity. Consequently, this structure could become a target for a custom-designed drug. It is evident that bone mass loss, observed during long-time stay in Space, represents an accelerated model of what happens in aging osteoporosis. Therefore, the discovery and design of drugs able to interfere with the bone-loss process, could help also in preventing negative physiological processes normally observed on Earth. Considering the aims stated above, my research is designed to:

Marginal bone levels at single tooth implants with a conical fixture design. The influence of surface macro- and microstructure.

PubMed

Norton, M R

1998-04-01

The concept of a conical implant design to accommodate single tooth replacement, has previously been shown to result in excessive bone loss, around the machined titanium conical collar, usually down to the 1st thread. This unusually aggressive loss of bone was shown to occur within a short period of time, post loading, with greater than 3 mm of bone loss occurring within the 1st 6 months to 1 year. The influence of implant design, surface texture and microleakage have all been highlighted as a potential cause. A modification of the surface structure, both at the macroscopic and microscopic level, as well as an altered fixture-abutment interface design has resulted in the maintenance of marginal bone around a single tooth titanium implant with a similar conical design. The radiographic follow-up of 33 implants loaded for up to 4 years, has revealed, by comparison, a most favourable maintenance of marginal bone around the conical collar, with a mean marginal bone loss of 0.32 mm mesially and 0.34 mm distally for the whole group. The cumulative mean marginal bone loss mesially and distally is 0.42 mm and 0.40 mm from 1 to 2 years, 0.54 mm and 0.43 mm from 2 to 3 years, 0.51 mm and 0.24 mm from 3 to 4 years, and 0.62 mm and 0.60 mm for implants past their 4 year recall.

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.

Quantifying Leisure Physical Activity and Its Relation to Bone Density and Strength

PubMed Central

SHEDD, KRISTINE M.; HANSON, KATHY B.; ALEKEL, D. LEE; SCHIFERL, DANIEL J.; HANSON, LAURA N.; VAN LOAN, MARTA D.

2010-01-01

Purpose Compare three published methods of quantifying physical activity (total activity, peak strain, and bone-loading exposure (BLE) scores) and identify their associations with areal bone mineral density (aBMD), volumetric BMD (vBMD), and bone strength. Methods Postmenopausal women (N = 239; mean age: 53.8 yr) from Iowa (ISU) and California (UCD) completed the Paffenbarger Physical Activity Questionnaire, which was scored with each method. Dual energy x-ray absorptiometry assessed aBMD at the spine, hip, and femoral neck, and peripheral quantitative computed tomography (pQCT) measured vBMD and bone strength properties at the distal tibia and midshaft femur. Results UCD women had higher total activity scores and hours per week of leisure activity. All scoring methods were correlated with each other. No method was associated with aBMD. Peak strain score was negatively associated with polar moment of inertia and strength–strain index at the tibia, and total activity score was positively associated with cortical area and thickness at the femur. Separating by geographic site, the peak strain and hip BLE scores were negatively associated with pQCT measures at the tibia and femur among ISU subjects. Among UCD women, no method was significantly associated with any tibia measure, but total activity score was positively associated with measures at the femur (P < 0.05 for all associations). Conclusion Given the significantly greater hours per week of leisure activity done by UCD subjects, duration may be an important determinant of the effect physical activity has on bone. The positive association between leisure physical activity (assessed by the total activity score) and cortical bone measures in postmenopausal women may indicate a lifestyle factor that can help offset age-related bone loss. PMID:18046190

Quantifying leisure physical activity and its relation to bone density and strength.

PubMed

Shedd, Kristine M; Hanson, Kathy B; Alekel, D Lee; Schiferl, Daniel J; Hanson, Laura N; Van Loan, Marta D

2007-12-01

Compare three published methods of quantifying physical activity (total activity, peak strain, and bone-loading exposure (BLE) scores) and identify their associations with areal bone mineral density (aBMD), volumetric BMD (vBMD), and bone strength. Postmenopausal women (N = 239; mean age: 53.8 yr) from Iowa (ISU) and California (UCD) completed the Paffenbarger Physical Activity Questionnaire, which was scored with each method. Dual energy x-ray absorptiometry assessed aBMD at the spine, hip, and femoral neck, and peripheral quantitative computed tomography (pQCT) measured vBMD and bone strength properties at the distal tibia and midshaft femur. UCD women had higher total activity scores and hours per week of leisure activity. All scoring methods were correlated with each other. No method was associated with aBMD. Peak strain score was negatively associated with polar moment of inertia and strength-strain index at the tibia, and total activity score was positively associated with cortical area and thickness at the femur. Separating by geographic site, the peak strain and hip BLE scores were negatively associated with pQCT measures at the tibia and femur among ISU subjects. Among UCD women, no method was significantly associated with any tibia measure, but total activity score was positively associated with measures at the femur (P < 0.05 for all associations). Given the significantly greater hours per week of leisure activity done by UCD subjects, duration may be an important determinant of the effect physical activity has on bone. The positive association between leisure physical activity (assessed by the total activity score) and cortical bone measures in postmenopausal women may indicate a lifestyle factor that can help offset age-related bone loss.

Bone and hormonal changes induced by skeletal unloading in the mature male rat

NASA Technical Reports Server (NTRS)

Dehority, W.; Halloran, B. P.; Bikle, D. D.; Curren, T.; Kostenuik, P. J.; Wronski, T. J.; Shen, Y.; Rabkin, B.; Bouraoui, A.; Morey-Holton, E.

1999-01-01

To determine whether the rat hindlimb elevation model can be used to study the effects of spaceflight and loss of gravitational loading on bone in the adult animal, and to examine the effects of age on bone responsiveness to mechanical loading, we studied 6-mo-old rats subjected to hindlimb elevation for up to 5 wk. Loss of weight bearing in the adult induced a mild hypercalcemia, diminished serum 1,25-dihydroxyvitamin D, decreased vertebral bone mass, and blunted the otherwise normal increase in femoral mass associated with bone maturation. Unloading decreased osteoblast numbers and reduced periosteal and cancellous bone formation but had no effect on bone resorption. Mineralizing surface, mineral apposition rate, and bone formation rate decreased during unloading. Our results demonstrate the utility of the adult rat hindlimb elevation model as a means of simulating the loss of gravitational loading on the skeleton, and they show that the effects of nonweight bearing are prolonged and have a greater relative effect on bone formation in the adult than in the young growing animal.

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.

The orally available Btk inhibitor ibrutinib (PCI-32765) protects against osteoclast-mediated bone loss.

PubMed

Shinohara, Masahiro; Chang, Betty Y; Buggy, Joseph J; Nagai, Yusuke; Kodama, Tatsuhiko; Asahara, Hiroshi; Takayanagi, Hiroshi

2014-03-01

Bone-resorbing osteoclasts play an essential role in normal bone homeostasis, as well as in various bone disorders such as osteoporosis and rheumatoid arthritis. Previously we showed that the Tec family of tyrosine kinases is essential for the differentiation of osteoclasts and the inhibition of Btk is a promising strategy for the prevention of the bone loss in osteoclast-associated bone disorders. Here we demonstrate that an orally available Btk inhibitor, ibrutinib (PCI-32765), suppresses osteoclastic bone resorption by inhibiting both osteoclast differentiation and function. Ibrutinib downregulated the expression of NFATc1, the key transcription factor for osteoclastogenesis, and disrupted the formation of the actin ring in mature osteoclasts. In addition, genome-wide screening revealed that Btk regulates the expression of the genes involved in osteoclast differentiation and function in both an NFATc1-dependent and -independent manner. Finally, we showed that ibrutinib administration ameliorated the bone loss that developed in a RANKL-induced osteoporosis mouse model. Thus, this study suggests ibrutinib to be a promising therapeutic agent for osteoclast-associated bone diseases. Copyright © 2013 Elsevier Inc. All rights reserved.

Awareness, concern, and communication between physicians and patients on bone health in cancer.

PubMed

Tripathy, Debu; Durie, Brian G M; Mautner, Beatrice; Ferenz, Krag S; Moul, Judd W

2014-06-01

This study aims to explore physician-patient communications about bone metastases and cancer treatment-induced bone loss (CTIBL). The study utilizes online survey of patients with breast cancer, prostate cancer, and multiple myeloma, and the physicians who treat them. Even though 69 and 48 % of patients with nonmetastatic breast and prostate cancer aware of treatment-induced bone loss, only 39 and 23 %, respectively, were concerned about bone loss. Yet, 62 and 71 % of oncologists treating breast and prostate cancer felt that their patients were concerned. Among patients with metastatic breast and prostate cancer, two thirds had not discussed treatment for bone metastases with their doctor; when discussed, 88 and 91 % of discussions were initiated by the doctor, usually prior to initiating treatment. Most myeloma patients (77 %) had discussed treatment options with their physicians; 99 % of hematologists reported discussing treatment of bone disease with patients. Physicians are primary sources of information to patients regarding bone health. There is a gap between what physicians assume their patients know about bone health and the patients' perceptions, presenting a need for systematic awareness and education.

Decursin from Angelica gigas suppresses RANKL-induced osteoclast formation and bone loss.

PubMed

Wang, Xin; Zheng, Ting; Kang, Ju-Hee; Li, Hua; Cho, Hyewon; Jeon, Raok; Ryu, Jae-Ha; Yim, Mijung

2016-03-05

Osteoclasts are the only cells capable of breaking down bone matrix, and excessive activation of osteoclasts is responsible for bone-destructive diseases. In this study, we investigated the effects of decursin from extract of Angelica gigas root on receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclast formation using mouse bone marrow-derived macrophages (BMMs). Decursin inhibited RANKL-induced osteoclast formation without cytotoxicity. In particular, decursin maintains the characteristics of macrophages by blocking osteoclast differentiation by RANKL. Furthermore, the RANKL-stimulated bone resorption was diminished by decursin. Mechanistically, decursin blocked the RANKL-triggered ERK mitogen-activated protein kinases (MAPK) phosphorylation, which results in suppression of c-Fos and the nuclear factor of activated T cells (NFATc1) expression. In accordance with the in vitro study, decursin reduced lipopolysaccharide (LPS)- or ovariectomy (OVX)-induced bone loss in vivo. Therefore, decursin exerted an inhibitory effect on osteoclast formation and bone loss in vitro and in vivo. Decursin could be useful for the treatment of bone diseases associated with excessive bone resorption. Copyright © 2016 Elsevier B.V. All rights reserved.

Quantitation of Bone Growth Rate Variability in Rats Exposed to Micro-(near zero G) and Macrogravity (2G)

NASA Technical Reports Server (NTRS)

Bromage, Timothy G.; Doty, Stephen B.; Smolyar, Igor; Holton, Emily

1997-01-01

Our stated primary objective is to quantify the growth rate variability of rat lamellar bone exposed to micro- (near zero G: e.g., Cosmos 1887 & 2044; SLS-1 & SLS-2) and macrogravity (2G). The primary significance of the proposed work is that an elegant method will be established that unequivocally characterizes the morphological consequences of gravitational factors on developing bone. The integrity of this objective depends upon our successful preparation of thin sections suitable for imaging individual bone lamellae, and our imaging and quantitation of growth rate variability in populations of lamellae from individual bone samples.

Bone formation: roles of genistein and daidzein

USDA-ARS?s Scientific Manuscript database

Bone remodeling consists of a balance between bone formation by osteoblasts and bone resorption by osteoclasts. Osteoporosis is the result of increased bone resorption and decreased bone formation causing a decreased bone mass density, loss of bone microarchitecture, and an increased risk of fractu...

Osteoporosis: An Update on Pathogenesis and Treatment

PubMed Central

Josse, Robert G.

1983-01-01

Both hormonal and nonhormonal factors appear to contribute to bone loss in osteoporosis. Decreased estrogen production, not enough calcium and too much protein, phosphorus and caffeine in the diet all have a probable effect. Aims of treatment include giving symptomatic relief, rehabilitation, arresting further bone loss, increasing the useful bone mass and restoring damaged skeletal architecture where possible. Current treatment includes ensuring that the patient avoids excess protein and caffeine and has adequate calcium in her diet. Estrogen therapy is still subject to debate, but does seem to prevent bone loss if initiated within three to five years of menopause. Much research is currently being done on sodium fluoride, the only agent that appears actually able to produce new bone. PMID:21283471

Infrared spectroscopy reveals both qualitative and quantitative differences in equine subchondral bone during maturation

NASA Astrophysics Data System (ADS)

Kobrina, Yevgeniya; Isaksson, Hanna; Sinisaari, Miikka; Rieppo, Lassi; Brama, Pieter A.; van Weeren, René; Helminen, Heikki J.; Jurvelin, Jukka S.; Saarakkala, Simo

2010-11-01

The collagen phase in bone is known to undergo major changes during growth and maturation. The objective of this study is to clarify whether Fourier transform infrared (FTIR) microspectroscopy, coupled with cluster analysis, can detect quantitative and qualitative changes in the collagen matrix of subchondral bone in horses during maturation and growth. Equine subchondral bone samples (n = 29) from the proximal joint surface of the first phalanx are prepared from two sites subjected to different loading conditions. Three age groups are studied: newborn (0 days old), immature (5 to 11 months old), and adult (6 to 10 years old) horses. Spatial collagen content and collagen cross-link ratio are quantified from the spectra. Additionally, normalized second derivative spectra of samples are clustered using the k-means clustering algorithm. In quantitative analysis, collagen content in the subchondral bone increases rapidly between the newborn and immature horses. The collagen cross-link ratio increases significantly with age. In qualitative analysis, clustering is able to separate newborn and adult samples into two different groups. The immature samples display some nonhomogeneity. In conclusion, this is the first study showing that FTIR spectral imaging combined with clustering techniques can detect quantitative and qualitative changes in the collagen matrix of subchondral bone during growth and maturation.

Short-term, daily exposure to cold temperature may be an efficient way to prevent muscle atrophy and bone loss in a microgravity environment

NASA Astrophysics Data System (ADS)

Deng, Claudia; Wang, Ping; Zhang, Xiangming; Wang, Ya

2015-04-01

Microgravity induces less pressure on muscle/bone, which is a major reason for muscle atrophy as well as bone loss. Currently, physical exercise is the only countermeasure used consistently in the U.S. human space program to counteract the microgravity-induced skeletal muscle atrophy and bone loss. However, the routinely almost daily time commitment is significant and represents a potential risk to the accomplishment of other mission operational tasks. Therefore, development of more efficient exercise programs (with less time) to prevent astronauts from muscle atrophy and bone loss are needed. Consider the two types of muscle contraction: exercising forces muscle contraction and prevents microgravity-induced muscle atrophy/bone loss, which is a voluntary response through the motor nervous system; and cold temperature exposure-induced muscle contraction is an involuntary response through the vegetative nervous system, we formed a new hypothesis. The main purpose of this pilot study was to test our hypothesis that exercise at 4 °C is more efficient than at room temperature to prevent microgravity-induced muscle atrophy/bone loss and, consequently reduces physical exercise time. Twenty mice were divided into two groups with or without daily short-term (10 min × 2, at 12 h interval) cold temperature (4 °C) exposure for 30 days. The whole bodyweight, muscle strength and bone density were measured after terminating the experiments. The results from the one-month pilot study support our hypothesis and suggest that it would be reasonable to use more mice, in a microgravity environment and observe for a longer period to obtain a conclusion. We believe that the results from such a study will help to develop efficient exercise, which will finally benefit astronauts' heath and NASA's missions.

Short-term, daily exposure to cold temperature may be an efficient way to prevent muscle atrophy and bone loss in a microgravity environment

PubMed Central

Deng, Claudia; Wang, Ping; Zhang, Xiangming; Wang, Ya

2015-01-01

Microgravity induces less pressure on muscle/bone, which is a major reason for muscle atrophy as well as bone loss. Currently, physical exercise is the only countermeasure used consistently in the U.S. human space program to counteract the microgravity-induced skeletal muscle atrophy and bone loss. However, the routinely almost daily time commitment is significant and represents a potential risk to the accomplishment of other mission operational tasks. Therefore, development of more efficient exercise programs (with less time) to prevent astronauts from muscle atrophy and bone loss are needed. Consider the two types of muscle contraction: exercising forces muscle contraction and prevents microgravity-induced muscle atrophy/bone loss, which is a voluntary response through the motor nervous system; and cold temperature exposure-induced muscle contraction is an involuntary response through the vegetative nervous system, we formed a new hypothesis. The main purpose of this pilot study was to test our hypothesis that exercise at 4°C is more efficient than at room temperature to prevent microgravity-induced muscle atrophy/bone loss and, consequently reduces physical exercise time. Twenty mice were divided into two groups with or without daily short-term (10 min × 2, at 12 h interval) cold temperature (4°C) exposure for 30 days. The whole bodyweight, muscle strength and bone density were measured after terminating the experiments. The results from the one-month pilot study support our hypothesis and suggest that it would be reasonable to use more mice, in a microgravity environment and observe for a longer period to obtain a conclusion. We believe that the results from such a study will help to develop efficient exercise, which will finally benefit astronauts’ heath and NASA’s mission. PMID:25821722

Autologous distal clavicle versus autologous coracoid bone grafts for restoration of anterior-inferior glenoid bone loss: a biomechanical comparison.

PubMed

Petersen, Steve A; Bernard, Johnathan A; Langdale, Evan R; Belkoff, Stephen M

2016-06-01

Treating anterior glenoid bone loss in patients with recurrent shoulder instability is challenging. Coracoid transfer techniques are associated with neurologic complications and neuroanatomic alterations. The purpose of our study was to compare the contact area and pressures of a distal clavicle autograft with a coracoid bone graft for the restoration of anterior glenoid bone loss. We hypothesized that a distal clavicle autograft would be as effective as a coracoid graft. In 13 fresh-frozen cadaveric shoulder specimens, we harvested the distal 1.0 cm of each clavicle and the coracoid bone resection required for a Latarjet procedure. A compressive load of 440 N was applied across the glenohumeral joint at 30° and 60° of abduction, as well as 60° of abduction with 90° of external rotation. Pressure-sensitive film was used to determine normal glenohumeral contact area and pressures. In each specimen, we created a vertical, 25% anterior bone defect, reconstructed with distal clavicle (articular surface and undersurface) and coracoid bone grafts, and determined the glenohumeral contact area and pressures. We used analysis of variance for group comparisons and a Tukey post hoc test for individual comparisons (with P <.05 indicating a significant difference). The articular distal clavicle bone graft provided the lowest mean pressure in all testing positions. The coracoid bone graft provided the greatest contact area in all humeral positions, but the difference was not significant. An articular distal clavicle bone graft is comparable in glenohumeral contact area and pressures to an optimally placed coracoid bone graft for restoring glenoid bone loss. Basic Science Study; Biomechanics. Copyright © 2016 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Bone Formation Rate in Experimental Disuse Osteoporosis in Monkeys

NASA Technical Reports Server (NTRS)

Cann, Christopher; Young, Donald R.

1976-01-01

Specific mechanisms underlying weightless and hypodynamic bone loss are obscure. A principal relationship which must be affected is the balance between bone formation and bone resorption rates. In order to better define the influence of those parameters on bone loss, and also to develop measurements in other species as a useful adjunct to human research, studies were undertaken with experimental monkeys. Tests were conducted with a total of 6 adult male monkeys, weighing 10-13 kg, and approximately 10-12 yrs. of age to evaluate specifically bone formation rate during the development of disuse osteoporosis and osteopenia. Three animals were restrained in a semi-recumbent position for six months; three animals served as normal caged controls. Food intake (Purina) was held relatively constant at 200g/day for each animal. Using a Norland Bone Mineral Analyzer, bone mineral losses of 3.5 to 6% were seen in the mid-shaft of the tibia and in the distal radius. Bone loss was confirmed radiographically, with observation of thinning of the proximal tibial cortex and trabeculae in the calcaneus. Bone formation rate was determined using standard Ca-47 kinetics under metabolic balance conditions. After six months of restraint, accretion was 7.2-13.2 mg Ca/kg/day, compared to 3.2-4.1 mg Ca/kg/day in caged controls and 3-8 mg Ca/kg/day in normal adult humans. Fecal and urine calcium was 25-40% higher in restrained animals than in controls. Dietary calcium absorption decreases during restraint, and calcium turnover increases, implying a rise in bone resorption rate concommitant with the observed rise in bone accretion rate. Further studies dealing specifically with bone resorption are underway to define this more fully.

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.

Intrasocket reactive soft tissue for primary closure after augmentation of extraction sites with severe bone loss before implant placement.

PubMed

Mardinger, Ofer; Chaushu, Gavriel; Ghelfan, Oded; Nissan, Joseph

2009-06-01

The normal bone resorption after tooth extraction can be significantly aggravated in the case of pre-existing severe bone loss and chronic infection. Bone augmentation procedures have been proposed, but they require adequate closure of soft tissues. We propose the use of intrasocket reactive tissue to cover extraction sites augmented by bovine bone mineral graft to promote the success of the graft procedure. The study included 24 patients with severe bone loss and chronic pathology in 27 sites. The intrasocket reactive soft tissue was elevated from the bony walls in a subperiosteal plane. Porous bovine or allograft bone mineral was placed in the extraction site without membranes, and the intrasocket reactive soft tissue was sutured over the grafting material to seal the coronal portion of the socket. Twenty-seven implants were placed 6 months after bone augmentation. Healing progressed uneventfully. Postoperative morbidity was minimal. There was no leakage or infection of the grafting material. The mean time to implant placement was 7.8 months. Supplemental augmentation was not needed. There were no implant failures. Follow-up ranged from 6 to 36 months (mean, 15 months). All implants were rehabilitated with fixed prostheses. Intrasocket reactive soft tissue can be used predictably to obtain primary closure of augmented extraction sites with severe bone loss with minimal postoperative morbidity.

Morse taper dental implants and platform switching: The new paradigm in oral implantology

PubMed Central

Macedo, José Paulo; Pereira, Jorge; Vahey, Brendan R.; Henriques, Bruno; Benfatti, Cesar A. M.; Magini, Ricardo S.; López-López, José; Souza, Júlio C. M.

2016-01-01

The aim of this study was to conduct a literature review on the potential benefits with the use of Morse taper dental implant connections associated with small diameter platform switching abutments. A Medline bibliographical search (from 1961 to 2014) was carried out. The following search items were explored: “Bone loss and platform switching,” “bone loss and implant-abutment joint,” “bone resorption and platform switching,” “bone resorption and implant-abutment joint,” “Morse taper and platform switching.” “Morse taper and implant-abutment joint,” Morse taper and bone resorption,” “crestal bone remodeling and implant-abutment joint,” “crestal bone remodeling and platform switching.” The selection criteria used for the article were: meta-analysis; randomized controlled trials; prospective cohort studies; as well as reviews written in English, Portuguese, or Spanish languages. Within the 287 studies identified, 81 relevant and recent studies were selected. Results indicated a reduced occurrence of peri-implantitis and bone loss at the abutment/implant level associated with Morse taper implants and a reduced-diameter platform switching abutment. Extrapolation of data from previous studies indicates that Morse taper connections associated with platform switching have shown less inflammation and possible bone loss with the peri-implant soft tissues. However, more long-term studies are needed to confirm these trends. PMID:27011755

Comparison of peri-implant bone loss between conventional drilling with irrigation versus low-speed drilling without irrigation.

PubMed

Pellicer-Chover, H; Peñarrocha-Oltra, D; Aloy-Prosper, A; Sanchis-Gonzalez, J-C; Peñarrocha-Diago, M-A; Peñarrocha-Diago, M

2017-11-01

To compare the technique of high speed drilling with irrigation and low speed drilling without irrigation in order to evaluate the success rate and peri-implant bone loss at 12 months of follow-up. A randomized, controlled, parallel-group clinical trial was carried out in patients requiring dental implants to rehabilitate their unitary edentulism. Patients were recruited from the Oral Surgery Unit of the University of Valencia (Spain) between September 2014 and August 2015. Patients who met the inclusion criteria were randomized to two groups: group A (high-speed drilling with irrigation) and group B (low-speed drilling without irrigation). The success rate and peri-implant bone loss were recorded at 12 months of follow-up. Twenty-five patients (9 men and 16 women) with 30 implants were enrolled in the study: 15 implants in group A and 15 implants in group B. The mean bone loss of the implants in group A and group B was 0.83 ± 0.73 mm and 0.62 ± 0.70 mm, respectively (p> 0.05). In the maxilla, the bone loss was 1.04 ± 0.63 mm in group A and 0.71 ± 0.36 mm in group B (p> 0.05), while bone loss in the mandible was 0.59 ± 0.80 mm in group A and 0.69 ± 0.77 mm in group B (p> 0.05). The implant success rate at 12 months was 93.3% in group A and 100% in group B. Within the limitations of the study, the low-speed drilling technique presented peri-implant bone loss outcomes similar to those of the conventional drilling technique at 12 months of follow-up.

Vegetarianism, bone loss, fracture and vitamin D: a longitudinal study in Asian vegans and non-vegans.

PubMed

Ho-Pham, L T; Vu, B Q; Lai, T Q; Nguyen, N D; Nguyen, T V

2012-01-01

The effect of vegan diet on bone loss has not been studied. The aim of this study was to examine the association between veganism and bone loss in postmenopausal women. The study was designed as a prospective longitudinal investigation with 210 women, including 105 vegans and 105 omnivores. Femoral neck (FN) bone mineral density (BMD) was measured in 2008 and 2010 by dual-energy X-ray absorptiometry (Hologic QDR4500). The incidence of vertebral fracture was ascertained by X-ray report. Serum levels of C-terminal telopeptide of type I collagen (βCTX) and N-terminal propeptide of type I procollagen (PINP) were measured by Roche Elecsys assays. Serum concentration of 25-hydroxyvitamin D and parathyroid hormone were measured by electrochemiluminescence. Among the 210 women who initially participated in the study in 2008, 181 women had completed the study and 29 women were lost to follow-up. The rate of loss in FN BMD was -1.91±3.45%/year in omnivores and -0.86±3.81%/year (P=0.08) in vegans. Lower body weight, higher intakes of animal protein and lipid, and corticosteroid use were associated with greater rate of bone loss. The 2-year incidence of fracture was 5.7% (n=5/88) in vegans, which was not significantly different from omnivores (5.4%, n=6/93). There were no significant differences in βCTX and PINP between vegans and omnivores. The prevalence of vitamin D insufficiency in vegans was higher than in omnivores (73% versus 46%; P=0.0003). Vegan diet did not have adverse effect on bone loss and fracture. Corticosteroid use and high intakes of animal protein and animal lipid were negatively associated with bone loss.

Serum FGF-21 levels are associated with worsened radial trabecular bone microarchitecture and decreased radial bone strength in women with anorexia nervosa.

PubMed

Fazeli, Pouneh K; Faje, Alexander T; Cross, Ela J; Lee, Hang; Rosen, Clifford J; Bouxsein, Mary L; Klibanski, Anne

2015-08-01

Anorexia nervosa (AN) is a psychiatric disorder characterized by self-induced starvation and low body weight. Women with AN have impaired bone formation, low bone mass and an increased risk of fracture. FGF-21 is a hormone secreted by the liver in starvation and FGF-21 transgenic mice have significant bone loss due to an uncoupling of bone resorption and bone formation. We hypothesized that FGF-21 may contribute to the low bone mass state of AN. We studied 46 women: 20 with AN (median age [interquartile range]: 27.5 [25, 30.75] years) and 26 normal-weight controls (NWC) of similar age (25 [24, 28.5] years). We investigated associations between serum FGF-21 and 1) aBMD measured by dual energy X-ray absorptiometry, 2) parameters of bone microarchitecture in the distal radius and tibia measured by high-resolution peripheral quantitative CT and 3) bone strength, estimated by microfinite element analysis. FGF-21 levels were similar in AN and NWC (AN: 33.1 [18.1, 117.0] pg/ml vs. NWC: 57.4 [23.8, 107.1] pg/ml; p = 0.54). There was a significant inverse association between log FGF-21 and trabecular number in the radius in both AN (R = -0.57, p < 0.01) and NWC (R=-0.53, p < 0.01) and a significant positive association between log FGF-21 and trabecular separation in the radius in AN (R = 0.50, p < 0.03) and NWC (R = 0.52, p < 0.01). Estimates of radial bone strength were inversely associated with log FGF-21 in AN (R = -0.50, p < 0.03 for both stiffness and failure load). There were no associations between FGF-21 and aBMD, cortical parameters or tibial parameters in the AN or NWC groups. FGF-21 may be an important determinant of trabecular skeletal homeostasis in AN. Copyright © 2015 Elsevier Inc. All rights reserved.

Screening, prevention, detection, and treatment of cancer therapy-induced bone loss in patients with breast cancer.

PubMed

Limburg, Connie E

2007-01-01

To identify protocols to screen, detect, prevent, and treat cancer therapy-induced bone loss resulting in osteoporosis in patients with breast cancer. Published books and articles. Normal bone remodeling is affected by hormonal stimulation. Breast cancer therapies target hormones that promote cancer cell growth. Chemotherapy regimens and hormone ablation may cause ovarian failure, resulting in decreased hormone levels. A decrease in hormones, in estrogen- and progesterone-positive and -negative patients, introduces an environment for decreased bone remodeling, which may result in thinning bone and osteoporosis. The acceleration of bone loss leading to osteoporosis can result in higher fracture rates among breast cancer survivors. With proper use of screening tools, patient education, and advice about lifestyle changes, all prior to cancer treatment, healthcare professionals may decrease or prevent bone loss in patients with breast cancer. Doing so minimizes healthcare costs and decreases morbidity and mortality rates in breast cancer survivors. As more individuals diagnosed with breast cancer are surviving for extended periods of time, oncology nurses are providing long-term follow-up care. Part of the care should include proper screening and patient education for healthier recovery and prevention of further healthcare complications as a result of cancer treatment.

Bone Markers, Calcium Metabolism, and Calcium Kinetics During Extended-Duration Space Flight on the Mir Space Station

NASA Technical Reports Server (NTRS)

Smith, Scott M.; Wastney, Meryl E.; O'Brien, Kimberly O.; Morukov, Boris V.; Larina, Irina M.; Abrams, Steven A.; Davis-Street, Janis E.; Oganov, Victor; Shackelford, Linda C.

2005-01-01

Bone loss is a current limitation for long-term space exploration. Bone markers, calcitropic hormones, and calcium kinetics of crew members on space missions of 4-6 months were evaluated. Spaceflight-induced bone loss was associated with increased bone resorption and decreased calcium absorption. INTRODUCTION: Bone loss is a significant concern for the health of astronauts on long-duration missions. Defining the time course and mechanism of these changes will aid in developing means to counteract these losses during space flight and will have relevance for other clinical situations that impair weight-bearing activity. MATERIALS AND METHODS: We report here results from two studies conducted during the Shuttle-Mir Science Program. Study 1 was an evaluation of bone and calcium biochemical markers of 13 subjects before and after long-duration (4-6 months) space missions. In study 2, stable calcium isotopes were used to evaluate calcium metabolism in six subjects before, during, and after flight. Relationships between measures of bone turnover, biochemical markers, and calcium kinetics were examined. RESULTS: Pre- and postflight study results confirmed that, after landing, bone resorption was increased, as indicated by increases in urinary calcium (p < 0.05) and collagen cross-links (N-telopeptide, pyridinoline, and deoxypyridinoline were all increased >55% above preflight levels, p < 0.001). Parathyroid hormone and vitamin D metabolites were unchanged at landing. Biochemical markers of bone formation were unchanged at landing, but 2-3 weeks later, both bone-specific alkaline phosphatase and osteocalcin were significantly (p < 0.01) increased above preflight levels. In studies conducted during flight, bone resorption markers were also significantly higher than before flight. The calcium kinetic data also validated that bone resorption was increased during flight compared with preflight values (668 +/- 130 versus 427 +/- 153 mg/day; p < 0.001) and clearly documented that true intestinal calcium absorption was significantly lower during flight compared with preflight values (233 +/- 87 versus 460 +/- 47 mg/day; p < 0.01). Weightlessness had a detrimental effect on the balance in bone turnover such that the daily difference in calcium retention during flight compared with preflight values approached 300 mg/day (-234 +/- 102 versus 63 +/- 75 mg/day; p < 0.01). CONCLUSIONS: These bone marker and calcium kinetic studies indicated that the bone loss that occurs during space flight is a consequence of increased bone resorption and decreased intestinal calcium absorption.

Reverse total shoulder glenoid baseplate stability with superior glenoid bone loss.

PubMed

Martin, Elise J; Duquin, Thomas R; Ehrensberger, Mark T

2017-10-01

Superior wear of the glenoid bone is common in patients with rotator cuff arthropathy. This can become a treatment challenge for patients who require shoulder arthroplasty. In reverse shoulder arthroplasty (RSA), glenoid bone loss may affect the stability of baseplate fixation. The primary purpose of this biomechanical laboratory study was to assess the initial fixation stability of RSA glenosphere baseplates in the presence of variable amounts of superior glenoid bone loss. High-density solid rigid polyurethane foam (30 pounds/cubic foot) was machined to model the glenoid with variable superior defects that provided different levels of support (100%, 90%, 75%, and 50%) for the glenosphere baseplate. The samples were cyclically loaded (0-750 N at 1 Hz for 5000 cycles) at a 60° glenohumeral angle. The micromotion and migration of the baseplate were calculated from displacement data captured during the loading tests with an array of 3 linear variable differential transformers mounted around the baseplate. Micromotion was significantly greater in samples with 50% defects compared with those with smaller defects. Migration was significantly greater after testing for all defect sizes. Initial fixation of RSA glenosphere baseplates was significantly reduced in models with 50% bone loss on the superior edge compared with models with less bone loss in this high-density bone foam model. Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Does the Laser-Microtextured Short Implant Collar Design Reduce Marginal Bone Loss in Comparison with a Machined Collar?

PubMed Central

Sirali, Ali; Gultekin, Pinar; Yalcin, Serdar; Mijiritsky, Eitan

2016-01-01

Purpose. To compare marginal bone loss between subgingivally placed short-collar implants with machined collars and those with machined and laser-microtextured collars. Materials and Methods. The investigators used a retrospective study design and included patients who needed missing posterior teeth replaced with implants. Short-collar implants with identical geometries were divided into two groups: an M group, machined collar; and an L group, machined and laser-microtextured collar. Implants were evaluated according to marginal bone loss, implant success, and probing depth (PD) at 3 years of follow-up. Results. Sixty-two patients received 103 implants (56 in the M group and 47 in the L group). The cumulative survival rate was 100%. All implants showed clinically acceptable marginal bone loss, although bone resorption was lower in the L group (0.49 mm) than in the M group (1.38 mm) at 3 years (p < 0.01). A significantly shallower PD was found for the implants in the L group during follow-up (p < 0.01). Conclusions. Our results suggest predictable outcomes with regard to bone loss for both groups; however, bone resorption was less in the L group than in the M group before and after loading. The laser-microtextured collar implant may provide a shallower PD than the machined collar implant. PMID:27660765

Inhibitory effects of Persicariae Rhizoma aqueous extracts on experimental periodontitis and alveolar bone loss in Sprague-Dawley rats

PubMed Central

Kang, Su Jin; Lee, Eun Kyung; Han, Chang Hyun; Lee, Bong Hyo; Lee, Young Joon; Ku, Sae Kwang

2016-01-01

Persicariae Rhizoma (PR) is the dried stem parts of Persicaria tinctoria H. Gross (Polygonaceae), and has been traditionally used as anti-inflammatory and detoxifying agent. In the present study, the effects of PR aqueous extracts on ligation-induced experimental periodontitis (EPD) and associated alveolar bone loss in rats were examined. Following the induction of EPD in rats, PR extracts were orally administered once a day for 10 days, and the changes and gains in body weight, alveolar bone loss and total aerobic bacterial counts of buccal gingiva were observed with histopathological analysis. In addition, anti-inflammatory effects were evaluated by monitoring myeloperoxidase (MPO) activities, and interleukin (IL)-1β and tumor necrosis factor (TNF)-α contents, and anti-oxidant effects were investigated by measuring inducible nitric oxide synthase (iNOS) activities and malondialdehyde (MDA) levels. Bacterial proliferation, periodontitis and associated alveolar bone loss induced by ligature placement were significantly and dose-dependently inhibited by the treatment with PR extracts. The inhibitory effects of 200 mg/kg PR were similar to those of 5 mg/kg indomethacin on ligation-induced periodontitis and associated alveolar bone losses in this study. The results suggest that PR effectively inhibits ligature placement-induced periodontitis and alveolar bone loss in rats via antibacterial, antioxidative and anti-inflammatory activities. PMID:27588077

Subtraction micro-computed tomography of angiogenesis and osteogenesis during bone repair using synchrotron radiation with a novel contrast agent.

PubMed

Matsumoto, Takeshi; Goto, Daichi; Sato, Syota

2013-09-01

Quantitative three-dimensional (3D) imaging of angiogenesis during bone repair remains an experimental challenge. We developed a novel contrast agent containing 0.07- to 0.1-μm particles of zirconium dioxide (ZrCA) and established subtraction μCT using synchrotron radiation (sSRCT) for quantitative imaging of angiogenesis and bone repair. This method was applied to a rat model of tibial bone repair 3 days (DAY3; n = 2), 5 days (DAY5; n = 8), or 10 days (DAY10; n = 8) after drill-hole injury. Using the same drill-hole defect model, its potential use was illustrated by comparison of bone repair between hindlimbs subjected to mechanical unloading (n = 6) and normal weight bearing (n = 6) for 10 days. Following vascular casting with ZrCA, the defect site was scanned with 17.9- and 18.1-keV X-rays. In the latter, image contrast between ZrCA-filled vasculature and bone was enhanced owing to the sharp absorption jump of zirconium dioxide at 18.0 keV (k-edge). The two scan data sets were reconstructed with 2.74-μm voxel resolution, registered by mutual information, and digitally subtracted to extract the contrast-enhanced vascular image. K2HPO4 phantom solutions were scanned at 17.9 keV for quantitative evaluation of bone mineral. Angiogenesis had already started, but new bone formation was not found on DAY3. New bone emerged near the defect boundary on DAY5 and took the form of trabecular-like structure invaded by microvessels on DAY10. Vascular and bone volume fractions, blood vessel and bone thicknesses, and mineralization were higher on DAY10 than on DAY5. All these parameters were found to be decreased after 10 days of hindlimb unloading, indicating the possible involvement of angiogenesis in bone repair impairment caused by reduced mechanical stimuli. In conclusion, the combined technique of sSRCT and ZrCA vascular casting is suitable for quantitative 3D imaging of angiogenesis and its surrounding bone regeneration. This method will be useful for better understanding the linkage between angiogenesis and bone repair.

Exercise during energy restriction mitigates bone loss but not alterations in estrogen status or metabolic hormones.

PubMed

Metzger, C E; Baek, K; Swift, S N; De Souza, M J; Bloomfield, S A

2016-09-01

Energy restriction causes bone loss, increasing stress fracture risk. The impact of exercise during energy restriction on bone and endocrine factors is examined. Exercise with energy restriction did not influence endocrine factors, but did mitigate some bone loss seen with energy restriction in sedentary rats. Chronic dietary energy restriction (ER) leads to bone loss and increased fracture risk. Strictly controlled trials of long-term ER with and without vigorous exercise are required to determine whether exercise loading can counterbalance ER-induced bone loss. The aim of this current project is to elucidate the impact of exercise and ER on bone mass, estrogen status, and metabolic hormones. Twenty-four virgin female Sprague-Dawley rats (n = 8/group) were divided into three groups-ad libitum fed + exercise (Adlib + EX), 40 % energy restricted + exercise (ER + EX), and 40 % energy restricted + sedentary (ER + SED). Energy availability between ER groups was equal. Treadmill running was performed 4 days/week at 70 % VO2max for 12 weeks. Fat and lean mass and areal bone mineral density (aBMD) were lower after 12 weeks (p < 0.05) for ER + EX vs Adlib + EX, but ER + EX aBMD was higher than ER + SED (p < 0.0001). Serum leptin and a urinary estrogen metabolite, estrone-1-glucuronide (E1G), were lower at week 12 (p = 0.0002) with ER, with no impact of exercise. Serum insulin-like growth factor I (IGF-I) declined (p = 0.02) from baseline to week 12 in both ER groups. ER + EX exhibited higher cortical volumetric bone mineral density (vBMD) at the midshaft tibia (p = 0.006) vs ER + SED. Exercise during ER mitigated some, but not all, of the bone loss observed in sedentary ER rats, but had little impact on changes in urinary E1G and serum IGF-I and leptin. These data highlight the importance of both adequate energy intake and the mechanical loading of exercise in maintaining bone mass.

A losing battle: weight regain does not restore weight loss-induced bone loss in postmenopausal women.

PubMed

Villalon, Karen L; Gozansky, Wendolyn S; Van Pelt, Rachael E; Wolfe, Pam; Jankowski, Catherine M; Schwartz, Robert S; Kohrt, Wendy M

2011-12-01

Previously, we reported significant bone mineral density (BMD) loss in postmenopausal women after modest weight loss. It remains unclear whether the magnitude of BMD change in response to weight loss is appropriate (i.e., proportional to weight loss) and whether BMD is recovered with weight regain. We now report changes in BMD after a 1-year follow-up. Subjects (n = 23) in this secondary analysis were postmenopausal women randomized to placebo as part of a larger trial. They completed a 6-month exercise-based weight loss program and returned for follow-up at 18 months. Dual-energy X-ray absorptiometry (DXA) was performed at baseline, 6, and 18 months. At baseline, subjects were aged 56.8 ± 5.4 years (mean ± s.d.), 10.0 ± 9.2 years postmenopausal, and BMI was 29.6 ± 4.0 kg/m(2). They lost 3.9 ± 3.5 kg during the weight loss intervention. During follow-up, they regained 2.9 ± 3.9 kg. Six months of weight loss resulted in a significant decrease in lumbar spine (LS) (-1.7 ± 3.5%; P = 0.002) and hip (-0.04 ± 3.5%; P = 0.03) BMD that was accompanied by an increase in a biomarker of bone resorption (serum C-terminal telopeptide of type I collagen, CTX: 34 ± 54%; P = 0.08). However, weight regain was not associated with LS (0.05 ± 3.8%; P = 0.15) or hip (-0.6 ± 3.0%; P = 0.81) bone regain or decreased bone resorption (CTX: -3 ± 37%; P = 0.73). The findings suggest that BMD lost during weight reduction may not be fully recovered with weight regain in hormone-deficient, postmenopausal women. Future studies are needed to identify effective strategies to prevent bone loss during periods of weight loss.

Association of aircraft noise stress to periodontal disease in aircrew members.

PubMed

Haskell, B S

1975-08-01

A review of the literature reveals a multitude of effects that noise may contribute to periodontal disease, including cardiovascular disease, angiospasm of peripheral vessels, hypertension, and an increase in inflammatory cells with concurrent inhibition of healing. Three groups of 25 men were selected from the Pennsylvania Air National Guard for study. Group 1 consisted of F-102 jet fighter pilots; Group 2, pilots and crew of a four-engine, propeller-driven C-121 aircraft; and Group 3, enlisted men not exposed to aircraft noise, as a control. The degree of alveolar, intraceptal bone loss for each subject was measured from full-mouth radiographs of all groups. The greatest amount of bone loss occurred in crew members of propeller-driven aircraft. Jet pilots had considerably less bone loss while the average number of millimeters of bone lost per tooth revealed a difference between the three groups to the 0.01 significance level (F=24.7). The data suggests there is a degree of alveolar bone loss over a period of years associated with exposure to propeller aircraft noise and vibration, and negligible loss for jet aircraft noise.

Effect of thread size on the implant neck area: preliminary results at 1 year of function.

PubMed

Kang, Young-Il; Lee, Dong-Won; Park, Kwang-Ho; Moon, Ik-Sang

2012-10-01

To evaluate and compare the effect of the coronal thread size on the marginal bone loss around the fixtures, when both implants were provided with threads to the top of fixture. Two groups of implants, one with a macro-thread to the top of the fixture (A) and the other with a micro-thread to the top of the fixture (B), were placed adjacent to each other in the partially edentulous areas of 20 patients. Bone loss around each implant was analyzed after 1 year of functional loading. The bone losses after loading were compared using Wilcoxon's signed-rank test. The mean marginal bone losses (A, 0.154 ± 0.144 mm; B, 0.125 ± 0.136 mm) were not statistically significant between the two groups (P = 0.669). There was no significant difference between implant with macro- and micro-neck thread in terms of marginal bone loss after 1 year of loading. © 2011 John Wiley & Sons A/S.

Absence of ERRα in Female Mice Confers Resistance to Bone Loss Induced by Age or Estrogen-Deficiency

PubMed Central

Rabier, Bénédicte; Monfoulet, Laurent; Dine, Julien; Macari, Claire; Espallergues, Julie; Horard, Béatrice; Giguère, Vincent; Cohen-Solal, Martine; Chassande, Olivier; Vanacker, Jean-Marc

2009-01-01

Background ERRα is an orphan member of the nuclear hormone receptor superfamily, which acts as a transcription factor and is involved in various metabolic processes. ERRα is also highly expressed in ossification zones during mouse development as well as in human bones and cell lines. Previous data have shown that this receptor up-modulates the expression of osteopontin, which acts as an inhibitor of bone mineralization and whose absence results in resistance to ovariectomy-induced bone loss. Altogether this suggests that ERRα may negatively regulate bone mass and could impact on bone fragility that occurs in the absence of estrogens. Methods/Principal Findings In this report, we have determined the in vivo effect of ERRα on bone, using knock-out mice. Relative to wild type animals, female ERRαKO bones do not age and are resistant to bone loss induced by estrogen-withdrawal. Strikingly male ERRαKO mice are indistinguishable from their wild type counterparts, both at the unchallenged or gonadectomized state. Using primary cell cultures originating from ERRαKO bone marrow, we also show that ERRα acts as an inhibitor of osteoblast differentiation. Conclusion/Significance Down-regulating ERRα could thus be beneficial against osteoporosis. PMID:19936213

A "Bony" Proposition: Pathways Mediating Responses to Simulated Weightlessness and Radiation

NASA Technical Reports Server (NTRS)

Tahimic, Candice; Globus, Ruth

2016-01-01

There is evidence that weightlessness and radiation, two elements of the spaceflight environment, can lead to detrimental changes in human musculoskeletal tissue, including bone loss and muscle atrophy. This bone loss is thought to be brought about by the increased activity of bone-resorbing osteoclasts and functional changes in bone-forming osteoblasts, cells that give rise to mature osteocytes. My current area of research focuses on understanding the mechanistic basis for the responses of bone to the spaceflight environment using earth-based animal and cellular models. The overarching goal is to identify molecular targets to prevent bone loss in space exploration and earth-based scenarios of radiotherapy, accidental radiation exposure and reduced mobility. In this talk, I will highlight two signaling pathways that potentially play a role in the response of bone to spaceflight-like conditions. Firstly, I will discuss the role of insulin-like growth factor 1 (IGF1) signaling as it pertains to the recovery of bone from simulated weightlessness (rodent hindlimb unloading model). Secondly, I will share recent findings from our study that aims to understand the emerging role of autophagy in maintaining the balance between bone formation and resorption (bone homeostasis) as well as normal skeletal structure.

Marginal bone level changes in association with different vertical implant positions: a 3-year retrospective study

PubMed Central

2017-01-01

Purpose To retrospectively evaluate the relationship between the vertical position of the implant-abutment interface and marginal bone loss over 3 years using radiological analysis. Methods In total, 286 implant surfaces of 143 implants from 61 patients were analyzed. Panoramic radiographic images were taken immediately after implant installation and at 6, 12, and 36 months after loading. The implants were classified into 3 groups based on the vertical position of the implant-abutment interface: group A (above bone level), group B (at bone level), and group C (below bone level). The radiographs were analyzed by a single examiner. Results Changes in marginal bone levels of 0.99±1.45, 1.13±0.91, and 1.76±0.78 mm were observed at 36 months after loading in groups A, B, and C, respectively, and bone loss was significantly greater in group C than in groups A and B. Conclusions The vertical position of the implant-abutment interface may affect marginal bone level change. Marginal bone loss was significantly greater in cases where the implant-abutment interface was positioned below the marginal bone. Further long-term study is required to validate our results. PMID:28861287

Skeletal scintigraphy and quantitative tracer studies in metabolic bone disease

NASA Astrophysics Data System (ADS)

Fogelman, Ignac

Bone scan imaging with the current bone seeking radiopharmaceuticals, the technetium-99m labelled diphosphonates, has dramatically improved our ability to evaluate skeletal pathology. In this thesis, chapter 1 presents a review of the history of bone scanning, summarises present concepts as to the mechanism of uptake of bone seeking agents and briefly illustrates the role of bone scanning in clinical practice. In chapter 2 the applications of bone scan imaging and quantitative tracer techniques derived from the bone scan in the detection of metabolic bone disease are discussed. Since skeletal uptake of Tc-99m diphosphonate depends upon skeletal metabolism one might expect that the bone scan would be of considerable value in the assessment of metabolic bone disease. However in these disorders the whole skeleton is often diffusely involved by the metabolic process and simple visual inspection of the scan image may not reveal the uniformly increased uptake of tracer. Certain patterns of bone scan abnormality have, however, been reported in patients with primary hyperparathyroidism and renal osteo-dystrophy; the present studies extend these observations and introduce the concept of "metabolic features" which are often recognisable in conditions with generalised increased bone turnover. As an aid to systematic recognition of these features on a given bone scan image a semi-quantitative scoring system, the metabolic index, was introduced. The metabolic index allowed differentiation between various groups of patients with metabolic disorders and a control population. In addition, in a bone scan study of patients with acromegaly, it was found that the metabolic index correlated well with disease activity as measured by serum growth hormone levels. The metabolic index was, however, found to be a relatively insensitive means of identifying disease in individual patients. Patients with increased bone turnover will have an absolute increase in skeletal uptake of tracer. As a means of quantitating this uptake the use of bone to soft-tissue ratios derived from the bone scan image by computer was critically evaluated. The technique was shown to be observer dependent and again found to be of limited value due to the large overlap of patient results with those from control subjects. In chapter 3 the use of bone scan imaging in metabolic bone disease has been compared with radiology. Despite the difficulties mentioned above the metabolic index was employed, and the bone scan found to be the more sensitive investigation in primary hyperparathyroidism, renal osteodystrophy and osteomalacia. In osteoporosis, however, the bone scan was often unable to identify disease and radiology remains the investigation of choice. In a further study comparing bone scanning and radiology in Paget's disease, the bone scan was found to be clearly the more sensitive investigation. As a result of the work described in chapter 2 it became apparent that a sensitive means of quantitating absolute bone uptake of tracer could be of diagnostic value. In chapter 4 a promising new quantitative technique is described in which the 24-hour whole-body retention of Tc-99m diphosphonate (WBR) is measured using a shadow-shield whole-body monitor. At 24 hours after injection, diphosphonate has reached a stable equilibrium in bone reflecting skeletal metabolic activity, while tracer in the soft-tissues of the body has been largely excreted via the urinary tract. It was found that this technique provided a sensitive means of detecting patients with primary hyperparathyroidism, osteomalacia, renal osteodystrophy and Paget's disease and that in these conditions all the results from individual patients lay outside the control range. In further studies the WBR technique was shown to be highly reproducible and not subject to any significant technical errors.

Decreased bone turnover with balanced resorption and formation prevent cortical bone loss during disuse (hibernation) in grizzly bears (Ursus arctos horribilis).

PubMed

McGee, Meghan E; Maki, Aaron J; Johnson, Steven E; Nelson, O Lynne; Robbins, Charles T; Donahue, Seth W

2008-02-01

Disuse uncouples bone formation from resorption, leading to increased porosity, decreased bone geometrical properties, and decreased bone mineral content which compromises bone mechanical properties and increases fracture risk. However, black bear bone properties are not adversely affected by aging despite annual periods of disuse (i.e., hibernation), which suggests that bears either prevent bone loss during disuse or lose bone and subsequently recover it at a faster rate than other animals. Here we show decreased cortical bone turnover during hibernation with balanced formation and resorption in grizzly bear femurs. Hibernating grizzly bear femurs were less porous and more mineralized, and did not demonstrate any changes in cortical bone geometry or whole bone mechanical properties compared to active grizzly bear femurs. The activation frequency of intracortical remodeling was 75% lower during hibernation than during periods of physical activity, but the normalized mineral apposition rate was unchanged. These data indicate that bone turnover decreases during hibernation, but osteons continue to refill at normal rates. There were no changes in regional variation of porosity, geometry, or remodeling indices in femurs from hibernating bears, indicating that hibernation did not preferentially affect one region of the cortex. Thus, grizzly bears prevent bone loss during disuse by decreasing bone turnover and maintaining balanced formation and resorption, which preserves bone structure and strength. These results support the idea that bears possess a biological mechanism to prevent disuse osteoporosis.

Design, synthesis, and osteogenic activity of daidzein analogs on human mesenchymal stem cells

USDA-ARS?s Scientific Manuscript database

Osteoporosis, defined by the loss of bone mass and strength, results in the loss of structural and mechanical support in bone, and leads to an increased risk of fractures. In the adult skeleton, the bone undergoes continuous resorption carried out by osteoclast cells, and formation by osteoblast cel...

Synergistic Effect of Green Tea Polyphenols and Vitamin D on Chronic Inflammation-Induced Bone Loss in Female Rats

USDA-ARS?s Scientific Manuscript database

Our recent study demonstrated a bone-protective role of green tea polyphenols (GTPs), extracted from green tea, in chronic inflammation-induced bone loss of female rats through reduction of inflammation and oxidative stress. This study further examines effects of GTPs in conjunction with vitamin D (...

Evidence that Resorption of Bone by Rat Peritoneal Macrophages Occurs in an Acidic Environment

NASA Technical Reports Server (NTRS)

Blair, H. C.

1985-01-01

Skeletal loss in space, like any form of osteoporosis, reflects a relative imbalance of the activities of cells resorbing (degrading) or forming bone. Consequently, prevention of weightlessness induced bone loss may theoretically be accomplished by (1) stimulating bone formation or (2) inhibiting bone resorption. This approach, however, requires fundamental understanding of the mechanisms by which cells form or degrade bone, information not yet at hand. An issue central to bone resorption is the pH at which resorption takes place. The pH dependent spectral shift of a fluorescent dye (fluorescein isothiocyanate) conjugated to bone matrix was used to determine the pH at the resorptive cell bone matrix interface. Devitalized rat bone was used as the substrate, and rat peritoneal macrophages were used as the bone resorbing cells. The results suggest that bone resorption is the result of generation of an acidic microenvironment at the cell matrix junction.

Rapid Loss of Bone Mass and Strength in Mice after Abdominal Irradiation

PubMed Central

Jia, Dan; Gaddy, Dana; Suva, Larry J.; Corry, Peter M.

2011-01-01

Localized irradiation is a common treatment modality for malignancies in the pelvic-abdominal cavity. We report here on the changes in bone mass and strength in mice 7–14 days after abdominal irradiation. Male C57BL/6 mice of 10–12 weeks of age were given a single-dose (0, 5, 10, 15 or 20 Gy) or fractionated (3 Gy × 2 per day × 7.5 days) X rays to the abdomen and monitored daily for up to 14 days. A decrease in the serum bone formation marker and ex vivo osteoblast differentiation was detected 7 days after a single dose of radiation, with little change in the serum bone resorption marker and ex vivo osteoclast formation. A single dose of radiation elicited a loss of bone mineral density (BMD) within 14 days of irradiation. The BMD loss was up to 4.1% in the whole skeleton, 7.3% in tibia, and 7.7% in the femur. Fractionated abdominal irradiation induced similar extents of BMD loss 10 days after the last fraction: 6.2% in the whole skeleton, 5.1% in tibia, and 13.8% in the femur. The loss of BMD was dependent on radiation dose and was more profound in the trabecula-rich regions of the long bones. Moreover, BMD loss in the total skeleton and the femurs progressed with time. Peak load and stiffness in the mid-shaft tibia from irradiated mice were 11.2–14.2% and 11.5–25.0% lower, respectively, than sham controls tested 7 days after a single-dose abdominal irradiation. Our data demonstrate that abdominal irradiation induces a rapid loss of BMD in the mouse skeleton. These effects are bone type- and region-specific but are independent of radiation fractionation. The radiation-induced abscopal damage to the skeleton is manifested by the deterioration of biomechanical properties of the affected bone. PMID:21859327

An improved design of electrodes for measurement of streaming potentials on wet bone in vitro and in vivo.

PubMed

Cochran, G V; Dell, D G; Palmieri, V R; Johnson, M W; Otter, M W; Kadaba, M P

1989-01-01

Streaming potentials are generated by mechanical stress in wet bone and may constitute a control mechanism for bone remodeling. Measurement of streaming potentials in bone has attracted considerable effort in past years but quantitative studies have been hampered by relatively poor repeatability when using Ag.AgCl electrodes which contact bone via a wick moistened with electrolyte. Improvement now has been achieved with an electrode design that limits the specific area of contact of an agar/salt bridge by means of a silastic seal, thus permitting the same equipotential surface to be contacted for each set of measurements. This reduces variations caused by bone structure and impedance, and facilitates quantitative comparisons of the response of bone samples to selected variables. The new design also permits considerable qualitative improvement in recordings made from bone during locomotor function in experimental animals in vivo.

Simulated Space Radiation and Weightlessness: Vascular-Bone Coupling Mechanisms to Preserve Skeletal Health

NASA Technical Reports Server (NTRS)

Alwood, J. S.; Limoli, C. L.; Delp, M. D.; Castillo, A. B.; Globus, R. K.

2012-01-01

Weightlessness causes a cephalad fluid shift and reduction in mechanical stimulation, adversely affecting both cortical and trabecular bone tissue in astronauts. In rodent models of weightlessness, the onset of bone loss correlates with reduced skeletal perfusion, reduced and rarified vasculature and lessened vasodilation, which resembles blood-bone symbiotic events that can occur with fracture repair and aging. These are especially serious risks for long term, exploration class missions when astronauts will face the challenge of increased exposure to space radiation and abrupt transitions between different gravity environments upon arrival and return. Previously, we found using the mouse hindlimb unloading model and exposure to heavy ion radiation, both disuse and irradiation cause an acute bone loss that was associated with a reduced capacity to produce bone-forming osteoblasts from the bone marrow. Together, these findings led us to hypothesize that exposure to space radiation exacerbates weightlessness-induced bone loss and impairs recovery upon return, and that treatment with anti-oxidants may mitigate these effects. The specific aims of this recently awarded grant are to: AIM 1 Determine the functional and structural consequences of prolonged weightlessness and space radiation (simulated spaceflight) for bone and skeletal vasculature in the context of bone cell function and oxidative stress. AIM 2 Determine the extent to which an anti-oxidant protects against weightlessness and space radiation-induced bone loss and vascular dysfunction. AIM 3 Determine how space radiation influences later skeletal and vasculature recovery from prolonged weightlessness and the potential of anti-oxidants to preserve adaptive remodeling.

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.

Dietary nutraceuticals as backbone for bone health.

PubMed

Pandey, Manoj K; Gupta, Subash C; Karelia, Deepkamal; Gilhooley, Patrick J; Shakibaei, Mehdi; Aggarwal, Bharat B

2018-03-27

Bone loss or osteoporosis, is a slow-progressing disease that results from dysregulation of pro-inflammatory cytokines. The FDA has approved number of drugs for bone loss prevention, nonetheless all are expensive and have multiple side effects. The nutraceuticals identified from dietary agents such as butein, cardamonin, coronarin D curcumin, diosgenin, embelin, gambogic acid, genistein, plumbagin, quercetin, reseveratrol, zerumbone and more, can modulate cell signaling pathways and reverse/slow down osteoporosis. Most of these nutraceuticals are inexpensive; show no side effect while still possessing anti-inflammatory properties. This review provides various mechanisms of osteoporosis and how nutraceuticals can potentially prevent the bone loss. Published by Elsevier Inc.

Oral Health and Bone Disease

MedlinePlus

... Oral Health and Bone Disease Oral Health and Bone Disease Osteoporosis and tooth loss are health concerns ... for Healthy Bones Resources For Your Information Skeletal Bone Density and Dental Concerns The portion of the ...

Exercise Countermeasures for Bone Loss During Space Flight: A Method for the Study of Ground Reaction Forces and Their Implications for Bone Strain

NASA Technical Reports Server (NTRS)

Peterman, M.; McCrory, J. L.; Sharkey, N. A.; Piazza, S.; Cavanagh, P. R.

1999-01-01

The human zero-gravity locomotion simulator and the cadaver simulator offer a powerful combination for the study of the implications of exercise for maintaining bone quality during space flight. Such studies, when compared with controlled in-flight exercise programs, could help in the identification of a strain threshold for the prevention of bone loss during space flight.

The Digital Astronaut Project Bone Remodeling Model

NASA Technical Reports Server (NTRS)

Pennline, James A.; Mulugeta, Lealem; Lewandowski, Beth E.; Thompson, William K.; Sibonga, Jean D.

2014-01-01

Under the conditions of microgravity, astronauts lose bone mass at a rate of 1% to 2% a month, particularly in the lower extremities such as the proximal femur: (1) The most commonly used countermeasure against bone loss has been prescribed exercise, (2) However, current exercise countermeasures do not completely eliminate bone loss in long duration, 4 to 6 months, spaceflight, (3,4) leaving the astronaut susceptible to early onset osteoporosis and a greater risk of fracture later in their lives. The introduction of the Advanced Resistive Exercise Device, coupled with improved nutrition, has further minimized the 4 to 6 month bone loss. But further work is needed to implement optimal exercise prescriptions, and (5) In this light, NASA's Digital Astronaut Project (DAP) is working with NASA physiologists to implement well-validated computational models that can help understand the mechanisms of bone demineralization in microgravity, and enhance exercise countermeasure development.

The botanical molecule p-hydroxycinnamic acid as a new osteogenic agent: insight into the treatment of cancer bone metastases.

PubMed

Yamaguchi, Masayoshi

2016-10-01

Bone homeostasis is maintained through a balance between osteoblastic bone formation and osteoclastic bone resorption. Bone loss with aging is induced by decreasing in osteoblastic bone formation and increasing in osteoclastic bone resorption, thereby leading to osteoporosis. Osteoporosis with its accompanying decrease in bone mass is widely recognized as a major public heath problem. Pharmacologic and nutritional factors may play a role in the prevention and treatment of bone loss with aging. p-Hydroxycinnamic acid (HCA), which stimulates bone mineralization in mouse bone tissues in vitro, has been found to be present in the leafstalk of wasabi (Wasabi japonica MATSUM) among various food and plants. Other phenolic acids including cinnamic acid, ferulic acid, caffeic acid and 3,4-dimethoxycinnamic acid did not have osteogenic effects. HCA was demonstrated to stimulate osteoblastic bone formation and suppresses osteoclastic bone resorption in vitro by antagonizing activation of the nuclear factor kappa B. Oral administration of HCA was found to exhibit restorative effects on bone loss induced by ovariectomy and diabetic states, supporting a role in the treatment of osteoporosis. Moreover, HCA was demonstrated to prevent the suppressed osteoblastic mineralization and the enhanced osteoclastogenesis in mouse bone marrow cells cocultured with bone metastatic MDA-MB-231 human breast cancer cells in vitro. The botanical molecule HCA, as a new osteogenic agent, is suggested to play a role in the treatment of cancer bone metastases. This review will discuss an advanced recent finding that HCA may be a useful agent to treat bone metabolic disorder.

Dried plum diet protects from bone loss caused by ionizing radiation

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

Schreurs, A. -S.; Shirazi-Fard, Y.; Shahnazari, M.

Bone loss caused by ionizing radiation is a potential health concern for radiotherapy patients, radiation workers and astronauts. In animal studies, exposure to ionizing radiation increases oxidative damage in skeletal tissues, and results in an imbalance in bone remodeling initiated by increased bone-resorbing osteoclasts. Therefore, we evaluated various candidate interventions with antioxidant or antiinflammatory activities (antioxidant cocktail, dihydrolipoic acid, ibuprofen, dried plum) both for their ability to blunt the expression of resorption-related genes in marrow cells after irradiation with either gamma rays (photons, 2 Gy) or simulated space radiation (protons and heavy ions, 1 Gy) and to prevent bone loss.more » Dried plum was most effective in reducing the expression of genes related to bone resorption ( Nfe2l2, Rankl, Mcp1, Opg, TNF-α) and also preventing later cancellous bone decrements caused by irradiation with either photons or heavy ions. Furthermore, dietary supplementation with DP may prevent the skeletal effects of radiation exposures either in space or on Earth.« less

Dried plum diet protects from bone loss caused by ionizing radiation

DOE PAGES

Schreurs, A. -S.; Shirazi-Fard, Y.; Shahnazari, M.; ...

2016-02-11

Bone loss caused by ionizing radiation is a potential health concern for radiotherapy patients, radiation workers and astronauts. In animal studies, exposure to ionizing radiation increases oxidative damage in skeletal tissues, and results in an imbalance in bone remodeling initiated by increased bone-resorbing osteoclasts. Therefore, we evaluated various candidate interventions with antioxidant or antiinflammatory activities (antioxidant cocktail, dihydrolipoic acid, ibuprofen, dried plum) both for their ability to blunt the expression of resorption-related genes in marrow cells after irradiation with either gamma rays (photons, 2 Gy) or simulated space radiation (protons and heavy ions, 1 Gy) and to prevent bone loss.more » Dried plum was most effective in reducing the expression of genes related to bone resorption ( Nfe2l2, Rankl, Mcp1, Opg, TNF-α) and also preventing later cancellous bone decrements caused by irradiation with either photons or heavy ions. Furthermore, dietary supplementation with DP may prevent the skeletal effects of radiation exposures either in space or on Earth.« less

Dried plum diet protects from bone loss caused by ionizing radiation

PubMed Central

Schreurs, A.-S.; Shirazi-Fard, Y.; Shahnazari, M.; Alwood, J. S.; Truong, T. A.; Tahimic, C. G. T.; Limoli, C. L.; Turner, N. D.; Halloran, B.; Globus, R. K.

2016-01-01

Bone loss caused by ionizing radiation is a potential health concern for radiotherapy patients, radiation workers and astronauts. In animal studies, exposure to ionizing radiation increases oxidative damage in skeletal tissues, and results in an imbalance in bone remodeling initiated by increased bone-resorbing osteoclasts. Therefore, we evaluated various candidate interventions with antioxidant or anti-inflammatory activities (antioxidant cocktail, dihydrolipoic acid, ibuprofen, dried plum) both for their ability to blunt the expression of resorption-related genes in marrow cells after irradiation with either gamma rays (photons, 2 Gy) or simulated space radiation (protons and heavy ions, 1 Gy) and to prevent bone loss. Dried plum was most effective in reducing the expression of genes related to bone resorption (Nfe2l2, Rankl, Mcp1, Opg, TNF-α) and also preventing later cancellous bone decrements caused by irradiation with either photons or heavy ions. Thus, dietary supplementation with DP may prevent the skeletal effects of radiation exposures either in space or on Earth. PMID:26867002

Oxidation-specific epitopes restrain bone formation.

PubMed

Ambrogini, Elena; Que, Xuchu; Wang, Shuling; Yamaguchi, Fumihiro; Weinstein, Robert S; Tsimikas, Sotirios; Manolagas, Stavros C; Witztum, Joseph L; Jilka, Robert L

2018-06-06

Atherosclerosis and osteoporosis are epidemiologically linked and oxidation specific epitopes (OSEs), such as phosphocholine (PC) of oxidized phospholipids (PC-OxPL) and malondialdehyde (MDA), are pathogenic in both. The proatherogenic effects of OSEs are opposed by innate immune antibodies. Here we show that high-fat diet (HFD)-induced bone loss is attenuated in mice expressing a single chain variable region fragment of the IgM E06 (E06-scFv) that neutralizes PC-OxPL, by increasing osteoblast number and stimulating bone formation. Similarly, HFD-induced bone loss is attenuated in mice expressing IK17-scFv, which neutralizes MDA. Notably, E06-scFv also increases bone mass in mice fed a normal diet. Moreover, the levels of anti-PC IgM decrease in aged mice. We conclude that OSEs, whether produced chronically or increased by HFD, restrain bone formation, and that diminished defense against OSEs may contribute to age-related bone loss. Anti-OSEs, therefore, may represent a novel therapeutic approach against osteoporosis and atherosclerosis simultaneously.

Polar bears (Ursus maritimus), the most evolutionary advanced hibernators, avoid significant bone loss during hibernation.

PubMed

Lennox, Alanda R; Goodship, Allen E

2008-02-01

Some hibernating animals are known to reduce muscle and bone loss associated with mechanical unloading during prolonged immobilisation,compared to humans. However, here we show that wild pregnant polar bears (Ursus maritimus) are the first known animals to avoid significant bone loss altogether, despite six months of continuous hibernation. Using serum biochemical markers of bone turnover, we showed that concentrations for bone resorption are not significantly increased as a consequence of hibernation in wild polar bears. This is in sharp contrast to previous studies on other hibernating species, where for example, black bears (Ursus americanus), show a 3-4 fold increase in serum bone resorption concentrations posthibernation,and must compensate for this loss through rapid bone recovery on remobilisation, to avoid the risk of fracture. In further contrast to black bears, serum concentrations of bone formation markers were highly significantly increased in pregnant female polar bears compared to non-pregnant,thus non-hibernating females both prior to and after hibernation. However, bone formation concentrations in new mothers were significantly reduced compared to pre-hibernation concentrations. The de-coupling of bone turnover in favour of bone formation prior to hibernation, suggests that wild polar bears may posses a unique physiological mechanism for building bone in protective preparation against expected osteopenia associated with disuse,starvation, and hormonal drives to mobilise calcium for reproduction, during hibernation. Understanding this physiological mechanism could have profound implications for a natural solution for the prevention of osteoporosis in animals subjected to captivity with inadequate space for exercise,humans subjected to prolonged bed rest while recovering from illness, or astronauts exposed to antigravity during spaceflight.© 2008 Elsevier Inc. All rights reserved.

Histomorphometrical analysis following augmentation of infected extraction sites exhibiting severe bone loss and primarily closed by intrasocket reactive soft tissue.

PubMed

Mardinger, Ofer; Vered, Marilena; Chaushu, Gavriel; Nissan, Joseph

2012-06-01

Intrasocket reactive soft tissue can be used for primary closure during augmentation of infected extraction sites exhibiting severe bone loss prior to implant placement. The present study evaluated the histological characteristics of the initially used intrasocket reactive soft tissue, the overlying soft tissue, and the histomorphometry of the newly formed bone during implant placement. Thirty-six consecutive patients (43 sites) were included in the study. Extraction sites demonstrating extensive bone loss on preoperative periapical and panoramic radiographs served as inclusion criteria. Forty-three implants were inserted after a healing period of 6 months. Porous bovine xenograft bone mineral was used as a single bone substitute. The intrasocket reactive soft tissue was sutured over the grafting material to seal the coronal portion of the socket. Biopsies of the intrasocket reactive soft tissue at augmentation, healed mucosa, and bone cores at implant placement were retrieved and evaluated. The intrasocket reactive soft tissue demonstrated features compatible with granulation tissue and long junctional epithelium. The mucosal samples at implant placement demonstrated histopathological characteristics of keratinized mucosa with no residual elements of granulation tissue. Histomorphometrically, the mean composition of the bone cores was - vital bone 40 ± 19% (13.7-74.8%); bone substitute 25.7 ± 13% (0.6-51%); connective tissue 34.3 ± 15% (13.8-71.9%). Intrasocket reactive soft tissue used for primary closure following ridge augmentation is composed of granulation tissue and long junctional epithelium. At implant placement, clinical and histological results demonstrate its replacement by keratinized gingiva. The histomorphometrical results reveal considerable bone formation. Fresh extraction sites of hopeless teeth demonstrating chronic infection and severe bone loss may be grafted simultaneously with their removal. © 2010 Wiley Periodicals, Inc.

Effects of O-methylated (-)-epigallocatechin gallate (EGCG) on LPS-induced osteoclastogenesis, bone resorption, and alveolar bone loss in mice.

PubMed

Tominari, Tsukasa; Ichimaru, Ryota; Yoshinouchi, Shosei; Matsumoto, Chiho; Watanabe, Kenta; Hirata, Michiko; Grundler, Florian M W; Inada, Masaki; Miyaura, Chisato

2017-12-01

(-)-Epigallocatechin-3- O -gallate (EGCG), present in green tea, exhibits antioxidant and antiallergy effects. EGCG3″Me, a 3- O -methylated derivative of EGCG, has been reported to show similar biological functions; the inhibitory activity of EGCG3″Me in a mouse allergy model was more potent than that of EGCG, probably due to the efficiency of absorption from the intestine. However, the functional potency of these EGCGs is controversial in each disease model. We previously observed that EGCG suppressed inflammatory bone resorption and prevented alveolar bone loss in a mouse model of periodontosis. In this study, we examined the role of EGCG3″Me in bone resorption using a mouse model of periodontitis. Lipopolysaccharide (LPS)-induced osteoclast formation was suppressed by adding EGCG3″Me to cocultures of osteoblasts and bone marrow cells, and LPS-induced bone resorption was also inhibited by EGCG3″Me in calvarial organ cultures. EGCG3″Me acted on osteoblasts and suppressed prostaglandin E (PGE) production, which is critical for inflammatory bone resorption, by inhibiting the expression of COX-2 and mPGES-1, key enzymes for PGE synthesis. In osteoclast precursor macrophages, EGCG3″Me suppressed RANKL-dependent differentiation into mature osteoclasts. In a mouse model of periodontitis, LPS-induced bone resorption was suppressed by EGCG3″Me in organ culture of mouse alveolar bone, and the alveolar bone loss was further attenuated by the treatment of EGCG3″Me in the lower gingiva in vivo . EGCG3″Me may be a potential natural compound for the protection of inflammatory bone loss in periodontitis.

Inhibiting the osteocyte-specific protein sclerostin increases bone mass and fracture resistance in multiple myeloma

PubMed Central

Mohanty, Sindhu T.; Seckinger, Anja; Terry, Rachael L.; Pettitt, Jessica A.; Simic, Marija K.; Le, Lawrence M. T.; Kramer, Ina; Falank, Carolyne; Fairfield, Heather; Ghobrial, Irene M.; Baldock, Paul A.; Little, David G.; Kneissel, Michaela; Vanderkerken, Karin; Bassett, J. H. Duncan; Williams, Graham R.; Oyajobi, Babatunde O.; Hose, Dirk

2017-01-01

Multiple myeloma (MM) is a plasma cell cancer that develops in the skeleton causing profound bone destruction and fractures. The bone disease is mediated by increased osteoclastic bone resorption and suppressed bone formation. Bisphosphonates used for treatment inhibit bone resorption and prevent bone loss but fail to influence bone formation and do not replace lost bone, so patients continue to fracture. Stimulating bone formation to increase bone mass and fracture resistance is a priority; however, targeting tumor-derived modulators of bone formation has had limited success. Sclerostin is an osteocyte-specific Wnt antagonist that inhibits bone formation. We hypothesized that inhibiting sclerostin would prevent development of bone disease and increase resistance to fracture in MM. Sclerostin was expressed in osteocytes from bones from naive and myeloma-bearing mice. In contrast, sclerostin was not expressed by plasma cells from 630 patients with myeloma or 54 myeloma cell lines. Mice injected with 5TGM1-eGFP, 5T2MM, or MM1.S myeloma cells demonstrated significant bone loss, which was associated with a decrease in fracture resistance in the vertebrae. Treatment with anti-sclerostin antibody increased osteoblast numbers and bone formation rate but did not inhibit bone resorption or reduce tumor burden. Treatment with anti-sclerostin antibody prevented myeloma-induced bone loss, reduced osteolytic bone lesions, and increased fracture resistance. Treatment with anti-sclerostin antibody and zoledronic acid combined increased bone mass and fracture resistance when compared with treatment with zoledronic acid alone. This study defines a therapeutic strategy superior to the current standard of care that will reduce fractures for patients with MM. PMID:28515094

Effect of microdose transdermal 17beta-estradiol compared with raloxifene in the prevention of bone loss in healthy postmenopausal women: a 2-year, randomized, double-blind trial.

PubMed

Schaefers, Matthias; Muysers, Christoph; Alexandersen, Peter; Christiansen, Claus

2009-01-01

Declining estrogen levels after menopause result in bone loss and increased fracture risk. This study investigated whether transdermal microdose 17beta-estradiol (E2) has efficacy and safety comparable to those of raloxifene, a selective estrogen-receptor modulator approved for the prevention and treatment of postmenopausal osteoporosis. This study involved a multicenter, randomized, double-blind, active-controlled, noninferiority trial in 500 osteopenic postmenopausal women comparing transdermal microdose E2 (0.014 mg/d) versus oral raloxifene (60 mg/d), administered for 2 years. Percent change from baseline in bone mineral density at the lumbar spine was measured after 2 years of treatment. Secondary endpoints included proportion of women with no loss of bone mineral density in lumbar spine, change in bone mineral density at hip, biochemical markers of bone turnover, and safety parameters. In the per protocol set, lumbar spine bone mineral density increased by 2.4% (95% CI, 1.9-2.9) with microdose E2 versus 3.0% (95% CI, 2.5-3.5) with raloxifene after 2 years; 77.3% of E2 recipients and 80.5% of those taking raloxifene had no bone loss in the lumbar spine. Both treatments were well tolerated. Most women (99% in the E2 group and 100% in the raloxifene group) showed no histological evidence of endometrial stimulation after 2 years. Mean dense area in breast mammograms was 19.8% in the E2 group versus 19.0% in the raloxifene group after 2 years. Transdermal microdose E2 was similarly effective as raloxifene in preventing bone loss at the lumbar spine. Both treatments were well tolerated, with no clinically significant effect on endometrium or breast density.

Advances in Imaging Approaches to Fracture Risk Evaluation

PubMed Central

Manhard, Mary Kate; Nyman, Jeffry S.; Does, Mark D.

2016-01-01

Fragility fractures are a growing problem worldwide, and current methods for diagnosing osteoporosis do not always identify individuals who require treatment to prevent a fracture and may misidentify those not a risk. Traditionally, fracture risk is assessed using dual-energy X-ray absorptiometry, which provides measurements of areal bone mineral density (BMD) at sites prone to fracture. Recent advances in imaging show promise in adding new information that could improve the prediction of fracture risk in the clinic. As reviewed herein, advances in quantitative computed tomography (QCT) predict hip and vertebral body strength; high resolution HR-peripheral QCT (HR-pQCT) and micro-magnetic resonance imaging (μMRI) assess the micro-architecture of trabecular bone; quantitative ultrasound (QUS) measures the modulus or tissue stiffness of cortical bone; and quantitative ultra-short echo time MRI methods quantify the concentrations of bound water and pore water in cortical bone, which reflect a variety of mechanical properties of bone. Each of these technologies provides unique characteristics of bone and may improve fracture risk diagnoses and reduce prevalence of fractures by helping to guide treatment decisions. PMID:27816505

Effects of Cinnamoyloxy-mammeisin from Geopropolis on Osteoclast Differentiation and Porphyromonas gingivalis-Induced Periodontitis.

PubMed

da Cunha, Marcos Guilherme; Ramos-Junior, Erivan Schnaider; Franchin, Marcelo; Taira, Thaise Mayumi; Beutler, John A; Franco, Gilson Cesar Nobre; Ikegaki, Masaharu; de Alencar, Severino Matias; Fukada, Sandra Yasuyo; Rosalen, Pedro Luiz

2017-06-23

Bone-loss-related diseases such as rheumatoid arthritis, osteomyelitis, osteoporosis, and periodontitis are associated with high rates of morbidity worldwide. These disorders are characterized by an imbalance between the formation and activity of osteoblasts and osteoclasts, leading to bone loss. In this context, we evaluated the effect of cinnamoyloxy-mammeisin (CNM), an anti-inflammatory coumarin found in Melipona scutellaris geopropolis, on key targets related to bone remodeling. In the present study we investigated the in vitro effects of CNM on osteoclast differentiation and M-CSF+RANKL-induced osteoclastogenic marker expression. Additionally, the interference of CNM treatment on osteoclast activity was evaluated by zymography and resorption area. Finally, we assessed the capacity of the compound to mitigate alveolar bone loss in vivo in experimental murine periodontitis induced by Porphyromonas gingivalis. We observed that treatment with CNM impaired osteoclast differentiation, as evidenced by a reduced number of tartrate-resistant acid-phosphatase-positive multinucleated cells (TRAP+) as well as the expression of osteoclastogenic markers upon M-CSF+RANKL-induced stimulation. Similarly, we observed reduced gelatinolytic and resorption capacity in M-CSF+RANKL-induced cells in vitro. Lastly, CNM attenuated alveolar bone loss in an experimental murine periodontitis model. These findings indicate that CNM may be considered a promising treatment for bone loss diseases.

Surgical and Patient Factors Affecting Marginal Bone Levels Around Dental Implants: A Comprehensive Overview of Systematic Reviews.

PubMed

Ting, Miriam; Tenaglia, Matthew S; Jones, Gary H; Suzuki, Jon B

2017-04-01

The objective of this systematic review was to perform a comprehensive overview of systematic reviews and meta-analyses of surgical and patient factors affecting marginal bone loss around osseointegrated dental implants in humans. Electronic databases were searched for systematic reviews and meta-analyses published up to November 2015. Of the 41 articles selected, 11 evaluated implant factors, 10 evaluated patient factors, 19 evaluated surgical protocol-related factors, and one evaluated all three factors. The chosen studies were AMSTAR rated for quality. The following parameters have statistically significant effect on marginal bone loss: (1) marginal bone loss was significantly more in patients with periodontitis than in periodontally healthy patients; (2) significantly greater in generalized aggressive periodontitis patients compared with chronic periodontitis patients; (3) significantly less in alveolar socket preservation techniques; (4) significantly more in alveolar ridge augmentation sites; (5) significantly more in men than in women; (6) significantly more in smokers than in nonsmokers; and (7) smokers also have significantly more marginal bone loss in the maxilla than in the mandible. Knowledge of the surgical and patient factors that affect marginal bone loss can aid the clinician in making informed choices in selecting implant treatment options that will enhance the longevity and long-term success of their implant-supported cases.

Preventing and Treating Brittle Bones and Osteoporosis | NIH MedlinePlus the Magazine

MedlinePlus

... Javascript on. Feature: Osteoporosis Preventing and Treating Brittle Bones and Osteoporosis Past Issues / Winter 2011 Table of ... at high risk due to low bone mass. Bone and Bone Loss Bone is living, growing tissue. ...

Massive bone allograft: a salvage procedure for complex bone loss due to high-velocity missiles--a long-term follow-up.

PubMed

Salai, M; Volks, S; Blankstein, A; Chechik, A; Amit, Y; Horosowski, H

1990-07-01

The treatment of high-velocity missile injury to the limbs is often associated with segmental bone loss, as well as damage to neurovascular and soft tissue. In such "limb threatening" cases, massive bone allograft can fill the bone defect and offer stability to the soft tissue reconstruction. The return of function in the affected limb is relatively rapid when using this method as a primary procedure. The indications for use of this technique and illustrative case reports are presented and discussed.

SECONDARY OSTEOPOROSIS: PATHOPHYSIOLOGY AND MANAGEMENT

PubMed Central

Mirza, Faryal; Canalis, Ernesto

2015-01-01

Osteoporosis is a skeletal disorder characterized by decreased bone mineral density and compromised bone strength predisposing to an increased risk of fractures. Although idiopathic osteoporosis is the most common form of osteoporosis, secondary factors may contribute to the bone loss and increased fracture risk in patients presenting with fragility fractures or osteoporosis. Several medical conditions and medications significantly increase the risk for bone loss and skeletal fragility. This review focuses on some of the common causes of osteoporosis, addressing the underlying mechanisms, diagnostic approach and treatment of low bone mass in the presence of these conditions. PMID:25971649

Dental implants typically help retain peri-implant vertical bone height: evidence-based analysis.

PubMed

Greenstein, Gary; Cavallaro, John

2013-01-01

The dental literature is assessed regarding the ability of dental implants to maintain vertical bone height after various implant placement scenarios: immediate, delayed, insertion into partially and fully edentate healed ridges, and under overdentures. Studies are also reviewed to determine if bone loss after implant insertion is continuous. Numerous investigations that support the concept that implants preserve bone height are identified. In addition, the data indicate that a minuscule amount of annual bone loss usually persists after implant placement, but it is often clinically imperceptible.

Bone mineral density changes during pregnancy in actively exercising women as measured by quantitative ultrasound.

PubMed

To, William W K; Wong, Margaret W N

2012-08-01

To evaluate whether bone mineral density (BMD) changes in women engaged in active exercises during pregnancy would be different from non-exercising women. Consecutive patients with singleton pregnancies who were engaged in active exercise training during pregnancy were prospectively recruited over a period of 6 months. Quantitative USG measurements of the os calcis BMD were performed at 14-20 weeks and at 36-38 weeks. These patients were compared to a control cohort of non-exercising low-risk women. A total of 24 physically active women undergoing active physical training of over 10 h per week at 20 weeks gestation and beyond (mean 13.1 h, SD 3.3) were compared to 94 non-exercising low-risk women. A marginal fall in BMD of 0.015 g/cm(2) (SD 0.034) was demonstrable from early to late gestation in the exercising women, which was significantly lower than that of non-exercising women (0.041 g/cm(2); SD 0.042; p = 0.005). Logistic regression models confirmed that active exercises in pregnancy were significantly associated with the absence of or less BMD loss in pregnancy. In women actively engaged in physical training during pregnancy, the physiological fall in BMD during pregnancy was apparently less compared to those who did not regularly exercise.

The Implications of Reduced Ground Reaction Forces During Space Flight for Bone Strains

NASA Technical Reports Server (NTRS)

Peterman, Marc M.; Hamel, Andrew J.; Sharkey, Neil A.; Piazza, Stephen J.; Cavanagh, Peter R.

1998-01-01

The specific mechanisms regulating bone mass are not known, but most investigators agree that bone maintenance is largely dependent upon mechanical demand and the resultant local bone strains. During space flight, bone loss such as that reported by LeBlanc et al. may result from failure to effectively load the skeleton and generate sufficient localized bone strains. In microgravity, a gravity replacement system can be used to tether an exercising subject to a treadmill. It follows that the ability to prevent bone loss is critically dependent upon the external ground reaction forces (GRFs) and skeletal loads imparted by the tethering system. To our knowledge, the loads during orbital flight have been measured only once (on STS 81). Based on these data and data from ground based experiments, it appears likely that interventions designed to prevent bone loss in micro-gravity generate GRFs substantially less than body weight. It is unknown to what degree reductions in external GRFs will affect internal bone strain and thus the bone maintenance response. To better predict the efficacy of treadmill exercise in micro-gravity we used a unique cadaver model to measure localized bone strains under conditions representative of those that might be produced by a gravity replacement system in space.

Dual reporter transgene driven by 2.3Col1a1 promoter is active in differentiated osteoblasts

NASA Technical Reports Server (NTRS)

Marijanovic, Inga; Jiang, Xi; Kronenberg, Mark S.; Stover, Mary Louise; Erceg, Ivana; Lichtler, Alexander C.; Rowe, David W.

2003-01-01

AIM: As quantitative and spatial analyses of promoter reporter constructs are not easily performed in intact bone, we designed a reporter gene specific to bone, which could be analyzed both visually and quantitatively by using chloramphenicol acetyltransferase (CAT) and a cyan version of green fluorescent protein (GFPcyan), driven by a 2.3-kb fragment of the rat collagen promoter (Col2.3). METHODS: The construct Col2.3CATiresGFPcyan was used for generating transgenic mice. Quantitative measurement of promoter activity was performed by CAT analysis of different tissues derived from transgenic animals; localization was performed by visualized GFP in frozen bone sections. To assess transgene expression during in vitro differentiation, marrow stromal cell and neonatal calvarial osteoblast cultures were analyzed for CAT and GFP activity. RESULTS: In mice, CAT activity was detected in the calvaria, long bone, teeth, and tendon, whereas histology showed that GFP expression was limited to osteoblasts and osteocytes. In cell culture, increased activity of CAT correlated with increased differentiation, and GFP activity was restricted to mineralized nodules. CONCLUSION: The concept of a dual reporter allows a simultaneous visual and quantitative analysis of transgene activity in bone.

Epigallocatechin gallate (EGCG) suppresses lipopolysaccharide-induced inflammatory bone resorption, and protects against alveolar bone loss in mice.

PubMed

Tominari, Tsukasa; Matsumoto, Chiho; Watanabe, Kenta; Hirata, Michiko; Grundler, Florian M W; Miyaura, Chisato; Inada, Masaki

2015-01-01

Epigallocatechin gallate (EGCG), a major polyphenol in green tea, possesses antioxidant properties and regulates various cell functions. Here, we examined the function of EGCG in inflammatory bone resorption. In calvarial organ cultures, lipopolysaccharide (LPS)-induced bone resorption was clearly suppressed by EGCG. In osteoblasts, EGCG suppressed the LPS-induced expression of COX-2 and mPGES-1 mRNAs, as well as prostaglandin E2 production, and also suppressed RANKL expression, which is essential for osteoclast differentiation. LPS-induced bone resorption of mandibular alveolar bones was attenuated by EGCG in vitro, and the loss of mouse alveolar bone mass was inhibited by the catechin in vivo.

The purinergic receptor P2X5 regulates inflammasome activity and hyper-multinucleation of murine osteoclasts

DOE PAGES

Kim, Hyunsoo; Walsh, Matthew C.; Takegahara, Noriko; ...

2017-03-15

Excessive bone resorption by osteoclasts (OCs) can result in serious clinical outcomes, including bone loss that may weaken skeletal or periodontal strength. Proper bone homeostasis and skeletal strength are maintained by balancing OC function with the bone-forming function of osteoblasts. Unfortunately, current treatments that broadly inhibit OC differentiation or function may also interfere with coupled bone formation. We therefore identified a factor, the purinergic receptor P2X5 that is highly expressed during the OC maturation phase, and which we show here plays no apparent role in early bone development and homeostasis, but which is required for osteoclast-mediated inflammatory bone loss andmore » hyper-multinucleation of OCs. We further demonstrate that P2X5 is required for ATP-mediated inflammasome activation and IL-1β production by OCs, and that P2X5-deficient OC maturation is rescued in vitro by addition of exogenous IL-1β. These findings identify a mechanism by which OCs react to inflammatory stimuli, and may identify purinergic signaling as a therapeutic target for bone loss related inflammatory conditions.« less

OSTEOCLAST-INDUCED FOXP3+ CD8 T-CELLS LIMIT BONE LOSS IN MICE

PubMed Central

Buchwald, Zachary S.; Kiesel, Jennifer R.; Yang, Chang; DiPaolo, Richard; Novack, Deborah V.; Aurora, Rajeev

2014-01-01

Osteoimmunology is the crosstalk between the skeletal and immune system. We have previously shown in vitro that osteoclasts (OC) crosspresent antigens to induce FoxP3 in CD8 T-cells (OCiTcREG), which then suppress osteoclast activity. Here we assessed the ability of OC-iTcREG to limit bone resorption in vivo. Mice lacking CD8 T-cells lose more bone in response to RANKL (Tnfsf11) administration. Using adoptive transfer experiments we demonstrate that FoxP3+ CD8 T-cells limit bone loss by RANKL administration. In ovariectomized mice, a murine model of postmenopausal osteoporosis, OC-iTcREG limited bone loss and increased bone density as assessed by serum markers, micro computed tomography (μCT) and histomorphometry. Indeed, OC-iTcREG—treated ovariectomized mice had decreased levels of effector T-cells in the bone marrow compared to untreated mice, and increased bone formation rates relative to bisphosphonate-treated mice. Our results provide the first in vivo evidence that OC-iTcREG have anti-resorptive activity and repress the immune system, thus extending the purview of osteoimmunology. PMID:23756229

Protection of trabecular bone in ovariectomized rats by turmeric (Curcuma longa L.) is dependent on extract composition.

PubMed

Wright, Laura E; Frye, Jennifer B; Timmermann, Barbara N; Funk, Janet L

2010-09-08

Extracts prepared from turmeric (Curcuma longa L., [Zingiberaceae]) containing bioactive phenolic curcuminoids were evaluated for bone-protective effects in a hypogonadal rat model of postmenopausal osteoporosis. Three-month female Sprague-Dawley rats were ovariectomized (OVX) and treated with a chemically complex turmeric fraction (41% curcuminoids by weight) or a curcuminoid-enriched turmeric fraction (94% curcuminoids by weight), both dosed at 60 mg/kg 3x per week, or vehicle alone. Effects of two months of treatment on OVX-induced bone loss were followed prospectively by serial assessment of bone mineral density (BMD) of the distal femur using dual-energy X-ray absorptiometry (DXA), while treatment effects on trabecular bone microarchitecture were assessed at two months by microcomputerized tomography (microCT). Chemically complex turmeric did not prevent bone loss, however, the curcuminoid-enriched turmeric prevented up to 50% of OVX-induced loss of trabecular bone and also preserved the number and connectedness of the strut-like trabeculae. These results suggest that turmeric may have bone-protective effects but that extract composition is a critical factor.

Protection of Trabecular Bone in Ovariectomized Rats by Turmeric (Curcuma longa L.) is Dependent on Extract Composition

PubMed Central

Wright, Laura E.; Frye, Jennifer B.; Timmermann, Barbara N.; Funk, Janet L.

2010-01-01

Extracts prepared from turmeric (Curcuma longa L., [Zingiberaceae]) containing bioactive phenolic curcuminoids were evaluated for bone-protective effects in a hypogonadal rat model of postmenopausal osteoporosis. Three-month female Sprague Dawley rats were ovariectomized (OVX) and treated with a chemically complex turmeric fraction (41% curcuminoids by weight) or a curcuminoid-enriched turmeric fraction (94% curcuminoids by weight), both dosed at 60mg/kg 3x per week, or vehicle alone. Effects of two months of treatment on OVX-induced bone loss were followed prospectively by serial assessment of bone mineral density (BMD) of the distal femur using dual-energy x-ray absorptiometry (DXA), while treatment effects on trabecular bone microarchitecture were assessed at two months by micro-computerized tomography (μCT). Chemically complex turmeric did not prevent bone loss, however, the curcuminoid-enriched turmeric prevented up to 50% of OVX-induced loss of trabecular bone and also preserved the number and connectedness of the strut-like trabeculae. These results suggest that turmeric may have bone-protective effects but that extract composition is a critical factor. PMID:20695490

The purinergic receptor P2X5 regulates inflammasome activity and hyper-multinucleation of murine osteoclasts

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

Kim, Hyunsoo; Walsh, Matthew C.; Takegahara, Noriko

Excessive bone resorption by osteoclasts (OCs) can result in serious clinical outcomes, including bone loss that may weaken skeletal or periodontal strength. Proper bone homeostasis and skeletal strength are maintained by balancing OC function with the bone-forming function of osteoblasts. Unfortunately, current treatments that broadly inhibit OC differentiation or function may also interfere with coupled bone formation. We therefore identified a factor, the purinergic receptor P2X5 that is highly expressed during the OC maturation phase, and which we show here plays no apparent role in early bone development and homeostasis, but which is required for osteoclast-mediated inflammatory bone loss andmore » hyper-multinucleation of OCs. We further demonstrate that P2X5 is required for ATP-mediated inflammasome activation and IL-1β production by OCs, and that P2X5-deficient OC maturation is rescued in vitro by addition of exogenous IL-1β. These findings identify a mechanism by which OCs react to inflammatory stimuli, and may identify purinergic signaling as a therapeutic target for bone loss related inflammatory conditions.« less

Comparison of blood loss between using non central part cutting knee prosthesis and distal central part cutting.

PubMed

Malairungsakul, Anan

2014-12-01

Patients who undergo knee replacement surgery may need to receive a blood transfusion due to blood loss during the operation. Therefore it was important to improve the design of knee implant operative procedures in an attempt to reduce the rate of blood loss. The present study aimed to compare the blood loss between two types of knee replacement surgery. This is a retrospective study in which 78 patients received cemented knee replacements in Phayao Hospital between October 2010 and March 2012. There were two types of surgical procedure: 1) using an implant position covering the end of the femoral bone without cutting into the central part of the distal femoral, 2) using an implant position covering the end of the femoral bone cutting the central part of the distal femoral. Blood loss, blood transfusion, hemoglobin and hematocrit were recorded preoperatively, immediately postsurgery and 48 hours after surgery. Findings revealed that the knee replacement surgery using the implant position covering the end of the femoral bone without cutting the central part of the distal femoral significantly lowered the rate of blood loss when compared to using the implant position covering the end of the femoral bone with central cutting of the distal femor. The average blood loss during the operation without cutting at the central part of distal femoral was 49.50 ± 11.11 mL; whereas the operation cutting the central part of the distal femoral was 58.50 ± 11.69 mL. As regards blood loss, the knee replacement surgery using the implant position covering the end ofthefemoral bone without cutting the central part of distal femor was better than using the implant position covering the end of the femoral bone cutting at the central part of the distal femor.

Impact of intra- and extra-osseous soft tissue composition on changes in bone mineral density with weight loss and regain.

PubMed

Bosy-Westphal, Anja; Later, Wiebke; Schautz, Britta; Lagerpusch, Merit; Goele, Kristin; Heller, Martin; Glüer, Claus-C; Müller, Manfred J

2011-07-01

Recent studies report a significant gain in bone mineral density (BMD) after diet-induced weight loss. This might be explained by a measurement artefact. We therefore investigated the impact of intra- and extra-osseous soft tissue composition on bone measurements by dual X-ray absorptiometry (DXA) in a longitudinal study of diet-induced weight loss and regain in 55 women and 17 men (19-46 years, BMI 28.2-46.8 kg/m(2)). Total and regional BMD were measured before and after 12.7 ± 2.2 week diet-induced weight loss and 6 months after significant weight regain (≥30%). Hydration of fat free mass (FFM) was assessed by a 3-compartment model. Skeletal muscle (SM) mass, extra-osseous adipose tissue, and bone marrow were measured by whole body magnetic resonance imaging (MRI). Mean weight loss was -9.2 ± 4.4 kg (P < 0.001) and was followed by weight regain in a subgroup of 24 subjects (+6.3 ± 2.9 kg; P < 0.001). With weight loss, bone marrow and extra-osseous adipose tissue decreased whereas BMD increased at the total body, lumbar spine, and the legs (women only) but decreased at the pelvis (men only, all P < 0.05). The decrease in BMD(pelvis) correlated with the loss in visceral adipose tissue (VAT) (P < 0.05). Increases in BMD(legs) were reversed after weight regain and inversely correlated with BMD(legs) decreases. No other associations between changes in BMD and intra- or extra-osseous soft tissue composition were found. In conclusion, changes in extra-osseous soft tissue composition had a minor contribution to changes in BMD with weight loss and decreases in bone marrow adipose tissue (BMAT) were not related to changes in BMD.

FRET-Aptamer Assays for Bone Marker Assessment, C-Telopeptide, Creatinine, and Vitamin D

NASA Technical Reports Server (NTRS)

Bruno, John G.

2013-01-01

Astronauts lose 1.0 to 1.5% of their bone mass per month on long-duration spaceflights. NASA wishes to monitor the bone loss onboard spacecraft to develop nutritional and exercise countermeasures, and make adjustments during long space missions. On Earth, the same technology could be used to monitor osteoporosis and its therapy. Aptamers bind to targets against which they are developed, much like antibodies. However, aptamers do not require animal hosts or cell culture and are therefore easier, faster, and less expensive to produce. In addition, aptamers sometimes exhibit greater affinity and specificity vs. comparable antibodies. In this work, fluorescent dyes and quenchers were added to the aptamers to enable pushbutton, one-step, bind-and-detect fluorescence resonance energy transfer (FRET) assays or tests that can be freeze-dried, rehydrated with body fluids, and used to quantitate bone loss of vitamin D levels with a handheld fluorometer in the spacecraft environment. This work generated specific, rapid, one-step FRET assays for the bone loss marker C-telopeptide (CTx) when extracted from urine, creatinine from urine, and vitamin D congeners in diluted serum. The assays were quantified in nanograms/mL using a handheld fluorometer connected to a laptop computer to convert the raw fluorescence values into concentrations of each analyte according to linear standard curves. DNA aptamers were selected and amplified for several rounds against a 26- amino acid form of CTx, creatinine, and vitamin D. The commonalities between loop structures were studied, and several common loop structures were converted into aptamer beacons with a fluorophore and quencher on each end. In theory, when the aptamer beacon binds its cognate target (CTx bone peptide, creatinine, or vitamin D), it is forced open and no longer quenched, so it gives off fluorescent light (when excited) in proportion to the amount of target present in a sample. This proportional increase in fluorescence is called a "lights on" FRET response. The vitamin D aptamer beacon gives a "lights off" or inversely proportional fluorescence response to the amount of vitamin D present in diluted serum. These FRET-aptamer assays are rapid (<30 minutes), sensitive (low ng/mL detection limits), and quite easy to carry out (add sample, mix, and detect in the handheld reader). Benefits include the speed of the assays as well as the small amount of space taken up by the handheld reader and cuvette assays. The aptamer DNA sequences represent novel additional features of the existing (patent-pending) FRET-aptamer assay platform.

A study of stress-free living bone and its application to space flight

NASA Technical Reports Server (NTRS)

Leblanc, A.; Spira, M.

1983-01-01

Observations of animals and human subjects in weightless space flight (Skylab and COSMOS) document altered bone metabolism. Bone metabolism is affected by a number of local and systemic factors. The calcification and growth of transplanted bone is independent of local muscle, nervous, and mechanical forces; therefore, transplanted bone would provide data on the role of local vs. systematic factors. Bone metabolism in living transplanted bone, devoid of stress, was investigated as a possible tool for the investigation of countermeasures against disuse bone loss. An animal model using Sprague-Dawley rats was developed for transplantation of femur bone tissue on a nutrient vascular pedicel. The long term course of these implants was assessed through the measure of regional and total bone mineral, blood flow, and methylene diphosphonate (MDP) uptake. Clomid, an estrogen agonist/antagonist, was shown to protect bone from disuse loss of minerals by retarding trabecular and cortical resorption.

Progressive cell-mediated changes in articular cartilage and bone in mice are initiated by a single session of controlled cyclic compressive loading

PubMed Central

Ko, Frank C.; Dragomir, Cecilia L.; Plumb, Darren A.; Hsia, Allison W.; Adebayo, Olufunmilayo O.; Goldring, Steven R.; Wright, Timothy M.; Goldring, Mary B.; van der Meulen, Marjolein C.H.

2017-01-01

We previously showed that repetitive cyclic loading of the mouse knee joint causes changes that recapitulate the features of osteoarthritis (OA) in humans. By applying a single loading session, we characterized the temporal progression of the structural and compositional changes in subchondral bone and articular cartilage. We applied loading during a single 5-minute session to the left tibia of adult (26-week-old) C57Bl/6 male mice at a peak load of 9.0N for 1200 cycles. Knee joints were collected at times 0, 1, and 2 weeks after loading. The changes in articular cartilage and subchondral bone were analyzed by histology, immunohistochemistry (caspase-3 and cathepsin K), and microcomputed tomography. At time 0, no change was evident in chondrocyte viability or cartilage or subchondral bone integrity. However, cartilage pathology demonstrated by localized thinning and proteoglycan loss occurred at 1 and 2 weeks after the single session of loading. Transient cancellous bone loss was evident at 1 week, associated with increased osteoclast number. Bone loss was reversed to control levels at 2 weeks. We observed formation of fibrous and cartilaginous tissues at the joint margins at 1 and 2 weeks. Our findings demonstrate that a single session of noninvasive loading leads to the development of OA-like morphological and cellular alterations in articular cartilage and subchondral bone. The loss in subchondral trabecular bone mass and thickness returns to control levels at 2 weeks, whereas the cartilage thinning and proteoglycan loss persist. PMID:26896841

Does Quantitative Tibial Ultrasound Predict Low Bone Mineral Density Defined by Dual Energy X-Ray Absorptiometry?

PubMed Central

Birtane, Murat; Ekuklu, Galip; Cermik, Fikret; Tuna, Filiz; Kokino, Siranus

2008-01-01

Purpose Efforts for the early detection of bone loss and subsequent fracture risk by quantitative ultrasound (QUS), which is a non-invasive, radiation free, and cheaper method, seem rational to reduce the management costs. We aimed in this study to assess the probable correlation of speed of sound (SOS) values obtained by QUS with bone mineral density (BMD) as measured by the gold standard method, dual energy X-ray absorptiometry (DEXA), and to investigate the diagnostic value of QUS to define low BMD. Materials and Methods One hundred twenty-two postmenopausal women having prior standard DEXA measurements were included in the study. Spine and proximal femur (neck, trochanter and Ward's triangle) BMD were assessed in a standard protocol by DEXA. The middle point of the right tibia was chosen for SOS measurement by tibial QUS. Results The SOS values were observed to be significantly higher in the normal BMD (t score > - 1) group at all measurement sites except for the lumbar region, when compared with the low BMD group (t score < - 1). SOS was negatively correlated with age (r = - 0.66) and month since menopause (r = - 0.57). The sensitivity, specificity, and positive and negative predictive values for QUS t score to diagnose low BMD did not seem to be satisfactory at either of the measurement sites. Conclusion Tibial SOS was correlated weakly with BMD values of femur and lumbar spine as measured by DEXA and its diagnostic value did not seem to be high for discriminating between normal and low BMD, at these sites. PMID:18581594