Human bone hardness seems to depend on tissue type but not on anatomical site in the long bones of an old subject.

PubMed

Ohman, Caroline; Zwierzak, Iwona; Baleani, Massimiliano; Viceconti, Marco

2013-02-01

It has been hypothesised that among different human subjects, the bone tissue quality varies as a function of the bone segment morphology. The aim of this study was to assess and compare the quality, evaluated in terms of hardness of packages of lamellae, of cortical and trabecular bones, at different anatomical sites within the human skeleton. The contralateral six long bones of an old human subject were indented at different levels along the diaphysis and at both epiphyses of each bone. Hardness value, which is correlated to the degree of mineralisation, of both cortical and trabecular bone tissues was calculated for each indentation location. It was found that the cortical bone tissue was harder (+18%) than the trabecular one. In general, the bone hardness was found to be locally highly heterogeneous. In fact, considering one single slice obtained for a bone segment, the coefficient of variation of the hardness values was up to 12% for cortical bone and up to 17% for trabecular bone. However, the tissue hardness was on average quite homogeneous within and among the long bones of the studied donor, although differences up to 9% among levels and up to 7% among bone segments were found. These findings seem not to support the mentioned hypothesis, at least not for the long bones of an old subject.

Assessing bone banking activities at University of Malaya medical centre.

PubMed

Mohd, Suhaili; Samsuddin, Sharifah Mazni; Ramalingam, Saravana; Min, Ng Wuey; Yusof, Norimah; Zaman, T Kamarul; Mansor, Azura

2015-12-01

The main advantage of establishing in-house bone banks is its ability to readily provide allograft bones for local surgeries. Bone procurement activities of our university bone bank during the 10 years of operation were reviewed. Socio-demographic data of donors, types of bone procured, cases of rejected bones and types of allograft bones transplanted are presented. From 179 potential donors, 73 % were accepted with 213 procured bones. Femoral head was the common bone transplanted (45 %), as it was also the most common procured (82 %). Bones were rejected mainly due to non-technical reasons (83 %) rather than positive results of microbiological (13 %) and serological (4 %) tests. Comprehensive data could not be obtained for further analysis due to difficulties in retrieving information. Therefore, quality assurance system was improved to establish more systematic documentations, as the basis of good banking practice with process control hence allowing traceability.

Clinical evaluation of reducing acquisition time on single-photon emission computed tomography image quality using proprietary resolution recovery software.

PubMed

Aldridge, Matthew D; Waddington, Wendy W; Dickson, John C; Prakash, Vineet; Ell, Peter J; Bomanji, Jamshed B

2013-11-01

A three-dimensional model-based resolution recovery (RR) reconstruction algorithm that compensates for collimator-detector response, resulting in an improvement in reconstructed spatial resolution and signal-to-noise ratio of single-photon emission computed tomography (SPECT) images, was tested. The software is said to retain image quality even with reduced acquisition time. Clinically, any improvement in patient throughput without loss of quality is to be welcomed. Furthermore, future restrictions in radiotracer supplies may add value to this type of data analysis. The aims of this study were to assess improvement in image quality using the software and to evaluate the potential of performing reduced time acquisitions for bone and parathyroid SPECT applications. Data acquisition was performed using the local standard SPECT/CT protocols for 99mTc-hydroxymethylene diphosphonate bone and 99mTc-methoxyisobutylisonitrile parathyroid SPECT imaging. The principal modification applied was the acquisition of an eight-frame gated data set acquired using an ECG simulator with a fixed signal as the trigger. This had the effect of partitioning the data such that the effect of reduced time acquisitions could be assessed without conferring additional scanning time on the patient. The set of summed data sets was then independently reconstructed using the RR software to permit a blinded assessment of the effect of acquired counts upon reconstructed image quality as adjudged by three experienced observers. Data sets reconstructed with the RR software were compared with the local standard processing protocols; filtered back-projection and ordered-subset expectation-maximization. Thirty SPECT studies were assessed (20 bone and 10 parathyroid). The images reconstructed with the RR algorithm showed improved image quality for both full-time and half-time acquisitions over local current processing protocols (P<0.05). The RR algorithm improved image quality compared with local processing protocols and has been introduced into routine clinical use. SPECT acquisitions are now acquired at half of the time previously required. The method of binning the data can be applied to any other camera system to evaluate the reduction in acquisition time for similar processes. The potential for dose reduction is also inherent with this approach.

Systematic Review and Meta-Analysis of Objective and Subjective Quality of Life among Pediatric, Adolescent, and Young Adult Bone Tumor Survivors

PubMed Central

Stokke, Jamie; Sung, Lillian; Gupta, Abha; Lindberg, Antoinette; Rosenberg, Abby R.

2015-01-01

Background Pediatric, adolescent and young adult (AYA) survivors of bone sarcomas are at risk for poor quality of life (QOL). We conducted a systematic review and meta-analysis to summarize the literature describing QOL in this population and differences in QOL based on local control procedures. Procedure Included studies described ≥5 patients <25 years-old who had completed local control treatment for bone sarcoma, defined QOL as a main outcome, and measured it with a validated instrument. Data extraction and quality assessments were conducted with standardized tools. Meta-analyses compared QOL based on surgical procedure (limb-sparing versus amputation) and were stratified by assessment type (objective physical function, clinician-assessed disability, patient-reported disability and patient-reported QOL). Effect sizes were reported as the Standard Mean Difference when multiple instruments were used within a comparison and Weighted Mean Difference otherwise. All were weighted by inverse variance and modeled with random effects. Results Twenty-two of 452 unique manuscripts were included in qualitative syntheses, 8 of which were included in meta-analyses. Manuscripts were heterogeneous with respect to included patient populations (age, tumor type, time since treatment) and QOL instruments. Prospective studies suggested that QOL improves over time, and that female sex and older age at diagnosis are associated with poor QOL. Meta-analyses showed no differences in outcomes between patients who underwent limb-sparing versus amputation for local control. Conclusion QOL studies among children and AYAs with bone sarcoma are remarkably diverse, making it difficult to detect trends in patient outcomes. Future research should focus on standardized QOL instruments and interpretations. PMID:25820683

Severely impaired bone material quality in Chihuahua zebrafish resembles classical dominant human osteogenesis imperfecta.

PubMed

Fiedler, Imke A K; Schmidt, Felix N; Wölfel, Eva M; Plumeyer, Christine; Milovanovic, Petar; Gioia, Roberta; Tonelli, Francesca; Bale, Hrishikesh A; Jähn, Katharina; Besio, Roberta; Forlino, Antonella; Busse, Björn

2018-04-17

Excessive skeletal deformations and brittle fractures in the vast majority of patients suffering from osteogenesis imperfecta (OI) are a result of substantially reduced bone quality. Since the mechanical competence of bone is dependent on the tissue characteristics at small length scales, it is of crucial importance to assess how osteogenesis imperfecta manifests at the micro- and nanoscale of bone. In this context, the Chihuahua (Chi/ +) zebrafish, carrying a heterozygous glycine substitution in the α1 chain of collagen type I, has recently been proposed as suitable animal model of classical dominant OI, showing skeletal deformities, altered mineralization patterns and a smaller body size. This study assessed the bone quality properties of Chi/+ at multiple length scales using micro-computed tomography (micro-CT), histomorphometry, quantitative back-scattered electron imaging, Fourier transform infrared spectroscopy, nanoindentation and X-ray microscopy. At the skeletal level, Chi/+ display smaller body size, deformities and fracture calli in the ribs. Morphological changes at the whole bone level showed that the vertebrae in Chi/+ had a smaller size, smaller thickness and distorted shape. At the tissue level, Chi/+ displayed a higher degree of mineralization, lower collagen maturity, lower mineral maturity, altered osteoblast morphology, and lower osteocyte lacunar density compared to WT. The alterations in the cellular, compositional and structural properties of Chi/+ bones bear an explanation for the impaired local mechanical properties, which promote an increase in overall bone fragility in Chi/ +. The quantitative assessment of bone quality in Chi/+ thus further validates this mutant as an important model reflecting osseous characteristics associated with human classical dominant osteogenesis imperfecta. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Reduction of bone resorption by the application of fibrin glue in the reconstruction of the alveolar cleft.

PubMed

Segura-Castillo, José L; Aguirre-Camacho, Humberto; González-Ojeda, Alejandro; Michel-Perez, Jorge

2005-01-01

A major complication in 30% to 75% of cases of surgical treatment of alveolar cleft is resorption of the bone graft. A treatment alternative is the application of fibrin glue, which has the capacity to favor the integration of the graft. The main objective of the study was to evaluate if the use of the fibrin glue reduces bone resorption when it is applied locally. The authors designed a randomized clinical trial. Patients were divided into two groups: group 1, fibrin glue; and group 2, control. Pre- and postoperative graft volume, bone density, bone quality (Lekholm and Zarb, and Norton and Gamble classifications), and postoperative complications were evaluated. The follow-up for all patients was 3 months after discharge. Twenty-seven patients were surgically treated, 13 in group 1 and 14 in group 2. Group 1 had increased graft volume compared with group 2 (64.32 cm v 21.70 cm; P < 0.0001). Bone density was higher in group 1 than in group 2 (396.57 v 245.68; P > 0.076). Bone quality was type 1, 2 and 3 and 4 in group 1. Resorption in group 2 was 62.26%; in group 1, it was 29.72% (P > 0.081). The observed complications were infection and dehiscence of sutures (P > 0.537). The authors conclude that the fibrin glue significantly diminishes bone resorption, allowing improved graft integration and quality.

Prevalence of vitamin D insufficiency among adolescents and its correlation with bone parameters using high-resolution peripheral quantitative computed tomography.

PubMed

Cheung, T F; Cheuk, K Y; Yu, F W P; Hung, V W Y; Ho, C S; Zhu, T Y; Ng, B K W; Lee, K M; Qin, L; Ho, S S Y; Wong, G W K; Cheng, J C Y; Lam, T P

2016-08-01

Vitamin D deficiency and insufficiency are highly prevalent among adolescents in Hong Kong, which is a sub-tropical city with ample sunshine. Vitamin D level is significantly correlated with key bone density and bone quality parameters. Further interventional studies are warranted to define the role of vitamin D supplementation for improvement of bone health among adolescents. The relationship between bone quality parameters and vitamin D (Vit-D) status remains undefined among adolescents. The aims of this study were to evaluate Vit-D status and its association with both bone density and bone quality parameters among adolescents. Three hundred thirty-three girls and 230 boys (12-16 years old) with normal health were recruited in summer and winter separately from local schools. Serum 25(OH) Vit-D level, bone density and quality parameters by Dual Energy X-ray Absorptiometry (DXA) and High-Resolution peripheral Quantitative Computed Tomography (HR-pQCT), dietary calcium intake, and physical activity level were assessed. Sixty-four point seven percent and 11.4 % of subjects were insufficient [25 ≤ 25(OH)Vit-D ≤ 50 nmol/L] and deficient [25(OH)Vit-D < 25 nmol/L] in Vit-D, respectively. The mean level of serum 25(OH)Vit-D in summer was significantly higher than that in winter (44.7 ± 13.6 and 35.9 ± 12.6 nmol/L, respectively) without obvious gender difference. In girls, areal bone mineral density (aBMD) and bone mineral content (BMC) of bilateral femoral necks, cortical area, cortical thickness, total volumetric bone mineral density (vBMD), and trabecular thickness were significantly correlated with 25(OH)Vit-D levels. In boys, aBMD of bilateral femoral necks, BMC of the dominant femoral neck, cortical area, cortical thickness, total vBMD, trabecular vBMD, BV/TV, and trabecular separation were significantly correlated with 25(OH)Vit-D levels. Vit-D insufficiency was highly prevalent among adolescents in Hong Kong with significant correlation between Vit-D levels and key bone density and bone quality parameters being detected in this study. Given that this is a cross-sectional study and causality relationship cannot be inferred, further interventional studies investigating the role of Vit-D supplementation on improving bone health among adolescents are warranted.

Automated classification of bone marrow cells in microscopic images for diagnosis of leukemia: a comparison of two classification schemes with respect to the segmentation quality

NASA Astrophysics Data System (ADS)

Krappe, Sebastian; Benz, Michaela; Wittenberg, Thomas; Haferlach, Torsten; Münzenmayer, Christian

2015-03-01

The morphological analysis of bone marrow smears is fundamental for the diagnosis of leukemia. Currently, the counting and classification of the different types of bone marrow cells is done manually with the use of bright field microscope. This is a time consuming, partly subjective and tedious process. Furthermore, repeated examinations of a slide yield intra- and inter-observer variances. For this reason an automation of morphological bone marrow analysis is pursued. This analysis comprises several steps: image acquisition and smear detection, cell localization and segmentation, feature extraction and cell classification. The automated classification of bone marrow cells is depending on the automated cell segmentation and the choice of adequate features extracted from different parts of the cell. In this work we focus on the evaluation of support vector machines (SVMs) and random forests (RFs) for the differentiation of bone marrow cells in 16 different classes, including immature and abnormal cell classes. Data sets of different segmentation quality are used to test the two approaches. Automated solutions for the morphological analysis for bone marrow smears could use such a classifier to pre-classify bone marrow cells and thereby shortening the examination duration.

Open-Wedge High Tibial Osteotomy: RCT 2 Years RSA Follow-Up.

PubMed

Lind-Hansen, Thomas Bruno; Lind, Martin Carøe; Nielsen, Poul Torben; Laursen, Mogens Berg

2016-11-01

We investigated the influence of three different bone grafting materials on stability and clinical outcome of the healing open-wedge high tibial osteotomy (OW-HTO) with immediate partial weight bearing. A total of 45 (3 × 15) patients were randomized to injectable calcium phosphate cement (Calcibon; Biomet-Merck Biomaterials GmbH, Darmstadt, Germany), local bone autograft, or iliac crest autograft. Stability of the bony healing was evaluated with radiostereometric analysis (RSA) up to 24 months postoperatively. Clinical outcome was evaluated with the knee injury and osteoarthritis outcome score (KOOS). RSA revealed translations and rotations close to zero regardless of bone grafting material, with no statistically significant differences between the groups. Clinically, the Calcibon group had lower quality of life KOOS subscore at 2 years follow-up. We conclude that with a stable implant and 6 weeks of partial weight bearing, local autografting is sufficient to achieve solid bone consolidation following OW-HTO. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

The Influence of Local Bone Density on the Outcome of One Hundred and Fifty Proximal Humeral Fractures Treated with a Locking Plate.

PubMed

Kralinger, Franz; Blauth, Michael; Goldhahn, Jörg; Käch, Kurt; Voigt, Christine; Platz, Andreas; Hanson, Beate

2014-06-18

There is biomechanical evidence that bone density predicts the mechanical failure of implants. The aim of this prospective study was to evaluate the influence of local bone mineral density on the rate of mechanical failure after locking plate fixation of proximal humeral fractures. We enrolled 150 patients who were from fifty to ninety years old with a closed, displaced proximal humeral fracture fixed with use of a locking plate from July 2007 to April 2010. There were 118 women and thirty-two men who had a mean age of sixty-nine years. Preoperative computed tomography (CT) scans were done to assess bone mineral density of the contralateral humerus, and dual x-ray absorptiometry of the distal end of the radius of the unaffected arm was conducted within the first six weeks postoperatively. At follow-up evaluations at six weeks, three months, and one year postoperatively, pain, shoulder mobility, strength, and multiple functional and quality-of-life outcome measures (Disabilities of the Arm, Shoulder and Hand [DASH] questionnaire; Shoulder Pain and Disability Index [SPADI]; Constant score; and EuroQuol-5D [EQ-5D]) were done and standard radiographs were made. We defined mechanical failure as all complications related to bone quality experienced within one year. After locking plate fixation, fifty-three (35%) of 150 patients had mechanical failure; loss of reduction and secondary screw loosening with perforation were common. CT assessments of local bone mineral density showed no difference between patients with and without mechanical failure (89.82 versus 91.51 mg/cm 3 , respectively; p = 0.670). One-year DASH, SPADI, and Constant scores were significantly better for patients without mechanical failure (p ≤ 0.05). We did not find evidence of an association between bone mineral density and the rate of mechanical failures, which may suggest that patients with normal bone mineral density are less prone to sustain a proximal humeral fracture. Future studies should target other discriminating factors between patients with and without mechanical failure. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence. Copyright © 2014 by The Journal of Bone and Joint Surgery, Incorporated.

Animal Models of Bone Metastasis

PubMed Central

Simmons, J. K.; Hildreth, B. E.; Supsavhad, W.; Elshafae, S. M.; Hassan, B. B.; Dirksen, W. P.; Toribio, R. E.; Rosol, T. J.

2015-01-01

Bone is one of the most common sites of cancer metastasis in humans and is a significant source of morbidity and mortality. Bone metastases are considered incurable and result in pain, pathologic fracture, and decreased quality of life. Animal models of skeletal metastases are essential to improve the understanding of the molecular pathways of cancer metastasis and growth in bone and to develop new therapies to inhibit and prevent bone metastases. The ideal animal model should be clinically relevant, reproducible, and representative of human disease. Currently, an ideal model does not exist; however, understanding the strengths and weaknesses of the available models will lead to proper study design and successful cancer research. This review provides an overview of the current in vivo animal models used in the study of skeletal metastases or local tumor invasion into bone and focuses on mammary and prostate cancer, lymphoma, multiple myeloma, head and neck squamous cell carcinoma, and miscellaneous tumors that metastasize to bone. PMID:26021553

Using Anisotropic 3D Minkowski Functionals for Trabecular Bone Characterization and Biomechanical Strength Prediction in Proximal Femur Specimens

PubMed Central

Nagarajan, Mahesh B.; De, Titas; Lochmüller, Eva-Maria; Eckstein, Felix; Wismüller, Axel

2017-01-01

The ability of Anisotropic Minkowski Functionals (AMFs) to capture local anisotropy while evaluating topological properties of the underlying gray-level structures has been previously demonstrated. We evaluate the ability of this approach to characterize local structure properties of trabecular bone micro-architecture in ex vivo proximal femur specimens, as visualized on multi-detector CT, for purposes of biomechanical bone strength prediction. To this end, volumetric AMFs were computed locally for each voxel of volumes of interest (VOI) extracted from the femoral head of 146 specimens. The local anisotropy captured by such AMFs was quantified using a fractional anisotropy measure; the magnitude and direction of anisotropy at every pixel was stored in histograms that served as a feature vectors that characterized the VOIs. A linear multi-regression analysis algorithm was used to predict the failure load (FL) from the feature sets; the predicted FL was compared to the true FL determined through biomechanical testing. The prediction performance was measured by the root mean square error (RMSE) for each feature set. The best prediction performance was obtained from the fractional anisotropy histogram of AMF Euler Characteristic (RMSE = 1.01 ± 0.13), which was significantly better than MDCT-derived mean BMD (RMSE = 1.12 ± 0.16, p<0.05). We conclude that such anisotropic Minkowski Functionals can capture valuable information regarding regional trabecular bone quality and contribute to improved bone strength prediction, which is important for improving the clinical assessment of osteoporotic fracture risk. PMID:29170581

Automatic bone outer contour extraction from B-modes ultrasound images based on local phase symmetry and quadratic polynomial fitting

NASA Astrophysics Data System (ADS)

Karlita, Tita; Yuniarno, Eko Mulyanto; Purnama, I. Ketut Eddy; Purnomo, Mauridhi Hery

2017-06-01

Analyzing ultrasound (US) images to get the shapes and structures of particular anatomical regions is an interesting field of study since US imaging is a non-invasive method to capture internal structures of a human body. However, bone segmentation of US images is still challenging because it is strongly influenced by speckle noises and it has poor image quality. This paper proposes a combination of local phase symmetry and quadratic polynomial fitting methods to extract bone outer contour (BOC) from two dimensional (2D) B-modes US image as initial steps of three-dimensional (3D) bone surface reconstruction. By using local phase symmetry, the bone is initially extracted from US images. BOC is then extracted by scanning one pixel on the bone boundary in each column of the US images using first phase features searching method. Quadratic polynomial fitting is utilized to refine and estimate the pixel location that fails to be detected during the extraction process. Hole filling method is then applied by utilize the polynomial coefficients to fill the gaps with new pixel. The proposed method is able to estimate the new pixel position and ensures smoothness and continuity of the contour path. Evaluations are done using cow and goat bones by comparing the resulted BOCs with the contours produced by manual segmentation and contours produced by canny edge detection. The evaluation shows that our proposed methods produces an excellent result with average MSE before and after hole filling at the value of 0.65.

A paradigm shift for bone quality in dentistry: A literature review.

PubMed

Kuroshima, Shinichiro; Kaku, Masaru; Ishimoto, Takuya; Sasaki, Muneteru; Nakano, Takayoshi; Sawase, Takashi

2017-10-01

The aim of this study was to present the current concept of bone quality based on the proposal by the National Institutes of Health (NIH) and some of the cellular and molecular factors that affect bone quality. This is a literature review which focuses on collagen, biological apatite (BAp), and bone cells such as osteoblasts and osteocytes. In dentistry, the term "bone quality" has long been considered to be synonymous with bone mineral density (BMD) based on radiographic and sensible evaluations. In 2000, the NIH proposed the concept of bone quality as "the sum of all characteristics of bone that influence the bone's resistance to fracture," which is completely independent of BMD. The NIH defines bone quality as comprising bone architecture, bone turnover, bone mineralization, and micro-damage accumulation. Moreover, our investigations have demonstrated that BAp, collagen, and bone cells such as osteoblasts and osteocytes play essential roles in controlling the current concept of bone quality in bone around hip and dental implants. The current concept of bone quality is crucial for understanding bone mechanical functions. BAp, collagen and osteocytes are the main factors affecting bone quality. Moreover, mechanical loading dynamically adapts bone quality. Understanding the current concept of bone quality is required in dentistry. Copyright © 2017 Japan Prosthodontic Society. Published by Elsevier Ltd. All rights reserved.

Biological Regulation of Bone Quality

PubMed Central

Alliston, Tamara

2014-01-01

The ability of bone to resist fracture is determined by the combination of bone mass and bone quality. Like bone mass, bone quality is carefully regulated. Of the many aspects of bone quality, this review focuses on biological mechanisms that control the material quality of the bone extracellular matrix (ECM). Bone ECM quality depends upon ECM composition and organization. Proteins and signaling pathways that affect the mineral or organic constituents of bone ECM impact bone ECM material properties, such as elastic modulus and hardness. These properties are also sensitive to pathways that regulate bone remodeling by osteoblasts, osteoclasts, and osteocytes. Several extracellular proteins, signaling pathways, intracellular effectors, and transcription regulatory networks have been implicated in the control of bone ECM quality. A molecular understanding of these mechanisms will elucidate the biological control of bone quality and suggest new targets for the development of therapies to prevent bone fragility. PMID:24894149

Identification of optimal mask size parameter for noise filtering in 99mTc-methylene diphosphonate bone scintigraphy images.

PubMed

Pandey, Anil K; Bisht, Chandan S; Sharma, Param D; ArunRaj, Sreedharan Thankarajan; Taywade, Sameer; Patel, Chetan; Bal, Chandrashekhar; Kumar, Rakesh

2017-11-01

Tc-methylene diphosphonate (Tc-MDP) bone scintigraphy images have limited number of counts per pixel. A noise filtering method based on local statistics of the image produces better results than a linear filter. However, the mask size has a significant effect on image quality. In this study, we have identified the optimal mask size that yields a good smooth bone scan image. Forty four bone scan images were processed using mask sizes 3, 5, 7, 9, 11, 13, and 15 pixels. The input and processed images were reviewed in two steps. In the first step, the images were inspected and the mask sizes that produced images with significant loss of clinical details in comparison with the input image were excluded. In the second step, the image quality of the 40 sets of images (each set had input image, and its corresponding three processed images with 3, 5, and 7-pixel masks) was assessed by two nuclear medicine physicians. They selected one good smooth image from each set of images. The image quality was also assessed quantitatively with a line profile. Fisher's exact test was used to find statistically significant differences in image quality processed with 5 and 7-pixel mask at a 5% cut-off. A statistically significant difference was found between the image quality processed with 5 and 7-pixel mask at P=0.00528. The identified optimal mask size to produce a good smooth image was found to be 7 pixels. The best mask size for the John-Sen Lee filter was found to be 7×7 pixels, which yielded Tc-methylene diphosphonate bone scan images with the highest acceptable smoothness.

The role of bone scintigraphy in detecting child abuse.

PubMed

Conway, J J; Collins, M; Tanz, R R; Radkowski, M A; Anandappa, E; Hernandez, R; Freeman, E L

1993-10-01

This review of diagnostic imaging in cases of suspected child abuse characterizes the significant differences between bone scintigraphy and x-ray evaluation, describes the advantages and disadvantages of each modality, postulates on the specific mechanisms of injury that produce the characteristic scintigraphic findings, and emphasizes the influences that scintigraphic studies have on the medical, social, and legal aspects of child abuse. The major advantages of bone scintigraphy are its increased sensitivity (25% to 50%) in detecting evidence of soft tissue as well as bone trauma in child abuse. Furthermore, it is postulated that the specific mechanisms of inflicting the trauma relate to the patient's size and are characterized by bone scintigraphy. During fits of anger or frustration, the perpetrator of child abuse grasps the small infant or child by the thorax during the shaking activity. This produces characteristic rib injuries. The older and heavier child is more likely to be grabbed by the extremities, which produces periosteal injuries manifested as characteristic abnormal localizations in the diaphyses of the extremities. The roentgenograms of these injuries are frequently normal. The importance of bone scintigraphy is its complementary nature in defining and characterizing the extent and severity of trauma from child abuse. Such findings have direct bearing on the medical, social, and legal outcomes for the abused child. The quality of scintigraphic imaging is important, requiring the use of magnification techniques in the infant. The interpretation of the scintigraphic images depends on an understanding of the mechanisms by which the radionuclide localizes in bone. The same traumatic incident can lead to decreased, normal, or increased localization at the trauma site. Radionuclide scintigraphy is a complementary rather than competitive imaging modality to X-ray evaluation in the diagnosis and management of physical child abuse.

Effects of Plantar Vibration on Bone and Deep Fascia in a Rat Hindlimb Unloading Model of Disuse

PubMed Central

Huang, Yunfei; Fan, Yubo; Salanova, Michele; Yang, Xiao; Sun, Lianwen; Blottner, Dieter

2018-01-01

The deep fascia of the vertebrate body comprises a biomechanically unique connective cell and tissue layer with integrative functions to support global and regional strain, tension, and even muscle force during motion and performance control. However, limited information is available on deep fascia in relation to bone in disuse. We used rat hindlimb unloading as a model of disuse (21 days of hindlimb unloading) to study biomechanical property as well as cell and tissue changes to deep fascia and bone unloading. Rats were randomly divided into three groups (n = 8, each): hindlimb unloading (HU), HU + vibration (HUV), and cage-control (CON). The HUV group received local vibration applied to the plantar of both hind paws. Micro-computed tomography analyzed decreased bone mineral density (BMD) of vertebra, tibia, and femur in HU vs. CON. Biomechanical parameters (elastic modulus, max stress, yield stress) of spinal and crural fascia in HU were always increased vs. CON. Vibration in HUV only counteracted HU-induced tibia bone loss and crural fascia mechanical changes but failed to show comparable changes in the vertebra and spinal fascia on lumbar back. Tissue and cell morphometry (size and cell nuclear density), immunomarker intensity levels of anti-collagen-I and III, probed on fascia cryosections well correlated with biomechanical changes suggesting crural fascia a prime target for plantar vibration mechano-stimulation in the HU rat. We conclude that the regular biomechanical characteristics as well as tissue and cell properties in crural fascia and quality of tibia bone (BMD) were preserved by local plantar vibration in disuse suggesting common mechanisms in fascia and bone adaptation to local mechanovibration stimulation following hind limb unloading in the HUV rat. PMID:29875702

Effects of Plantar Vibration on Bone and Deep Fascia in a Rat Hindlimb Unloading Model of Disuse.

PubMed

Huang, Yunfei; Fan, Yubo; Salanova, Michele; Yang, Xiao; Sun, Lianwen; Blottner, Dieter

2018-01-01

The deep fascia of the vertebrate body comprises a biomechanically unique connective cell and tissue layer with integrative functions to support global and regional strain, tension, and even muscle force during motion and performance control. However, limited information is available on deep fascia in relation to bone in disuse. We used rat hindlimb unloading as a model of disuse (21 days of hindlimb unloading) to study biomechanical property as well as cell and tissue changes to deep fascia and bone unloading. Rats were randomly divided into three groups ( n = 8, each): hindlimb unloading (HU), HU + vibration (HUV), and cage-control (CON). The HUV group received local vibration applied to the plantar of both hind paws. Micro-computed tomography analyzed decreased bone mineral density (BMD) of vertebra, tibia, and femur in HU vs. CON. Biomechanical parameters (elastic modulus, max stress, yield stress) of spinal and crural fascia in HU were always increased vs. CON. Vibration in HUV only counteracted HU-induced tibia bone loss and crural fascia mechanical changes but failed to show comparable changes in the vertebra and spinal fascia on lumbar back. Tissue and cell morphometry (size and cell nuclear density), immunomarker intensity levels of anti-collagen-I and III, probed on fascia cryosections well correlated with biomechanical changes suggesting crural fascia a prime target for plantar vibration mechano-stimulation in the HU rat. We conclude that the regular biomechanical characteristics as well as tissue and cell properties in crural fascia and quality of tibia bone (BMD) were preserved by local plantar vibration in disuse suggesting common mechanisms in fascia and bone adaptation to local mechanovibration stimulation following hind limb unloading in the HUV rat.

Osteocyte-Intrinsic TGF-β Signaling Regulates Bone Quality through Perilacunar/Canalicular Remodeling

DOE PAGES

Dole, Neha S.; Mazur, Courtney M.; Acevedo, Claire; ...

2017-11-28

Poor bone quality contributes to bone fragility in diabetes, aging, and osteogenesis imperfecta. However, the mechanisms controlling bone quality are not well understood, contributing to the current lack of strategies to diagnose or treat bone quality deficits. Transforming growth factor beta (TGF-β) signaling is a crucial mechanism known to regulate the material quality of bone, but its cellular target in this regulation is unknown. Studies showing that osteocytes directly remodel their perilacunar/canalicular matrix led us to hypothesize that TGF-β controls bone quality through perilacunar/canalicular remodeling (PLR). Using inhibitors and mice with an osteocyte-intrinsic defect in TGF-β signaling (TβRII ocy-/-), wemore » show that TGF-β regulates PLR in a cell-intrinsic manner to control bone quality. Altogether, this study emphasizes that osteocytes are key in executing the biological control of bone quality through PLR, thereby highlighting the fundamental role of osteocyte-mediated PLR in bone homeostasis and fragility. Resistance to fracture requires healthy bone mass and quality. However, the cellular mechanisms regulating bone quality are unclear. Dole et al. show that osteocyte-intrinsic TGF-β signaling maintains bone quality through perilacunar/canalicular remodeling. Thus, osteocytes mediate perilacunar/canalicular remodeling and osteoclast-directed remodeling to cooperatively maintain bone quality and mass and prevent fragility.« less

Osteocyte-Intrinsic TGF-β Signaling Regulates Bone Quality through Perilacunar/Canalicular Remodeling

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

Dole, Neha S.; Mazur, Courtney M.; Acevedo, Claire

Poor bone quality contributes to bone fragility in diabetes, aging, and osteogenesis imperfecta. However, the mechanisms controlling bone quality are not well understood, contributing to the current lack of strategies to diagnose or treat bone quality deficits. Transforming growth factor beta (TGF-β) signaling is a crucial mechanism known to regulate the material quality of bone, but its cellular target in this regulation is unknown. Studies showing that osteocytes directly remodel their perilacunar/canalicular matrix led us to hypothesize that TGF-β controls bone quality through perilacunar/canalicular remodeling (PLR). Using inhibitors and mice with an osteocyte-intrinsic defect in TGF-β signaling (TβRII ocy-/-), wemore » show that TGF-β regulates PLR in a cell-intrinsic manner to control bone quality. Altogether, this study emphasizes that osteocytes are key in executing the biological control of bone quality through PLR, thereby highlighting the fundamental role of osteocyte-mediated PLR in bone homeostasis and fragility. Resistance to fracture requires healthy bone mass and quality. However, the cellular mechanisms regulating bone quality are unclear. Dole et al. show that osteocyte-intrinsic TGF-β signaling maintains bone quality through perilacunar/canalicular remodeling. Thus, osteocytes mediate perilacunar/canalicular remodeling and osteoclast-directed remodeling to cooperatively maintain bone quality and mass and prevent fragility.« less

Quality of Life, Physical and Mental Status and Contentment of Patients with Localized Soft Tissue or Bone Sarcoma: A Questionnaire Analysis

PubMed Central

Sachsenmaier, Saskia M.; Ipach, Ingmar; Kluba, Torsten

2015-01-01

Extremity soft tissue and bone sarcomas represent a rare group of bone and connective tissue cancers. In literature, there is little information about psycho-emotional status and impact on quality of life after the diagnosis and treatment of this kind of tumors. The aim of this survey was to define the profile of the patients at risk and their need for psychooncological care. Our self-created questionnaire consists of 71 items related to the individual emotional, mental and physical situation after the diagnosis of soft tissue and bone sarcoma. Sixty-six patients, surgically treated at our department, were included. Only 37.5% of the patients considered themselves to be completely emotional stable. Psychooncological treatment was accepted mostly by female patients, by patients with higher education level and by married patients. Emotional stability and confidence in future were associated with a strong familiar background, with numerous consultations of psychooncological service and also to gender and physical condition. Current quality of life was strongly correlated to physical condition. Thanks to our questionnaire, we disclosed few risk factors for negative emotional outcome after therapy, such as higher age, social isolation, female gender and poor physical status. PMID:26330994

[Regional blood flow and bone uptake of methylene-diphosphonate-technetium-99m].

PubMed

Vattimo, A; Martini, G; Pisani, M

1983-05-30

Sudeck's atrophy of the foot is an acute, patchy osteoporosis that, on bone scan, shows an increase in both bone blood flow and local bone uptake of bone-seeking radionuclides. The purpose of this study was to evaluate the relationship between bone uptake of 99mTc-MDP and local bone blood flow. In some patients with Sudeck's atrophy of one foot we measured local bone blood flow and bone uptake of 99mTc-MDP. External counting of radioactivity, with a count-rate of 1 second was performed for 60 minutes after i.v. injection of a known dose of 99mTc-MDP in some patients with Sudeck's atrophy of the foot. The regions of interest (ROI) were selected on the basis of a bone scan performed 24 hours earlier. We assumed that the data recorded during the first seconds (7-10) reflect local blood flow and the data at 60 minutes reflect the bone uptake. The ratio between the local blood flow in the involved and healthy foot was higher than the local bone uptake ratio. The ratio between bone uptake and local bone blood flow was higher in the normal foot than in the affected one. These results suggest that the bone avidity for bone-seeking radionuclides is lower in Sudeck's atrophy than in normal bone.

[Bone Cell Biology Assessed by Microscopic Approach. Assessment of bone quality using Raman and infrared spectroscopy].

PubMed

Suda, Hiromi Kimura

2015-10-01

Bone quality, which was defined as "the sum total of characteristics of the bone that influence the bone's resistance to fracture" at the National Institute of Health (NIH) conference in 2001, contributes to bone strength in combination with bone mass. Bone mass is often measured as bone mineral density (BMD) and, consequently, can be quantified easily. On the other hand, bone quality is composed of several factors such as bone structure, bone matrix, calcification degree, microdamage, and bone turnover, and it is not easy to obtain data for the various factors. Therefore, it is difficult to quantify bone quality. We are eager to develop new measurement methods for bone quality that make it possible to determine several factors associated with bone quality at the same time. Analytic methods based on Raman and FTIR spectroscopy have attracted a good deal of attention as they can provide a good deal of chemical information about hydroxyapatite and collagen, which are the main components of bone. A lot of studies on bone quality using Raman and FTIR imaging have been reported following the development of the two imaging systems. Thus, both Raman and FTIR imaging appear to be promising new bone morphometric techniques.

Heterotopic bone formation around sintered porous-surfaced Ti-6Al-4V implants coated with native bone morphogenetic proteins.

PubMed

Simon, Ziv; Deporter, Douglas A; Pilliar, Robert M; Clokie, Cameron M

2006-09-01

Coating endosseous dental implants with growth factors such as bone morphogenetic proteins (BMPs) may be one way to accelerate and/or enhance the quality of osseointegration. The purpose of this study was to investigate in the murine muscle pouch model whether sintered porous-surfaced titanium alloy implants coated with BMPs would lead to heterotopic bone formation around and within the implant surface geometry. Porous-surfaced dental implants were coated with partially purified native human BMPs, with or without a carrier of Poloxamer 407 (BASF Corp., Parsippany, NJ), placed in gelatin capsules and implanted into the hindquarter muscles of mice. Mice were euthanized after 28 days. Sections of retrieved specimens were subsequently prepared for morphometric analysis of bone formation using backscatter electron microscopic images. Human BMPs, either with or without the carrier of Poloxamer 407, led to bone formation within and outside of the sintered porous implant surface. When the sintered implant surface region was subdivided into inner and outer halves, similar levels of bone ingrowth and contact were seen in the 2 halves. Evidence of bone formation to the depth of the solid implant core (i.e., the deepest level possible) also was seen. Sintered porous-surfaced dental implants can be used as substrate for partially purified BMPs in the murine muscle pouch model. With the addition of these osteoinductive factors, the porous implant surface supported bone formation within the surface porosity provided, in some instances, all the way to the solid implant core. The addition of growth factors to a sintered porous surface may be an efficient method for altering locally the healing sequence and quality of bone associated with osseointegration of bone-interfacing implants.

Doping dose of salbutamol and exercise training: impact on the skeleton of ovariectomized rats.

PubMed

Bonnet, N; Laroche, N; Beaupied, H; Vico, L; Dolleans, E; Benhamou, C L; Courteix, D

2007-08-01

Previous studies in healthy rats have demonstrated a deleterious bone impact of beta-agonist treatment. The purpose of this study was to examine the trabecular and cortical effects of beta(2)-agonists at doping dose on treadmill exercising rats with estrogen deficiency. Adult female rats were ovariectomized (OVX; n = 44) or sham operated (n = 12). Then, OVX rats received a subcutaneous injection of salbutamol (SAB) or vehicle with (EXE) or without treadmill exercise for 10 wk. Bone mineral density (BMD) was analyzed by densitometry. Microcomputed tomography and histomorphometric analysis were performed to study trabecular bone structure and bone cell activities. After 10 wk, SAB rats presented a much more marked decrease of BMD and trabecular parameters. Exercise did not change the high level of bone resorption in OVX EXE SAB compared with OVX SAB group (both on COOH-terminal collagen cross-links and osteoclast number). These results confirm the deleterious effect of beta(2)-agonists on bone quantity (femoral BMD gain: OVX EXE, +6.8%, vs. OVX EXE SAB, -1.8%; P < 0.01) and quality (-8.0% of femoral trabecular thickness in OVX EXE SAB vs. OVX EXE), indicating that SAB suppresses the effect of EXE in OVX rats. Furthermore, we notice that the slight beneficial effect of exercise was mainly localized in the tibia. These findings indicate the presence of a bone alteration threshold below which there is no more alteration in structural bone quantity and quality. The negative effects of SAB on bone observed in this study in trained rats may indicate potential complications in doping female athletes with exercise-induced amenorrhea.

Ultrasound elastography assessment of bone/soft tissue interface

NASA Astrophysics Data System (ADS)

Parmar, Biren J.; Yang, Xu; Chaudhry, Anuj; Shafeeq Shajudeen, Peer; Nair, Sanjay P.; Weiner, Bradley K.; Tasciotti, Ennio; Krouskop, Thomas A.; Righetti, Raffaella

2016-01-01

We report on the use of elastographic imaging techniques to assess the bone/soft tissue interface, a region that has not been previously investigated but may provide important information about fracture and bone healing. The performance of axial strain elastograms and axial shear strain elastograms at the bone/soft tissue interface was studied ex vivo on intact and fractured canine and ovine tibias. Selected ex vivo results were corroborated on intact sheep tibias in vivo. The elastography results were statistically analyzed using elastographic image quality tools. The results of this study demonstrate distinct patterns in the distribution of the normalized local axial strains and axial shear strains at the bone/soft tissue interface with respect to the background soft tissue. They also show that the relative strength and distribution of the elastographic parameters change in the presence of a fracture and depend on the degree of misalignment between the fracture fragments. Thus, elastographic imaging modalities might be used in the future to obtain information regarding the integrity of bones and to assess the severity of fractures, alignment of bone fragments as well as to follow bone healing.

Magnetic resonance guided focused ultrasound surgery (MRgFUS) of bone metastases: From primary pain palliation to local tumor control

NASA Astrophysics Data System (ADS)

Napoli, A.; Leonardi, A.; Andrani, F.; Boni, F.; Anzidei, M.; Catalano, C.

2017-03-01

Purpose: To evaluate the clinical performance of MRgFUS in primary pain palliation of painful bone metastases and in local tumor control. Materials and Methods: We enrolled 26 consecutive patients (female/male 12/14; age: 64.7±7.5yrs) with painful bone metastases. Before and 3 months after MRgFUS treatment pain severity and pain interference scores were assessed according to Brief Pain Inventory-Quality of Life (BPI-QoL) criteria and patients underwent both CT and MRI. Local tumor control was evaluated according to lesion size, density and perfusion at CT, dynamic contrast enhancement at MRI (Discovery 750HD, GE; Gd-Bopta, Bracco) and metabolic activity at PET or scintigraphy. Patients were classified as responders or non-responders. Results: No treatment-related adverse events were recorded during the study. As statistically significant difference between baseline and follow-up values for both pain severity and pain interference scores was observed (p<0.05). Increased bone density was observed in 9/26 (34.6%) patients. Non-Perfused Volume values ranged between 20% and 92%. There was no difference in NPV values between responders and non-responders (46.7±24.2% [25 - 90 %] vs. 45±24.9% [20 - 93 %]; p=0.7). In 6 patients (5 prostate and 1 breast primary cancer) there was nearly absence of metabolic activity after treatment (mean SUV=1.2). Conclusion: MRgFUS can be safely and effectively used as the primary treatment for pain palliation in patients with painful bone metastases; moreover our experience demonstrated also a potential role for the MRgFUS in local tumor control.

[Is local bone graft sufficient to maintain the surgical correction in adolescent idiopathic scoliosis curves?].

PubMed

Mardomingo, A; Sánchez-Mariscal, F; Alvarez, P; Pizones, J; Zúñica, L; Izquierdo, E

2013-01-01

The purpose of this study was to compare postoperative clinical and radiological results in adolescent idiopathic scoliosis curves treated by posterior arthrodesis using autogenous bone graft from iliac crest (CI) versus only local autograft bone (HL). A retrospective matched cohort study was conducted on 73 patients (CI n=37 and HL n=36) diagnosed with adolescent idiopathic scoliosis and treated surgically by posterior arthrodesis. The mean post-operative follow-up was 126 months in the CI group vs. 66 months in the HL group. The radiographic data collected consisted of preoperative, postoperative, and final follow-up antero-posterior and lateral full-length radiographs. Loss of correction and quality of arthrodesis were evaluated by comparing the scores obtained from the Spanish version of the SRS-22 questionnaire. There were significant differences in the post-operative results as regards the correction of the Cobb angle of the main curve (HL 61 ± 15% vs. CI 51 ± 14%, P<.004), however a greater loss of correction was found in the local bone group (CI 4.5 ± 7.3° vs. HL 8.5 ± 6.3°, P=.02). There were no significant differences as regards the correction of the Cobb angle of the main curve at the end of follow-up. There were no clinical differences between the two groups in the SRS-22 scores. At 5 years of follow-up, there was a statistically significant greater loss of radiographic correction at the end of final follow-up in the local bone graft group. However clinical differences were not observed as regards the SRS-22 scores. Copyright © 2013 SECOT. Published by Elsevier Espana. All rights reserved.

Local bone graft harvesting and volumes in posterolateral lumbar fusion: a technical report.

PubMed

Carragee, Eugene J; Comer, Garet C; Smith, Micah W

2011-06-01

In lumbar surgery, local bone graft is often harvested and used in posterolateral fusion procedures. The volume of local bone graft available for posterolateral fusion has not been determined in North American patients. Some authors have described this as minimal, but others have suggested the volume was sufficient to be reliably used as a stand-alone bone graft substitute for single-level fusion. To describe the technique used and determine the volume of local bone graft available in a cohort of patients undergoing single-level primary posterolateral fusion by the authors harvesting technique. Technical description and cohort report. Consecutive patients undergoing lumbar posterolateral fusion with or without instrumentation for degenerative processes. Local bone graft volume. Consecutive patients undergoing lumbar posterolateral fusion with or without instrumentation for degenerative processes of were studied. Local bone graft was harvested by a standard method in each patient and the volume measured by a standard procedure. Twenty-five patients were studied, and of these 11 (44%) had a previous decompression. The mean volume of local bone graft harvested was measured to be 25 cc (range, 12-36 cc). Local bone graft was augmented by iliac crest bone in six of 25 patients (24%) if the posterolateral fusion bed was not well packed with local bone alone. There was a trend to greater local bone graft volumes in men and in patients without previous decompression. Large volumes of local bone can be harvested during posterolateral lumbar fusion surgery. Even in patients with previous decompression the volume harvested is similar to that reported harvested from the posterior iliac crest for single-level fusion. Copyright © 2011 Elsevier Inc. All rights reserved.

Bone images from dual-energy subtraction chest radiography in the detection of rib fractures.

PubMed

Szucs-Farkas, Zsolt; Lautenschlager, Katrin; Flach, Patricia M; Ott, Daniel; Strautz, Tamara; Vock, Peter; Ruder, Thomas D

2011-08-01

To assess the sensitivity and image quality of chest radiography (CXR) with or without dual-energy subtracted (ES) bone images in the detection of rib fractures. In this retrospective study, 39 patients with 204 rib fractures and 24 subjects with no fractures were examined with a single exposure dual-energy subtraction digital radiography system. Three blinded readers first evaluated the non-subtracted posteroanterior and lateral chest radiographs alone, and 3 months later they evaluated the non-subtracted images together with the subtracted posteroanterior bone images. The locations of rib fractures were registered with confidence levels on a 3-grade scale. Image quality was rated on a 5-point scale. Marks by readers were compared with fracture localizations in CT as a standard of reference. The sensivity for fracture detection using both methods was very similar (34.3% with standard CXR and 33.5% with ES-CXR, p=0.92). At the patient level, both sensitivity (71.8%) and specificity (92.9%) with or without ES were identical. Diagnostic confidence was not significantly different (2.61 with CXR and 2.75 with ES-CXR, p=0.063). Image quality with ES was rated higher than that on standard CXR (4.08 vs. 3.74, p<0.001). Despite a better image quality, adding ES bone images to standard radiographs of the chest does not provide better sensitivity or improved diagnostic confidence in the detection of rib fractures. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Evaluating bone quality in patients with chronic kidney disease

PubMed Central

Malluche, Hartmut H.; Porter, Daniel S.; Pienkowski, David

2013-01-01

Bone of normal quality and quantity can successfully endure physiologically imposed mechanical loads. Chronic kidney disease–mineral and bone disorder (CKD–MBD) adversely affects bone quality through alterations in bone turnover and mineralization, whereas bone quantity is affected through changes in bone volume. Changes in bone quality can be associated with altered bone material, structure, or microdamage, which can result in an elevated rate of fracture in patients with CKD–MBD. Fractures cannot always be explained by reduced bone quantity and, therefore, bone quality should be assessed with a variety of techniques from the macro-organ level to the nanoscale level. In this Review, we demonstrate the importance of evaluating bone from multiple perspectives and hierarchical levels to understand CKD–MBD-related abnormalities in bone quality. Understanding the relationships between variations in material, structure, microdamage, and mechanical properties of bone in patients with CKD–MBD should aid in the development of new modalities to prevent, or treat, these abnormalities. PMID:24100399

Bone cysts after osteochondral allograft repair of cartilage defects in goats suggest abnormal interaction between subchondral bone and overlying synovial joint tissues.

PubMed

Pallante-Kichura, Andrea L; Cory, Esther; Bugbee, William D; Sah, Robert L

2013-11-01

The efficacy of osteochondral allografts (OCAs) may be affected by osseous support of the articular cartilage, and thus affected by bone healing and remodeling in the OCA and surrounding host. Bone cysts, and their communication pathways, may be present in various locations after OCA insertion and reflect distinct pathogenic mechanisms. Previously, we analyzed the effect of OCA storage (FRESH, 4°C/14d, 4°C/28d, FROZEN) on cartilage quality in fifteen adult goats after 12months in vivo. The objectives of this study were to further analyze OCAs and contralateral non-operated (Non-Op) CONTROLS from the medial femoral condyle to (1) determine the effect of OCA storage on local subchondral bone (ScB) and trabecular bone (TB) structure, (2) characterize the location and structure of bone cysts and channels, and (3) assess the relationship between cartilage and bone properties. (1) Overall bone structure after OCAs was altered compared to Non-Op, with OCA samples displaying bone cysts, ScB channels, and ScB roughening. ScB BV/TV in FROZEN OCAs was lower than Non-Op and other OCAs. TB BV/TV in FRESH, 4°C/14d, and 4°C/28d OCAs did not vary compared to Non-Op, but BS/TV was lower. (2) OCAs contained "basal" cysts, localized to deeper regions, some "subchondral" cysts, localized near the bone-cartilage interface, and some ScB channels. TB surrounding basal cysts exhibited higher BV/TV than Non-Op. (3) Basal cysts occurred (a) in isolation, (b) with subchondral cysts and ScB channels, (c) with ScB channels, or (d) with subchondral cysts, ScB channels, and ScB erosion. Deterioration of cartilage gross morphology was strongly associated with abnormal μCT bone structure. Evidence of cartilage-bone communication following OCA repair may favor fluid intrusion as a mechanism for subchondral cyst formation, while bone resorption at the graft-host interface without affecting overall bone and cartilage structure may favor bony contusion mechanism for basal cyst formation. These findings suggest that cysts occurring after OCAs may result from aberrant mechanobiology due to (1) altered compartmentalization that normally separates overlying cartilage and subchondral bone, either from distinct ScB channels or more general ScB plate deterioration, and (2) bone resorption at the basal graft-host interface. © 2013.

Bone Cysts After Osteochondral Allograft Repair of Cartilage Defects in Goats Suggest Abnormal Interaction Between Subchondral Bone and Overlying Synovial Joint Tissues

PubMed Central

Pallante-Kichura, Andrea L.; Cory, Esther; Bugbee, William D.; Sah, Robert L.

2013-01-01

The efficacy of osteochondral allografts (OCA) may be affected by osseous support of the articular cartilage, and thus affected by bone healing and remodeling in the OCA and surrounding host. Bone cysts, and their communication pathways, may be present in various locations after OCA insertion and reflect distinct pathogenic mechanisms. Previously, we analyzed the effect of OCA storage (FRESH, 4°C/14d, 4°C/28d, FROZEN) on cartilage quality in fifteen adult goats after 12 months in vivo. The objectives of this study were to further analyze OCA and contralateral non-operated (Non-Op) CONTROLS from the medial femoral condyle to (1) determine the effect of OCA storage on local subchondral (ScB) and trabecular (TB) bone structure, (2) characterize the location and structure of bone cysts and channels, and (3) assess the relationship between cartilage and bone properties. (1) Overall bone structure after OCA was altered compared to Non-Op, with OCA samples displaying bone cysts, ScB channels, and ScB roughening. ScB BV/TV in FROZEN OCA was lower than Non-Op and other OCA. TB BV/TV in FRESH, 4°C/14d, and 4°C/28d OCA did not vary compared to Non-Op, but BS/TV was lower. (2) OCA contained “basal” cysts, localized to deeper regions, some “subchondral” cysts, localized near the bone-cartilage interface, and some ScB channels. TB surrounding basal cysts exhibited higher BV/TV than Non-Op. (3) Basal cysts occurred (a) in isolation, (b) with subchondral cysts and ScB channels, (c) with ScB channels, or (d) with subchondral cysts, ScB channels, and ScB erosion. Deterioration of cartilage gross morphology was strongly associated with abnormal μCT bone structure. Evidence of cartilage-bone communication following OCA repair may favor fluid intrusion as a mechanism for subchondral cyst formation, while bone resorption at the graft-host interface without affecting overall bone and cartilage structure may favor bony contusion mechanism for basal cyst formation. These findings suggest that cysts occurring after OCA may result from aberrant mechanobiology due to (1) altered compartmentalization that normally separates overlying cartilage and subchondral bone, either from distinct ScB channels or more general ScB plate deterioration, and (2) bone resorption at the basal graft-host interface. PMID:23958821

Is fatty acid composition of human bone marrow significant to bone health?

PubMed

Pino, Ana María; Rodríguez, J Pablo

2017-12-16

The bone marrow adipose tissue (BMAT) is a conserved component of the marrow microenvironment, providing storage and release of energy and stabilizing the marrow extent. Also, it is recognized both the amount and quality of BMAT are relevant to preserve the functional relationships between BMAT, bone, and blood cell production. In this article we ponder the information supporting the tenet that the quality of BMAT is relevant to bone health. In the human adult the distribution of BMAT is heterogeneous over the entire skeleton, and both BMAT accumulation and bone loss come about with aging in healthy populations. But some pathological conditions which increase BMAT formation lead to bone impairment and fragility. Analysis in vivo of the relative content of saturated and unsaturated fatty acids (FA) in BMAT indicates site-related bone marrow fat composition and an association between increased unsaturation index (UI) and bone health. With aging some impairment ensues in the regulation of bone marrow cells and systemic signals leading to local chronic inflammation. Most of the bone loss diseases which evolve altered BMAT composition have as common factors aging and/or chronic inflammation. Both saturated and unsaturated FAs originate lipid species which are active mediators in the inflammation process. Increased free saturated FAs may lead to lipotoxicity of bone marrow cells. The pro-inflammatory, anti-inflammatory or resolving actions of compounds derived from long chain poly unsaturated FAs (PUFA) on bone cells is varied, and depending on the metabolism of the parent n:3 or n:6 PUFAs series. Taking together the evidence substantiate that marrow adipocyte function is fundamental for an efficient link between systemic and marrow fatty acids to accomplish specific energy or regulatory needs of skeletal and marrow cells. Further, they reveal marrow requirements of PUFAs. Copyright © 2017 Elsevier Inc. All rights reserved.

Bone Engineering of Maxillary Sinus Bone Deficiencies Using Enriched CD90+ Stem Cell Therapy: A Randomized Clinical Trial.

PubMed

Kaigler, Darnell; Avila-Ortiz, Gustavo; Travan, Suncica; Taut, Andrei D; Padial-Molina, Miguel; Rudek, Ivan; Wang, Feng; Lanis, Alejandro; Giannobile, William V

2015-07-01

Bone engineering of localized craniofacial osseous defects or deficiencies by stem cell therapy offers strong prospects to improve treatment predictability for patient care. The aim of this phase 1/2 randomized, controlled clinical trial was to evaluate reconstruction of bone deficiencies of the maxillary sinus with transplantation of autologous cells enriched with CD90+ stem cells and CD14+ monocytes. Thirty human participants requiring bone augmentation of the maxillary sinus were enrolled. Patients presenting with 50% to 80% bone deficiencies of the maxillary sinus were randomized to receive either stem cells delivered onto a β-tricalcium phosphate scaffold or scaffold alone. Four months after treatment, clinical, radiographic, and histologic analyses were performed to evaluate de novo engineered bone. At the time of alveolar bone core harvest, oral implants were installed in the engineered bone and later functionally restored with dental tooth prostheses. Radiographic analyses showed no difference in the total bone volume gained between treatment groups; however, density of the engineered bone was higher in patients receiving stem cells. Bone core biopsies showed that stem cell therapy provided the greatest benefit in the most severe deficiencies, yielding better bone quality than control patients, as evidenced by higher bone volume fraction (BVF; 0.5 versus 0.4; p = 0.04). Assessment of the relation between degree of CD90+ stem cell enrichment and BVF showed that the higher the CD90 composition of transplanted cells, the greater the BVF of regenerated bone (r = 0.56; p = 0.05). Oral implants were placed and restored with functionally loaded dental restorations in all patients and no treatment-related adverse events were reported at the 1-year follow-up. These results provide evidence that cell-based therapy using enriched CD90+ stem cell populations is safe for maxillary sinus floor reconstruction and offers potential to accelerate and enhance tissue engineered bone quality in other craniofacial bone defects and deficiencies (Clinicaltrials.gov NCT00980278). © 2015 American Society for Bone and Mineral Research.

Label-free Raman spectroscopy provides early determination and precise localization of breast cancer-colonized bone alterations.

PubMed

Zhang, Chi; Winnard, Paul T; Dasari, Sidarth; Kominsky, Scott L; Doucet, Michele; Jayaraman, Swaathi; Raman, Venu; Barman, Ishan

2018-01-21

Breast neoplasms frequently colonize bone and induce development of osteolytic bone lesions by disrupting the homeostasis of the bone microenvironment. This degenerative process can lead to bone pain and pathological bone fracture, a major cause of cancer morbidity and diminished quality of life, which is exacerbated by our limited ability to monitor early metastatic disease in bone and assess fracture risk. Spurred by its label-free, real-time nature and its exquisite molecular specificity, we employed spontaneous Raman spectroscopy to assess and quantify early metastasis driven biochemical alterations to bone composition. As early as two weeks after intracardiac inoculations of MDA-MB-435 breast cancer cells in NOD-SCID mice, Raman spectroscopic measurements in the femur and spine revealed consistent changes in carbonate substitution, overall mineralization as well as crystallinity increase in tumor-bearing bones when compared with their normal counterparts. Our observations reveal the possibility of early stage detection of biochemical changes in the tumor-bearing bones - significantly before morphological variations are captured through radiographic diagnosis. This study paves the way for a better molecular understanding of altered bone remodeling in such metastatic niches, and for further clinical studies with the goal of establishing a non-invasive tool for early metastasis detection and prediction of pathological fracture risk in breast cancer.

The efficacy of porous hydroxyapatite bone chip as an extender of local bone graft in posterior lumbar interbody fusion.

PubMed

Kim, Hyoungmin; Lee, Choon-Ki; Yeom, Jin-Sup; Lee, Jae-Hyup; Lee, Ki-Ho; Chang, Bong-Soon

2012-07-01

To evaluate whether a synthetic bone chip made of porous hydroxyapatite can effectively extend local decompressed bone graft in instrumented posterior lumbar interbody fusion (PLIF). 130 patients, 165 segments, who had undergone PLIF with cages and instrumentation for single or double level due to degenerative conditions, were investigated retrospectively by independent blinded observer. According to the material of graft, patients were divided into three groups. HA group (19 patients, 25 segments): with hydroxyapatite bone chip in addition to autologous local decompressed bone, IBG group (25 patients, 28 segments): with autologous iliac crest bone graft in addition to local decompressed bone and LB group (86 patients, 112 segments): with local decompressed bone only. Radiologic and clinical outcome were compared among groups and postoperative complications, transfusion, time and cost of operation and duration of hospitalization were also investigated. Radiologic fusion rate and clinical outcome were not different. Economic cost, transfusion and hospital stay were also similar. But operation time was significantly longer in IBG group than in other groups. There were no lasting complications associated with HA and LB group with contrast to five cases with persisting donor site pain in IBG group. Porous hydroxyapatite bone chip is a useful bone graft extender in PLIF when used in conjunction with local decompressed bone.

T Lymphocytes Influence the Mineralization Process of Bone

PubMed Central

El Khassawna, Thaqif; Serra, Alessandro; Bucher, Christian H.; Petersen, Ansgar; Schlundt, Claudia; Könnecke, Ireen; Malhan, Deeksha; Wendler, Sebastian; Schell, Hanna; Volk, Hans-Dieter; Schmidt-Bleek, Katharina; Duda, Georg N.

2017-01-01

Bone is a unique organ able to regenerate itself after injuries. This regeneration requires the local interplay between different biological systems such as inflammation and matrix formation. Structural reconstitution is initiated by an inflammatory response orchestrated by the host immune system. However, the individual role of T cells and B cells in regeneration and their relationship to bone tissue reconstitution remain unknown. Comparing bone and fracture healing in animals with and without mature T and B cells revealed the essential role of these immune cells in determining the tissue mineralization and thus the bone quality. Bone without mature T and B cells is stiffer when compared to wild-type bone thus lacking the elasticity that helps to absorb forces, thus preventing fractures. In-depth analysis showed dysregulations in collagen deposition and osteoblast distribution upon lack of mature T and B cells. These changes in matrix deposition have been correlated with T cells rather than B cells within this study. This work presents, for the first time, a direct link between immune cells and matrix formation during bone healing after fracture. It illustrates specifically the role of T cells in the collagen organization process and the lack thereof in the absence of T cells. PMID:28596766

Comparison of two interpolation methods for empirical mode decomposition based evaluation of radiographic femur bone images.

PubMed

Udhayakumar, Ganesan; Sujatha, Chinnaswamy Manoharan; Ramakrishnan, Swaminathan

2013-01-01

Analysis of bone strength in radiographic images is an important component of estimation of bone quality in diseases such as osteoporosis. Conventional radiographic femur bone images are used to analyze its architecture using bi-dimensional empirical mode decomposition method. Surface interpolation of local maxima and minima points of an image is a crucial part of bi-dimensional empirical mode decomposition method and the choice of appropriate interpolation depends on specific structure of the problem. In this work, two interpolation methods of bi-dimensional empirical mode decomposition are analyzed to characterize the trabecular femur bone architecture of radiographic images. The trabecular bone regions of normal and osteoporotic femur bone images (N = 40) recorded under standard condition are used for this study. The compressive and tensile strength regions of the images are delineated using pre-processing procedures. The delineated images are decomposed into their corresponding intrinsic mode functions using interpolation methods such as Radial basis function multiquadratic and hierarchical b-spline techniques. Results show that bi-dimensional empirical mode decomposition analyses using both interpolations are able to represent architectural variations of femur bone radiographic images. As the strength of the bone depends on architectural variation in addition to bone mass, this study seems to be clinically useful.

Optimally oriented grooves on dental implants improve bone quality around implants under repetitive mechanical loading.

PubMed

Kuroshima, Shinichiro; Nakano, Takayoshi; Ishimoto, Takuya; Sasaki, Muneteru; Inoue, Maaya; Yasutake, Munenori; Sawase, Takashi

2017-01-15

The aim was to investigate the effect of groove designs on bone quality under controlled-repetitive load conditions for optimizing dental implant design. Anodized Ti-6Al-4V alloy implants with -60° and +60° grooves around the neck were placed in the proximal tibial metaphysis of rabbits. The application of a repetitive mechanical load was initiated via the implants (50N, 3Hz, 1800 cycles, 2days/week) at 12weeks after surgery for 8weeks. Bone quality, defined as osteocyte density and degree of biological apatite (BAp) c-axis/collagen fibers, was then evaluated. Groove designs did not affect bone quality without mechanical loading; however, repetitive mechanical loading significantly increased bone-to-implant contact, bone mass, and bone mineral density (BMD). In +60° grooves, the BAp c-axis/collagen fibers preferentially aligned along the groove direction with mechanical loading. Moreover, osteocyte density was significantly higher both inside and in the adjacent region of the +60° grooves, but not -60° grooves. These results suggest that the +60° grooves successfully transmitted the load to the bone tissues surrounding implants through the grooves. An optimally oriented groove structure on the implant surface was shown to be a promising way for achieving bone tissue with appropriate bone quality. This is the first report to propose the optimal design of grooves on the necks of dental implants for improving bone quality parameters as well as BMD. The findings suggest that not only BMD, but also bone quality, could be a useful clinical parameter in implant dentistry. Although the paradigm of bone quality has shifted from density-based assessments to structural evaluations of bone, clarifying bone quality based on structural bone evaluations remains challenging in implant dentistry. In this study, we firstly demonstrated that the optimal design of dental implant necks improved bone quality defined as osteocytes and the preferential alignment degree of biological apatite c-axis/collagen fibers using light microscopy, polarized light microscopy, and a microbeam X-ray diffractometer system, after application of controlled mechanical load. Our new findings suggest that bone quality around dental implants could become a new clinical parameter as well as bone mineral density in order to completely account for bone strength in implant dentistry. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Systematic Review and Meta-Analysis of Recombinant Human Bone Morphogenetic Protein-2 in Localized Alveolar Ridge and Maxillary Sinus Augmentation.

PubMed

Kelly, Mick P; Vaughn, Olushola L Akinshemoyin; Anderson, Paul A

2016-05-01

Recombinant human bone morphogenetic protein-2 (rhBMP-2) is approved by the Food and Drug Administration as a viable alternative to bone graft in spinal fusion and maxillary sinus lift. The research questions for meta-analysis were: Is rhBMP-2 an effective bone graft substitute in localized alveolar ridge augmentation and maxillary sinus floor augmentation? What are the potential adverse events? A search of MEDLINE from January 1980 to January 2014 using PubMed, the Cochrane Database of Systematic Reviews and Controlled Trials, CINAHL, and EMBASE was performed. Searches were performed from Medical Subject Headings. The quality of each study included was graded by Review Manager software. The primary outcome variable was bone formation measured as change in bone height on computed tomogram. A systematic review of adverse events also was performed. A random-effects model was chosen. Continuous variables were calculated using the standardized mean difference and 95% confidence intervals (CIs) comparing improvement from baseline of the experimental group with that of the control group. Change in bone height was calculated using logarithmic odds ratio. Test of significance used the Z statistic with a P value of .05. Ten studies met the criteria for systematic review; 8 studies were included in the meta-analysis. Five studies assessed localized alveolar ridge augmentation and resulted in an overall standardized mean difference of 0.56 (CI, 0.20-0.92) in favor of BMP; this result was statistically important. Three studies assessed maxillary sinus floor augmentation and resulted in an overall standardized mean difference of -0.50 (CI, -0.93 to -0.09), which was meaningfully different in favor of the control group. Adverse events were inconsistently reported, ranging from no complications to widespread adverse events. For localized alveolar ridge augmentation, this meta-analysis showed that rhBMP-2 substantially increases bone height. However, rhBMP-2 does not perform as well as the autograft or allograft in maxillary sinus floor augmentation. Long-term clinical success and adverse events need to be reported with more consistency before definitive conclusions can be made. Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Local strategies to prevent and treat osteoporosis.

PubMed

Torstrick, F Brennan; Guldberg, Robert E

2014-03-01

Despite advances in systemic osteoporosis therapeutic outcomes, management of fragility fractures and implant fixation in osteoporotic bone remain difficult clinical challenges. Low initial bone density and a prolonged healing response can lead to fracture nonunion and aseptic implant loosening. Local treatment strategies could be used to prevent fracture, accelerate healing, and increase implant fixation by locally stimulating anabolic pathways or inhibiting catabolic pathways. Local strategies under investigation include direct drug release from injectable materials or implant surface coatings. Common locally delivered drugs include bisphosphonates, parathyroid hormone, and bone morphogenetic proteins, yet additional compounds targeting novel pathways in bone biology are also being actively explored. Mechanical stimulation via low intensity pulsed ultrasound, alone or in combination with drug therapy, may also prove effective to promote local bone healing and implant fixation within osteoporotic bone.

[Interventional radiology for bone metastases].

PubMed

Iannessi, Antoine; Garnon, Julien; Cormier, Évelyne; Clarencon, Frédéric; Chiras, Jacques

2013-11-01

The management of bone metastases requires a multidisciplinary staff to include systemic and local treatments like radiotherapy, surgery or interventional radiology (IR). Patients are often fragile. Imaging allows safe guidance to create "mini-invasive" procedures under adequate anesthesia. Patients' selection is important. If the goal is pain relief, cementoplasty provides a very effective bone consolidation and pain control. Simple and low-risk, vertebroplasty is the technique of choice in case of lytic bone metastases with spinal fracture risk or after failure of analgesic radiotherapy. If the medical project is curative, the tumor ablation procedures are realised through thermic or embolic techniques. After 60°C, the heat induces a coagulative necrose. Under -20°C, the cold leads to destroy the tissues. The major advantage of the cryotherapy is the predictibility of the ablation zone due to the well-visualized ice ball on perprocedural images. This technique is much more adapted to spare the nervous structures closed to the metastasis. The development of these new techniques of IR will treat bone metastases earlier, sometimes asymptomatic and thus improves the quality of life in patients with bone metastases.

Hormonal and Local Regulation of Bone Formation.

ERIC Educational Resources Information Center

Canalis, Ernesto

1985-01-01

Reviews effects of hormones, systemic factors, and local regulators on bone formation. Identifies and explains the impact on bone growth of several hormones as well as the components of systemic and local systems. Concentrates on bone collagen and DNA synthesis. (Physicians may earn continuing education credit by completing an appended test). (ML)

Clinical assessment of bone quality of human extraction sockets after conversion with growth factors.

PubMed

Ntounis, Athanasios; Geurs, Nico; Vassilopoulos, Philip; Reddy, Michael

2015-01-01

The study was conducted to evaluate the effect of mineralized freeze-dried bone allograft (FDBA), alone or in combination with growth factors in extraction sockets, on subjective assessment of bone quality during implant placement. Forty-one patients whose treatment plan involved extraction of anterior or premolar teeth were randomized into four groups: Group 1, collagen plug (control); Group 2, FDBA/β-tricalcium phosphate (β-TCP)/collagen plug; Group 3, FDBA/β-TCP/platelet-rich plasma (PRP)/collagen plug; Group 4, FDBA/β-TCP/recombinant human platelet-derived growth factor BB (rhPDGF-BB)/collagen plug. After 8 weeks of healing, implants were placed. The clinicians assessed bone quality according to the Misch classification. A benchtop calibration exercise test was conducted to evaluate agreement and accuracy of operators in recognizing different bone qualities. Differences were analyzed using one-way analysis of variance (ANOVA) or chi-square tests for continuous and categorical data. Pairwise comparisons were tested using least squares means (LS means). Spearman correlation coefficients were used to evaluate the relationship of bone growth with potential confounders. P < .05 was considered statistically significant. A simple (not weighted) kappa statistic was used to assess the agreement between raters. To assess accuracy in identifying bone quality, a chi-square test was used to compare the percent correct for each rater. The benchtop calibration exercise test demonstrated agreement among clinicians (0.75 and 0.92 between raters 1 and 2 and raters 1 and 3, respectively). Raters were more likely to identify the correct bone quality (P > .05). Inclusion of bone grafting is associated with a shift from D4 quality to D3 quality bone. Inclusion of PRP in bone grafting eliminates the incidence of D4 bone, establishing D3 and D2 quality bone as prevalent (56% vs. 42%, respectively). Inclusion of rhPDGF-BB and β-TCP in combination with the bone grafting has the same effect, although D2 quality is less prevalent. When compared to sockets grafted with FDBA/β-TCP/collagen plug alone, the sockets with growth factors demonstrated fewer residual bone graft particles. (1) Inclusion of bone grafting enhanced bone quality as assessed during implant placement. (2) Overall inclusion of PRP and rhPDGF-BB enhanced subjective bone quality, eliminating incidence of D4 quality in human extraction sockets. (3) The use of PRP or rhPDGF-BB may enhance healing within extraction sockets and decrease the healing time prior to dental implant placement.

Label-free Raman spectroscopy provides early determination and precise localization of breast cancer-colonized bone alterations† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c7sc02905e

PubMed Central

Zhang, Chi; Winnard Jr, Paul T.; Dasari, Sidarth; Kominsky, Scott L.; Doucet, Michele; Jayaraman, Swaathi

2017-01-01

Breast neoplasms frequently colonize bone and induce development of osteolytic bone lesions by disrupting the homeostasis of the bone microenvironment. This degenerative process can lead to bone pain and pathological bone fracture, a major cause of cancer morbidity and diminished quality of life, which is exacerbated by our limited ability to monitor early metastatic disease in bone and assess fracture risk. Spurred by its label-free, real-time nature and its exquisite molecular specificity, we employed spontaneous Raman spectroscopy to assess and quantify early metastasis driven biochemical alterations to bone composition. As early as two weeks after intracardiac inoculations of MDA-MB-435 breast cancer cells in NOD-SCID mice, Raman spectroscopic measurements in the femur and spine revealed consistent changes in carbonate substitution, overall mineralization as well as crystallinity increase in tumor-bearing bones when compared with their normal counterparts. Our observations reveal the possibility of early stage detection of biochemical changes in the tumor-bearing bones – significantly before morphological variations are captured through radiographic diagnosis. This study paves the way for a better molecular understanding of altered bone remodeling in such metastatic niches, and for further clinical studies with the goal of establishing a non-invasive tool for early metastasis detection and prediction of pathological fracture risk in breast cancer. PMID:29629144

An interdisciplinary consensus on the management of bone metastases from renal cell carcinoma.

PubMed

Grünwald, Viktor; Eberhardt, Berit; Bex, Axel; Flörcken, Anne; Gauler, Thomas; Derlin, Thorsten; Panzica, Martin; Dürr, Hans Roland; Grötz, Knut Achim; Giles, Rachel H; von Falck, Christian; Graser, Anno; Muacevic, Alexander; Staehler, Michael

2018-06-14

Bone is a major site of haematogenous tumour cell spread in renal cell carcinoma (RCC), and most patients with RCC will develop painful and functionally disabling bone metastases at advanced disease stages. The prognosis of these patients is generally poor and the treatment is, therefore, aimed at palliation. However, RCC-associated bone metastases can be curable in select patients. Current data support a multimodal management strategy that includes wide resection of lesions, radiotherapy, systemic therapy, and other local treatment options, which can improve quality of life and survival. Nevertheless, the optimal approach for metastatic bone disease in RCC has not yet been defined and practical recommendations are rare. To improve the management and outcomes of patients with RCC and bone metastases, the International Kidney Cancer Coalition and the interdisciplinary working group on renal tumours of the German Cancer Society convened a meeting of experts with a global perspective to perform an unstructured review and elaborate on current treatment strategies on the basis of published data and expertise. The panel formulated recommendations for the diagnosis and treatment of patients with RCC and metastasis to the bone. Furthermore, the experts summarized current challenges and unmet patient needs that should be addressed in the future.

Interplay between Cartilage and Subchondral Bone Contributing to Pathogenesis of Osteoarthritis

PubMed Central

Sharma, Ashish R.; Jagga, Supriya; Lee, Sang-Soo; Nam, Ju-Suk

2013-01-01

Osteoarthritis (OA) is a common debilitating joint disorder, affecting large sections of the population with significant disability and impaired quality of life. During OA, functional units of joints comprising cartilage and subchondral bone undergo uncontrolled catabolic and anabolic remodeling processes to adapt to local biochemical and biological signals. Changes in cartilage and subchondral bone are not merely secondary manifestations of OA but are active components of the disease, contributing to its severity. Increased vascularization and formation of microcracks in joints during OA have suggested the facilitation of molecules from cartilage to bone and vice versa. Observations from recent studies support the view that both cartilage and subchondral bone can communicate with each other through regulation of signaling pathways for joint homeostasis under pathological conditions. In this review we have tried to summarize the current knowledge on the major signaling pathways that could control the cartilage-bone biochemical unit in joints and participate in intercellular communication between cartilage and subchondral bone during the process of OA. An understanding of molecular communication that regulates the functional behavior of chondrocytes and osteoblasts in both physiological and pathological conditions may lead to development of more effective strategies for treating OA patients. PMID:24084727

Iliac crest bone graft: a 23-years hystory of infection at donor site in vertebral arthrodesis and a review of current bone substitutes.

PubMed

Babbi, L; Barbanti-Brodano, G; Gasbarrini, A; Boriani, S

2016-11-01

This is an exemplary case report underlining a relevant morbidity which could be associated to the use of autologous iliac crest bone graft (ICBG) for spine fusion. Starting from 1990, a 25-years-old woman underwent two subsequent surgical treatments for non-Hodgkin lymphoma vertebral localizations. In the second surgery, arthrodesis was obtained with autograft through right posterior iliac crest osteotomy. During the chemotherapy treatment following the surgery, the patient suffered from infection at posterior iliac crest scar, the site of previous graft, caused by methicillin-resistant Staphylococcus aureus. She was subjected to surgical debridement and specific antibiotic treatment with local healing and phlogosis index reduction. Chemotherapy protocol was concluded and the patient healed with definitive lymphoma remission. After 22 years the patient had a relapse of donor site infection, requiring a new antibiotic therapy and a new surgical debridement. The relapsed infection at donor site lasted for a long period, more than one year, despite of specific care. It finally healed after another accurate surgical debridement and postoperative antibiotic therapy. This case report underlines the possible consequences on the patient's quality of life of a long-term disease affecting the iliac crest bone graft donor site. Literature concerning alternatives to autograft for spine fusion is also reviewed.

Drilling resistance: A method to investigate bone quality.

PubMed

Lughmani, Waqas A; Farukh, Farukh; Bouazza-Marouf, Kaddour; Ali, Hassan

2017-01-01

Bone drilling is a major part of orthopaedic surgery performed during the internal fixation of fractured bones. At present, information related to drilling force, drilling torque, rate of drill-bit penetration and drill-bit rotational speed is not available to orthopaedic surgeons, clinicians and researchers as bone drilling is performed manually. This study demonstrates that bone drilling force data if recorded in-vivo, during the repair of bone fractures, can provide information about the quality of the bone. To understand the variability and anisotropic behaviour of cortical bone tissue, specimens cut from three anatomic positions of pig and bovine were investigated at the same drilling speed and feed rate. The experimental results showed that the drilling force does not only vary from one animal bone to another, but also vary within the same bone due to its changing microstructure. Drilling force does not give a direct indication of bone quality; therefore it has been correlated with screw pull-out force to provide a realistic estimation of the bone quality. A significantly high value of correlation (r2 = 0.93 for pig bones and r2 = 0.88 for bovine bones) between maximum drilling force and normalised screw pull-out strength was found. The results show that drilling data can be used to indicate bone quality during orthopaedic surgery.

Defective Bone Repair in C57Bl6 Mice With Acute Systemic Inflammation.

PubMed

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

2017-03-01

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

Differences in Bone Quality between High versus Low Turnover Renal Osteodystrophy

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

Porter, Daniel S.; Pienkowski, David; Faugere, Marie-Claude

2012-01-01

Abnormal bone turnover is common in chronic kidney disease (CKD), but its effects on bone quality remain unclear. This study sought to quantify the relationship between abnormal bone turnover and bone quality. Iliac crest bone biopsies were obtained from CKD-5 patients on dialysis with low (n=18) or high (n=17) turnover, and from volunteers (n=12) with normal turnover and normal kidney function. Histomorphometric methods were used to quantify the microstructural parameters; Fourier transform infrared spectroscopy and nanoindentation were used to quantify the material and mechanical properties in bone. Reduced mineral-to-matrix ratio, mineral crystal size, stiffness and hardness were observed in bonemore » with high turnover compared to bone with normal or low turnover. Decreased cancellous bone volume and trabecular thickness were seen in bone with low turnover compared to bone with normal or high turnover. Bone quality, as defined by its microstructural, material, and mechanical properties, is related to bone turnover. These data suggest that turnover related alterations in bone quality may contribute to the known diminished mechanical competence of bone in CKD patients, albeit from different mechanisms for bone with high (material abnormality) vs. low (microstructural alteration) turnover. The present findings suggest that improved treatments for renal osteodystrophy should seek to avoid low or high bone turnover and aim for turnover rates as close to normal as possible.« less

Application of nonlinear phenomena induced by focused ultrasound to bone imaging.

PubMed

Callé, Samuel; Remenieras, Jean-Pierre; Bou Matar, Olivier; Defontaine, Marielle; Patat, Frederic

2003-03-01

A tissue deformability image is obtained with the vibroacoustography imaging method using mechanical low-frequency (LF) excitation. This ultrasonic excitation is created locally by means of a focused annular array emitting two primary beams at two close frequencies, f(1) and f(2) (f(2) = f(1) + f(LF)). The LF acoustic emission resulting from the vibration of the medium is detected by a sensitive hydrophone and then used to form the image. This noninvasive imaging method was demonstrated in this study to be suitable for bone imaging, with x and y transverse resolutions less than 300 micro m. Two bone sites susceptible to demineralization were tested: the calcaneus and the neck of the femur. The vibroacoustic method provides valuable ultrasonic images regarding the structure and the elastic properties of bone tissue. Correlation was made between vibroacoustic bone images, performed in vitro, and images acquired by other imaging methods (i.e., bone ultrasound attenuation and x-ray computerized tomography (CT)). Moreover, the amplitudes of vibroacoustic signals radiating from phosphocalcic ceramic samples (bone substitute) of different porosity were evaluated. The good correlation between these results and the description of our images and the quality of vibroacoustic images indicate that bone decalcification could be detected using vibroacoustography.

Local effect of zoledronic acid on new bone formation in posterolateral spinal fusion with demineralized bone matrix in a murine model.

PubMed

Zwolak, Pawel; Farei-Campagna, Jan; Jentzsch, Thorsten; von Rechenberg, Brigitte; Werner, Clément M

2018-01-01

Posterolateral spinal fusion is a common orthopaedic surgery performed to treat degenerative and traumatic deformities of the spinal column. In posteriolateral spinal fusion, different osteoinductive demineralized bone matrix products have been previously investigated. We evaluated the effect of locally applied zoledronic acid in combination with commercially available demineralized bone matrix putty on new bone formation in posterolateral spinal fusion in a murine in vivo model. A posterolateral sacral spine fusion in murine model was used to evaluate the new bone formation. We used the sacral spine fusion model to model the clinical situation in which a bone graft or demineralized bone matrix is applied after dorsal instrumentation of the spine. In our study, group 1 received decortications only (n = 10), group 2 received decortication, and absorbable collagen sponge carrier, group 3 received decortication and absorbable collagen sponge carrier with zoledronic acid in dose 10 µg, group 4 received demineralized bone matrix putty (DBM putty) plus decortication (n = 10), and group 5 received DBM putty, decortication and locally applied zoledronic acid in dose 10 µg. Imaging was performed using MicroCT for new bone formation assessment. Also, murine spines were harvested for histopathological analysis 10 weeks after surgery. The surgery performed through midline posterior approach was reproducible. In group with decortication alone there was no new bone formation. Application of demineralized bone matrix putty alone produced new bone formation which bridged the S1-S4 laminae. Local application of zoledronic acid to demineralized bone matrix putty resulted in significant increase of new bone formation as compared to demineralized bone matrix putty group alone. A single local application of zoledronic acid with DBM putty during posterolateral fusion in sacral murine spine model increased significantly new bone formation in situ in our model. Therefore, our results justify further investigations to potentially use local application of zoledronic acid in future clinical studies.

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.

Local vs. systemic administration of bisphosphonates in rat cleft bone graft: A comparative study

PubMed Central

Lin, Lawrence; Olson, Jeffrey; Kwon, Taewoo; Bezouglaia, Olga; Tran, Jaime; Hoang, Michael; Bui, Kimberly; Kim, Reuben H.; Tetradis, Sotirios

2018-01-01

A majority of patients with orofacial cleft deformity requires cleft repair through a bone graft. However, elevated amount of bone resorption and subsequent bone graft failure remains a significant clinical challenge. Bisphosphonates (BPs), a class of anti-resorptive drugs, may offer great promise in enhancing the clinical success of bone grafting. In this study, we compared the effects of systemic and local delivery of BPs in an intraoral bone graft model in rats. We randomly divided 34 female 20-week-old Fischer F344 Inbred rats into four groups to repair an intraoral critical-sized defect (CSD): (1) Control: CSD without graft (n = 4); (2) Graft/Saline: bone graft with systemic administration of saline 1 week post-operatively (n = 10); (3) Graft/Systemic: bone graft with systemic administration of zoledronic acid 1 week post-operatively (n = 10); and (4) Graft/Local: bone graft pre-treated with zoledronic acid (n = 10). At 6-weeks post-operatively, microCT volumetric analysis showed a significant increase in bone fraction volume (BV/TV) in the Graft/Systemic (62.99 ±14.31%) and Graft/Local (69.35 ±13.18%) groups compared to the Graft/Saline (39.18±10.18%). Similarly, histological analysis demonstrated a significant increase in bone volume in the Graft/Systemic (78.76 ±18.00%) and Graft/Local (89.95 ±4.93%) groups compared to the Graft/Saline (19.74±18.89%). The local delivery approach resulted in the clinical success of bone grafts, with reduced graft resorption and enhanced osteogenesis and bony integration with defect margins while avoiding the effects of BPs on peripheral osteoclastic function. In addition, local delivery of BPs may be superior to systemic delivery with its ease of procedure as it involves simple soaking of bone graft materials in BP solution prior to graft placement into the defect. This new approach may provide convenient and promising clinical applications towards effectively managing cleft patients. PMID:29304080

Interventional radiology in bone metastases.

PubMed

Chiras, J; Shotar, E; Cormier, E; Clarençon, F

2017-11-01

Interventional radiology plays a significant role in the treatment of bone metastases by various techniques, percutaneous or endovascular. Vertebroplasty is the most well-studied technique for stabilisation of spine metastases as it induces satisfactory stabilisation of the vertebra and offers clear improvement of the quality of life. Due to the success of this technique cementoplasty of other bones, mainly pelvic girdle, has been largely developed. The development of reinforced cementoplasty allows treatment of pre-fractural osteolysis of some long bones. The heat due to the polymerisation of the cement induces carcinolytic effect but this effect is not as important as that which results from radiofrequency destruction. This last technique appears currently as the most important development to definitively destroy bone metastases and is progressively replacing percutaneous alcoholic destruction of such lesions. Angiographic techniques, such as endovascular embolisation, can also be very useful to reduce the risk of surgical treatment of hyper vascular metastases. Chemoembolisation is currently developed to associate pain relief induced by Endovascular embolisation and the carcinolytic effect obtained by local endovascular chemotherapy. All these techniques should develop largely during the next years. © 2017 John Wiley & Sons Ltd.

Strontium ranelate: a novel mode of action leading to renewed bone quality.

PubMed

Ammann, Patrick

2005-01-01

Various bone resorption inhibitors and bone stimulators have been shown to decrease the risk of osteoporotic fractures. However, there is still a need for agents promoting bone formation by inducing positive uncoupling between bone formation and bone resorption. In vitro studies have suggested that strontium ranelate enhances osteoblast cell replication and activity. Simultaneously, strontium ranelate dose-dependently inhibits osteoclast activity. In vivo studies indicate that strontium ranelate stimulates bone formation and inhibits bone resorption and prevents bone loss and/or promotes bone gain. This positive uncoupling between bone formation and bone resorption results in bone gain and improvement in bone geometry and microarchitecture, without affecting the intrinsic bone tissue quality. Thus, all the determinants of bone strength are positively influenced. In conclusion, strontium ranelate, a new treatment of postmenopausal osteoporosis, acts through an innovative mode of action, both stimulating bone formation and inhibiting bone resorption, resulting in the rebalancing of bone turnover in favor of bone formation. Strontium ranelate increases bone mass while preserving the bone mineralization process, resulting in improvement in bone strength and bone quality.

Clinical Considerations of Adapted Drilling Protocol by Bone Quality Perception.

PubMed

Toia, Marco; Stocchero, Michele; Cecchinato, Francesca; Corrà, Enrico; Jimbo, Ryo; Cecchinato, Denis

To evaluate insertion torque value (ITV) and marginal bone loss (MBL) of an implant system after a clinically perceived bone quality-adapted drilling. This multicenter retrospective study included patients treated with implants, conventionally loaded, in completely healed sites. Operators customized the osteotomy preparation according to radiographic assessment and their perception of bone quality. Drilling sequence, bone quality, and ITV were recorded at the time of surgery. Radiographs were taken at the time of implant placement and permanent restoration. MBL between implant placement and permanent restoration was calculated. The implant was used as the statistical unit. Demographic and implant characteristics were shown by means of descriptive statistics. Outcome values were compared using analysis of variance (ANOVA) and Kruskal-Wallis tests. Multiple regression models were used to test the effect of independent variables on ITV and MBL. One hundred eighty-eight implants placed in 87 patients were included in the analysis. The mean observation period was 144 ± 59 days. The mean ITV was 30.8 ± 15.1 Ncm. ITV differed significantly based on arches (mandible/maxilla) (P = .001), bone quality (P < .001), implant diameter (P = .032), and drilling protocol (P = .019). Median MBL was 0.05 mm (0.00; 0.24). A significant difference was found between the mandible and maxilla (P = .008) and between drilling protocols (P = .011). In particular, significantly higher MBL was found in the undersized drilling protocol. Multiple regression analysis showed that ITV was influenced by bone quality and implant diameter. MBL was influenced by bone quality, implant diameter, ITV, and the interaction between bone quality and ITV. It was estimated that MBL was greater with increased bone density and ITV. Excessive ITV in dense bone can cause negative marginal bone responses. A presurgical radiographic assessment and the perception of bone quality are necessary to select an optimal drilling protocol and to minimize surgical trauma.

A new quality of bone ultrasound research.

PubMed

Gluer, C C

2008-07-01

Quantitative ultrasound (QUS) methods have strong power to predict osteoporotic fractures, but they are also very relevant for the assessment of bone quality. A representative sample of recent studies addressing these topics can be found in this special issue. Further pursuit of these methods will establish micro-QUS imaging methods as tools for measuring specific aspects of bone quality. Once this is achieved, we will be able to link such data to the clinical QUS methods used in vivo to determine which aspects of bone quality cause QUS to be a predictor of fracture risk that is independent of bone mineral density (BMD). Potentially this could lead to the development of a new generation of QUS devices for improved and expanded clinical assessment. Good quality of basic science work will thus lead to good quality of clinical patient examinations on the basis of a more detailed assessment of bone quality.

How does bone quality differ between healthy-weight and overweight adolescents and young adults?

PubMed

Hoy, Christa L; Macdonald, Heather M; McKay, Heather A

2013-04-01

Overweight youth have greater bone mass than their healthy-weight peers but sustain more fractures. However, it is unclear whether and how excess body fat influences bone quality in youth. We determined whether overweight status correlated with three-dimensional aspects of bone quality influencing bone strength in adolescent and young adult females and males. We categorized males (n=103; mean age, 17 years) and females (n=85; mean age, 18 years) into healthy-weight and overweight groups. We measured lean mass (LM) and fat mass (FM) with dual-energy x-ray absorptiometry (DXA). We used high-resolution peripheral quantitative CT to assess the distal radius (7% site) and distal tibia (8% site). Bone quality measures included total bone mineral density (Tt.BMD), total area (Tt.Ar), trabecular bone volume fraction (BV/TV), trabecular number (Tb.N), separation (Tb.Sp), and thickness (Tb.Th). We used multiple regression to compare bone quality between healthy-weight and overweight adolescents adjusting for age, ethnicity, limb length, LM, and FM. Overweight males had higher (10%-21%) Tt.BMD, BV/TV, and Tb.N and lower Tb.Sp at the tibia and lower Tt.Ar at the radius than healthy-weight males. No differences were observed between overweight and healthy-weight females. LM attenuated the differences in bone quality between groups in males while FM negatively predicted Tt.BMD, BV/TV, Tb.N, and Tb.Th. Our data suggest overweight males have enhanced bone quality compared with healthy-weight males; however, when group differences are interpreted in the context of the mechanostat theory, it appears bone quality of overweight adolescents adapts to LM and not to greater FM.

[Augmentation technique on the proximal humerus].

PubMed

Scola, A; Gebhard, F; Röderer, G

2015-09-01

The treatment of osteoporotic fractures is still a challenge. The advantages of augmentation with respect to primary in vitro stability and the clinical use for the proximal humerus are presented in this article. In this study six paired human humeri were randomized into an augmented and a non-augmented group. Osteosynthesis was performed with a PHILOS plate (Synthes®). In the augmented group the two screws finding purchase in the weakest cancellous bone were augmented. The specimens were tested in a 3-part fracture model in a varus bending test. The augmented PHILOS plates withstood significantly more load cycles until failure. The correlation to bone mineral density (BMD) showed that augmentation could partially compensate for low BMD. The augmentation of the screws in locked plating in a proximal humerus fracture model is effective in improving the primary stability in a cyclic varus bending test. The targeted augmentation of two particular screws in a region of low bone quality within the humeral head was almost as effective as four screws with twice the amount of bone cement. Screw augmentation combined with a knowledge of the local bone quality could be more effective in enhancing the primary stability of a proximal humerus locking plate because the effect of augmentation can be exploited more effectively limiting it to the degree required. The technique of augmentation is simple and can be applied in open and minimally invasive procedures. When the correct procedure is used, complications (cement leakage into the joint) can be avoided.

Evaluation of bone quality in osteoporosis model mice by Raman spectroscopy

NASA Astrophysics Data System (ADS)

Ishimaru, Yasumitsu; Oshima, Yusuke; Imai, Yuuki; Iimura, Tadahiro; Takanezawa, Sota; Hino, Kazunori; Miura, Hiromasa

2017-04-01

To evaluate the bone quality in the osteoporosis, we generated sciatic nerve resection (NX) mice as an osteoporosis model and analyzed by Raman spectroscopy. Raman spectra were measured in anterior cortical surface of the proximal tibia at 5 points in each bone. After that, the samples were fixed with 70% ethanol. We then performed DXA and μCT measurement. Raman peak intensity ratios were significantly different between NX and Control. Those changes in the Raman peak intensity ratios may reflect loss of bone quality in the osteoporosis model. Raman spectroscopy is a promising technique for measuring the bone quality and bone strength.

Heterogeneous glycation of cancellous bone and its association with bone quality and fragility.

PubMed

Karim, Lamya; Vashishth, Deepak

2012-01-01

Non-enzymatic glycation (NEG) and enzymatic biochemical processes create crosslinks that modify the extracellular matrix (ECM) and affect the turnover of bone tissue. Because NEG affects turnover and turnover at the local level affects microarchitecture and formation and removal of microdamage, we hypothesized that NEG in cancellous bone is heterogeneous and accounts partly for the contribution of microarchitecture and microdamage on bone fragility. Human trabecular bone cores from 23 donors were subjected to compression tests. Mechanically tested cores as well as an additional 19 cores were stained with lead-uranyl acetate and imaged to determine microarchitecture and measure microdamage. Post-yield mechanical properties were measured and damaged trabeculae were extracted from a subset of specimens and characterized for the morphology of induced microdamage. Tested specimens and extracted trabeculae were quantified for enzymatic and non-enzymatic crosslink content using a colorimetric assay and Ultra-high Performance Liquid Chromatography (UPLC). Results show that an increase in enzymatic crosslinks was beneficial for bone where they were associated with increased toughness and decreased microdamage. Conversely, bone with increased NEG required less strain to reach failure and were less tough. NEG heterogeneously modified trabecular microarchitecture where high amounts of NEG crosslinks were found in trabecular rods and with the mechanically deleterious form of microdamage (linear microcracks). The extent of NEG in tibial cancellous bone was the dominant predictor of bone fragility and was associated with changes in microarchitecture and microdamage.

Heterogeneous Glycation of Cancellous Bone and Its Association with Bone Quality and Fragility

PubMed Central

Karim, Lamya; Vashishth, Deepak

2012-01-01

Non-enzymatic glycation (NEG) and enzymatic biochemical processes create crosslinks that modify the extracellular matrix (ECM) and affect the turnover of bone tissue. Because NEG affects turnover and turnover at the local level affects microarchitecture and formation and removal of microdamage, we hypothesized that NEG in cancellous bone is heterogeneous and accounts partly for the contribution of microarchitecture and microdamage on bone fragility. Human trabecular bone cores from 23 donors were subjected to compression tests. Mechanically tested cores as well as an additional 19 cores were stained with lead-uranyl acetate and imaged to determine microarchitecture and measure microdamage. Post-yield mechanical properties were measured and damaged trabeculae were extracted from a subset of specimens and characterized for the morphology of induced microdamage. Tested specimens and extracted trabeculae were quantified for enzymatic and non-enzymatic crosslink content using a colorimetric assay and Ultra-high Performance Liquid Chromatography (UPLC). Results show that an increase in enzymatic crosslinks was beneficial for bone where they were associated with increased toughness and decreased microdamage. Conversely, bone with increased NEG required less strain to reach failure and were less tough. NEG heterogeneously modified trabecular microarchitecture where high amounts of NEG crosslinks were found in trabecular rods and with the mechanically deleterious form of microdamage (linear microcracks). The extent of NEG in tibial cancellous bone was the dominant predictor of bone fragility and was associated with changes in microarchitecture and microdamage. PMID:22514706

Multiscale imaging of bone microdamage

PubMed Central

Poundarik, Atharva A.; Vashishth, Deepak

2015-01-01

Bone is a structural and hierarchical composite that exhibits remarkable ability to sustain complex mechanical loading and resist fracture. Bone quality encompasses various attributes of bone matrix from the quality of its material components (type-I collagen, mineral and non-collagenous matrix proteins) and cancellous microarchitecture, to the nature and extent of bone microdamage. Microdamage, produced during loading, manifests in multiple forms across the scales of hierarchy in bone and functions to dissipate energy and avert fracture. Microdamage formation is a key determinant of bone quality, and through a range of biological and physical mechanisms, accumulates with age and disease. Accumulated microdamage in bone decreases bone strength and increases bone’s propensity to fracture. Thus, a thorough assessment of microdamage, across the hierarchical levels of bone, is crucial to better understand bone quality and bone fracture. This review article details multiple imaging modalities that have been used to study and characterize microdamage; from bulk staining techniques originally developed by Harold Frost to assess linear microcracks, to atomic force microscopy, a modality that revealed mechanistic insights into the formation diffuse damage at the ultrastructural level in bone. New automated techniques using imaging modalities such as microcomputed tomography are also presented for a comprehensive overview. PMID:25664772

Local Bisphosphonate Treatment Increases Fixation of Hydroxyapatite-Coated Implants Inserted with Bone Compaction

PubMed Central

Jakobsen, Thomas; Baas, Jørgen; Kold, Søren; Bechtold, Joan E.; Elmengaard, Brian; Søballe, Kjeld

2013-01-01

It has been shown that fixation of primary cementless joint replacement can independently be enhanced by either: (1) use of hydroxyapatite (HA) coated implants, (2) compaction of the peri-implant bone, or (3) local application of bisphosphonate. We investigated whether the combined effect ofHAcoating and bone compaction can be further enhanced with the use of local bisphosphonate treatment .HA-coated implants were bilaterally inserted into the proximal tibiae of 10 dogs. On one side local bisphosphonate was applied prior to bone compaction. Saline was used as control on the contralateral side. Implants were evaluated with histomorphometry and biomechanical pushout test. We found that bisphosphonate increased the peri-implant bone volume fraction (1.3-fold), maximum shear strength (2.1-fold), and maximum shear stiffness (2.7-fold). No significant difference was found in bone-to-implant contact or total energy absorption. This study indicates that local alendronate treatment can further improve the fixation of porous-coated implants that have also undergone HA-surface coating and peri-implant bone compaction. PMID:18752278

Whole-body vibration improves fracture healing and bone quality in rats with ovariectomy-induced osteoporosis.

PubMed

Butezloff, Mariana Maloste; Zamarioli, Ariane; Leoni, Graziela Bianchi; Sousa-Neto, Manoel Damião; Volpon, Jose Batista

2015-11-01

To investigate the effect of vibration therapy on the bone callus of fractured femurs and the bone quality of intact femurs in ovariectomized rats. Fifty-six rats aged seven weeks were divided into four groups: control with femoral fracture (CON, n=14), ovariectomized with femoral fracture (OVX, n=14), control with femoral fracture plus vibration therapy (CON+VT, n=14), and ovariectomized with femoral fracture plus vibration therapy (OVX+VT, n=14). Three months after ovariectomy or sham surgery, a complete fracture was produced at the femoral mid-diaphysis and stabilized with a 1-mm-diameter intramedullary Kirschner wire. X-rays confirmed the fracture alignment and fixation. Three days later, the VT groups underwent vibration therapy (1 mm, 60 Hz for 20 minutes, three times per week for 14 or 28 days). The bone and callus quality were assessed by densitometry, three-dimensional microstructure, and mechanical test. Ovariectomized rats exhibited a substantial loss of bone mass and severe impairment in bone microarchitecture, both in the non-fractured femur and the bone callus. Whole-body vibration therapy exerted an important role in ameliorating the bone and fracture callus parameters in the osteoporotic bone. Vibration therapy improved bone quality and the quality of the fracture bone callus in ovariectomized rats.

Micro Finite Element models of the vertebral body: Validation of local displacement predictions.

PubMed

Costa, Maria Cristiana; Tozzi, Gianluca; Cristofolini, Luca; Danesi, Valentina; Viceconti, Marco; Dall'Ara, Enrico

2017-01-01

The estimation of local and structural mechanical properties of bones with micro Finite Element (microFE) models based on Micro Computed Tomography images depends on the quality bone geometry is captured, reconstructed and modelled. The aim of this study was to validate microFE models predictions of local displacements for vertebral bodies and to evaluate the effect of the elastic tissue modulus on model's predictions of axial forces. Four porcine thoracic vertebrae were axially compressed in situ, in a step-wise fashion and scanned at approximately 39μm resolution in preloaded and loaded conditions. A global digital volume correlation (DVC) approach was used to compute the full-field displacements. Homogeneous, isotropic and linear elastic microFE models were generated with boundary conditions assigned from the interpolated displacement field measured from the DVC. Measured and predicted local displacements were compared for the cortical and trabecular compartments in the middle of the specimens. Models were run with two different tissue moduli defined from microindentation data (12.0GPa) and a back-calculation procedure (4.6GPa). The predicted sum of axial reaction forces was compared to the experimental values for each specimen. MicroFE models predicted more than 87% of the variation in the displacement measurements (R2 = 0.87-0.99). However, model predictions of axial forces were largely overestimated (80-369%) for a tissue modulus of 12.0GPa, whereas differences in the range 10-80% were found for a back-calculated tissue modulus. The specimen with the lowest density showed a large number of elements strained beyond yield and the highest predictive errors. This study shows that the simplest microFE models can accurately predict quantitatively the local displacements and qualitatively the strain distribution within the vertebral body, independently from the considered bone types.

Surgical and Technical Modalities for Hearing Restoration in Ear Malformations.

PubMed

Dazert, Stefan; Thomas, Jan Peter; Volkenstein, Stefan

2015-12-01

Malformations of the external and middle ear often go along with an aesthetic and functional handicap. Independent of additional aesthetic procedures, a successful functional hearing restoration leads to a tremendous gain in quality of life for affected patients. The introduction of implantable hearing systems (bone conduction and middle ear devices) offers new therapeutic options in this field. We focus on functional rehabilitation of patients with malformations, either by surgical reconstruction or the use of different implantable hearing devices, depending on the disease itself and the severity of malformation as well as hearing impairment. Patients with an open ear canal and minor malformations are good candidates for surgical hearing restoration of middle ear structures with passive titanium or autologous implants. In cases with complete fibrous or bony atresia of the ear canal, the most promising functional outcome and gain in quality of life can be expected with an active middle ear implant or a bone conduction device combined with a surgical aesthetic rehabilitation in a single or multi-step procedure. Although the surgical procedure for bone conduction devices is straightforward and safe, more sophisticated operations for active middle ear implants (e.g., Vibrant Soundbridge, MED-EL, Innsbruck, Austria) provide an improved speech discrimination in noise and the ability of sound localization compared with bone conduction devices where the stimulation reaches both cochleae. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Research Perspectives: The 2013 AAOS/ORS Research Symposium on Bone Quality and Fracture Prevention

PubMed Central

Donnelly, Eve; Lane, Joseph M.; Boskey, Adele L.

2016-01-01

Bone fracture resistance is determined by the amount of bone present (“bone quantity”) and by a number of other geometric and material factors grouped under the term “bone quality.” In May 2013, a workshop was convened among a group of clinicians and basic science investigators to review the current state of the art in Bone Quality and Fracture Prevention and to make recommendations for future directions for research. The AAOS/ORS/OREF workshop was attended by 64 participants, including two representatives of the National Institutes of Arthritis and Musculoskeletal and Skin Diseases and 13 new investigators whose posters stimulated additional interest. A key outcome of the workshop was a set of recommendations regarding clinically relevant aspects of both bone quality and quantity that clinicians can use to inform decisions about patient care and management. The common theme of these recommendations was the need for more education of clinicians in areas of bone quality and for basic science studies to address specific topics of pathophysiology, diagnosis, prevention, and treatment of altered bone quality. In this report, the organizers with the assistance of the speakers and other attendees highlight the major findings of the meeting that justify the recommendations and needs for this field. PMID:24700449

Long-term outcomes of ultrasonic scalpel treatment in giant cell tumor of long bones

PubMed Central

SUN, SHENG; ZHANG, QIANG; ZHAO, CHANG-SONG; CAI, JUAN

2014-01-01

Giant cell tumors (GCTs) are generally benign, locally aggressive lesions with the potential to metastasize and a tendency of local recurrence. The present study aimed to investigate the advantages and long-term outcomes of application of ultrasonic scalpel in the treatment of GCT of long bones. This study retrospectively analyzed 32 cases of GCT of long bones, including 24 males and eight females. The age range was from 8 to 34 years old (mean age, 23.5 years old). The 32 cases were randomly divided into an observation group (n=10) and a control group (n=22). Patients in the observation group received curettage by ultrasonic scalpel combined with local methotrexate gelfoam adjuvant treatment, and then the cavity was filled with allograft and/or homograft bone. Patients in the control group eceived curettage by local methotrexate gelfoam adjuvant treatment and bone grafting. No local recurrence or pulmonary metastases were observed among patients in the observation group, however, six patients in the control group exhibited recurrence following surgery, although none of the patients demonstrated distant metastasis (P<0.05). Additionally, all 10 patients showed good bone knitting and rehabilitation without deformity and functional issues. The segmental bone graft was perfectly incorporated without obvious immune rejection, collapse and fracture. Curettage by ultrasonic scalpel with local methotrexate gelfoam adjuvant treatment and filling the site by allograft and/or homograft bone showed satisfactory results. PMID:24959235

Multicenter Cell Processing for Cardiovascular Regenerative Medicine Applications - The Cardiovascular Cell Therapy Research Network (CCTRN) Experience

PubMed Central

Gee, Adrian P.; Richman, Sara; Durett, April; McKenna, David; Traverse, Jay; Henry, Timothy; Fisk, Diann; Pepine, Carl; Bloom, Jeannette; Willerson, James; Prater, Karen; Zhao, David; Koç, Jane Reese; Ellis, Steven; Taylor, Doris; Cogle, Christopher; Moyé, Lemuel; Simari, Robert; Skarlatos, Sonia

2013-01-01

Background Aims Multi-center cellular therapy clinical trials require the establishment and implementation of standardized cell processing protocols and associated quality control mechanisms. The aims here were to develop such an infrastructure in support of the Cardiovascular Cell Therapy Research Network (CCTRN) and to report on the results of processing for the first 60 patients. Methods Standardized cell preparations, consisting of autologous bone marrow mononuclear cells, prepared using the Sepax device were manufactured at each of the five processing facilities that supported the clinical treatment centers. Processing staff underwent centralized training that included proficiency evaluation. Quality was subsequently monitored by a central quality control program that included product evaluation by the CCTRN biorepositories. Results Data from the first 60 procedures demonstrate that uniform products, that met all release criteria, could be manufactured at all five sites within 7 hours of receipt of the bone marrow. Uniformity was facilitated by use of the automated systems (the Sepax for processing and the Endosafe device for endotoxin testing), standardized procedures and centralized quality control. Conclusions Complex multicenter cell therapy and regenerative medicine protocols can, where necessary, successfully utilize local processing facilities once an effective infrastructure is in place to provide training, and quality control. PMID:20524773

Effects of mechanical repetitive load on bone quality around implants in rat maxillae.

PubMed

Uto, Yusuke; Kuroshima, Shinichiro; Nakano, Takayoshi; Ishimoto, Takuya; Inaba, Nao; Uchida, Yusuke; Sawase, Takashi

2017-01-01

Greater understanding and acceptance of the new concept "bone quality", which was proposed by the National Institutes of Health and is based on bone cells and collagen fibers, are required. The novel protein Semaphorin3A (Sema3A) is associated with osteoprotection by regulating bone cells. The aims of this study were to investigate the effects of mechanical loads on Sema3A production and bone quality based on bone cells and collagen fibers around implants in rat maxillae. Grade IV-titanium threaded implants were placed at 4 weeks post-extraction in maxillary first molars. Implants received mechanical loads (10 N, 3 Hz for 1800 cycles, 2 days/week) for 5 weeks from 3 weeks post-implant placement to minimize the effects of wound healing processes by implant placement. Bone structures, bone mineral density (BMD), Sema3A production and bone quality based on bone cells and collagen fibers were analyzed using microcomputed tomography, histomorphometry, immunohistomorphometry, polarized light microscopy and birefringence measurement system inside of the first and second thread (designated as thread A and B, respectively), as mechanical stresses are concentrated and differently distributed on the first two threads from the implant neck. Mechanical load significantly increased BMD, but not bone volume around implants. Inside thread B, but not thread A, mechanical load significantly accelerated Sema3A production with increased number of osteoblasts and osteocytes, and enhanced production of both type I and III collagen. Moreover, mechanical load also significantly induced preferential alignment of collagen fibers in the lower flank of thread B. These data demonstrate that mechanical load has different effects on Sema3A production and bone quality based on bone cells and collagen fibers between the inside threads of A and B. Mechanical load-induced Sema3A production may be differentially regulated by the type of bone structure or distinct stress distribution, resulting in control of bone quality around implants in jaw bones.

Efficacy of Bone-Anchored Hearing Aids in Single-Sided Deafness: A Systematic Review.

PubMed

Kim, Gaeun; Ju, Hyun Mi; Lee, Sun Hee; Kim, Hee-Soon; Kwon, Jeong A; Seo, Young Joon

2017-04-01

Bone-anchored hearing aids (BAHAs) have been known to partially restore some of the functions lost in subjects with single-sided deafness (SSD). Our aims in this systemic review were to analyze the present capabilities of BAHAs in the context of SSD, and to evaluate the efficacy of BAHAs in improving speech recognition in noisy conditions, sound localization, and subjective outcomes. A systematic search was undertaken until August 2015 by two independent reviewers, with disagreements resolved by consensus. Among 286 references, we analyzed 14 studies that used both subjective and objective indicators to assess the capabilities of a total of 296 patients in the unaided and aided situations. Although there was "no benefit" of BAHA implantation for sound localization, BAHAs certainly improved subjects' speech discrimination in noisy circumstances. In the six studies that dealt with sound localization, no significant difference was found after the implantation. Twelve studies showed the benefits of BAHAs for speech discrimination in noise. Regarding subjective outcomes of using the prosthesis in patients with SSD (abbreviated profile of hearing aid benefit [APHAB] and the Glasgow hearing aid benefit profile [GHABP], etc.), we noticed an improvement in the quality of life. This systematic review has indicated that BAHAs may successfully rehabilitate patients with SSD by alleviating the hearing handicap to a certain degree, which could improve patients' quality of life. This report has presented additional evidence of effective auditory rehabilitation for SSD and will be helpful to clinicians counseling patients regarding treatment options for SSD.

Single-dose local administration of parathyroid hormone (1-34, PTH) with β-tricalcium phosphate/collagen (β-TCP/COL) enhances bone defect healing in ovariectomized rats.

PubMed

Tao, Zhou-Shan; Zhou, Wan-Shu; Wu, Xin-Jing; Wang, Lin; Yang, Min; Xie, Jia-Bing; Xu, Zhu-Jun; Ding, Guo-Zheng

2018-02-01

Parathyroid hormone (1-34, PTH) combined β-tricalcium phosphate (β-TCP) achieves stable bone regeneration without cell transplantation in previous studies. Recently, with the development of tissue engineering slow release technology, PTH used locally to promote bone defect healing become possible. This study by virtue of collagen with a combination of drugs and has a slow release properties, and investigated bone regeneration by β-TCP/collagen (β-TCP/COL) with the single local administration of PTH. After the creation of a rodent critical-sized femoral metaphyseal bone defect, β-TCP/COL was prepared by mixing sieved granules of β-TCP and atelocollagen for medical use, then β-TCP/COL with dripped PTH solution (1.0 µg) was implanted into the defect of OVX rats until death at 4 and 8 weeks. The defected area in distal femurs of rats was harvested for evaluation by histology, micro-CT, and biomechanics. The results of our study show that single-dose local administration of PTH combined local usage of β-TCP/COL can increase the healing of defects in OVX rats. Furthermore, treatments with single-dose local administration of PTH and β-TCP/COL showed a stronger effect on accelerating the local bone formation than β-TCP/COL used alone. The results from our study demonstrate that combination of single-dose local administration of PTH and β-TCP/COL had an additive effect on local bone formation in osteoporosis rats.

[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.

Collaborative Pediatric Bone Tumor Program to Improve Access to Specialized Care: An Initiative by the Lebanese Children’s Oncology Group

PubMed Central

Merabi, Zeina; Abboud, Miguel R.; Muwakkit, Samar; Noun, Peter; Gemayel, Gladys; Bechara, Elie; Khalifeh, Hassan; Farah, Roula; Kabbara, Nabil; El-Khoury, Tarek; Al-Yousef, Rasha; Haidar, Rachid; Saghieh, Said; Eid, Toufic; Akel, Samir; Khoury, Nabil; Bayram, Layal; Krasin, Matthew J.; Jeha, Sima; El-Solh, Hassan

2017-01-01

Background Children with malignant bone tumors have average 5-year survival rates of 60% to 70% with current multimodality therapy. Local control modalities aimed at preserving function greatly influence the quality of life of long-term survivors. In developing countries, the limited availability of multidisciplinary care and limited expertise in specialized surgery and pediatric radiation therapy, as well as financial cost, all form barriers to achieving optimal outcomes in this population. Methods We describe the establishment of a collaborative pediatric bone tumor program among a group of pediatric oncologists in Lebanon and Syria. This program provides access to specialized local control at a tertiary children’s cancer center to pediatric patients with newly diagnosed bone tumors at participating sites. Central review of pathology, staging, and treatment planning is performed in a multidisciplinary tumor board setting. Patients receive chemotherapy at their respective centers on a unified treatment plan. Surgery and/or radiation therapy are performed centrally by specialized staff at the children’s cancer center. Cost barriers were resolved through a program development initiative led by St Jude Children’s Research Hospital. Once program feasibility was achieved, the Children’s Cancer Center of Lebanon Foundation, via fundraising efforts, provided continuation of program-directed funding. Results Findings over a 3-year period showed the feasibility of this project, with timely local control and protocol adherence at eight collaborating centers. We report success in providing standard-of-care multidisciplinary therapy to this patient population with complex needs and financially challenging surgical procedures. Conclusion This initiative can serve as a model, noting that facilitating access to specialized multidisciplinary care, resolution of financial barriers, and close administrative coordination all greatly contributed to the success of the program. PMID:28717738

Preventing Cartilage Degeneration in Warfighters by Elucidating Novel Mechanisms Regulating Osteocyte-Mediated Perilacunar Bone Remodeling

DTIC Science & Technology

2015-10-01

quality, and cartilage health in post-traumatic osteoarthritis (PTOA). Few molecular details are known about the regulation of PLR or bone quality...degeneration. 15. SUBJECT TERMS Osteocyte, remodeling, bone, bone quality, post-traumatic osteoarthritis , TGF-beta, mechanical load, matrix...joint health, and their contribution to post-traumatic osteoarthritis (PTOA). Osteocytes sense and respond to mechanical loads, and they are also

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.

High Resolution Peripheral Quantitative Computed Tomography for Assessment of Bone Quality

NASA Astrophysics Data System (ADS)

Kazakia, Galateia

2014-03-01

The study of bone quality is motivated by the high morbidity, mortality, and societal cost of skeletal fractures. Over 10 million people are diagnosed with osteoporosis in the US alone, suffering 1.5 million osteoporotic fractures and costing the health care system over 17 billion annually. Accurate assessment of fracture risk is necessary to ensure that pharmacological and other interventions are appropriately administered. Currently, areal bone mineral density (aBMD) based on 2D dual-energy X-ray absorptiometry (DXA) is used to determine osteoporotic status and predict fracture risk. Though aBMD is a significant predictor of fracture risk, it does not completely explain bone strength or fracture incidence. The major limitation of aBMD is the lack of 3D information, which is necessary to distinguish between cortical and trabecular bone and to quantify bone geometry and microarchitecture. High resolution peripheral quantitative computed tomography (HR-pQCT) enables in vivo assessment of volumetric BMD within specific bone compartments as well as quantification of geometric and microarchitectural measures of bone quality. HR-pQCT studies have documented that trabecular bone microstructure alterations are associated with fracture risk independent of aBMD.... Cortical bone microstructure - specifically porosity - is a major determinant of strength, stiffness, and fracture toughness of cortical tissue and may further explain the aBMD-independent effect of age on bone fragility and fracture risk. The application of finite element analysis (FEA) to HR-pQCT data permits estimation of patient-specific bone strength, shown to be associated with fracture incidence independent of aBMD. This talk will describe the HR-pQCT scanner, established metrics of bone quality derived from HR-pQCT data, and novel analyses of bone quality currently in development. Cross-sectional and longitudinal HR-pQCT studies investigating the impact of aging, disease, injury, gender, race, and therapeutics on bone quality will be discussed.

[Traumatology in the elderly : Multimodal prevention of delirium and use of augmentation techniques].

PubMed

Wähnert, D; Roos, A; Glasbrenner, J; Ilting-Reuke, K; Ohrmann, P; Hempel, G; Duning, T; Roeder, N; Raschke, M J

2017-02-01

Recent data show that 20-80% of surgery patients are affected by delirium during inpatient clinical treatment. The medical consequences are often dramatic and include a 20 times higher mortality and treatment expenses of the medical unit increase considerably. At the University Hospital of Münster a multimodal and interdisciplinary concept for prevention and management of delirium was developed: all patients older than 65 years admitted for surgery are screened by a specialized team for the risk of developing delirium and treated by members of the team if there is a risk of delirium. Studies proved that by this multimodal approach the incidence of delirium was lowered and therefore the quality of medical care improved.When surgical treatment of fractures in the elderly is required, limited bone quality as well as pre-existing implants can complicate the procedure. Secondary loss of reduction after osteosynthesis and avulsion of the implant in particular must be prevented. Augmentation of the osteosynthetic implant with bone cement can increase the bone-implant interface and therefore stability can be improved. Additional intraoperative 3D imaging can be necessary depending on the localization of the fracture. In biomechanical studies we could prove greater stability in the osteosynthesis of osteoporotic fractures of the distal femur when using additional bone cement; therefore, the use of bone cement is an important tool, which helps to prevent complications in the surgical treatment of fractures in the elderly. Nevertheless, special implants and technical skills are required and some safety aspects should be considered.

ALPHA-CTX is associated with subchondral bone turnover and predicts progression of joint space narrowing and osteophytes in osteoarthritis

PubMed Central

Huebner, Janet L; Bay-Jensen, Anne C; Huffman, Kim M; He, Yi; Leeming, Diana J; McDaniel, Gary E; Karsdal, Morten A; Kraus, Virginia B

2014-01-01

Objective To evaluate joint tissue remodeling, with urinary collagen biomarkers, uALPHA CTX and uCTXII, and their association with osteoarthritis (OA) severity, progression, and localized knee bone turnover. Methods Participants (N=149) with symptomatic and radiographic knee OA underwent fixed flexion knee radiography at baseline and 3 years, and late-phase bone scintigraphy of both knees at baseline, scored semi-quantitatively for osteophyte (OST) and joint space narrowing (JSN) severity and uptake intensity with scores summed across knees. Urinary concentrations of ALPHA CTX and CTXII were determined by ELISA. Immunohistochemistry of human OA knees was performed to localize the joint tissue origin of the biomarker epitopes. Results uALPHA CTX correlated strongly with intensity of bone scintigraphic uptake, and JSN and OST progression (risk ratio=13.2 and 3, respectively). uCTXII was strongly associated with intensity of bone scintigraphic uptake, with JSN and OST severity, and OA progression based on OST. uALPHA CTX localized primarily to high bone turnover areas in subchondral bone; CTXII localized to the bone-cartilage interface, the tidemark, and damaged articular cartilage. Conclusion Baseline uALPHA CTX, localized to high turnover areas of subchondral bone, was associated with dynamic bone turnover of knees signified by scintigraphy, and progression of both OST and JSN. uCTXII correlated with JSN and OST severity, and progression of OST. To our knowledge, this represents the first report of serological markers reflecting subchondral bone turnover. These collagen markers may be useful for non-invasive detection and quantification of active subchondral bone turnover and joint remodeling in knee OA. PMID:24909851

The role of midazolam-induced sedation in bone marrow aspiration/trephine biopsies.

PubMed

Mainwaring, C J; Wong, C; Lush, R J; Smith, J G; Singer, C R

1996-12-01

This study was undertaken in 102 adult patients to evaluate the safety and efficacy of intravenous (i.v.) midazolam in the setting of bone marrow aspiration and trephine biopsy (BMAT). Combined local anaesthetic (LA) and sedation was used in 87% of patients and 13% received LA alone. Amnesia occurred in all sedated patients with only 9% experiencing a mild degree of post-procedure pain. This contrasted sharply with the non-sedated group, in whom 85% had intense pain during the biopsy followed by protracted local discomfort in approximately 54%. Drowsiness and some psychomotor impairment were the only notable sedation-related side-effects in approximately 20%. None required assisted ventilation. There was a resounding patient preference for BMAT with sedation. Considering the ease of use, safety and efficacy of i.v. midazolam, the availability of flumazenil as a reversal agent and the undoubted positive effects on quality of life, we would advocate using it in BMAT provided that there were no contraindications.

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.

Unique local bone tissue characteristics in iliac crest bone biopsy from adolescent idiopathic scoliosis with severe spinal deformity

PubMed Central

Wang, Zhiwei; Chen, Huanxiong; Yu, Y. Eric; Zhang, Jiajun; Cheuk, Ka-Yee; Ng, Bobby K. W.; Qiu, Yong; Guo, X. Edward; Cheng, Jack C. Y.; Lee, Wayne Y. W.

2017-01-01

Adolescent idiopathic scoliosis is a complex disease with unclear etiopathogenesis. Systemic and persistent low bone mineral density is an independent prognostic factor for curve progression. The fundamental question of how bone quality is affected in AIS remains controversy because there is lack of site-matched control for detailed analysis on bone-related parameters. In this case-control study, trabecular bone biopsies from iliac crest were collected intra-operatively from 28 severe AIS patients and 10 matched controls with similar skeletal and sexual maturity, anthropometry and femoral neck BMD Z-score to control confounding effects. In addition to static histomorphometry, micro-computed tomography (μCT) and real time-PCR (qPCR) analyses, individual trabecula segmentation (ITS)-based analysis, finite element analysis (FEA), energy dispersive X-ray spectroscopy (EDX) were conducted to provide advanced analysis of structural, mechanical and mineralization features. μCT and histomorphometry showed consistently reduced trabecular number and connectivity. ITS revealed predominant change in trabecular rods, and EDX confirmed less mineralization. The structural and mineralization abnormality led to slight reduction in apparent modulus, which could be attributed to differential down-regulation of Runx2, and up-regulation of Spp1 and TRAP. In conclusion, this is the first comprehensive study providing direct evidence of undefined unique pathological changes at different bone hierarchical levels in AIS. PMID:28054655

Strain-guided mineralization in the bone–PDL–cementum complex of a rat periodontium

DOE PAGES

Grandfield, Kathryn; Herber, Ralf -Peter; Chen, Ling; ...

2015-04-18

Objective: The objective of this study was to investigate the effect of mechanical strain by mapping physicochemical properties at periodontal ligament (PDL)–bone and PDL–cementum attachment sites and within the tissues per se. Design: Accentuated mechanical strain was induced by applying a unidirectional force of 0.06 N for 14 days on molars in a rat model. The associated changes in functional space between the tooth and bone, mineral forming and resorbing events at the PDL–bone and PDL–cementum attachment sites were identified by using micro-X-ray computed tomography (micro-XCT), atomic force microscopy (AFM), dynamic histomorphometry, Raman microspectroscopy, and AFM-based nanoindentation technique. Results frommore » these analytical techniques were correlated with histochemical strains specific to low and high molecular weight GAGs, including biglycan, and osteoclast distribution through tartrate resistant acid phosphatase (TRAP) staining. Results: Unique chemical and mechanical qualities including heterogeneous bony fingers with hygroscopic Sharpey's fibers contributing to a higher organic (amide III — 1240 cm⁻¹) to inorganic (phosphate — 960 cm⁻¹) ratio, with lower average elastic modulus of 8 GPa versus 12 GPa in unadapted regions were identified. Furthermore, an increased presence of elemental Zn in cement lines and mineralizing fronts of PDL–bone was observed. Adapted regions containing bony fingers exhibited woven bone-like architecture and these regions rich in biglycan (BGN) and bone sialoprotein (BSP) also contained high-molecular weight polysaccharides predominantly at the site of polarized bone growth. Conclusions: From a fundamental science perspective the shift in local properties due to strain amplification at the soft–hard tissue attachment sites is governed by semiautonomous cellular events at the PDL–bone and PDL–cementum sites. Over time, these strain-mediated events can alter the physicochemical properties of tissues per se, and consequently the overall biomechanics of the bone–PDL–tooth complex. From a clinical perspective, the shifts in magnitude and duration of forces on the periodontal ligament can prompt a shift in physiologic mineral apposition in cementum and alveolar bone albeit of an adapted quality owing to the rapid mechanical translation of the tooth.« less

Strain-guided mineralization in the bone–PDL–cementum complex of a rat periodontium

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

Grandfield, Kathryn; Herber, Ralf -Peter; Chen, Ling

Objective: The objective of this study was to investigate the effect of mechanical strain by mapping physicochemical properties at periodontal ligament (PDL)–bone and PDL–cementum attachment sites and within the tissues per se. Design: Accentuated mechanical strain was induced by applying a unidirectional force of 0.06 N for 14 days on molars in a rat model. The associated changes in functional space between the tooth and bone, mineral forming and resorbing events at the PDL–bone and PDL–cementum attachment sites were identified by using micro-X-ray computed tomography (micro-XCT), atomic force microscopy (AFM), dynamic histomorphometry, Raman microspectroscopy, and AFM-based nanoindentation technique. Results frommore » these analytical techniques were correlated with histochemical strains specific to low and high molecular weight GAGs, including biglycan, and osteoclast distribution through tartrate resistant acid phosphatase (TRAP) staining. Results: Unique chemical and mechanical qualities including heterogeneous bony fingers with hygroscopic Sharpey's fibers contributing to a higher organic (amide III — 1240 cm⁻¹) to inorganic (phosphate — 960 cm⁻¹) ratio, with lower average elastic modulus of 8 GPa versus 12 GPa in unadapted regions were identified. Furthermore, an increased presence of elemental Zn in cement lines and mineralizing fronts of PDL–bone was observed. Adapted regions containing bony fingers exhibited woven bone-like architecture and these regions rich in biglycan (BGN) and bone sialoprotein (BSP) also contained high-molecular weight polysaccharides predominantly at the site of polarized bone growth. Conclusions: From a fundamental science perspective the shift in local properties due to strain amplification at the soft–hard tissue attachment sites is governed by semiautonomous cellular events at the PDL–bone and PDL–cementum sites. Over time, these strain-mediated events can alter the physicochemical properties of tissues per se, and consequently the overall biomechanics of the bone–PDL–tooth complex. From a clinical perspective, the shifts in magnitude and duration of forces on the periodontal ligament can prompt a shift in physiologic mineral apposition in cementum and alveolar bone albeit of an adapted quality owing to the rapid mechanical translation of the tooth.« less

Local delivery of a selective androgen receptor modulator failed as an anabolic agent in a rat bone marrow ablation model

PubMed Central

Aro, Hannu T; Kulkova, Julia; Moritz, Niko; Kähkönen, Esa; Mattila, Riina H

2015-01-01

Background and purpose — Selective androgen receptor modulators (SARMs) have been developed to have systemic anabolic effects on bones and muscles without the adverse effects of steroidal androgens. One unexplored therapeutic option is the targeted application of SARMs for the enhancement of local new bone formation. We evaluated the osteogenic efficacy of a locally released SARM (ORM-11984). Methods — ORM-11984 was mixed with a copolymer of L-lactide and ɛ-caprolactone (PLCL). An in vitro dissolution test confirmed the sustainable release of ORM-11984 from the matrix. A bone marrow ablation model was used in female Sprague-Dawley rats. Implants containing 10%, 30%, or 50% ORM-11984 by weight or pure PLCL were inserted into the medullary canal of the ablated tibia. At 6 and 12 weeks, the volume of intramedullary new bone and the perimeter of bone-implant contact were measured by micro-computed tomography and histomorphometry. Results — Contrary to our hypothesis, there was a negative correlation between the amount of new bone around the implant and the dose of ORM-11984. There was only a mild (and not statistically significant) enhancement of bone formation in ablated bones subjected to the lowest dose of the SARM (10%). Interpretation — This study suggests that intramedullary/endosteal osteogenesis had a negative, dose-dependent response to locally released SARM. This result highlights the complexity of androgenic effects on bones and also suggests that there are biological limits to the targeted local application of SARMs. PMID:26198725

[Interventional radiology in bone metastases].

PubMed

Chiras, Jacques; Cormier, Evelyne; Baragan, Hector; Jean, Betty; Rose, Michèle

2007-02-01

Interventional radiology takes a large place in the treatment of bone metastases by numerous techniques, percutaneous or endovascular. Vertebroplasty appears actually as the most important technique for stabilisation of spine metastases as it induces satisfactory stabilisation of the vertebra and offer clear improvement of the quality of life. Due to the success of this technique cementoplasty of other bones, mainly pelvic girdle, largely develop. The heath due to the polymerisation of the cement induce carcinolytic effect but this effect is not as important as that can be created with radiofrequency destruction. This last technique appears actually as the most important development to destroy definitively some bone metastases and replace progressively alcoholic destruction of such lesions. Angiographic techniques appear more confidential but endovascular embolization is very useful to diminish the risk of surgical treatment of hyper vascular metastases. Chemoembolization is actually developped to associate the relief of pain induced by endovascular embolization and the carcinolytic effect obtained by local endovascular chemotherapy. All these techniques should develop largely during the next years and their efficacy and safety should improve largely by treating earlier the metastasis.

Detection of changes in bone quality of osteoporotic model induced by sciatic nerve resection by using Raman spectroscopy

NASA Astrophysics Data System (ADS)

Ishimaru, Yasumitsu; Oshima, Yusuke; Imai, Yuuki; Iimura, Tadahiro; Takanezawa, Sota; Hino, Kazunori; Miura, Hiromasa

2018-02-01

To detect the bone quality loss in osteoporosis, we performed Raman spectroscopic analysis of sciatic nerve resection (NX) mice. Eight months after surgery, lower limbs were collected from the mice and fixed with 70% ethanol. Raman spectra of anterior cortical surface of the proximal tibia at 5 points in each bone were measured by RENISHAW inVia Raman Microscope. Excitation wave length was 785 nm. We also performed DXA and micro CT measurement to confirm the bone mineral density and bone microstructure in the osteoporotic model induced by sciatic nerve resection. In the result of Raman spectroscopy, we detected changes of Raman peak intensity ratio in carbonate/phosphate, mineral/combined proline and hydroxyproline and mineral/phenylalanine. In addition, in the result of micro CT, we found significant changes in VOX BV/TV, Trabecular number, thickness, cancellous bone mineral density, cortical thickness and cortical bone mineral density. The results suggest that not only the bone mineral density but also bone quality reduced in the NX mice. We conclude that Raman spectroscopy is a useful for bone quality assessment as a complementary technique for conventional diagnostics.

An in vivo study on the metabolism and osteogenic activity of bioabsorbable Mg-1Sr alloy.

PubMed

Tie, Di; Guan, Renguo; Liu, Huinan; Cipriano, Aaron; Liu, Yili; Wang, Qiang; Huang, Yuanding; Hort, Norbert

2016-01-01

Previous studies indicated that local delivery of strontium effectively increased bone quality and formation around osseointegrating implants. Therefore, implant materials with long-lasting and controllable strontium release are avidly pursued. The central objective of the present study was to investigate the in vivo biocompatibility, metabolism and osteogenic activity of the bioabsorbable Mg-1Sr (wt.%, nominal composition) alloy for bone regeneration. The general corrosion rate of the alloy implant as a femoral fracture fixation device was 0.55±0.03mm·y(-1) (mean value±standard deviation) in New Zealand White rabbits which meet the bone implantation requirements and can be adjusted by material processing methods. All rabbits survived and the histological evaluation showed no abnormal physiology or diseases 16 weeks post-implantation. The degradation process of the alloy did not significantly alter 16 primary indexes of hematology, cardiac damage, inflammation, hepatic functions and metabolic process. Significant increases in peri-implant bone volume and direct bone-to-implant contact (48.3%±15.3% and 15.9%±5.6%, respectively) as well as the expressions of four osteogenesis related genes (runt-related transcription factor 2, alkaline phosphatase, osteocalcin, and collagen, type I, alpha 1) were observed after 16 weeks implantation for the Mg-1Sr group when compared to the pure Mg group. The sound osteogenic properties of the Mg-1Sr alloy by long-lasting and controllable Sr release suggesting a very attractive clinical potential. Sr (strontium) has exhibited pronounced effects to reduce the bone fracture risk in osteoporotic patients. Nonetheless, long-lasting local Sr release is hardly achieved by traditional methods like surface treatment. Therefore, a more efficient Sr local delivery platform is in high clinical demand. The stable and adjustable degradation process of Mg alloy makes it an ideal Sr delivery platform. We combine the well-known osteogenic properties of strontium with magnesium to manufacture bioabsorbable Mg-1Sr alloy with stable Sr release based on our previous studies. The in vitro and in vivo results both showed the alloy's suitable degradation rate and biocompatibility, and the sound osteogenic properties and stimulation effect on bone formation suggest its very attractive clinical potential. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Effects of bone drilling on local temperature and bone regeneration: an in vivo study.

PubMed

Karaca, Faruk; Aksakal, Bünyamin; Köm, Mustafa

2014-01-01

The aim of this study was to examine the influence of bone drilling on local bone temperature and bone regeneration and determine optimal drilling speed and pressure in an animal model. The study included 12 skeletally mature New Zealand white rabbits, weighing between 2.8 to 3.2 kg. Rabbits were divided into 2 groups and euthanized at the end of Day 21 (Group A) and Day 42 (Group B). The same drilling protocol was used in both groups. Three drill holes with different pressure (5, 10 and 20 N) were made in each rabbit tibias using 3 different rotational drill speeds (230, 370 and 570 rpm). During drilling, local temperature was recorded. Rabbit tibia underwent histopathological exam for bone regeneration. Bone temperature was affected by drilling time and depth. Lower drill speeds reduced the bone temperature and revealed better bone regeneration when compared to the drilled bones at higher drill speeds. Titanium boron nitride coating on the drill bits had no significant effects on bone temperature and structure. Bone regeneration was superior in Group B rabbits that had drilling at 230 rpm and 20 N. Our results suggested that lower drilling speed with higher pressure is necessary for better bone regeneration. The optimal drilling speed is 230 rpm and optimal drilling pressure 20 N.

Correlation between bone quality and microvascular damage in systemic sclerosis patients.

PubMed

Ruaro, Barbara; Casabella, Andrea; Paolino, Sabrina; Pizzorni, Carmen; Alessandri, Elisa; Seriolo, Chiara; Botticella, Giulia; Molfetta, Luigi; Odetti, Patrizio; Smith, Vanessa; Cutolo, Maurizio

2018-05-18

SSc patients are recognized as presenting an increased risk of altered bone mass. The aim of this study was to assess the bone quality, by trabecular bone score (TBS), in SSc patients in correlation with different levels of microvascular damage, as evaluated by nailfold videocapillaroscopy (NVC), and to compare the results regarding bone quality with RA patients and healthy subjects (CNT). Eighty-four SSc patients, 98 RA patients and 60 CNT, were studied. BMD (g/cm2) of the lumbar spine (L1-L4) was analysed by DXA scan. Lumbar spine bone quality was derived from each spine DXA examination using the TBS analysis. NVC patterns were analysed. A total of 56/84 SSc patients (66%) as well as 78/98 RA patients (80%) showed bone loss at DXA and BMD was found to be significantly lower than in the CNT (P < 0.001). Similarly, lumbar spine TBS was found to be significantly lower in SSc and RA patients than in CNT (P < 0.001). TBS values were found to be lower in SSc with a late NVC pattern, compared with the active or early pattern (late vs active and early pattern, P < 0.001). There was no statistically significant difference in the mean lumbar spine TBS between SSc and RA patients (P = 0.238). The data obtained showed significantly lower bone quality (lower TBS and BMD) in SSc and RA patients compared with CNT. The bone quality seemed lower in SSc patients with more altered microvasculature (late NVC pattern).

The effect of antiresorptives on bone quality.

PubMed

Recker, Robert R; Armas, Laura

2011-08-01

Currently, antiresorptive therapy in the treatment and prevention of osteoporosis includes bisphosphonates, estrogen replacement, selective estrogen receptor modulators (raloxifene), and denosumab (a human antibody that inactivates RANKL). The original paradigm driving the development of antiresorptive therapy was that inhibition of bone resorption would allow bone formation to continue and correct the defect. However, it is now clear increases in bone density account for little of the antifracture effect of these treatments. We examined the antifracture benefit of antiresorptives deriving from bone quality changes. We searched the archive of nearly 30,000 articles accumulated over more than 40 years in our research center library using a software program (Refman™). Approximately 250 publications were identified in locating the 69 cited here. The findings document antiresorptive agents are not primarily anabolic. All cause a modest increase in bone density due to a reduction in the bone remodeling space; however, the majority of their efficacy is due to suppression of the primary cause of osteoporosis, ie, excessive bone remodeling not driven by mechanical need. All of them improve some element(s) of bone quality. Antiresorptive therapy reduces risk of fracture by improving bone quality through halting removal of bone tissue and the resultant destruction of microarchitecture of bone and, perhaps to some extent, by improving the intrinsic material properties of bone tissue. Information presented here may help clinicians to improve selection of patients for antiresorptive therapy by avoiding them in cases clearly not due to excessive bone remodeling.

Effects of 25-hydroxycholecalciferol supplementation in maternal diets on milk quality and serum bone status markers of sows and bone quality of piglets.

PubMed

Zhou, Hui; Chen, Yuling; Zhuo, Yong; Lv, Gang; Lin, Yan; Feng, Bin; Fang, Zhengfeng; Che, Lianqiang; Li, Jian; Xu, Shengyu; Wu, De

2017-03-01

Twenty primiparous sows were allocated to two treatments to evaluate the effects of maternal 25-hydroxycholecalciferol (25OHD 3 ) supplementation during gestation and lactation on milk quality and serum bone status markers of sows and bone quality of piglets. Immediately after mating, sows were randomly allotted to one of two diets supplemented with 50 µg/kg 25OHD 3 or basal diets without 25OHD 3 . Blood and milk samples were obtained. At birth and weaning, 10 piglets from each treatment were killed for bone quality analysis. 25OHD 3 -fed sows provided one more piglet at farrowing and 1.17 more piglets at weaning than sows fed basal diets. The contents of solids not-fat, protein, fat or lactose were increased in milk from days 7 and 14 of lactation in 25OHD 3 -supplemented sows and 25OHD 3 concentrations in milk were increased by dietary 25OHD 3 supplementation. Dietary 25OHD 3 supplementation increased serum alkaline phosphatase activity but had no effect on serum tartrate-resistant acid phosphatase activity of sows. Maternal 25OHD 3 supplementation improved bone strength, density and ash content of newborn piglets rather than those of weaning piglets. In conclusion, 25OHD 3 supplementation in maternal diets improved reproductive performance, milk quality and bone status of sows as well as bone quality of newborn piglets. © 2016 Japanese Society of Animal Science.

Impact of skeletal unloading on bone formation: Role of systemic and local factors

NASA Astrophysics Data System (ADS)

Bikle, Daniel D.; Halloran, Bernard P.; Morey-Holton, Emily

We have developed a model of skeletal unloading using growing rats whose hindlimbs are unweighted by tail suspension. The bones in the hindlimbs undergo a transient cessation of bone growth; when reloaded bone formation is accelerated until bone mass is restored. These changes do not occur in the normally loaded bones of the forelimbs. Associated with the fall in bone formation is a fall in 1,25(OH) 2D 3 production and osteocalcin levels. In contrast, no changes in parathyroid hormone, calcium, or corticosterone levels are seen. To examine the role of locally produced growth factors, we have measured the mRNA and protein levels of insulin like growth factor-1 (IGF-1) in bone during tail suspension. Surprisingly, both the mRNA and protein levels of IGF-1 increase during tail suspension as bone formation is reduced. Furthermore, the bones in the hindlimbs of the suspended animals develop a resistance to the growth promoting effects of both growth hormone and IGF-1 when given parenterally. Thus, the cessation of bone growth with skeletal unloading is apparently associated with a resistance to rather than failure to produce local growth factors. The cause of this resistance remains under active investigation.

Effects of mechanical repetitive load on bone quality around implants in rat maxillae

PubMed Central

Uto, Yusuke; Nakano, Takayoshi; Ishimoto, Takuya; Inaba, Nao; Uchida, Yusuke; Sawase, Takashi

2017-01-01

Greater understanding and acceptance of the new concept “bone quality”, which was proposed by the National Institutes of Health and is based on bone cells and collagen fibers, are required. The novel protein Semaphorin3A (Sema3A) is associated with osteoprotection by regulating bone cells. The aims of this study were to investigate the effects of mechanical loads on Sema3A production and bone quality based on bone cells and collagen fibers around implants in rat maxillae. Grade IV-titanium threaded implants were placed at 4 weeks post-extraction in maxillary first molars. Implants received mechanical loads (10 N, 3 Hz for 1800 cycles, 2 days/week) for 5 weeks from 3 weeks post-implant placement to minimize the effects of wound healing processes by implant placement. Bone structures, bone mineral density (BMD), Sema3A production and bone quality based on bone cells and collagen fibers were analyzed using microcomputed tomography, histomorphometry, immunohistomorphometry, polarized light microscopy and birefringence measurement system inside of the first and second thread (designated as thread A and B, respectively), as mechanical stresses are concentrated and differently distributed on the first two threads from the implant neck. Mechanical load significantly increased BMD, but not bone volume around implants. Inside thread B, but not thread A, mechanical load significantly accelerated Sema3A production with increased number of osteoblasts and osteocytes, and enhanced production of both type I and III collagen. Moreover, mechanical load also significantly induced preferential alignment of collagen fibers in the lower flank of thread B. These data demonstrate that mechanical load has different effects on Sema3A production and bone quality based on bone cells and collagen fibers between the inside threads of A and B. Mechanical load-induced Sema3A production may be differentially regulated by the type of bone structure or distinct stress distribution, resulting in control of bone quality around implants in jaw bones. PMID:29244883

[Local injection of exogenous nerve growth factor improves early bone maturation of implants].

PubMed

Yao, Yang; Du, Yu; Gu, Xia; Guang, Meng-Kai; Huang, Bo; Gong, Ping

2018-04-01

To investigate the effects of nerve growth factor (NGF) in the osteogenic action of implants and the maturation and reconstruction changes in bone tissues in the early stage of osseointegration. The mouse implant model was established by placing titanium in the femoral head of the mouse and locally injecting NGF in the implant zone. On 1, 2 and 4 weeks after operation, stain samples were collected from animals using hematoxylin-eosin (HE) staining and Masson staining. The effect of NGF on the bone maturation was compared at different time points of early stage osseointegration. The results of HE and Masson staining indicated that the local injection of external NGF can up-regulate bone mass, amount of bone trabecula, and bone maturity in the mouse model. The mature bone rate in treatment group of 1 week and 4 weeks after operation were significantly higher than those in the control group (P<0.05). NGF can shorten the period of bone maturation.

Osteogenic effect of a gastric pentadecapeptide, BPC-157, on the healing of segmental bone defect in rabbits: a comparison with bone marrow and autologous cortical bone implantation.

PubMed

Sebecić, B; Nikolić, V; Sikirić, P; Seiwerth, S; Sosa, T; Patrlj, L; Grabarević, Z; Rucman, R; Petek, M; Konjevoda, P; Jadrijević, S; Perović, D; Slaj, M

1999-03-01

Gastrectomy often results in increased likelihood of osteoporosis, metabolic aberration, and risk of fracture, and there is a need for a gastric peptide with osteogenic activity. A novel stomach pentadecapeptide, BPC-157, improves wound and fracture healing in rats in addition to having an angiogenic effect. Therefore, in the present study, using a segmental osteoperiosteal bone defect (0.8 cm, in the middle of the left radius) that remained incompletely healed in all control rabbits for 6 weeks (assessed in 2 week intervals), pentadecapeptide BPC-157 was further studied (either percutaneously given locally [10 microg/kg body weight] into the bone defect, or applied intramuscularly [intermittently, at postoperative days 7, 9, 14, and 16 at 10 microg/kg body weight] or continuously [once per day, postoperative days 7-21 at 10 microg or 10 ng/kg body weight]). For comparison, rabbits percutaneously received locally autologous bone marrow (2 mL, postoperative day 7). As standard treatment, immediately after its formation, the bone defect was filled with an autologous cortical graft. Saline-treated (2 mL intramuscularly [i.m.] and 2 mL locally into the bone defect), injured animals were used as controls. Pentadecapeptide BPC-157 significantly improved the healing of segmental bone defects. For instance, upon radiographic assessment, the callus surface, microphotodensitometry, quantitative histomorphometry (10 microg/kg body weight i.m. for 14 days), or quantitative histomorphometry (10 ng/kg body weight i.m. for 14 days) the effect of pentadecapeptide BPC-157 was shown to correspond to improvement after local application of bone marrow or autologous cortical graft. Moreover, a comparison of the number of animals with unhealed defects (all controls) or healed defects (complete bony continuity across the defect site) showed that besides pentadecapeptide intramuscular application for 14 days (i.e., local application of bone marrow or autologous cortical graft), also following other pentadecapeptide BPC-157 regimens (local application, or intermittent intramuscular administration), the number of animals with healed defect was increased. Hopefully, in the light of the suggested stomach significance for bone homeostasis, the possible relevance of this pentadecapeptide BPC-157 effect (local or intramuscular effectiveness, lack of unwanted effects) could be a basis for methods of choice in the future management of healing impairment in humans, and requires further investigation.

Outcome of bone recycling using liquid nitrogen as bone reconstruction procedure in malignant and recurrent benign aggressive bone tumour of distal tibia: A report of four cases.

PubMed

Gede, Eka Wiratnaya I; Ida Ayu, Arrisna Artha; Setiawan I Gn, Yudhi; Aryana Ign, Wien; I Ketut, Suyasa; I Ketut, Siki Kawiyana; Putu, Astawa

2017-01-01

Amputation still considered as primary choice of malignancy treatment in distal tibia. Bone recycling with liquid nitrogen for reconstruction following resection of malignant bone tumours offers many advantages. We presented four patients with osteosarcoma, Ewing sarcoma, adamantinoma and recurrent giant cell tumour over distal tibia. All of the patients underwent wide excision and bone recycling using liquid nitrogen as bone reconstruction. The mean functional Musculoskeletal Tumor Society (MSTS) score was 75% with no infection and local recurrent. The reconstruction provides good local control and functional outcome.

Changes in chemical composition of bone matrix in ovariectomized (OVX) rats detected by Raman spectroscopy and multivariate analysis

NASA Astrophysics Data System (ADS)

Oshima, Yusuke; Iimura, Tadahiro; Saitou, Takashi; Imamura, Takeshi

2015-02-01

Osteoporosis is a major bone disease that connotes the risk of fragility fractures resulting from alterations to bone quantity and/or quality to mechanical competence. Bone strength arises from both bone quantity and quality. Assessment of bone quality and bone quantity is important for prediction of fracture risk. In spite of the two factors contribute to maintain the bone strength, only one factor, bone mineral density is used to determine the bone strength in the current diagnosis of osteoporosis. On the other hand, there is no practical method to measure chemical composition of bone tissue including hydroxyapatite and collagen non-invasively. Raman spectroscopy is a powerful technique to analyze chemical composition and material properties of bone matrix non-invasively. Here we demonstrated Raman spectroscopic analysis of the bone matrix in osteoporosis model rat. Ovariectomized (OVX) rat was made and the decalcified sections of tibias were analyzed by a Raman microscope. In the results, Raman bands of typical collagen appeared in the obtained spectra. Although the typical mineral bands at 960 cm-1 (Phosphate) was absent due to decalcified processing, we found that Raman peak intensities of amide I and C-C stretching bands were significantly different between OVX and sham-operated specimens. These differences on the Raman spectra were statistically compared by multivariate analyses, principal component analysis (PCA) and liner discrimination analysis (LDA). Our analyses suggest that amide I and C-C stretching bands can be related to stability of bone matrix which reflects bone quality.

Moderate chronic kidney disease impairs bone quality in C57Bl/6J mice.

PubMed

Heveran, Chelsea M; Ortega, Alicia M; Cureton, Andrew; Clark, Ryan; Livingston, Eric W; Bateman, Ted A; Levi, Moshe; King, Karen B; Ferguson, Virginia L

2016-05-01

Chronic kidney disease (CKD) increases bone fracture risk. While the causes of bone fragility in CKD are not clear, the disrupted mineral homeostasis inherent to CKD may cause material quality changes to bone tissue. In this study, 11-week-old male C57Bl/6J mice underwent either 5/6th nephrectomy (5/6 Nx) or sham surgeries. Mice were fed a normal chow diet and euthanized 11weeks post-surgery. Moderate CKD with high bone turnover was established in the 5/6 Nx group as determined through serum chemistry and bone gene expression assays. We compared nanoindentation modulus and mineral volume fraction (assessed through quantitative backscattered scanning electron microscopy) at matched sites in arrays placed on the cortical bone of the tibia mid-diaphysis. Trabecular and cortical bone microarchitecture and whole bone strength were also evaluated. We found that moderate CKD minimally affected bone microarchitecture and did not influence whole bone strength. Meanwhile, bone material quality decreased with CKD; a pattern of altered tissue maturation was observed with 5/6 Nx whereby the newest 60μm of bone tissue adjacent to the periosteal surface had lower indentation modulus and mineral volume fraction than more interior, older bone. The variance of modulus and mineral volume fraction was also altered following 5/6 Nx, implying that tissue-scale heterogeneity may be negatively affected by CKD. The observed lower bone material quality may play a role in the decreased fracture resistance that is clinically associated with human CKD. Copyright © 2016 Elsevier Inc. All rights reserved.

Moderate Chronic Kidney Disease Impairs Bone Quality in C57Bl/6J Mice

PubMed Central

Heveran, Chelsea M.; Ortega, Alicia M.; Cureton, Andrew; Clark, Ryan; Livingston, Eric; Bateman, Ted; Levi, Moshe; King, Karen B.; Ferguson, Virginia L.

2016-01-01

Chronic kidney disease (CKD) increases bone fracture risk. While the causes of bone fragility in CKD are not clear, the disrupted mineral homeostasis inherent to CKD may cause material quality changes to bone tissue. In this study, 11-week old male C57Bl/6J mice underwent either 5/6th nephrectomy (5/6 Nx) or sham procedures. Mice were fed a normal chow diet and euthanized 11 weeks post-surgery. Moderate CKD with high bone turnover was established in the 5/6 Nx group as determined through serum chemistry and bone gene expression assays. We compared nanoindentation modulus and mineral volume fraction (assessed through quantitative backscattered scanning electron microscopy) at matched sites in arrays placed on the cortical bone of the tibia mid-diaphysis. Trabecular and cortical bone microarchitecture (μCT) and whole bone strength were also evaluated. We found that moderate CKD minimally affected bone microarchitecture and did not influence whole bone strength. Meanwhile, bone material quality decreased with CKD; a pattern of altered tissue maturation was observed with 5/6 Nx whereby the newest 60 micrometers of bone tissue adjacent to the periosteal surface had lower indentation modulus and mineral volume fraction than more interior, older bone. The variance of modulus and mineral volume fraction were also altered following 5/6 Nx, implying that tissue-scale heterogeneity may be negatively affected by CKD. The observed lower bone material quality may play a role in the decreased fracture resistance that is clinically associated with human CKD. PMID:26860048

Local vibration enhanced the efficacy of passive exercise on mitigating bone loss in hindlimb unloading rats

NASA Astrophysics Data System (ADS)

Huang, Yunfei; Luan, Huiqin; Sun, Lianwen; Bi, Jingfang; Wang, Ying; Fan, Yubo

2017-08-01

Spaceflight induced bone loss is seriously affecting astronauts. Mechanical stimulation from exercise has been shown to restrain bone resorption as well as improve bone formation. Current exercise countermeasures in space cannot prevent it completely. Active exercise may convert to passive exercise in some ways because of the loss of gravity stimulus and inertia of exercise equipment. The aim of this study was to compare the efficacy of passive exercise or/and local vibration on counteracting the deterioration of the musculoskeletal system, including bone, muscle and tendons in tail-suspended rats. We hypothesized that local vibration could enhance the efficacy of passive exercise on countering bone loss. 40 Sprague Dawley rats were randomly distributed into five groups (n = 8, each): tail-suspension (TS), TS+35 Hz vibration (TSV), TS + passive exercise (TSP), TS + passive exercise coupled with 35 Hz vibration (TSPV) and control (CON). Passive exercise or/and local vibration was performed for 21 days. On day 0 and 21, bone mineral density (BMD) was observed by dual energy X-ray absorptiometry (DXA), and trabecular microstructure was evaluated by microcomputer tomography (μCT) analysis in vivo. Mechanical properties of tibia and tendon were determined by a mechanical testing system. Soleus and bone ash weight was tested by an electronic balance. Results showed that the passive exercise could not prevent the decrease of trabecular BMD, microstructure and bone ash weight induced by TS, whereas vibration and passive exercise coupled with local vibration (PV) could. Biomechanical properties of the tibia and tendon in TSPV group significantly increased compared with TS group. In summary, PV in this study was the best method in preventing weightlessness-induced bone loss. Consistent with our hypothesis, local vibration partly enhanced the effect of passive exercise. Furthermore, this study will be useful in improving countermeasure for astronauts, but also for the rehabilitation of disused or aged osteoporosis.

Exercise does not enhance aged bone's impaired response to artificial loading in C57Bl/6 mice.

PubMed

Meakin, Lee B; Udeh, Chinedu; Galea, Gabriel L; Lanyon, Lance E; Price, Joanna S

2015-12-01

Bones adapt their structure to their loading environment and so ensure that they become, and are maintained, sufficiently strong to withstand the loads to which they are habituated. The effectiveness of this process declines with age and bones become fragile fracturing with less force. This effect in humans also occurs in mice which experience age-related bone loss and reduced adaptation to loading. Exercise engenders many systemic and local muscular physiological responses as well as engendering local bone strain. To investigate whether these physiological responses influence bones' adaptive responses to mechanical strain we examined whether a period of treadmill exercise influenced the adaptive response to an associated period of artificial loading in young adult (17-week) and old (19-month) mice. After treadmill acclimatization, mice were exercised for 30 min three times per week for two weeks. Three hours after each exercise period, right tibiae were subjected to 40 cycles of non-invasive axial loading engendering peak strain of 2250 με. In both young and aged mice exercise increased cross-sectional muscle area and serum sclerostin concentration. In young mice it also increased serum IGF1. Exercise did not affect bone's adaptation to loading in any measured parameter in young or aged bone. These data demonstrate that a level of exercise sufficient to cause systemic changes in serum, and adaptive changes in local musculature, has no effect on bone's response to loading 3h later. This study provides no support for the beneficial effects of exercise on bone in the elderly being mediated by systemic or local muscle-derived effects rather than local adaptation to altered mechanical strain. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

[Clinical usefulness of bone turnover markers in the management of osteoporosis].

PubMed

Yano, Shozo

2013-09-01

Osteoporosis is a state of elevated risk for bone fracture due to depressed bone strength, which is considered to be the sum of bone mineral density and bone quality. Since a measure of bone quality has not been established, bone mineral density and bone turnover markers are the only way to evaluate bone strength. Bone turnover markers are classified into bone formation marker and resorption marker, which are correlated with the bone formation rate and resorption rate, respectively, and bone matrix-related marker. Bone is always metabolized; old tissue is resorbed by acids and proteases derived from osteoclasts, whereas new bone is produced by osteoblasts. Bone formation and resorption rates should be balanced (also called coupled). When the bone resorption rate exceeds the formation rate(uncoupled state), bone volume will be reduced. Thus, we can comprehend bone metabolism by measuring both formation and resorption markers at the same time. Increased fracture risk is recognized by elevated bone resorption markers and undercarboxylated osteocalcin, which reflects vitamin K insufficiency and bone turnover. These values and the time course give us helpful information to choose medicine suitable for the patients and to judge the responsiveness. If the value is extraordinarily high without renal failure, metabolic bone disorder or bone metastatic tumor should be considered. Bone quality may be assessed by measuring bone matrix-related markers such as homocystein and pentosidine. Since recent studies indicate that the bone is a hormone-producing organ, it is possible that glucose metabolism or an unknown mechanism could be assessed in the future.

Alpha C-telopeptide of type I collagen is associated with subchondral bone turnover and predicts progression of joint space narrowing and osteophytes in osteoarthritis.

PubMed

Huebner, Janet L; Bay-Jensen, Anne C; Huffman, Kim M; He, Yi; Leeming, Diana J; McDaniel, Gary E; Karsdal, Morten A; Kraus, Virginia B

2014-09-01

To evaluate joint tissue remodeling using the urinary collagen biomarkers urinary α-C-telopeptide of type I collagen (α-CTX) and urinary C-telopeptide of type II collagen (CTX-II) and to determine the association of these biomarkers with osteoarthritis (OA) severity, progression, and localized knee bone turnover. Participants (n = 149) with symptomatic and radiographic knee OA underwent fixed-flexion knee radiography at baseline and 3 years, and late-phase bone scintigraphy of both knees at baseline, which were scored semiquantitatively for osteophyte and joint space narrowing (JSN) severity and uptake intensity, with scores summed across knees. Urinary concentrations of α-CTX and CTX-II were determined by enzyme-linked immunosorbent assay. Immunohistochemical analysis of human OA knees was performed to localize the joint tissue origin of the biomarker epitopes. Urinary α-CTX concentrations correlated strongly with the intensity of bone scintigraphic uptake and with JSN progression (risk ratio 13.2) and osteophyte progression (risk ratio 3). Urinary CTX-II concentrations were strongly associated with intensity of bone scintigraphic uptake, with JSN and osteophyte severity, and with OA progression based on osteophyte score. Urinary α-CTX localized primarily to high bone turnover areas in subchondral bone. CTX-II localized to the bone-cartilage interface, the tidemark, and damaged articular cartilage. Baseline urinary α-CTX, which was localized to high turnover areas of subchondral bone, was associated with dynamic bone turnover of knees, as signified by scintigraphy, and progression of both osteophytes and JSN. Urinary CTX-II correlated with JSN and osteophyte severity and progression of osteophytes. To our knowledge, this represents the first report of serologic markers reflecting subchondral bone turnover. These collagen markers may be useful for noninvasive detection and quantification of active subchondral bone turnover and joint remodeling in knee OA. Copyright © 2014 by the American College of Rheumatology.

Effects of Physical Activity and Muscle Quality on Bone Development in Girls

PubMed Central

Farr, Joshua N.; Laddu, Deepika R.; Blew, Robert M.; Lee, Vinson R.; Going, Scott B.

2013-01-01

Poor muscle quality and sedentary behavior are risk factors for metabolic dysfunction in children and adolescents. However, because longitudinal data are scarce, relatively little is known about how changes in muscle quality and physical activity influence bone development. Purpose In a 2-year longitudinal study, we examined the effects of physical activity and changes in muscle quality on bone parameters in young girls. Methods The sample included 248 healthy girls aged 9–12 years at baseline. Peripheral quantitative computed tomography was used to measure calf and thigh muscle density, an indicator of skeletal muscle fat content or muscle quality, as well as bone parameters at diaphyseal and metaphyseal sites of the femur and tibia. Physical activity was assessed using a validated questionnaire specific for youth. Results After controlling for covariates in multiple regression models, increased calf muscle density was independently associated with greater gains in cortical (β = 0.13, P < 0.01) and trabecular (β = 0.25, P < 0.001) volumetric bone mineral density (vBMD) and the bone strength index (BSI; β = 0.25, P < 0.001) of the tibia. Importantly, these relationships were generalized, as similar changes were present at the femur. Associations between physical activity and changes in bone parameters were weaker than those observed for muscle density. Nevertheless, physical activity was significantly (all P < 0.05) associated with greater gains in trabecular vBMD and the BSI of the distal femur. Conclusions These findings suggest that poor muscle quality may put girls at risk for suboptimal bone development. Physical activity is associated with more optimal gains in weight-bearing bone density and strength in girls, but to a lesser extent than changes in muscle quality. PMID:23698240

Applicability of strain measurements on a contra angle handpiece for the determination of alveolar bone quality during dental implant surgery.

PubMed

Krafft, Tim; Winter, Werner; Wichmann, Manfred; Karl, Matthias

2012-07-01

Alveolar bone quality is considered to be an important prognostic factor in dental implant stability. Although numerous methods have been described, no technique allows for reliable diagnostics. The purpose of this study was to determine if strain measurements on the shaft of a contra angle handpiece during implant bed preparation could be used for the determination of bone quality. Experiments in polyurethane foam and human cadaver bone were conducted to investigate whether strain measurements could be correlated with other diagnostic parameters, such as the surgeon's tactile sensation during drilling, implant insertion torque, implant stability, elastic modulus of bone and bone quality as assessed radiographically. Tests were also performed to determine if strain measurements could be used to distinguish various types of bone. As axial feed and contact pressure during the drilling process could not be standardized under simulated clinical conditions, substantial deviations in the time needed to complete the drilling occurred. Under controlled circumstances using polyurethane foam, this problem could be addressed by a normalization procedure, but great variations occurred in human cadaver bone. As bone quality could not be reliably determined, especially when a cortical layer was present, strain measurements on a contra angle handpiece appears to be inappropriate for this purpose. Copyright © 2011 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Study of tissue engineered bone nodules by Fourier transform infrared spectroscopy.

PubMed

Aydin, Halil Murat; Hu, Bin; Suso, Josep Sulé; El Haj, Alicia; Yang, Ying

2011-02-21

The key criteria for assessing the success of bone tissue engineering are the quality and quantity of the produced minerals within the cultured constructs. The accumulation of calcium ions and inorganic phosphates in culture medium serves as nucleating agents for the formation of hydroxyapatite, which is the main inorganic component of bone. Bone nodule formation is one of the hallmarks of mineralization in such cell cultures. In this study, we developed a new two-step procedure to accelerate bone formation in which mouse bone cell aggregates were produced first on various chemically treated non-adhesive substrates. After this step, the bone cells' growth and mineralization were followed in conventional culture plates. The number and size of cell aggregates were studied with light microscopy. The minerals' formation in the form of nodules produced by the cell aggregates and the bone crystal quality were studied with Fourier Transform Infrared (FTIR) spectroscopy. The FTIR spectra of the ash specimens (mineral phase only) from thermal gravimetric analysis (TGA) provided valuable information of the quality of the minerals. The υ(4) PO(4) region (550-650 cm(-1)), which reveals apatitic and non-apatitic HPO(4) or PO(4) environments, and phosphate region (910-1180 cm(-1)) were examined for the minerals produced in the form of nodules. The peak position and intensity of the spectra demonstrate that the quality of the bone produced by cell aggregates, especially from the bigger ones, which were formed on Plunoric treated substrates, exhibit a composition more similar to that of native bone. This work establishes a new protocol for high quality bone formation and characterization, with the potential to be applied to bone tissue engineering.

THE PROTECTIVE EFFECT OF LOCAL BONE MARROW ASPHYXIA IN ACUTE RADIATION SICKNESS IN ANIMALS (in Russian)

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

Zherebchenko, P.G.; Krasnykh, I.G.; Lebkova, N.P.

1960-10-01

In experiments on mice, rats, and dogs, a study was made of the effect of local bone marrow asphyxia on the course and outcome of radiation sickness. Asphyxia was induced by applying a hemostatic tourniquet on the extremity of animals during irradiation. It was established that local asphyxia of the bone marrow alleviates the severity of acute radiation sickness and increases the survival of animals. It is shown that at the basis of the radioprotective action lies the reduced degeneration of the bone marrow, subsequently facilitating the regeneration of hematopeiesis. Data are obtained relative to the intensification of the effectmore » of local asphyxia with the aid of prophylactic (mercamine) and curative (streptomycin) agents. (auth)« less

Understanding and Addressing the Global Need for Orthopaedic Trauma Care.

PubMed

Agarwal-Harding, Kiran J; von Keudell, Arvind; Zirkle, Lewis G; Meara, John G; Dyer, George S M

2016-11-02

➤The burden of musculoskeletal trauma is high worldwide, disproportionately affecting the poor, who have the least access to quality orthopaedic trauma care.➤Orthopaedic trauma care is essential, and must be a priority in the horizontal development of global health systems.➤The education of surgeons, nonphysician clinicians, and ancillary staff in low and middle income countries is central to improving access to and quality of care.➤Volunteer surgical missions from rich countries can sustainably expand and strengthen orthopaedic trauma care only when they serve a local need and build local capacity.➤Innovative business models may help to pay for care of the poor. Examples include reducing costs through process improvements and cross-subsidizing from profitable high-volume activities.➤Resource-poor settings may foster innovations in devices or systems with universal applicability in orthopaedics. Copyright © 2016 by The Journal of Bone and Joint Surgery, Incorporated.

3D printed bioceramics for dual antibiotic delivery to treat implant-associated bone infection

PubMed Central

Inzana, Jason A.; Trombetta, Ryan P.; Schwarz, Edward M.; Kates, Stephen L.; Awad, Hani A.

2015-01-01

Surgical implant-associated bone infections (osteomyelitis) have severe clinical and socioeconomic consequences. Treatment of chronic bone infections often involves antibiotics given systemically and locally to the affected site via poly(methyl methacrylate) (PMMA) bone cement. Given the high antibiotic concentrations required to affect bacteria in biofilm, local delivery is important to achieve high doses at the infection site. PMMA is not suitable to locally deliver some biofilm-specific antibiotics, including rifampin, due to interference with PMMA polymerization. To examine the efficacy of localized, combinational antibiotic delivery compared to PMMA standards, we fabricated rifampin- and vancomycin-laden calcium phosphate scaffolds (CPS) by three-dimensional (3D) printing to treat an implant-associated Staphylococcus aureus bone infection in a murine model. All vancomycin- and rifampin-laden CPS treatments significantly reduced the bacterial burden compared with vancomycin-laden PMMA. The bones were bacteria culture negative in 50% of the mice that received sustained release vancomycin- and rifampin-laden CPS. In contrast, 100% of the bones treated with vancomycin monotherapy via PMMA or CPS were culture positive. Yet, the monotherapy CPS significantly reduced the bacterial metabolic load following revision compared to PMMA. Biofilm persisted on the fixation hardware, but the infection-induced bone destruction was significantly reduced by local rifampin delivery. These data demonstrate that, despite the challenging implant-retaining infection model, co-delivery of rifampin and vancomycin from 3D printed CPS, which is not possible with PMMA, significantly improved the outcomes of implant-associated osteomyelitis. However, biofilm persistence on the fixation hardware reaffirms the importance of implant exchange or other biofilm eradication strategies to complement local antibiotics. PMID:26535494

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.

Resection followed by vascularized bone autograft in patients with possible recurrence of malignant bone tumors after conservative treatment

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

Metaizeau, J.P.; Olive, D.; Bey, P.

1984-04-01

In conservative treatment of malignant bone tumors, assessment of the local condition is difficult. The radiological changes seen in the irradiated tumor and the frequent occurrence of pathological fractures at this site may give rise to the fear that the tumor has relapsed. Resection of the whole of the involved bone is the best way to assure adequate local control but the extent of the bone defect and the bad local conditions secondary to irradiation make reconstruction hazardous. In two patients (one with Ewing's sarcoma of the femur and one with osteogenic sarcoma of the humerus) the authors used amore » free, vascularized fibular graft for the reconstruction having obtained consolidation of the limb after resection of the irradiated tumor, with preservation of its function. The encouraging results obtained have suggested a conservative attitude as primary treatment of specific malignant bone tumors.« less

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.

Inbred Strain-Specific Effects of Exercise in Wild Type and Biglycan Deficient Mice

PubMed Central

Wallace, Joseph M.; Golcuk, Kurtulus; Morris, Michael D.; Kohn, David H.

2010-01-01

Biglycan (bgn)-deficient mice (KO) have defective osteoblasts which lead to changes in the amount and quality of bone. Altered tissue strength in C57BL6/129 (B6;129) KO mice, a property which is independent of tissue quantity, suggests that deficiencies in tissue quality are responsible. However, the response to bgn-deficiency is inbred strain-specific. Mechanical loading influences bone matrix quality in addition to any increase in bone mass or change in bone formation activity. Since many diseases influence the mechanical integrity of bone through altered tissue quality, loading may be a way to prevent and treat extracellular matrix deficiencies. C3H/He (C3H) mice consistently have a less vigorous response to mechanical loading vs. other inbred strains. It was therefore hypothesized that the bones from both wild type (WT) and KO B6;129 mice would be more responsive to exercise than the bones from C3H mice. To test these hypotheses at 11 weeks of age, following 21 consecutive days of exercise, we investigated cross-sectional geometry, mechanical properties, and tissue composition in the tibiae of male mice bred on B6;129 and C3H backgrounds. This study demonstrated inbred strain-specific compositional and mechanical changes following exercise in WT and KO mice, and showed evidence of genotype-specific changes in bone in response to loading in a gene disruption model. This study further shows that exercise can influence bone tissue composition and/or mechanical integrity without changes in bone geometry. Together, these data suggest that exercise may represent a possible means to alter tissue quality and mechanical deficiencies caused by many diseases of bone. PMID:20033775

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

PubMed Central

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

2014-01-01

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

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

PubMed

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

2014-01-01

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

Impregnation of bone chips with alendronate and cefazolin, combined with demineralized bone matrix: a bone chamber study in goats

PubMed Central

2012-01-01

Background Bone grafts from bone banks might be mixed with bisphosphonates to inhibit the osteoclastic response. This inhibition prevents the osteoclasts to resorb the allograft bone before new bone has been formed by the osteoblasts, which might prevent instability. Since bisphosphonates may not only inhibit osteoclasts, but also osteoblasts and thus bone formation, we studied different bisphosphonate concentrations combined with allograft bone. We investigated whether locally applied alendronate has an optimum dose with respect to bone resorption and formation. Further, we questioned whether the addition of demineralized bone matrix (DBM), would stimulate bone formation. Finally, we studied the effect of high levels of antibiotics on bone allograft healing, since mixing allograft bone with antibiotics might reduce the infection risk. Methods 25 goats received eight bone conduction chambers in the cortical bone of the proximal medial tibia. Five concentrations of alendronate (0, 0.5 mg/mL, 1 mg/mL, 2 mg/mL, and 10 mg/mL) were tested in combination with allograft bone and supplemented with cefazolin (200 μg/mL). Allograft not supplemented with alendronate and cefazolin served as control. In addition, allograft mixed with demineralized bone matrix, with and without alendronate, was tested. After 12 weeks, graft bone area and new bone area were determined with manual point counting. Results Graft resorption decreased significantly (p < 0.001) with increasing alendronate concentration. The area of new bone in the 1 mg/mL alendronate group was significantly (p = 0.002) higher when compared to the 10 mg/mL group. No differences could be observed between the group without alendronate, but with demineralized bone, and the control groups. Conclusions A dose-response relationship for local application of alendronate has been shown in this study. Most new bone was present at 1 mg/mL alendronate. Local application of cefazolin had no effect on bone remodelling. PMID:22443362

Development of a protocol to quantify local bone adaptation over space and time: Quantification of reproducibility.

PubMed

Lu, Yongtao; Boudiffa, Maya; Dall'Ara, Enrico; Bellantuono, Ilaria; Viceconti, Marco

2016-07-05

In vivo micro-computed tomography (µCT) scanning of small rodents is a powerful method for longitudinal monitoring of bone adaptation. However, the life-time bone growth in small rodents makes it a challenge to quantify local bone adaptation. Therefore, the aim of this study was to develop a protocol, which can take into account large bone growth, to quantify local bone adaptations over space and time. The entire right tibiae of eight 14-week-old C57BL/6J female mice were consecutively scanned four times in an in vivo µCT scanner using a nominal isotropic image voxel size of 10.4µm. The repeated scan image datasets were aligned to the corresponding baseline (first) scan image dataset using rigid registration. 80% of tibia length (starting from the endpoint of the proximal growth plate) was selected as the volume of interest and partitioned into 40 regions along the tibial long axis (10 divisions) and in the cross-section (4 sectors). The bone mineral content (BMC) was used to quantify bone adaptation and was calculated in each region. All local BMCs have precision errors (PE%CV) of less than 3.5% (24 out of 40 regions have PE%CV of less than 2%), least significant changes (LSCs) of less than 3.8%, and 38 out of 40 regions have intraclass correlation coefficients (ICCs) of over 0.8. The proposed protocol allows to quantify local bone adaptations over an entire tibia in longitudinal studies, with a high reproducibility, an essential requirement to reduce the number of animals to achieve the necessary statistical power. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Potential osteogenic activity of ethanolic extract and oxoflavidin isolated from Pholidota articulata Lindley.

PubMed

Sharma, Chetan; Dixit, Manisha; Singh, Rohit; Agrawal, Manali; Mansoori, Mohd Nizam; Kureel, Jyoti; Singh, Divya; Narender, Tadigoppula; Arya, Kamal Ram

2015-07-21

Pholidota articulata Lindley (PA) locally known as Hadjojen (bone jointer) belongs to family Orchidaceae is used for healing fractures in folklore tradition of Kumaon region of Uttarakhand, Himalaya, India. Bone is a dynamic organ and is constantly being remodeled in order to facilitate growth and repair. This process requires the involvement of bone forming osteoblast and bone resorbing osteoclast cells, which function in generating and mineralizing bone, giving strength and rigidity to the skeletal system. Present study was aimed to determine the therapeutic potential of ethanolic extract of PA and its isolated compound oxoflavidin, by characterizing their fracture healing properties. Ovariectomized (Ovx) estrogen deficient adult female Balb/c mice were used for in vivo evaluation of osteogenic or bone healing potential of ethanolic extract of PA. Further, its isolated compounds were tested for their osteogenic efficacy using alkaline phosphatase assay and mineralization assay in vitro in mice calvarial osteoblasts. The ethanolic extract of PA exhibited significant restoration of trabecular micro-architecture in both femoral and tibial bones. Additionally, treatment with PA extract led to better bone quality and devoid of any uterine estrogenicity in ovariectomized estrogen deficient mice. One of the isolated compound, oxoflavidin enhanced ALP activity (a marker of osteoblast differentiation), mineral nodule formation and mRNA levels of osteogenic markers like BMP-2, Type 1 Collagen, RUNX-2 and osteocalcin. These results warrant that ethanolic extract of PA and it's pure compound oxoflavidin have fracture healing properties. The extract and oxoflavidin exhibit a strong threapeutical potential for the treatment and management of postmenopausal osteoporosis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Microdialysis Sampling from Wound Fluids Enables Quantitative Assessment of Cytokines, Proteins, and Metabolites Reveals Bone Defect-Specific Molecular Profiles.

PubMed

Förster, Yvonne; Schmidt, Johannes R; Wissenbach, Dirk K; Pfeiffer, Susanne E M; Baumann, Sven; Hofbauer, Lorenz C; von Bergen, Martin; Kalkhof, Stefan; Rammelt, Stefan

2016-01-01

Bone healing involves a variety of different cell types and biological processes. Although certain key molecules have been identified, the molecular interactions of the healing progress are not completely understood. Moreover, a clinical routine for predicting the quality of bone healing after a fracture in an early phase is missing. This is mainly due to a lack of techniques to comprehensively screen for cytokines, growth factors and metabolites at their local site of action. Since all soluble molecules of interest are present in the fracture hematoma, its in-depth assessment could reveal potential markers for the monitoring of bone healing. Here, we describe an approach for sampling and quantification of cytokines and metabolites by using microdialysis, combined with solid phase extractions of proteins from wound fluids. By using a control group with an isolated soft tissue wound, we could reveal several bone defect-specific molecular features. In bone defect dialysates the neutrophil chemoattractants CXCL1, CXCL2 and CXCL3 were quantified with either a higher or earlier response compared to dialysate from soft tissue wound. Moreover, by analyzing downstream adaptions of the cells on protein level and focusing on early immune response, several proteins involved in the immune cell migration and activity could be identified to be specific for the bone defect group, e.g. immune modulators, proteases and their corresponding inhibitors. Additionally, the metabolite screening revealed different profiles between the bone defect group and the control group. In summary, we identified potential biomarkers to indicate imbalanced healing progress on all levels of analysis.

Microdialysis Sampling from Wound Fluids Enables Quantitative Assessment of Cytokines, Proteins, and Metabolites Reveals Bone Defect-Specific Molecular Profiles

PubMed Central

Wissenbach, Dirk K.; Pfeiffer, Susanne E. M.; Baumann, Sven; Hofbauer, Lorenz C.; von Bergen, Martin; Kalkhof, Stefan; Rammelt, Stefan

2016-01-01

Bone healing involves a variety of different cell types and biological processes. Although certain key molecules have been identified, the molecular interactions of the healing progress are not completely understood. Moreover, a clinical routine for predicting the quality of bone healing after a fracture in an early phase is missing. This is mainly due to a lack of techniques to comprehensively screen for cytokines, growth factors and metabolites at their local site of action. Since all soluble molecules of interest are present in the fracture hematoma, its in-depth assessment could reveal potential markers for the monitoring of bone healing. Here, we describe an approach for sampling and quantification of cytokines and metabolites by using microdialysis, combined with solid phase extractions of proteins from wound fluids. By using a control group with an isolated soft tissue wound, we could reveal several bone defect-specific molecular features. In bone defect dialysates the neutrophil chemoattractants CXCL1, CXCL2 and CXCL3 were quantified with either a higher or earlier response compared to dialysate from soft tissue wound. Moreover, by analyzing downstream adaptions of the cells on protein level and focusing on early immune response, several proteins involved in the immune cell migration and activity could be identified to be specific for the bone defect group, e.g. immune modulators, proteases and their corresponding inhibitors. Additionally, the metabolite screening revealed different profiles between the bone defect group and the control group. In summary, we identified potential biomarkers to indicate imbalanced healing progress on all levels of analysis. PMID:27441377

The osteocyte: key player in regulating bone turnover

PubMed Central

Goldring, Steven R

2015-01-01

Osteocytes are the most abundant cell type in bone and are distributed throughout the mineralised bone matrix forming an interconnected network that ideally positions them to sense and to respond to local biomechanical and systemic stimuli to regulate bone remodelling and adaptation. The adaptive process is dependent on the coordinated activity of osteoclasts and osteoblasts that form a so called bone multicellular unit that remodels cortical and trabecular bone through a process of osteoclast-mediated bone resorption, followed by a phase of bone formation mediated by osteoblasts. Osteocytes mediate their effects on bone remodelling via both cell–cell interactions with osteoclasts and osteoblasts, but also via signaling through the release of soluble mediators. The remodelling process provides a mechanism for adapting the skeleton to local biomechanical factors and systemic hormonal influences and for replacing bone that has undergone damage from repetitive mechanical loading. PMID:26557372

Prevalence of Poor Bone Quality in Women Undergoing Spinal Fusion Using Biomechanical-CT Analysis.

PubMed

Burch, Shane; Feldstein, Michael; Hoffmann, Paul F; Keaveny, Tony M

2016-02-01

Retrospective, cross-sectional analysis of vertebral bone quality in spine-fusion patients at a single medical center. To characterize the prevalence of osteoporosis and fragile bone strength in a spine-fusion population of women with an age range of 50 years to 70 years. Fragile bone strength is defined as the level of vertebral strength below which a patient is at as high a risk of future vertebral fracture as a patient having bone density-defined osteoporosis. Poor bone quality--defined here as the presence of either osteoporosis or fragile bone strength--is a risk factor for spine-fusion patients that often goes undetected but can now be assessed preoperatively by additional postprocessing of computed tomography (CT) scans originally ordered for perioperative clinical assessment. Utilizing such perioperative CT scans for a cohort of 98 women (age range: 51-70 yr) about to undergo spine fusion, we retrospectively used a phantomless calibration technique and biomechanical-CT postprocessing analysis to measure vertebral trabecular bone mineral density (BMD) (in mg/cm³) and by nonlinear finite element analysis, vertebral compressive strength (in Newtons, N) in the L1 or L2 vertebra. Preestablished validated threshold values were used to define the presence of osteoporosis (trabecular BMD of 80 mg/cm³ or lower) and fragile bone strength (vertebral strength of 4500 N or lower). Fourteen percent of the women tested positive for osteoporosis, 27% tested positive for fragile bone strength, and 29% were classified as having poor bone quality (either osteoporosis or fragile bone strength). Over this narrow age range, neither BMD nor vertebral strength were significantly correlated with age, weight, height, or body mass index (P values 0.14-0.97 for BMD; 0.13-0.51 for strength). Poor bone quality appears to be common in women between ages 50 years and 70 years undergoing spinal fusion surgery. 3.

Micro Finite Element models of the vertebral body: Validation of local displacement predictions

PubMed Central

Costa, Maria Cristiana; Tozzi, Gianluca; Cristofolini, Luca; Danesi, Valentina; Viceconti, Marco

2017-01-01

The estimation of local and structural mechanical properties of bones with micro Finite Element (microFE) models based on Micro Computed Tomography images depends on the quality bone geometry is captured, reconstructed and modelled. The aim of this study was to validate microFE models predictions of local displacements for vertebral bodies and to evaluate the effect of the elastic tissue modulus on model’s predictions of axial forces. Four porcine thoracic vertebrae were axially compressed in situ, in a step-wise fashion and scanned at approximately 39μm resolution in preloaded and loaded conditions. A global digital volume correlation (DVC) approach was used to compute the full-field displacements. Homogeneous, isotropic and linear elastic microFE models were generated with boundary conditions assigned from the interpolated displacement field measured from the DVC. Measured and predicted local displacements were compared for the cortical and trabecular compartments in the middle of the specimens. Models were run with two different tissue moduli defined from microindentation data (12.0GPa) and a back-calculation procedure (4.6GPa). The predicted sum of axial reaction forces was compared to the experimental values for each specimen. MicroFE models predicted more than 87% of the variation in the displacement measurements (R2 = 0.87–0.99). However, model predictions of axial forces were largely overestimated (80–369%) for a tissue modulus of 12.0GPa, whereas differences in the range 10–80% were found for a back-calculated tissue modulus. The specimen with the lowest density showed a large number of elements strained beyond yield and the highest predictive errors. This study shows that the simplest microFE models can accurately predict quantitatively the local displacements and qualitatively the strain distribution within the vertebral body, independently from the considered bone types. PMID:28700618

CBCT-based bone quality assessment: are Hounsfield units applicable?

PubMed Central

Jacobs, R; Singer, S R; Mupparapu, M

2015-01-01

CBCT is a widely applied imaging modality in dentistry. It enables the visualization of high-contrast structures of the oral region (bone, teeth, air cavities) at a high resolution. CBCT is now commonly used for the assessment of bone quality, primarily for pre-operative implant planning. Traditionally, bone quality parameters and classifications were primarily based on bone density, which could be estimated through the use of Hounsfield units derived from multidetector CT (MDCT) data sets. However, there are crucial differences between MDCT and CBCT, which complicates the use of quantitative gray values (GVs) for the latter. From experimental as well as clinical research, it can be seen that great variability of GVs can exist on CBCT images owing to various reasons that are inherently associated with this technique (i.e. the limited field size, relatively high amount of scattered radiation and limitations of currently applied reconstruction algorithms). Although attempts have been made to correct for GV variability, it can be postulated that the quantitative use of GVs in CBCT should be generally avoided at this time. In addition, recent research and clinical findings have shifted the paradigm of bone quality from a density-based analysis to a structural evaluation of the bone. The ever-improving image quality of CBCT allows it to display trabecular bone patterns, indicating that it may be possible to apply structural analysis methods that are commonly used in micro-CT and histology. PMID:25315442

Cochlear Implant Electrode Localization Using an Ultra-High Resolution Scan Mode on Conventional 64-Slice and New Generation 192-Slice Multi-Detector Computed Tomography.

PubMed

Carlson, Matthew L; Leng, Shuai; Diehn, Felix E; Witte, Robert J; Krecke, Karl N; Grimes, Josh; Koeller, Kelly K; Bruesewitz, Michael R; McCollough, Cynthia H; Lane, John I

2017-08-01

A new generation 192-slice multi-detector computed tomography (MDCT) clinical scanner provides enhanced image quality and superior electrode localization over conventional MDCT. Currently, accurate and reliable cochlear implant electrode localization using conventional MDCT scanners remains elusive. Eight fresh-frozen cadaveric temporal bones were implanted with full-length cochlear implant electrodes. Specimens were subsequently scanned with conventional 64-slice and new generation 192-slice MDCT scanners utilizing ultra-high resolution modes. Additionally, all specimens were scanned with micro-CT to provide a reference criterion for electrode position. Images were reconstructed according to routine temporal bone clinical protocols. Three neuroradiologists, blinded to scanner type, reviewed images independently to assess resolution of individual electrodes, scalar localization, and severity of image artifact. Serving as the reference standard, micro-CT identified scalar crossover in one specimen; imaging of all remaining cochleae demonstrated complete scala tympani insertions. The 192-slice MDCT scanner exhibited improved resolution of individual electrodes (p < 0.01), superior scalar localization (p < 0.01), and reduced blooming artifact (p < 0.05), compared with conventional 64-slice MDCT. There was no significant difference between platforms when comparing streak or ring artifact. The new generation 192-slice MDCT scanner offers several notable advantages for cochlear implant imaging compared with conventional MDCT. This technology provides important feedback regarding electrode position and course, which may help in future optimization of surgical technique and electrode design.

3D printed bioceramics for dual antibiotic delivery to treat implant-associated bone infection.

PubMed

Inzana, J A; Trombetta, R P; Schwarz, E M; Kates, S L; Awad, H A

2015-11-04

Surgical implant-associated bone infections (osteomyelitis) have severe clinical and socioeconomic consequences. Treatment of chronic bone infections often involves antibiotics given systemically and locally to the affected site in poly (methyl methacrylate) (PMMA) bone cement. Given the high antibiotic concentrations required to affect bacteria in biofilm, local delivery is important to achieve high doses at the infection site. PMMA is not suitable to locally-deliver some biofilm-specific antibiotics, including rifampin, due to interference with PMMA polymerisation. To examine the efficacy of localised, combinational antibiotic delivery compared to PMMA standards, we fabricated rifampin- and vancomycin-laden calcium phosphate scaffolds (CPS) by three-dimensional (3D) printing to treat an implant-associated Staphylococcus aureus bone infection in a murine model. All vancomycin- and rifampin-laden CPS treatments significantly reduced the bacterial burden compared with vancomycin-laden PMMA. The bones were bacteria culture negative in 50 % of the mice that received sustained release vancomycin- and rifampin-laden CPS. In contrast, 100 % of the bones treated with vancomycin monotherapy using PMMA or CPS were culture positive. Yet, the monotherapy CPS significantly reduced the bacterial metabolic load following revision compared to PMMA. Biofilm persisted on the fixation hardware, but the infection-induced bone destruction was significantly reduced by local rifampin delivery. These data demonstrate that, despite the challenging implant-retaining infection model, co-delivery of rifampin and vancomycin from 3D printed CPS, which is not possible with PMMA, significantly improved the outcomes of implant-associated osteomyelitis. However, biofilm persistence on the fixation hardware reaffirms the importance of implant exchange or other biofilm eradication strategies to complement local antibiotics.

Differential effects of PPAR-{gamma} activation versus chemical or genetic reduction of DPP-4 activity on bone quality in mice.

PubMed

Kyle, Kimberly A; Willett, Thomas L; Baggio, Laurie L; Drucker, Daniel J; Grynpas, Marc D

2011-02-01

Patients with type 2 diabetes mellitus have an increased risk of fracture that can be further exacerbated by thiazolidinediones. A new class of antidiabetic agents control glucose through reduction of dipeptidyl peptidase-4 (DPP-4) activity; however the importance of DPP-4 for the control of bone quality has not been extensively characterized. We compared the effects of the thiazolidinedione pioglitazone and the DPP-4 inhibitor sitagliptin on bone quality in high-fat diet (HFD)-fed wild-type mice. In complementary studies, we examined bone quality in Dpp4(+/+) vs. Dpp4(-/-) mice. Pioglitazone produced yellow bones with greater bone marrow adiposity and significantly reduced vertebral bone mechanics in male, female, and ovariectomized (OVX) HFD fed female mice. Pioglitazone negatively affected vertebral volumetric bone mineral density, trabecular architecture, and mineral apposition rate in male mice. Sitagliptin treatment of HFD-fed wild-type mice significantly improved vertebral volumetric bone mineral density and trabecular architecture in female mice, but these improvements were lost in females after OVX. Genetic inactivation of Dpp4 did not produce a major bone phenotype in male and female Dpp4(-/-) mice; however, OVX Dpp4(-/-) mice exhibited significantly reduced femoral size and mechanics. These findings delineate the skeletal consequences of pharmacological and genetic reduction of DPP-4 activity and reveal significant differences in the effects of pioglitazone vs. sitagliptin vs. genetic Dpp4 inactivation on bone mechanics in mice.

Denosumab treatment for progressive skull base giant cell tumor of bone in a 14 year old female - a case report and literature review.

PubMed

Bardakhchyan, Samvel; Kager, Leo; Danielyan, Samvel; Avagyan, Armen; Karamyan, Nerses; Vardevanyan, Hovhannes; Mkhitaryan, Sergey; Papyan, Ruzanna; Zohrabyan, Davit; Safaryan, Liana; Sargsyan, Lilit; Harutyunyan, Lilit; Hakobyan, Lusine; Iskanyan, Samvel; Tamamyan, Gevorg

2017-03-29

Giant cell tumor of bone (GCT) is a rare primary bone tumor, which can metastasize and undergo malignant transformation. The standard treatment of GCT is surgery. In patients with unresectable or metastatic disease, additional therapeutic options are available. These include blocking of the receptor activator of NF-kappa B ligand (RANKL) signaling pathway, which plays a role in the pathogenesis of GCT of bone, via the anti-RANKL monoclonal antibody denosumab. Herein we report on a female teenager who presented in a very poor clinical condition (cachexia, diplopia, strabismus, dysphonia with palsy of cranial nerves V, VI, VIII, IX, X, XI and XII) due to progressive disease, after incomplete resection and adjuvant radiotherapy, of a GCT which affected the cervical spine (C1 and C2) as well as the skull base; and who had an impressive clinical response to denosumab therapy. To the best of our knowledge, this is the youngest patient ever reported with a skull base tumor treated with denosumab. In situations when surgery can be postponed and local aggressiveness of the tumor does not urge for acute surgical intervention, upfront use of denosumab in order to reduce the tumor size might be considered. Principally, the goal of denosumab therapy is to reduce tumor size as much as possible, with the ultimate goal to make local surgery (or as in our case re-surgery) amenable. However, improvement in quality of life, as demonstrated in our patient, is also an important aspect of such targeted therapies.

Correlation Between Resonance Frequency Analysis and Bone Quality Assessments at Dental Implant Recipient Sites.

PubMed

Fu, Min-Wen; Fu, Earl; Lin, Fu-Gong; Chang, Wei-Jeng; Hsieh, Yao-Dung; Shen, E-Chin

To evaluate whether primary implant stability could be used to predict bone quality, the association between the implant stability quotient (ISQ) value and the bone type at the implant site was evaluated. Ninety-five implant sites in 50 patients were included. Bone type (categorized by Lekholm and Zarb) at the implant site was initially assessed using presurgical dental radiography. During the preparation of the implant site, a bone core specimen was carefully obtained. The bone type was assessed by tactile sensation during the drilling operation, according to the Misch criteria. The primary stability of the inserted implant was evaluated by resonance frequency analysis (RFA). The ISQ value was recorded. The bone core specimen was then examined by stereomicroscopy or microcomputed tomography (micro-CT), and the bone type was determined by the surface characteristics of the specimen, based on Lekholm and Zarb classification. Agreement between the bone quality assessed by the four methods (ie, presurgical radiography, tactile sensation, stereomicroscopy, and micro-CT) was tested by Cohen's kappa statistics, whereas the association between the ISQ value and the bone type was evaluated by the generalized linear regression model. The mean ISQ score was 72.6, and the score was significantly influenced by the maxillary or mandibular arch (P = .001). The bone type at the implant sites varied according to the assessment method. However, a significant influence of the arch was repeatedly noted when using radiography or tactile sensation. Among the four bone-quality assessment methods, a weak agreement existed only between stereomicroscopy and micro-CT, especially in the maxilla (κ = 0.469). A negative association between the ISQ value and the bone type assessed by stereomicroscopy or by micro-CT was significant in the maxilla, but not in the mandible, after adjustments for sex, age, and right/left side (P = .013 and P = .027 for stereomicroscopy and micro-CT, respectively). The ISQ value was weakly associated with the bone type when assessed by stereomicroscopy or micro-CT in the maxilla. Caution is necessary if RFA is used as a tool to evaluate bone quality at the implant site, especially in the mandible.

A prospective international cooperative information technology platform built using open-source tools for improving the access to and safety of bone marrow transplantation in low- and middle-income countries.

PubMed

Agarwal, Rajat Kumar; Sedai, Amit; Dhimal, Sunil; Ankita, Kumari; Clemente, Luigi; Siddique, Sulman; Yaqub, Naila; Khalid, Sadaf; Itrat, Fatima; Khan, Anwar; Gilani, Sarah Khan; Marwah, Priya; Soni, Rajpreet; Missiry, Mohamed El; Hussain, Mohamed Hamed; Uderzo, Cornelio; Faulkner, Lawrence

2014-01-01

Jagriti Innovations developed a collaboration tool in partnership with the Cure2Children Foundation that has been used by health professionals in Italy, Pakistan, and India for the collaborative management of patients undergoing bone marrow transplantation (BMT) for thalassemia major since August 2008. This online open-access database covers data recording, analyzing, and reporting besides enabling knowledge exchange, telemedicine, capacity building, and quality assurance. As of February 2014, over 2400 patients have been registered and 112 BMTs have been performed with outcomes comparable to international standards, but at a fraction of the cost. This approach avoids medical emigration and contributes to local healthcare strengthening and competitiveness. This paper presents the experience and clinical outcomes associated with the use of this platform built using open-source tools and focusing on a locally pertinent tertiary care procedure-BMT. 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.

Development, validation and characterization of a novel mouse model of Adynamic Bone Disease (ABD).

PubMed

Ng, Adeline H; Willett, Thomas L; Alman, Benjamin A; Grynpas, Marc D

2014-11-01

The etiology of Adynamic Bone Disease (ABD) is poorly understood but the hallmark of ABD is a lack of bone turnover. ABD occurs in renal osteodystrophy (ROD) and is suspected to occur in elderly patients on long-term anti-resorptive therapy. A major clinical concern of ABD is diminished bone quality and an increased fracture risk. To our knowledge, experimental animal models for ABD other than ROD-ABD have not been developed or studied. The objectives of this study were to develop a mouse model of ABD without the complications of renal ablation, and to characterize changes in bone quality in ABD relative to controls. To re-create the adynamic bone condition, 4-month old female Col2.3Δtk mice were treated with ganciclovir to specifically ablate osteoblasts, and pamidronate was used to inhibit osteoclastic resorption. Four groups of animals were used to characterize bone quality in ABD: Normal bone controls, No Formation controls, No Resorption controls, and an Adynamic group. After a 6-week treatment period, the animals were sacrificed and the bones were harvested for analyses. Bone quality assessments were conducted using established techniques including bone histology, quantitative backscattered electron imaging (qBEI), dual energy X-ray absorptiometry (DXA), microcomputed tomography (microCT), and biomechanical testing. Histomorphometry confirmed osteoblast-related hallmarks of ABD in our mouse model. Bone formation was near complete suppression in the No Formation and Adynamic specimens. Inhibition of bone resorption in the Adynamic group was confirmed by tartrate-resistant acid phosphatase (TRAP) stain. Normal bone mineral density and architecture were maintained in the Adynamic group, whereas the No Formation group showed a reduction in bone mineral content and trabecular thickness relative to the Adynamic group. As expected, the No Formation group had a more hypomineralized profile and the Adynamic group had a higher mean mineralization profile that is similar to suppressed bone turnover in human. This data confirms successful replication of the adynamic bone condition in a mouse without the complication of renal ablation. Our approach is the first model of ABD that uses pharmacological manipulation in a transgenic mouse to mimic the bone cellular dynamics observed in the human ABD condition. We plan to use our mouse model to investigate the adynamic bone condition in aging and to study changes to bone quality and fracture risk as a consequence of over-suppressed bone turnover. Copyright © 2014 Elsevier Inc. All rights reserved.

Computational assessment of press-fit acetabular implant fixation: the effect of implant design, interference fit, bone quality, and frictional properties.

PubMed

Janssen, D; Zwartelé, R E; Doets, H C; Verdonschot, N

2010-01-01

Patients suffering from rheumatoid arthritis typically have a poor subchondral bone quality, endangering implant fixation. Using finite element analysis (FEA) an investigation was made to find whether a press-fit acetabular implant with a polar clearance would reduce interfacial micromotions and improve fixation compared with a standard hemispherical design. In addition, the effects of interference fit, friction, and implant material were analysed. Cups were introduced into an FEA model of a human pelvis with simulated subchondral bone plasticity. The models were loaded with a loading configuration simulating two cycles of normal walking, during which contact stresses and interfacial micromotions were monitored. Subsequently, a lever-out simulation was performed to assess the fixation strength of the various cases. A flattened cup with good bone quality produced the lowest interfacial micromotions. Poor bone decreased the fixation strength regardless of the geometry of the cup. Increasing the interference fit of the flattened cup compensated for the loss of fixation strength caused by poor bone quality. In conclusion, a flattened cup did not significantly improve implant fixation over a hemispherical cup in the case of poor bone quality. However, implant fixation can be optimized by increasing interference fit and avoiding inferior frictional properties and low-stiffness implants.

Development of model hydroxyapatite bone scaffolds with multiscale porosity for potential load bearing applications

NASA Astrophysics Data System (ADS)

Dellinger, Jennifer Gwynne

2005-11-01

Model hydroxyapatite (HA) bone scaffolds consisting of a latticed pattern of rods were fabricated by a solid freeform fabrication (SFF) technique based on the robotic deposition of colloidal pastes. An optimal HA paste formulation for this method was developed. Local porosity, i.e. microporosity (1--30 mum) and sintering porosity (less than 1 mum), were produced by including polymer microsphere porogens in the HA pastes and by controlling the sintering of the scaffolds. Scaffolds with and without local porosity were evaluated with and without in vitro accelerated degradation. Percent weight loss of the scaffolds and calcium and phosphorus concentrations in solution increased with degradation time. After degradation, compressive strength and modulus decreased significantly for scaffolds with local porosity, but did not change significantly for scaffolds without local porosity. The compressive strength and modulus of scaffolds without local porosity were comparable to human cortical bone and were significantly greater than the scaffolds with local porosity. Micropores in HA disks caused surface pits that increased the surface roughness as compared to non-microporous HA disks. Mouse mesenchymal stem cells extended their cell processes into these microporous pits on HA disks in vitro. ALP expression was prolonged, cell attachment strength increased, and ECM production appeared greater on microporous HA disks compared to non-microporous HA disks and tissue culture treated polystyrene controls. Scaffolds with and without microporosity were implanted in goats bones. Microporous scaffolds with rhBMP-2 increased the percent of the scaffold filled with bone tissue compared to microporous scaffolds without rhBMP-2. Lamellar bone inside scaffolds was aligned near the rods junctions whereas lamellar bone was aligned in a more random configuration away from the rod junctions. Microporous scaffolds stained darkly with toluidine blue beneath areas of contact with new bone. This staining might indicate either extracellular matrix (ECM) in the rods or dye bound to the degrading scaffold. Although the presence of microporous topography alone did not influence bone healing in vivo, micropores were shown to provide tailorability of scaffold mechanical properties, provide a location for the storage and controlled release of a growth factor, and provide a location for bone integration inside the scaffold rods.

Assessment of image quality in soft tissue and bone visualization tasks for a dedicated extremity cone-beam CT system.

PubMed

Demehri, S; Muhit, A; Zbijewski, W; Stayman, J W; Yorkston, J; Packard, N; Senn, R; Yang, D; Foos, D; Thawait, G K; Fayad, L M; Chhabra, A; Carrino, J A; Siewerdsen, J H

2015-06-01

To assess visualization tasks using cone-beam CT (CBCT) compared to multi-detector CT (MDCT) for musculoskeletal extremity imaging. Ten cadaveric hands and ten knees were examined using a dedicated CBCT prototype and a clinical multi-detector CT using nominal protocols (80 kVp-108mAs for CBCT; 120 kVp- 300 mAs for MDCT). Soft tissue and bone visualization tasks were assessed by four radiologists using five-point satisfaction (for CBCT and MDCT individually) and five-point preference (side-by-side CBCT versus MDCT image quality comparison) rating tests. Ratings were analyzed using Kruskal-Wallis and Wilcoxon signed-rank tests, and observer agreement was assessed using the Kappa-statistic. Knee CBCT images were rated "excellent" or "good" (median scores 5 and 4) for "bone" and "soft tissue" visualization tasks. Hand CBCT images were rated "excellent" or "adequate" (median scores 5 and 3) for "bone" and "soft tissue" visualization tasks. Preference tests rated CBCT equivalent or superior to MDCT for bone visualization and favoured the MDCT for soft tissue visualization tasks. Intraobserver agreement for CBCT satisfaction tests was fair to almost perfect (κ ~ 0.26-0.92), and interobserver agreement was fair to moderate (κ ~ 0.27-0.54). CBCT provided excellent image quality for bone visualization and adequate image quality for soft tissue visualization tasks. • CBCT provided adequate image quality for diagnostic tasks in extremity imaging. • CBCT images were "excellent" for "bone" and "good/adequate" for "soft tissue" visualization tasks. • CBCT image quality was equivalent/superior to MDCT for bone visualization tasks.

Evaluation of implants coated with recombinant human bone morphogenetic protein-2 and vacuum-dried using the critical-size supraalveolar peri-implant defect model in dogs.

PubMed

Decker, John F; Lee, Jaebum; Cortella, Carlo Alberto; Polimeni, Giuseppe; Rohrer, Michael D; Wozney, John M; Hall, Jan; Susin, Cristiano; Wikesjö, Ulf M E

2010-12-01

Endosseous implants coated with recombinant human bone morphogenetic protein-2 (rhBMP-2) in a laboratory bench setting and air-dried induce relevant bone formation but also resident bone remodeling. Thus, the objective of this study is to evaluate the effect of implants fully or partially coated with rhBMP-2 and vacuum-dried using an industrial process on local bone formation and resident bone remodeling. Twelve male adult Hound Labrador mongrel dogs were used. Critical-size, supraalveolar, peri-implant defects received titanium porous oxide surface implants coated in their most coronal aspect with rhBMP-2 (coronal-load, six animals), or by immersion of the entire implant in a rhBMP-2 solution (soak-load, six animals) for a total of 30 μg rhBMP-2 per implant. All implants were vacuum-dried. The animals were sacrificed at 8 weeks for histometric evaluation. Clinical healing was unremarkable. Bone formation was not significantly affected by the rhBMP-2 application protocol. New bone height and area averaged (± SE) 3.2 ± 0.5 versus 3.6 ± 0.3 mm, and 2.3 ± 0.5 versus 2.6 ± 0.8 mm(2) for coronal-load and soak-load implants, respectively (P >0.05). The corresponding bone density and bone-implant contact registrations averaged 46.7% ± 5.8% versus 31.6% ± 4.4%, and 28% ± 5.6% versus 36.9% ± 3.4% (P >0.05). In contrast, resident bone remodeling was significantly influenced by the rhBMP-2 application protocol. Peri-implant bone density averaged 72.2% ± 2.1% for coronal-load versus 60.6% ± 4.7% for soak-load implants (P <0.05); the corresponding bone-implant contact averaged 70.7% ± 6.1% versus 47.2% ± 6.0% (P <0.05). Local application of rhBMP-2 and vacuum-drying using industrial process seems to be a viable technology to manufacture implants that support local bone formation and osseointegration. Coronal-load implants obviate resident bone remodeling without compromising local bone formation.

The Effect of Rosiglitazone on Bone Quality in a Rat Model of Insulin Resistance and Osteoporosis

NASA Astrophysics Data System (ADS)

Sardone, Laura Donata

Rosiglitazone (RSG) is an insulin-sensitizing drug used to treat Type 2 Diabetes Mellitus (T2DM). Clinical trials show that women taking RSG experience more limb fractures than patients taking other T2DM drugs. The purpose of this study is to understand how RSG (3mg/kg/day and 10mg/kg/day) and the bisphosphonate alendronate (0.7mg/kg/week) alter bone quality in the male, female and female ovariectomized (OVX) Zucker fatty rat model over a 12 week period. Bone quality was evaluated by mechanical testing of cortical and trabecular bone. Microarchitecture, bone mineral density (BMD), cortical bone porosity, bone formation/resorption and mineralization were also measured. Female OVX RSG10mg/kg rats had significantly lower vertebral BMD and compromised trabecular architecture versus OVX controls. Increased cortical porosity and decreased mechanical properties occurred in these rats. ALN treatment prevented these negative effects in the OVX RSG model. Evidence of reduced bone formation and excess bone resorption was detected in female RSG-treated rats.

THE MEASUREMENT OF BONE QUALITY USING GRAY LEVEL CO-OCCURRENCE MATRIX TEXTURAL FEATURES.

PubMed

Shirvaikar, Mukul; Huang, Ning; Dong, Xuanliang Neil

2016-10-01

In this paper, statistical methods for the estimation of bone quality to predict the risk of fracture are reported. Bone mineral density and bone architecture properties are the main contributors of bone quality. Dual-energy X-ray Absorptiometry (DXA) is the traditional clinical measurement technique for bone mineral density, but does not include architectural information to enhance the prediction of bone fragility. Other modalities are not practical due to cost and access considerations. This study investigates statistical parameters based on the Gray Level Co-occurrence Matrix (GLCM) extracted from two-dimensional projection images and explores links with architectural properties and bone mechanics. Data analysis was conducted on Micro-CT images of 13 trabecular bones (with an in-plane spatial resolution of about 50μm). Ground truth data for bone volume fraction (BV/TV), bone strength and modulus were available based on complex 3D analysis and mechanical tests. Correlation between the statistical parameters and biomechanical test results was studied using regression analysis. The results showed Cluster-Shade was strongly correlated with the microarchitecture of the trabecular bone and related to mechanical properties. Once the principle thesis of utilizing second-order statistics is established, it can be extended to other modalities, providing cost and convenience advantages for patients and doctors.

THE MEASUREMENT OF BONE QUALITY USING GRAY LEVEL CO-OCCURRENCE MATRIX TEXTURAL FEATURES

PubMed Central

Shirvaikar, Mukul; Huang, Ning; Dong, Xuanliang Neil

2016-01-01

In this paper, statistical methods for the estimation of bone quality to predict the risk of fracture are reported. Bone mineral density and bone architecture properties are the main contributors of bone quality. Dual-energy X-ray Absorptiometry (DXA) is the traditional clinical measurement technique for bone mineral density, but does not include architectural information to enhance the prediction of bone fragility. Other modalities are not practical due to cost and access considerations. This study investigates statistical parameters based on the Gray Level Co-occurrence Matrix (GLCM) extracted from two-dimensional projection images and explores links with architectural properties and bone mechanics. Data analysis was conducted on Micro-CT images of 13 trabecular bones (with an in-plane spatial resolution of about 50μm). Ground truth data for bone volume fraction (BV/TV), bone strength and modulus were available based on complex 3D analysis and mechanical tests. Correlation between the statistical parameters and biomechanical test results was studied using regression analysis. The results showed Cluster-Shade was strongly correlated with the microarchitecture of the trabecular bone and related to mechanical properties. Once the principle thesis of utilizing second-order statistics is established, it can be extended to other modalities, providing cost and convenience advantages for patients and doctors. PMID:28042512

SU-E-T-13: A Comparative Dosimetric Study On Radio-Dynamic Therapy for Pelvic Cancer Treatment: Strategies for Bone Marrow Dose and Volume Reduction

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

Li, C; Renmin Hospital of Wuhan University, Wuhan, Hubei Province; Wang, B

Purpose: Radio-dynamic therapy (RDT) is a potentially effective modality for local and systemic cancer treatment. Using RDT, the administration of a radio-sensitizer enhances the biological effect of high-energy photons. Although the sensitizer uptake ratio of tumor to normal tissue is normally high, one cannot simply neglect its effect on critical structures. In this study, we aim to explore planning strategies to improve bone marrow sparing without compromising the plan quality for RDT treatment of pelvic cancers. Methods: Ten cervical and ten prostate cancer patients who previously received radiotherapy at our institution were selected for this study. For each patient, ninemore » plans were created using the Varian Eclipse treatmentplanning-system (TPS) with 3D-CRT, IMRT, and VMAT delivery techniques containing various gantry angle combinations and optimization parameters (dose constraints to the bone marrow). To evaluate the plans for bone marrow sparing, the dose-volume parameters V5, V10, V15, V20, V30, and V40 for bone marrow were examined. Effective doseenhancement factors for the sensitizer were used to weigh the dose-volume histograms for various tissues from individual fractions. Results: The planning strategies had different impacts on bone marrow sparing for the cervical and prostate cases. For the cervical cases, provided the bone marrow constraints were properly set during optimization, the dose to bone marrow sparing was found to be comparable between different IMRT and VMAT plans regardless of the gantry angle selection. For the prostate cases, however, careful selection of gantry angles could dramatically improve the bone marrow sparing, although the dose distribution in bone marrow was clinically acceptable for all prostate plans that we created. Conclusion: For intensity-modulated RDT planning for cervical cancer, planners should set bone marrow constraints properly to avoid any adverse damage, while for prostate cancer one can carefully select gantry angles to improve bone marrow sparing when necessary.« less

Anabolic agents and bone quality.

PubMed

Sibai, Tarek; Morgan, Elise F; Einhorn, Thomas A

2011-08-01

The definition of bone quality is evolving particularly from the perspective of anabolic agents that can enhance not only bone mineral density but also bone microarchitecture, composition, morphology, amount of microdamage, and remodeling dynamics. This review summarizes the molecular pathways and physiologic effects of current and potential anabolic drugs. From a MEDLINE search (1996-2010), articles were identified by the search terms "bone quality" (1851 articles), "anabolic agent" (5044 articles), "PTH or parathyroid hormone" (32,229 articles), "strontium" or "strontium ranelate" (283 articles), "prostaglandin" (77,539 articles), and "statin" or "statins" (14,233 articles). The search strategy included combining each with the phrase "bone quality." Another more limited search aimed at finding more novel potential agents. Parathyroid hormone is the only US Food and Drug Administration-approved bone anabolic agent in the United States and has been the most extensively studied in in vitro animal and human trials. Strontium ranelate is approved in Europe but has not undergone Food and Drug Administration trials in the United States. All the studies on prostaglandin agonists have used in vivo animal models and there are no human trials examining prostaglandin agonist effects. The advantages of statins include the long-established advantages and safety profile, but they are limited by their bioavailability in bone. Other potential pathways include proline-rich tyrosine kinase 2 (PYK2) and sclerostin (SOST) inhibition, among others. The ongoing research to enhance the anabolic potential of current agents, identify new agents, and develop better delivery systems will greatly enhance the management of bone quality-related injuries and diseases in the future.

Effects of Mixed Bone and Brisket Meat on Physico-Chemical Characteristics of Shank Bone and Rib Extracts from Hanwoo

PubMed Central

Jung, Myung-Ok; Choi, Jung-Seok

2016-01-01

This study was conducted to investigate the effects of mixed bone and brisket meat on the quality characteristics and nutritional components of shank bone extract and rib extract from Hanwoo. The pH values were influenced by the raw bones, mixed bone, brisket meat and their interactions (p<0.05). The salinity, sugar content, turbidity, and essential amino acid values increased significantly with addition of mixed bone and brisket meat. All attributes of sensory evaluation score were the highest in T6 (Rib 500 g + Mixed bone 500 g + Brisket meat 400 g) (p<0.05). The mixed bone significantly increased the saturated fatty acids of shank bone extract (p<0.001). Thus, the addition of mixed bone and brisket meat had a positive effect on the quality and nutritional components in shank and rib extracts of Hanwoo cattle. PMID:27499665

Morphometric analysis - Cone beam computed tomography to predict bone quality and quantity.

PubMed

Hohlweg-Majert, B; Metzger, M C; Kummer, T; Schulze, D

2011-07-01

Modified quantitative computed tomography is a method used to predict bone quality and quantify the bone mass of the jaw. The aim of this study was to determine whether bone quantity or quality was detected by cone beam computed tomography (CBCT) combined with image analysis. MATERIALS AND PROCEDURES: Different measurements recorded on two phantoms (Siemens phantom, Comac phantom) were evaluated on images taken with the Somatom VolumeZoom (Siemens Medical Solutions, Erlangen, Germany) and the NewTom 9000 (NIM s.r.l., Verona, Italy) in order to calculate a calibration curve. The spatial relationships of six sample cylinders and the repositioning from four pig skull halves relative to adjacent defined anatomical structures were assessed by means of three-dimensional visualization software. The calibration curves for computer tomography (CT) and cone beam computer tomography (CBCT) using the Siemens phantom showed linear correlation in both modalities between the Hounsfield Units (HU) and bone morphology. A correction factor for CBCT was calculated. Exact information about the micromorphology of the bone cylinders was only available using of micro computer tomography. Cone-beam computer tomography is a suitable choice for analysing bone mass, but, it does not give any information about bone quality. 2010 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Alendronate promotes bone formation by inhibiting protein prenylation in osteoblasts in rat tooth replantation model.

PubMed

Komatsu, Koichiro; Shimada, Akemi; Shibata, Tatsuya; Wada, Satoshi; Ideno, Hisashi; Nakashima, Kazuhisa; Amizuka, Norio; Noda, Masaki; Nifuji, Akira

2013-11-01

Bisphosphonates (BPs) are a major class of antiresorptive drug, and their molecular mechanisms of antiresorptive action have been extensively studied. Recent studies have suggested that BPs target bone-forming cells as well as bone-resorbing cells. We previously demonstrated that local application of a nitrogen-containing BP (N-BP), alendronate (ALN), for a short period of time increased bone tissue in a rat tooth replantation model. Here, we investigated cellular mechanisms of bone formation by ALN. Bone histomorphometry confirmed that bone formation was increased by local application of ALN. ALN increased proliferation of bone-forming cells residing on the bone surface, whereas it suppressed the number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts in vivo. Moreover, ALN treatment induced more alkaline phosphatase-positive and osteocalcin-positive cells on the bone surface than PBS treatment. In vitro studies revealed that pulse treatment with ALN promoted osteocalcin expression. To track the target cells of N-BPs, we applied fluorescence-labeled ALN (F-ALN) in vivo and in vitro. F-ALN was taken into bone-forming cells both in vivo and in vitro. This intracellular uptake was inhibited by endocytosis inhibitors. Furthermore, the endocytosis inhibitor dansylcadaverine (DC) suppressed ALN-stimulated osteoblastic differentiation in vitro and it suppressed the increase in alkaline phosphatase-positive bone-forming cells and subsequent bone formation in vivo. DC also blocked the inhibition of Rap1A prenylation by ALN in the osteoblastic cells. These data suggest that local application of ALN promotes bone formation by stimulating proliferation and differentiation of bone-forming cells as well as inhibiting osteoclast function. These effects may occur through endocytic incorporation of ALN and subsequent inhibition of protein prenylation.

A new stable GIP-Oxyntomodulin hybrid peptide improved bone strength both at the organ and tissue levels in genetically-inherited type 2 diabetes mellitus.

PubMed

Mansur, Sity Aishah; Mieczkowska, Aleksandra; Flatt, Peter R; Bouvard, Beatrice; Chappard, Daniel; Irwin, Nigel; Mabilleau, Guillaume

2016-06-01

Obesity and type 2 diabetes mellitus (T2DM) progress worldwide with detrimental effects on several physiological systems including bone tissue mainly by affecting bone quality. Several gut hormones analogues have been proven potent in ameliorating bone quality. In the present study, we used the leptin receptor-deficient db/db mice as a model of obesity and severe T2DM to assess the extent of bone quality alterations at the organ and tissue levels. We also examined the beneficial effects of gut hormone therapy in this model by using a new triple agonist ([d-Ala(2)]GIP-Oxm) active at the GIP, GLP-1 and glucagon receptors. As expected, db/db mice presented with dramatic alterations of bone strength at the organ level associated with deterioration of trabecular and cortical microarchitectures and an augmentation in osteoclast numbers. At the tissue level, these animals presented also with alterations of bone strength (reduced hardness, indentation modulus and dissipated energy) with modifications of tissue mineral distribution, collagen glycation and collagen maturity. The use of [d-Ala(2)]GIP-Oxm considerably improved bone strength at the organ level with modest effects on trabecular microarchitecture. At the tissue level, [d-Ala(2)]GIP-Oxm ameliorated bone strength reductions with positive effects on collagen glycation and collagen maturity. This study provides support for including gut hormone analogues as possible new therapeutic strategies for improving bone quality in bone complications associated to T2DM. Copyright © 2016 Elsevier Inc. All rights reserved.

Estimation of Local Bone Loads for the Volume of Interest.

PubMed

Kim, Jung Jin; Kim, Youkyung; Jang, In Gwun

2016-07-01

Computational bone remodeling simulations have recently received significant attention with the aid of state-of-the-art high-resolution imaging modalities. They have been performed using localized finite element (FE) models rather than full FE models due to the excessive computational costs of full FE models. However, these localized bone remodeling simulations remain to be investigated in more depth. In particular, applying simplified loading conditions (e.g., uniform and unidirectional loads) to localized FE models have a severe limitation in a reliable subject-specific assessment. In order to effectively determine the physiological local bone loads for the volume of interest (VOI), this paper proposes a novel method of estimating the local loads when the global musculoskeletal loads are given. The proposed method is verified for the three VOI in a proximal femur in terms of force equilibrium, displacement field, and strain energy density (SED) distribution. The effect of the global load deviation on the local load estimation is also investigated by perturbing a hip joint contact force (HCF) in the femoral head. Deviation in force magnitude exhibits the greatest absolute changes in a SED distribution due to its own greatest deviation, whereas angular deviation perpendicular to a HCF provides the greatest relative change. With further in vivo force measurements and high-resolution clinical imaging modalities, the proposed method will contribute to the development of reliable patient-specific localized FE models, which can provide enhanced computational efficiency for iterative computing processes such as bone remodeling simulations.

Operative management of patients with non-spinal metastatic bone disease. Does it actually improve quality of life?

PubMed

Umer, Masood; Mohib, Yasir; Umer, Hafiz

2014-12-01

To determine the survival rate and functional outcome of skeletal stabilisation in patients with metastatic bone disease. The retrospective study was conducted at Aga Khan University Hospital, Karachi, and comprised data of patients with non-spinal metastatic bone disease managed surgically from January 2002 to December 2010. All patients had been managed by experienced orthopaedic, oncology and multidisciplinary teams. Patients managed by non-oncologic orthopaedic surgeons were excluded. The prognostic influence of clinical, pathological and treatment variables on Musculoskeletal Tumour Society score, range of motion, local complications and death rate were measured. SPSS 19 was used for statistical analysis. Of the 49 patients whose records were included in the study, 21(42.9%) males and 28(57.1%) females with an overall median age of 59 years. Most common primary tumour site was breast in 15(3.8%) followed by lungs in 11(22.4%), Open reduction and internal fixation was the mpst commonly used procedure in 18(36.7%) patients. Mean duration of follow-up was 30.20±29.2 SD months (range: 10-48 months). The median patient survival was 23 months. 23% patients have superficial surgical site infection. Mean Musculoskeletal Tumour Society score was 23.73±14.3 SD. The results confirm the principle that surgery for metastatic disease is done primarily to improve quality of life and ambulation status, and to alleviate pain.

Reconstruction of a large calvarial traumatic defect using a custom-made porous hydroxyapatite implant covered by a free latissimus dorsi muscle flap in an 11-year-old patient.

PubMed

Morice, Anne; Kolb, Frédéric; Picard, Arnaud; Kadlub, Natacha; Puget, Stéphanie

2017-01-01

Reconstruction of complex skull defects requires collaboration between neurosurgeons and plastic surgeons to choose the most appropriate procedure, especially in growing children. The authors describe herein the reconstruction of an extensive traumatic bone and soft tissue defect of the cranial vault in an 11-year-old boy. The size of the defect, quality of the tissues, and patient's initial condition required a 2-stage approach. Ten months after an initial emergency procedure in which lacerated bone and soft tissue were excised, reconstruction was performed. The bone defect, situated on the left frontoparietal region, was 85 cm 2 and was filled by a custom-made porous hydroxyapatite implant. The quality of the overlying soft tissue did not allow the use of classic local and locoregional coverage techniques. A free latissimus dorsi muscle flap branched on the contralateral superficial temporal pedicle was used and left for secondary healing to take advantage of scar retraction and to minimize alopecia. Stable well-vascularized implant coverage as well as an esthetically pleasing skull shape was achieved. Results in this case suggest that concomitant reconstruction of large calvarial defects by cranioplasty with a custom-made hydroxyapatite implant covered by a free latissimus dorsi muscle flap is a safe and efficient procedure in children, provided that there is no underlying infection of the operative site.

Accounting for spatial variation of trabecular anisotropy with subject-specific finite element modeling moderately improves predictions of local subchondral bone stiffness at the proximal tibia.

PubMed

Nazemi, S Majid; Kalajahi, S Mehrdad Hosseini; Cooper, David M L; Kontulainen, Saija A; Holdsworth, David W; Masri, Bassam A; Wilson, David R; Johnston, James D

2017-07-05

Previously, a finite element (FE) model of the proximal tibia was developed and validated against experimentally measured local subchondral stiffness. This model indicated modest predictions of stiffness (R 2 =0.77, normalized root mean squared error (RMSE%)=16.6%). Trabecular bone though was modeled with isotropic material properties despite its orthotropic anisotropy. The objective of this study was to identify the anisotropic FE modeling approach which best predicted (with largest explained variance and least amount of error) local subchondral bone stiffness at the proximal tibia. Local stiffness was measured at the subchondral surface of 13 medial/lateral tibial compartments using in situ macro indentation testing. An FE model of each specimen was generated assuming uniform anisotropy with 14 different combinations of cortical- and tibial-specific density-modulus relationships taken from the literature. Two FE models of each specimen were also generated which accounted for the spatial variation of trabecular bone anisotropy directly from clinical CT images using grey-level structure tensor and Cowin's fabric-elasticity equations. Stiffness was calculated using FE and compared to measured stiffness in terms of R 2 and RMSE%. The uniform anisotropic FE model explained 53-74% of the measured stiffness variance, with RMSE% ranging from 12.4 to 245.3%. The models which accounted for spatial variation of trabecular bone anisotropy predicted 76-79% of the variance in stiffness with RMSE% being 11.2-11.5%. Of the 16 evaluated finite element models in this study, the combination of Synder and Schneider (for cortical bone) and Cowin's fabric-elasticity equations (for trabecular bone) best predicted local subchondral bone stiffness. Copyright © 2017 Elsevier Ltd. All rights reserved.

Locally Produced BDNF Promotes Sclerotic Change in Alveolar Bone after Nerve Injury

PubMed Central

Ida-Yonemochi, Hiroko; Yamada, Yurie; Yoshikawa, Hiroyuki

2017-01-01

Brain-derived neurotrophic factor (BDNF), which is released due to nerve injury, is known to promote the natural healing of injured nerves. It is often observed that damage of mandibular canal induces local sclerotic changes in alveolar bone. We reported that peripheral nerve injury promotes the local production of BDNF; therefore, it was possible to hypothesize that peripheral nerve injury affects sclerotic changes in the alveolar bone. This study aimed to evaluate the effect of BDNF on osteogenesis using in vitro osteoblast-lineage cell culture and an in vivo rat osteotomy model. MC3T3-E1 cells were cultured with BDNF and were examined for cell proliferative activity, chemotaxis and mRNA expression levels of osteoblast differentiation markers. For in vivo study, inferior alveolar nerve (IAN) injury experiments and mandibular cortical osteotomy were performed using a rat model. In the osteotomy model, exogenous BDNF was applied to bone surfaces after corticotomy of the mandible, and we morphologically analyzed the new bone formation. As a result, mRNA expression of osteoblast differentiation marker, osteocalcin, was significantly increased by BDNF, although cell proliferation and migration were not affected. In the in vivo study, osteopontin-positive new bone formation was significantly accelerated in the BDNF-grafted groups, and active bone remodeling, involving trkB-positive osteoblasts and osteocytes, continued after 28 days. In conclusion, BDNF stimulated the differentiation of MC3T3-E1 cells and it promoted new bone formation and maturation. These results suggested that local BDNF produced by peripheral nerve injury contributes to accelerating sclerotic changes in the alveolar bone. PMID:28072837

Palliative radiation therapy for bone metastases: Update of an ASTRO Evidence-Based Guideline.

PubMed

Lutz, Stephen; Balboni, Tracy; Jones, Joshua; Lo, Simon; Petit, Joshua; Rich, Shayna E; Wong, Rebecca; Hahn, Carol

The purpose is to provide an update the Bone Metastases Guideline published in 2011 based on evidence complemented by expert opinion. The update will discuss new high-quality literature for the 8 key questions from the original guideline and implications for practice. A systematic PubMed search from the last date included in the original Guideline yielded 414 relevant articles. Ultimately, 20 randomized controlled trials, 32 prospective nonrandomized studies, and 4 meta-analyses/pooled analyses were selected and abstracted into evidence tables. The authors synthesized the evidence and reached consensus on the included recommendations. Available literature continues to support pain relief equivalency between single and multiple fraction regimens for bone metastases. High-quality data confirm single fraction radiation therapy may be delivered to spine lesions with acceptable late toxicity. One prospective, randomized trial confirms both peripheral and spine-based painful metastases can be successfully and safely palliated with retreatment for recurrence pain with adherence to published dosing constraints. Advanced radiation therapy techniques such as stereotactic body radiation therapy lack high-quality data, leading the panel to favor its use on a clinical trial or when results will be collected in a registry. The panel's conclusion remains that surgery, radionuclides, bisphosphonates, and kyphoplasty/vertebroplasty do not obviate the need for external beam radiation therapy. Updated data analysis confirms that radiation therapy provides excellent palliation for painful bone metastases and that retreatment is safe and effective. Although adherence to evidence-based medicine is critical, thorough expert radiation oncology physician judgment and discretion regarding number of fractions and advanced techniques are also essential to optimize outcomes when considering the patient's overall health, life expectancy, comorbidities, tumor biology, anatomy, previous treatment including prior radiation at or near current site of treatment, tumor and normal tissue response history to local and systemic therapies, and other factors related to the patient, tumor characteristics, or treatment. Copyright © 2016 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

[Osteoporosis treatment in patients with hyperthyroidism].

PubMed

Saito, Jun; Nishikawa, Tetsuo

2009-05-01

Childhood thyroid hormone (T3) is essential for the normal development of endochondral and intramembranous bone and plays an important role in the linear growth and maintenance of bone mass. In adult, T3 stimulates osteoclastic bone resorption mediated primarily by TR alpha and local conversion by deiodinase D2 may play a role in local activation. TSH seems to be an inhibitor of bone resorption and formation. In thyrotoxicosis patients with Graves' disease, there is increased bone remodelling, characterized by an imbalance between bone resorption and formation, which results in a decrease of bone mineral density (BMD) and an increased risk for osteoporotic fracture. Antithyroid treatment is able to reduce dramatically the bone resorption and to normalize BMD reduction. But previous hyperthyroidism is independently associated with an increased risk for fracture. Although further studies relating to the mechanism for possible impaired bone strength in these patients will be needed, bisphosphonates may be beneficial treatment for prevention of bone fractures in patients with severe risk for fractures, such as post-menopausal women.

Combined Use of Mesenchymal Stromal Cell Sheet Transplantation and Local Injection of SDF-1 for Bone Repair in a Rat Nonunion Model.

PubMed

Chen, Guangnan; Fang, Tingting; Qi, Yiying; Yin, Xiaofan; Di, Tuoyu; Feng, Gang; Lei, Zhong; Zhang, Yuxiang; Huang, Zhongming

2016-10-01

Bone nonunion treatments pose a challenge in orthopedics. This study investigated the joint effects of using mesenchymal stem cell (MSC) sheets with local injection of stromal cell-derived factor-1 (SDF-1) on bone formation. In vitro, we found that migration of MSCs was mediated by SDF-1 in a dose-dependent manner. Moreover, stimulation with SDF-1 had no direct effect on the proliferation or osteogenic differentiation of MSCs. Furthermore, the results indicated elevated expression levels of bone morphogenetic protein 2, alkaline phosphatase, osteocalcin, and vascular endothelial growth factor in MSC sheets compared with MSCs cultured in medium. New bone formation in fractures was evaluated by X-ray, micro-computed tomography (micro-CT), hematoxylin and eosin (H&E) staining, Safranin-O staining, and immunohistochemistry in vivo. In the rat bone fracture model, the MSC sheets transplanted into the injured site along with injection of SDF-1 showed significantly more new bone formation within the gap. Moreover, at 8 weeks, complete bone union was obtained in this group. In contrast, the control group showed nonunion of the bone. Our study suggests a new strategy involving the use of MSC sheets with a local injection of SDF-1 for hard tissue reconstruction, such as the healing of nonunions and bone defects.

The effect of intracortical bone pin application on kinetics and tibiocalcaneal kinematics of walking gait.

PubMed

Maiwald, Christian; Arndt, Anton; Nester, Chris; Jones, Richard; Lundberg, Arne; Wolf, Peter

2017-02-01

Bone anchored markers using intracortical bone pins are one of the few available methods for analyzing skeletal motion during human gait in-vivo without errors induced by soft tissue artifacts. However, bone anchored markers require local anesthesia and may alter the motor control and motor output during gait. The purpose of this study was to examine the effect of local anesthesia and the use of bone anchored markers on typical gait analysis variables. Five subjects were analyzed in two different gait analysis sessions. In the first session, a protocol with skin markers was used. In the second session, bone anchored markers were added after local anesthesia was applied. For both sessions, three dimensional infrared kinematics of the calcaneus and tibia segments, ground reaction forces, and plantar pressure data were collected. 95% confidence intervals and boxplots were used to compare protocols and assess the data distribution and data variability for each subject. Although considerable variation was found between subjects, within-subject comparison of the two protocols revealed non-systematic effects on the target variables. Two of the five subjects walked at reduced gait speed during the bone pin session, which explained the between-session differences found in kinetic and kinematic variables. The remaining three subjects did not systematically alter their gait pattern between the two sessions. Results support the hypothesis that local anesthesia and the presence of bone pins still allow a valid gait pattern to be analyzed. Copyright © 2016 Elsevier B.V. All rights reserved.

[Oligometastatic bone disease. Can limited metastatic bone disease be cured? Is there room for local ablative treatments?].

PubMed

Thariat, J; Leysalle, A; Vignot, S; Marcy, P-Y; Lacout, A; Bera, G; Lagrange, J-L; Clezardin, P; Chiras, J

2012-09-01

Solitary metastases have been reported in up to 30% of cases in imaging series. Local treatment aims at consolidating the injured bone and to prevent neurologic complications. Since the prognosis of bony metastatic disease is about 30 months and includes some long survivors, the multisdisciplinary committee in charge of the patient should ask the question and decide on the type of radical/ablative intervention in case of oligometastases. A literature search was performed using MESH terms (bone, metastases, radiotherapy, radiology, cement, radiofrequency ablation, chemoembolisation). Local ablative treatments can yield symptomatic relief and local control rates of about 90%. Stereotactic hypofractionated irradiation and cementoplasty are increasingly used. In conclusion, local ablative treatment of bony oligometastases is an efficient treatment. Its potential impact on survival remains to be demonstrated prospectively in clinical trials. Copyright © 2012 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

A density distribution algorithm for bone incorporating local orthotropy, modal analysis and theories of cellular solids.

PubMed

Impelluso, Thomas J

2003-06-01

An algorithm for bone remodeling is presented which allows for both a redistribution of density and a continuous change of principal material directions for the orthotropic material properties of bone. It employs a modal analysis to add density for growth and a local effective strain based analysis to redistribute density. General re-distribution functions are presented. The model utilizes theories of cellular solids to relate density and strength. The code predicts the same general density distributions and local orthotropy as observed in reality.

Using laser-induced breakdown spectroscopy to assess preservation quality of archaeological bones by measurement of calcium-to-fluorine ratios.

PubMed

Rusak, David Alexander; Marsico, Ryan Matthew; Taroli, Brett Louis

2011-10-01

We determined calcium-to-fluorine (Ca/F) signal ratios at the surface and in the depth dimension in approximately 6000-year-old sheep and cattle bones using Ca I 671.8 and F I 685.6 emission lines. Because the bones had been previously analyzed for collagen preservation quality by measurement of C/N ratios at the Oxford Radiocarbon Accelerator Unit, we were able to examine the correlation between our ratios and quality of preservation. In the bones analyzed in this experiment, the Ca I 671.8/F I 685.6 ratio was generally lower and decreased with successive laser pulses into poorly preserved bones while the ratio was generally higher and increased with successive laser pulses into well-preserved bones. After 210 successive pulses, a discriminator value for this ratio (5.70) could be used to distinguish well-preserved and poorly preserved bones regardless of species. © 2011 Society for Applied Spectroscopy

Diagnostic imaging to detect and evaluate response to therapy in bone metastases from prostate cancer: current modalities and new horizons.

PubMed

Evangelista, Laura; Bertoldo, Francesco; Boccardo, Francesco; Conti, Giario; Menchi, Ilario; Mungai, Francesco; Ricardi, Umberto; Bombardieri, Emilio

2016-07-01

Different therapeutic options for the management of prostate cancer (PC) have been developed, and some are successful in providing crucial improvement in both survival and quality of life, especially in patients with metastatic castration-resistant PC. In this scenario, diverse combinations of radiopharmaceuticals (for targeting bone, cancer cells and receptors) and nuclear medicine modalities (e.g. bone scan, SPECT, SPECT/CT, PET and PET/CT) are now available for imaging bone metastases. Some radiopharmaceuticals are approved, currently available and used in the routine clinical setting, while others are not registered and are still under evaluation, and should therefore be considered experimental. On the other hand, radiologists have other tools, in addition to CT, that can better visualize bone localization and medullary involvement, such as multimodal MRI. In this review, the authors provide an overview of current management of advanced PC and discuss the choice of diagnostic modality for the detection of metastatic skeletal lesions in different phases of the disease. In addition to detection of bone metastases, the evaluation of response to therapy is another critical issue, since it remains one of the most important open questions that a multidisciplinary team faces when optimizing the management of PC. The authors emphasize the role of nuclear modalities that can presently be used in clinical practice, and also look at future perspectives based on relevant clinical data with novel radiopharmaceuticals.

Transplantation of bone: prerequisites for immunologic and inflammatory conditions - an overview.

PubMed

Knobe, M; Gradl, G

2013-01-01

In this review we have summarized the conditions under which bone grafts have a suitable environment for ingrowth into surrounding bone. Among the topics discussed are the immunological properties of bone and differences between bone grafting and organ transplants. Local osteogenic immune changes following fracture and bone graft transplants are outlined. Moreover, techniques of bone graft harvesting are summarized.

Evidence for the adverse effect of starvation on bone quality: a review of the literature.

PubMed

Kueper, Janina; Beyth, Shaul; Liebergall, Meir; Kaplan, Leon; Schroeder, Josh E

2015-01-01

Malnutrition and starvation's possible adverse impacts on bone health and bone quality first came into the spotlight after the horrors of the Holocaust and the ghettos of World War II. Famine and food restrictions led to a mean caloric intake of 200-800 calories a day in the ghettos and concentration camps, resulting in catabolysis and starvation of the inhabitants and prisoners. Severely increased risks of fracture, poor bone mineral density, and decreased cortical strength were noted in several case series and descriptive reports addressing the medical issues of these individuals. A severe effect of severely diminished food intake and frequently concomitant calcium- and Vitamin D deficiencies was subsequently proven in both animal models and the most common cause of starvation in developed countries is anorexia nervosa. This review attempts to summarize the literature available on the impact of the metabolic response to Starvation on overall bone health and bone quality.

Effects of simulated weightlessness on bone mineral metabolism

NASA Technical Reports Server (NTRS)

Globus, R. K.; Bikle, D. D.; Morey-Holton, E.

1984-01-01

It is pointed out that prolonged space flight, bedrest, and immobilization are three factors which can produce a negative calcium balance, osteopenia, and an inhibition of bone formation. It is not known whether the effects of gravity on bone mineral metabolism are mediated by systemic endocrine factors which affect all bones simultaneously, or by local factors which affect each bone individually. The present investigation has the objective to test the relative importance of local vs. systemic factors in regulating the bone mineral response to conditions simulating weightlessness. Experiments were conducted with male Sprague-Dawley rats. The test conditions made it possible to compare the data from weighted and unweighted bones in the same animal. The obtained findings indicate that a decrease in bone mass relative to control value occurs rapidly under conditions which simulate certain aspects of weightlessness. However, this decrease reaches a plateau after 10 days.

Bone Density and Dental External Apical Root Resorption

PubMed Central

Iglesias-Linares, Alejandro; Morford, Lorri Ann

2016-01-01

When orthodontic patients desire shorter treatment times with aesthetic results and long-term stability, it is important for the orthodontist to understand the potential limitations and problems that may arise during standard and/or technology-assisted accelerated treatment. Bone density plays an important role in facilitating orthodontic tooth movement (OTM), such that reductions in bone density can significantly increase movement velocity. Lifestyle, genetic background, environmental factors and disease status all can influence a patients’ overall health and bone density. In some individuals, these factors may create specific conditions that influence systemic-wide bone metabolism. Both genetic variation and the onset of a bone-related disease can influence systemic bone density and local bone density, such as is observed in the mandible and maxilla. These types of localized density changes can affect the rate of OTM and may also influence the risk of unwanted outcomes, i.e., the occurrence of dental external apical root resorption (EARR). PMID:27766484

Automated Quantification of Hematopoietic Cell – Stromal Cell Interactions in Histological Images of Undecalcified Bone

PubMed Central

Zehentmeier, Sandra; Cseresnyes, Zoltan; Escribano Navarro, Juan; Niesner, Raluca A.; Hauser, Anja E.

2015-01-01

Confocal microscopy is the method of choice for the analysis of localization of multiple cell types within complex tissues such as the bone marrow. However, the analysis and quantification of cellular localization is difficult, as in many cases it relies on manual counting, thus bearing the risk of introducing a rater-dependent bias and reducing interrater reliability. Moreover, it is often difficult to judge whether the co-localization between two cells results from random positioning, especially when cell types differ strongly in the frequency of their occurrence. Here, a method for unbiased quantification of cellular co-localization in the bone marrow is introduced. The protocol describes the sample preparation used to obtain histological sections of whole murine long bones including the bone marrow, as well as the staining protocol and the acquisition of high-resolution images. An analysis workflow spanning from the recognition of hematopoietic and non-hematopoietic cell types in 2-dimensional (2D) bone marrow images to the quantification of the direct contacts between those cells is presented. This also includes a neighborhood analysis, to obtain information about the cellular microenvironment surrounding a certain cell type. In order to evaluate whether co-localization of two cell types is the mere result of random cell positioning or reflects preferential associations between the cells, a simulation tool which is suitable for testing this hypothesis in the case of hematopoietic as well as stromal cells, is used. This approach is not limited to the bone marrow, and can be extended to other tissues to permit reproducible, quantitative analysis of histological data. PMID:25938636

Controlled-release of tetracycline and lovastatin by poly(d,l-lactide-co-glycolide acid)-chitosan nanoparticles enhances periodontal regeneration in dogs

PubMed Central

Lee, Bor-Shiunn; Lee, Chien-Chen; Wang, Yi-Ping; Chen, Hsiao-Jan; Lai, Chern-Hsiung; Hsieh, Wan-Ling; Chen, Yi-Wen

2016-01-01

Chronic periodontitis is characterized by inflammation of periodontal tissues, leading to bone resorption and tooth loss. The goal of treatment is to regenerate periodontal tissues including bone and cementum lost as a consequence of disease. The local delivery of tetracycline was proven to be effective in controlling localized periodontal infection without apparent side effects. Previous studies suggested that lovastatin has a significant role in new bone formation; however, the local delivery of lovastatin might enhance its therapeutic effects. A number of local delivery devices have been developed recently, including poly(d,l-lactide-co-glycolide acid) (PLGA) nanoparticles. The aim of this study was to develop a local delivery device, PLGA-lovastatin-chitosan-tetracycline nanoparticles, which allows the sequential release of tetracycline and lovastatin to effectively control local infection and promote bone regeneration in periodontitis. The size and microstructure of nanoparticles were examined by transmission electron microscopy, Nanoparticle Size Analyzer, and Fourier transform infrared spectroscopy. The release of tetracycline and lovastatin was quantified using a UV-Vis spectrophotometer. Furthermore, the cytotoxic effect and alkaline phosphatase activity of the nanoparticles in osteoblast cell cultures as well as antibacterial activity against periodontal pathogens were investigated. Finally, the bone regeneration potential of PLGA nanoparticles in three-walled defects in beagle dogs was investigated. The results indicated that PLGA-lovastatin-chitosan-tetracycline nanoparticles showed good biocompatibility, antibacterial activity, and increased alkaline phosphatase activity. The volumetric analysis from micro-CT revealed significantly increased new bone formation in defects filled with nanoparticles in dogs. This novel local delivery device might be useful as an adjunctive treatment in periodontal regenerative therapy. PMID:26848264

Controlled-release of tetracycline and lovastatin by poly(D,L-lactide-co-glycolide acid)-chitosan nanoparticles enhances periodontal regeneration in dogs.

PubMed

Lee, Bor-Shiunn; Lee, Chien-Chen; Wang, Yi-Ping; Chen, Hsiao-Jan; Lai, Chern-Hsiung; Hsieh, Wan-Ling; Chen, Yi-Wen

2016-01-01

Chronic periodontitis is characterized by inflammation of periodontal tissues, leading to bone resorption and tooth loss. The goal of treatment is to regenerate periodontal tissues including bone and cementum lost as a consequence of disease. The local delivery of tetracycline was proven to be effective in controlling localized periodontal infection without apparent side effects. Previous studies suggested that lovastatin has a significant role in new bone formation; however, the local delivery of lovastatin might enhance its therapeutic effects. A number of local delivery devices have been developed recently, including poly(D,L-lactide-co-glycolide acid) (PLGA) nanoparticles. The aim of this study was to develop a local delivery device, PLGA-lovastatin-chitosan-tetracycline nanoparticles, which allows the sequential release of tetracycline and lovastatin to effectively control local infection and promote bone regeneration in periodontitis. The size and microstructure of nanoparticles were examined by transmission electron microscopy, Nanoparticle Size Analyzer, and Fourier transform infrared spectroscopy. The release of tetracycline and lovastatin was quantified using a UV-Vis spectrophotometer. Furthermore, the cytotoxic effect and alkaline phosphatase activity of the nanoparticles in osteoblast cell cultures as well as antibacterial activity against periodontal pathogens were investigated. Finally, the bone regeneration potential of PLGA nanoparticles in three-walled defects in beagle dogs was investigated. The results indicated that PLGA-lovastatin-chitosan-tetracycline nanoparticles showed good biocompatibility, antibacterial activity, and increased alkaline phosphatase activity. The volumetric analysis from micro-CT revealed significantly increased new bone formation in defects filled with nanoparticles in dogs. This novel local delivery device might be useful as an adjunctive treatment in periodontal regenerative therapy.

Immunolocalization of matrix metalloproteinase-13 on bone surface under osteoclasts in rat tibia.

PubMed

Nakamura, Hiroaki; Sato, Ginga; Hirata, Azumi; Yamamoto, Toshio

2004-01-01

Matrix metalloproteinase (MMP)-13 (an interstitial collagenase also called collagenase 3) is involved in degradation of extracellular matrix in various tissues. Using immunohistochemistry and Western blotting, we investigated localization of MMP-13 in rat tibia, to clarify the role of MMP-13 in bone resorption. MMP-13 reactivity was mainly seen on bone surfaces under osteoclasts, and in some osteocytes and their lacunae near osteoclasts. However, immunoreactivity was not seen in chondrocytes or osteoclasts. MMP-13 was also localized on cement lines in the epiphysis. In the growth plate erosion zone, perivascular cells showed MMP-13 reactivity. Immunoelectron microscopy revealed that MMP-13 was localized on the bone surfaces, under the ruffled borders and some clear zones of osteoclasts. Gold-labeled MMP-13 was closely associated with collagen fibrils. Gold labeling was also detected in Golgi apparatus of osteocytes adjacent to osteoclasts and bone lining cells. Western blotting showed that MMP-13 was mainly associated with mineralized bone matrix. These findings suggest that MMP-13 synthesized and secreted by osteoblast-lineage cells is localized under the ruffled borders of osteoclasts. MMP-13 may play an important role in degradation of type I collagen in bone matrix, acting in concert with cathepsin K and MMP-9 produced by osteoclasts. MMP-13 in perivascular cells may be involved in removal of cartilage matrix proteins such as type II collagen and aggrecan.

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

Bone quality assessment for total hip arthroplasty with intraoperative trabecular torque measurements.

PubMed

Klotz, Matthias C M; Beckmann, Nicholas A; Bitsch, Rudi G; Seebach, Elisabeth; Reiner, Tobias; Jäger, Sebastian

2014-11-13

In cases of poor bone quality, intraoperative torque measurement might be an alternative to preoperative dual-energy X-ray absorptiometry (DXA) to assess bone quality in total hip arthroplasty (THA). Trabecular peak torque measurement was applied in 14 paired fresh frozen human femurs. Here, a 6.5 × 23 mm wingblade was inserted into the proximal femur without harming the lateral cortical bone. Further tests of the proximal femur also evaluated bone strength (DXA, micro-computed tomography (μCT), monoaxial compression test), and the results were compared to the trabecular torque measurement. Student's t-test was used to compare the values of the groups. Pearson product-moment was applied to correlate the values of the peak torque measurement with the bone strength measured by DXA, μCT, and monoaxial compression test. In the femoral head, the mean trabecular peak torque was 4.38 ± 1.86 Nm. These values showed a strong correlation with the values of the DXA, the μCT, and the biomechanical load test (Pearson's product-moment: DXA: 0.86, μCT-BMD: 0.80, load test: 0.85). Furthermore, the torque measurement showed a more pronounced correlation with the biomechanical load test compared to the DXA. The use of this method provides highly diagnostic information about bone quality. Since the approach was adjusted for THA, no harm of the lateral bone stock will result from this measurement during surgery. The results of this initial study employing small sample sizes indicate that this new method is as sensitive as DXA in predicting bone quality and may function as an intraoperative alternative to DXA in THA. Nevertheless, before this method will turn into clinical use, more research and clinical trials are necessary.

Quantitative ultrasound measurements of bone quality in female adolescents with idiopathic scoliosis compared to normal controls.

PubMed

Du, Qing; Zhou, Xuan; Li, Jian A; He, Xiao H; Liang, Ju P; Zhao, Li; Yang, Xiao Y; Chen, Nan; Zhang, Shu X; Chen, Pei J

2015-01-01

The aims of this study were to compare the speed-of-sound (SOS) between adolescent idiopathic scoliosis (AIS) patients and controls using quantitative ultrasound examination and to further analyze the relationship between the SOS and curve type, curve magnitude, maturation status and Risser's sign in AIS patients compared to controls. Seventy-eight female AIS patients and 58 healthy female controls 10 to 16 years of age were recruited to participate. Quantitative ultrasound measurements were performed at the non-dominant distal end of the radius. The standard method for estimating the SOS and z-score was used. Comparisons were made between the SOS values and z-score in AIS patients and age-matched Asian adolescents. The SOS values of the patients were significantly lower than the controls (P < .01). The percentage of cases with low bone quality was 25% in the entire AIS sample. The prevalence of low bone quality in AIS patients was 20.5%. However, there were no correlations between the SOS and types of scoliosis (P > .05). The SOS values among different severity groups were significant, particularly between the 10° to 19° and 20° to 39° groups as well as between 10° to 19° and ≥40° groups. However, there was no significant correlation between the SOS and Cobb angles. Significant correlations were also found between the pre- and post-menarchy status in patients. There was a significant difference in the SOS values for different Rissers' signs (P < .05). Compared to nonscoliotic controls, subjects with AIS had a generally lower SOS, indicating lower bone quality. The age, Risser's sign, or maturation status, may have an effect on the bone quality; however, the curve type and magnitude do not affect the bone quality. The results of this study indicate that slower bone maturation may affect the bone quality in adolescents with AIS. Copyright © 2015 National University of Health Sciences. Published by Elsevier Inc. All rights reserved.

Intraoperative /sup 99m/Tc bone imaging in the treatment of benign osteoblastic tumors

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

Sty, J.; Simons, G.

1982-05-01

Benign bone tumors can be successfully treated by local resection with the use of intraoperative bone imaging. Intraoperative bone imaging provided accurate localization of an osteoid osteoma in a patella of a 16-year-old girl when standard radiographs failed to demonstrate the lesion. In a case of osteoblastoma of the sacrum in a 12-year old girl, intraoperative scanning was used repeatedly to guide completeness of resection. In these cases in which routine intraoperative radiographs would have failed, intraoperative scanning proved to be essential for success.

The effectiveness of the bone bridge transtibial amputation technique: A systematic review of high-quality evidence.

PubMed

Kahle, Jason T; Highsmith, M Jason; Kenney, John; Ruth, Tim; Lunseth, Paul A; Ertl, Janos

2017-06-01

This literature review was undertaken to determine if commonly held views about the benefits of a bone bridge technique are supported by the literature. Four databases were searched for articles pertaining to surgical strategies specific to a bone bridge technique of the transtibial amputee. A total of 35 articles were identified as potential articles. Authors included methodology that was applied to separate topics. Following identification, articles were excluded if they were determined to be low quality evidence or not pertinent. Nine articles were identified to be pertinent to one of the topics: Perioperative Care, Acute Care, Subjective Analysis and Function. Two articles sorted into multiple topics. Two articles were sorted into the Perioperative Care topic, 4 articles sorted into the Acute Care topic, 2 articles into the Subjective Analysis topic and 5 articles into the Function topic. There are no high quality (level one or two) clinical trials reporting comparisons of the bone bridge technique to traditional methods. There is limited evidence supporting the clinical outcomes of the bone bridge technique. There is no agreement supporting or discouraging the perioperative and acute care aspects of the bone bridge technique. There is no evidence defining an interventional comparison of the bone bridge technique. Current level III evidence supports a bone bridge technique as an equivalent option to the non-bone bridge transtibial amputation technique. Formal level I and II clinical trials will need to be considered in the future to guide clinical practice. Clinical relevance Clinical Practice Guidelines are evidence based. This systematic literature review identifies the highest quality evidence to date which reports a consensus of outcomes agreeing bone bridge is as safe and effective as alternatives. The clinical relevance is understanding bone bridge could additionally provide a mechanistic advantage for the transtibial amputee.

Navigating Survival: Quality of Life Following Bone Marrow Transplantation.

DTIC Science & Technology

1991-01-01

This study explored the quality of life of adult Bone Marrow Transplantation (BMT) survivors and processes involved in maintaining or enhancing life...quality were identified. Ground theory methodology was used to explore quality of life from the survivor’s perspective. Five adults, 87 to 578 days...processes employed by BMT survivors to manage quality of life disruptions. BMT survivors identified disruptions in quality of life during the rapid

MO-FG-204-09: High Spatial Resolution and Artifact-Free CT Bone Imaging at Off-Centered Positions: An Application of Model-Based Iterative Reconstruction

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

Chen, G; Li, K; Gomez-Cardona, D

Purpose: Although the anatomy of interest should be positioned as close as possible to the isocenter of CT scanners, off-centering may be inevitable during certain exams in clinical practice such as lumbar spine and elbow imaging. Off-centering degrades image sharpness, generates streak artifacts, and sometimes creates blooming artifacts due to truncation. The purpose of this work was to investigate whether the use of model-based image reconstruction (MBIR) can alleviate the negative impacts of off-centering to achieve high quality CT bone imaging. Methods: Both an anthropomorphic phantom and an ex vivo swine elbow sample were scanned at centered and off-centered positionsmore » using clinical CT bone scan protocols. The magnitude of off-centering was determined from localizer radiographs. Both FBP and MBIR reconstructions were performed. For FBP, both standard and Bone Plus kernels commonly used in bone imaging were used. Objective assessment of image sharpness, noise standard deviation, and noise nonuniformity were performed. Additionally, we retrospectively analyzed human subject data acquired under off-centered conditions as a validation study. Results: In FBP images of the phantom, off-centering by 10 cm led to a 14% increase in noise (p<1e-3) and a 68% increase in noise nonuniformity (p<0.02). A visible drop in bone sharpness was observed. In contrast, no significant difference in the noise magnitude or the noise nonuniformity between the centered and off-centered MBIR images was found. The image sharpness of off-centered MBIR images outperformed that of FBP images reconstructed with the Bone Plus kernel. In images of the swine elbow off-centered by 20 cm, not only was the noise and spatial resolution performance improved by MBIR, truncation artifacts were also elliminated. The human subject study generated similar results, in which the visibility of the off-centered lumbar spine was significantly improved. Conclusion: High quality CT bone imaging at off-centered positions can be achieved using MBIR. This work was partially supported by an NIH grant R01CA169331 and GE Healthcare. K. Li, D. Gomez-Cardona: Nothing to disclose. G.-H. Chen: Research funded, GE Healthcare; Research funded, Siemens AX. A. Budde, J. Hsieh: Employee, GE Healthcare.« less

External bone marrow cytological examination quality assurance (EQAhem)--summary after 6 years in Poland.

PubMed

Lewandowski, Krzysztof; Kurpierz, Katarzyna; Sledzinska, Anna

2015-10-01

Bone marrow macroscopic examination remains one of the most difficult and subjective laboratory assessments in hematology. Only a few external quality assurance programs in the field are present worldwide. We have developed an external quality assurance program EQAhem that allows assessment of the whole process of bone marrow examination. The program participants assess blood and bone marrow smears from the patient, identify selected cells from photographs provided to them, and interpret the microscopic results. In this article, the results of the EQAhem program in Poland from 6 years are summarized. During this time, 62 labs were assessed in total, and positive results were achieved by 89.25 % labs, taking into account all tests. Correct responses with respect to the percentage of cell count were provided by ca. 77.5 % labs. Slightly worse results were obtained when megakaryocyte count and cell identification from photographs were tested. The worst results were obtained in case of dysplasia assessment and clinical interpretation of microscopic examination (54.1 and 58.6 % correct responses, respectively). EQAhem delivers precise information about the quality of bone marrow examinations performed in Poland and has a substantial educational value. We believe that after 6 years, EQAhem has significantly improved the quality of bone marrow microscopic examinations performed in Poland.

The role of serum osteoprotegerine in metastatic prostate cancer - a case control study.

PubMed

Siampanopoulou, M; El, Mantani; Moustakas, G; Haritanti, A; Gotzamani-Psarrakou, A

2016-01-01

Prostate cancer is one of the most common malignant neoplastic diseases in men. Early control of the disease progression contributes significantly to survival rates and patients' quality of life. Osteoprotegerin is a dimeric glycoprotein, which affects bone metabolism and inhibits osteoclastogenesis. In the present study, we evaluated the expression of osteoprotegerin in the serum of prostate cancer patients with or without skeletal metastases. The expression of serum osteoprotegerin, as measured by enzyme-linked immunosorbent assay, has been studied in 82 patients with locally controlled prostate cancer, in 49 patients with metastatic bone disease and in a control group of 41 healthy males. At sampling time 65/131 of included patients were newly diagnosed, while 66/131 patients were already under hormonal therapy. All eligible prostate cancer patients had histologically confirmed malignancy. Serum total prostate-specific antigen (PSA) was determined by an immunoradiometric assay. We investigated the expression of osteoprotegerin in hormone-dependent and hormone-refractory prostate cancer and its relation to disease progression. Among the 131 patients with prostate cancer, higher osteoprotegerin and PSA concentrations have been observed in metastatic bone patients' sera (p <0.001). ROC analysis between the metastatic and locally controlled prostate cancer patients has shown a statistically significant area curve (p <0.001) and a cut-off limit of 89.6 pg/ml. Moreover, 15.3 % of patients became hormone-resistant, with osteoprotegerin values significantly increased compared with hormone-sensitive prostate cancer patients (p <0.001). It seems that elevated levels of serum osteoprotegerin in patients with prostate cancer reflect the bone metastatic extent and may potentially be used in metastatic patients' follow-ups. Hippokratia 2016, 20(2): 133-138.

The prediction of cyclic proximal humerus fracture fixation failure by various bone density measures.

PubMed

Varga, Peter; Grünwald, Leonard; Windolf, Markus

2018-02-22

Fixation of osteoporotic proximal humerus fractures has remained challenging, but may be improved by careful pre-operative planning. The aim of this study was to investigate how well the failure of locking plate fixation of osteoporotic proximal humerus fractures can be predicted by bone density measures assessed with currently available clinical imaging (realistic case) and a higher resolution and quality modality (theoretical best-case). Various density measures were correlated to experimentally assessed number of cycles to construct failure of plated unstable low-density proximal humerus fractures (N = 18). The influence of density evaluation technique was investigated by comparing local (peri-implant) versus global evaluation regions; HR-pQCT-based versus clinical QCT-based image data; ipsilateral versus contralateral side; and bone mineral content (BMC) versus bone mineral density (BMD). All investigated density measures were significantly correlated with the experimental cycles to failure. The best performing clinically feasible parameter was the QCT-based BMC of the contralateral articular cap region, providing significantly better correlation (R 2  = 0.53) compared to a previously proposed clinical density measure (R 2  = 0.30). BMC had consistently, but not significantly stronger correlations with failure than BMD. The overall best results were obtained with the ipsilateral HR-pQCT-based local BMC (R 2  = 0.74) that may be used for implant optimization. Strong correlations were found between the corresponding density measures of the two CT image sources, as well as between the two sides. Future studies should investigate if BMC of the contralateral articular cap region could provide improved prediction of clinical fixation failure compared to previously proposed measures. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Local treatment of cancellous bone grafts with BMP-7 and zoledronate increases both the bone formation rate and bone density

PubMed Central

2011-01-01

Background and purpose The remodeling of morselized bone grafts in revision surgery can be enhanced by an anabolic substance such as a bone morphogenetic protein (BMP). On the other hand, BMPs boost catabolism and might cause a premature resorption, both of the graft and of the new-formed bone. Bisphosphonates inactivate osteoclasts and can be used to control the resorption. We studied a combination of both drugs as a local admix to a cancellous allograft. Methods Cancellous bone allografts were harvested and freeze-dried. Either saline, BMP-7, the bisphosphonate zoledronate, or a combination of BMP-7 and zoledronate were added in solution. The grafts were placed in bone conduction chambers and implanted in the proximal tibia of 34 rats. The grafts were harvested after 6 weeks and evaluated by histomorphometry. Results Bone volume/total volume (BV/TV) was 50% in the grafts treated with the combination of BMP-7 and zoledronate and 16% in the saline controls (p < 0.001). In the zoledronate group BV/TV was 56%, and in the BMP group it was 14%. The ingrowth distance of new bone into the graft was 3.5 mm for the combination of BMP-7 and zoledronate and 2.6 mm in the saline control (p = 0.002). The net amount of retained remodeled bone was more than 4 times higher when BMP-7 and zoledronate were combined than in the controls. Interpretation An anabolic drug like BMP-7 can be combined with an anti-catabolic bisphosphonate as local bone graft adjunct, and the combination increases the amount of remaining bone after remodeling is complete. PMID:21434769

Highly porous hydroxyapatite with and without local harvested bone in sinus floor augmentation: a histometric study in pigs.

PubMed

Möller, Björn; Acil, Yahya; Birkenfeld, Falk; Behrens, Eleonore; Terheyden, Hendrik; Wiltfang, Jörg

2014-07-01

Sinus floor augmentation with autologous bone is an accepted treatment option in dental implantology. In this study, an entirely synthetic, nano-structured, hydroxyapatite-based bone substitute material (SBSM, NanoBone(®); Artoss, Rostock, Germany) was supplemented with a mixture of locally harvested bone to enhance osteogenesis. Bilateral sinus augmentation procedures were performed in eight domestic pigs using the lateral window technique. On the right side (control), 2.6 ml of SBSM was used, and on the left side (test), 2.6 ml of SBSM with additional 15% (390 μl) autologous bone was used. At the time of augmentation, a titanium implant (ITI(®)) was inserted from a laterocaudal direction. After 3 months, the sites of augmentation were removed and examined in non-decalcified sections by microradiography and fluorescence microscopy of sequentially labelled specimens and histometry. On both sides, a significant amount of newly formed bone was observed. However, a statistically significant difference in the bone-implant contact was observed in the control group (median, 28.9%) compared with the test side with the additional autologous bone (median, 40.6%) (P = 0.01). Different bone density was achieved from the coronal to apical surfaces (medians, 54.6%, 9.6%, and 27.5%) compared with the test side (medians, 55.2%, 40.6%, and 44.2%). The median of augmentation height was 8.6 mm on the control side and 11.5 mm on the test side (P = 0.01). Bone apposition was observed in both groups after 15 days. The SBSM shows acceptable results in sinus floor augmentation. The additional use of locally harvested autologous bone enhances bone density and osseointegration of the implants. © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

Pregnancy-associated plasma protein-A modulates the anabolic effects of parathyroid hormone in mouse bone.

PubMed

Clifton, Kari B; Conover, Cheryl A

2015-12-01

Intermittent parathyroid hormone (PTH) is a potent anabolic therapy for bone, and several studies have implicated local insulin-like growth factor (IGF) signaling in mediating this effect. The IGF system is complex and includes ligands and receptors, as well as IGF binding proteins (IGFBPs) and IGFBP proteases. Pregnancy-associated plasma protein-A (PAPP-A) is a metalloprotease expressed by osteoblasts in vitro that has been shown to enhance local IGF action through cleavage of inhibitory IGFBP-4. This study was set up to test two specific hypotheses: 1) Intermittent PTH treatment increases the expression of IGF-I, IGFBP-4 and PAPP-A in bone in vivo, thereby increasing local IGF activity. 2) In the absence of PAPP-A, local IGF activity and the anabolic effects of PTH on bone are reduced. Wild-type (WT) and PAPP-A knock-out (KO) mice were treated with 80 μg/kg human PTH 1-34 or vehicle by subcutaneous injection five days per week for six weeks. IGF-I, IGFBP-4 and PAPP-A mRNA expression in bone were significantly increased in response to PTH treatment. PTH treatment of WT mice, but not PAPP-A KO mice, significantly increased expression of an IGF-responsive gene. Bone mineral density (BMD), as measured by DEXA, was significantly decreased in femurs of PAPP-A KO compared to WT mice with PTH treatment. Volumetric BMD, as measured by pQCT, was significantly decreased in femoral midshaft (primarily cortical bone), but not metaphysis (primarily trabecular bone), of PAPP-A KO compared to WT mice with PTH treatment. These data suggest that stimulation of PAPP-A expression by intermittent PTH treatment contributes to PTH bone anabolism in mice. Copyright © 2015 Elsevier Inc. All rights reserved.

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.

Localized ridge defect augmentation using human pericardium membrane and demineralized bone matrix.

PubMed

Vidyadharan, Arun Kumar; Ravindran, Anjana

2014-01-01

Patient wanted to restore her lost teeth with implants in the lower left first molar and second premolar region. Cone beam computerized tomography (CBCT) revealed inadequate bone width and height around future implant sites. The extraction socket of second premolar area revealed inadequate socket healing with sparse bone fill after 4 months of extraction. To evaluate the clinical feasibility of using a collagen physical resorbable barrier made of human pericardium (HP) to augment localized alveolar ridge defects for the subsequent placement of dental implants. Ridge augmentation was done in the compromised area using Puros® demineralized bone matrix (DBM) Putty with chips and an HP allograft membrane. Horizontal (width) and vertical hard tissue measurements with CBCT were recorded on the day of ridge augmentation surgery, 4 month and 7 months follow-up. Intra oral periapical taken 1 year after implant installation showed minimal crestal bone loss. Bone volume achieved through guided bone regeneration was a gain of 4.8 mm horizontally (width) and 6.8 mm vertically in the deficient ridge within a period of 7 months following the procedure. The results suggested that HP Allograft membrane may be a suitable component for augmentation of localized alveolar ridge defects in conjunction with DBM with bone chips.

Advances in imaging: impact on studying craniofacial bone structure.

PubMed

Majumdar, S

2003-01-01

Methods for measuring the structure of craniofacial bones are discussed in this paper. In addition to the three-dimensional macro-structure of the craniofacial skeleton, there is considerable interest in imaging the bone at a microscopic resolution in order to depict the micro-architecture of the trabecular bone itself. In addition to the density of the bone, the microarchitecture reflects bone quality. An understanding of bone quality and density changes has implications for a number of craniofacial pathologies, as well as for implant design and understanding the biomechanical function and loading of the jaw. Trabecular bone micro-architecture has been recently imaged using imaging methods such as micro-computed tomography, magnetic resonance imaging, and the images have been used in finite element models to assess bone mechanical properties. In this paper, some of the recent advances in micro-computed tomography and magnetic resonance imaging are reviewed, and their potential for imaging the trabecular bone in mandibular bones is presented. Examples of in vitro and in vivo images are presented.

Local administration of calcitriol positively influences bone remodeling and maturation during restoration of mandibular bone defects in rats.

PubMed

Liu, Hongrui; Cui, Jian; Feng, Wei; Lv, Shengyu; Du, Juan; Sun, Jing; Han, Xiuchun; Wang, Zhenming; Lu, Xiong; Yimin; Oda, Kimimitsu; Amizuka, Norio; Li, Minqi

2015-04-01

The aim of this study was to investigate the influence of calcitriol on osteoinduction following local administration into mandibular bone defects. Calcitriol-loaded absorbable collagen membrane scaffolds were prepared using the polydopamine coating method and characterized by scanning electron microscopy. Composite scaffolds were implanted into rat mandibular bone defects in the following groups: no graft material (control), bare collagen membrane (CM group), collagen membrane bearing polydopamine coating (DOP/CM group), and collagen membrane bearing polydopamine coating absorbed with calcitriol (CAL/DOP/CM group). At 1, 2, 4 and 8weeks post-surgery, the osteogenic potential of calcitriol was examined by histological and immunohistochemical methods. Following in vivo implantation, calcitriol-loaded composite scaffolds underwent rapid degradation with pronounced replacement by new bone and induced reunion of the bone marrow cavity. Calcitriol showed strong potential in inhibiting osteoclastogenesis and promotion of osteogenic differentiation at weeks 1, and 2. Furthermore, statistical analysis revealed that the newly formed bone volume in the CAL/DOP/CM group was significantly higher than other groups at weeks 1, and 2. At weeks 4, and 8, the CAL/DOP/CM group showed more mineralized bone and uniform collagen structure. These data suggest that local administration of calcitriol is promising in promoting osteogenesis and mineralization for restoration of mandibular bone defects. Copyright © 2014 Elsevier B.V. All rights reserved.

Steroid osteopathy

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

Conway, J.J.; Weiss, S.C.

1984-01-01

Patients receiving steroids or having disease processes which increase natural steroid production often demonstrate ''the classic x-ray changes'' of avascular necrosis of bone. Bone scintigraphy in these patients most frequently demonstrates an increased radionuclide localization. The literature suggests that the increased activity is related to healing of the avascular process. In a recent study of Legg-Calve-Perthes Disease (LCPD), 37 of the children had multiple studies and increased activity within the epiphysis during revascularization was extremely rare. Not only are the scintigraphic findings in steroid osteopathy dissimilar to that in healing LCPD, but the time interval for healing is much tomore » short for that of a vascular necrosis and no patients demonstrated an avascular phase on bone scintigraphy. Of 15 children with renal transplants on steroid therapy, 9 demonstrated x-ray and clinical findings of osteopathy. In 8 of 9 instances, bone scintigraphy showed increased localization of radionuclide in the affected bone. Improvement or a return to normal occurred in those patients in whom steroids were discontinued. The following is a proposed mechanism for steroid osteopathy. Steroids affect the osteoblastic and osteoclastic activity of bone and weaken its internal structure. Ordinary stress produces microtrabecular fractures. Fractures characteristically stimulate reactive hyperemia and increase bone metabolism. The result is increased bone radiopharmaceutical localization. The importance of recognizing this concept is that steroid osteopathy is preventable by reducing the administered steroid dose. As opposed to avascular necrosis, bone changes are reversible.« less

Evaluation of demineralized bone and bone transplants in vitro and in vivo with cone beam computed tomography imaging.

PubMed

Draenert, F G; Gebhart, F; Berthold, M; Gosau, M; Wagner, W

2010-07-01

The objective of this study was to determine the ability of two flat panel cone beam CT (CBCT) devices to identify demineralized bone and bone transplants in vivo and in vitro. Datasets from patients with autologous bone grafts (n = 9, KaVo 3DeXam (KaVo, Biberach, Germany); n = 38, Accuitomo 40 (Morita, Osaka, Japan)) were retrospectively evaluated. Demineralized and non-demineralized porcine cancellous bone blocks were examined with the two CBCT devices. A SawBone skull (Pacific Research Laboratories, Vashon, WA) was used as a positioning tool for the bone blocks. Descriptive evaluation and image quality assessment were conducted on the KaVo 3DeXam data (voxel size 0.3 mm) using the OsiriX viewer as well as on the Morita Accuitomo data (voxel size 0.25 mm) using proprietary viewer software. Both in vivo and in vitro, the descriptive analysis of the images of the two devices showed well-visualized bone transplants with clearly defined cancellous bones and well-defined single bone trabeculae in all cross-sections. In vitro, demineralized samples showed lower radiographic opacity but no significant loss of quality compared with fresh bone (P = 0.070). Single cancellous bone trabeculae were significantly better visualized with the Morita 3D Accuitomo device than with the KaVo 3DeXam device (P = 0.038). Both the KaVo 3DeXam and Morita 3D Accuitomo devices produce good-quality images of cancellous bones in in vivo remodelling as well as after in vitro demineralization.

Trained nurses can obtain satisfactory bone marrow aspirates and trephine biopsies.

PubMed Central

Lawson, S; Aston, S; Baker, L; Fegan, C D; Milligan, D W

1999-01-01

AIMS: To assess the feasibility of training nurse practitioners to perform bone marrow aspiration and trephine biopsy, and to compare the quality of these samples with those obtained by medical staff. METHODS: A retrospective audit was undertaken of nurse practitioner and medical staff performance in bone marrow procedures in a busy haematology day unit. RESULTS: Nurse practitioners fared favourably in comparison with medical staff in performing bone marrow trephine biopsies, with mean biopsy lengths of 11 mm and 10.7 mm respectively. However, only 78% of the smears obtained by the nurses were judged technically satisfactory, compared with 91% prepared by doctors. This discrepancy was thought to be due largely to the quality of slide spreading. CONCLUSIONS: With motivated staff and a structured educational and training programme it is possible for nurse practitioners to perform the techniques of bone marrow aspiration and biopsy, and obtain specimens of satisfactory quality, thus improving efficiency of the haematology day unit and increasing quality of patient care. Images PMID:10396248

Cyst-Like Osteolytic Formations in Recombinant Human Bone Morphogenetic Protein-2 (rhBMP-2) Augmented Sheep Spinal Fusion.

PubMed

Pan, Hsin Chuan; Lee, Soonchul; Ting, Kang; Shen, Jia; Wang, Chenchao; Nguyen, Alan; Berthiaume, Emily A; Zara, Janette N; Turner, A Simon; Seim, Howard B; Kwak, Jin Hee; Zhang, Xinli; Soo, Chia

2017-07-01

Multiple case reports using recombinant human bone morphogenetic protein-2 (rhBMP-2) have reported complications. However, the local adverse effects of rhBMP-2 application are not well documented. In this report we show that, in addition to promoting lumbar spinal fusion through potent osteogenic effects, rhBMP-2 augmentation promotes local cyst-like osteolytic formations in sheep trabecular bones that have undergone anterior lumbar interbody fusion. Three months after operation, conventional computed tomography showed that the trabecular bones of the rhBMP-2 application groups could fuse, whereas no fusion was observed in the control group. Micro-computed tomography analysis revealed that the core implant area's bone volume fraction and bone mineral density increased proportionately with rhBMP-2 dose. Multiple cyst-like bone voids were observed in peri-implant areas when using rhBMP-2 applications, and these sites showed significant bone mineral density decreases in relation to the unaffected regions. Biomechanically, these areas decreased in strength by 32% in comparison with noncystic areas. Histologically, rhBMP-2-affected void sites had an increased amount of fatty marrow, thinner trabecular bones, and significantly more adiponectin- and cathepsin K-positive cells. Despite promoting successful fusion, rhBMP-2 use in clinical applications may result in local adverse structural alterations and compromised biomechanical changes to the bone. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Effect of local administration of simvastatin on postorthodontic relapse in a rabbit model.

PubMed

AlSwafeeri, Hani; ElKenany, Walid; Mowafy, Mohamed; Karam, Sahar

2018-06-01

Posttreatment relapse is a major challenging clinical issue. The objective of this study was to evaluate the effect of local administration of simvastatin on posttreatment relapse. Orthodontic tooth movement was induced in 10 white New Zealand rabbits. After 21 days of active tooth movement, the orthodontic appliances were removed, and the experimental teeth were allowed to relapse for 21 days. During the relapse phase, 1 mandibular quadrant received local simvastatin administration, and the other received the control vehicle solution on a weekly basis. Three-dimensional models of the experimental teeth were created to allow the measurement of experimental tooth movement and posttreatment relapse. The animals were killed at the end of the relapse phase for histomorphometric analysis of alveolar bone remodeling. The mean relapse percentages were 75.83% in the quadrant receiving the control vehicle solution and 62.01% in the quadrant receiving simvastatin. Neither the relapse magnitude nor the relapse percentage showed a significant difference between the 2 quadrants. Histomorphometric analyses showed that local simvastatin administration yielded a significant reduction in the area of active bone-resorptive lacunae and a significant increase in newly formed bone area. Although local administration of simvastatin aids in bone remodeling associated with posttreatment relapse by reducing the area of active bone resorption and upregulating bone formation, it did not significantly minimize posttreatment relapse. Copyright © 2018 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

Localized ridge augmentation in the anterior maxilla using titanium mesh, an alloplast, and a nano-bone graft: a case report.

PubMed

Alagl, Adel S; Madi, Marwa

2018-05-01

Alveolar ridge deficiency is considered a major limitation for successful implant placement, as well as for the long-term success rate, especially in the anterior maxillary region. Various approaches have been developed to increase bone volume. Among those approaches, inlay and onlay grafts, alveolar ridge distraction, and guided bone regeneration have been suggested. The use of titanium mesh is a reliable method for ridge augmentation. We describe a patient who presented with a localized, combined, horizontal and vertical ridge defect in the anterior maxilla. The patient was treated using titanium mesh and alloplast material mixed with a nano-bone graft to treat the localized ridge deformity for future implant installation. The clinical and radiographic presentation, as well as relevant literature, are presented.

Local administration of bone morphogenetic protein-2 and bisphosphonate during non-weight-bearing treatment of ischemic osteonecrosis of the femoral head: an experimental investigation in immature pigs.

PubMed

Kim, Harry K W; Aruwajoye, Olumide; Du, Justin; Kamiya, Nobuhiro

2014-09-17

Non-weight-bearing decreases the femoral head deformity but increases bone resorption without increasing bone formation in an experimental animal model of Legg-Calvé-Perthes disease. We sought to determine if local administration of bone morphogenetic protein (BMP)-2 with or without bisphosphonate can increase the bone formation during the non-weight-bearing treatment in the large animal model of Legg-Calvé-Perthes disease. Eighteen piglets were surgically induced with femoral head ischemia. Immediately following the surgery, all animals received an above-the-knee amputation to enforce local non-weight-bearing (NWB). One to two weeks later, six animals received local BMP-2 to the necrotic head (BMP group), six received local BMP-2 and ibandronate (BMP+IB group), and the remaining six received no treatment (NWB group). All animals were killed at eight weeks after the induction of ischemia. Radiographic, microcomputed tomography (micro-CT), and histomorphometric assessments were performed. Radiographic assessment showed that the femoral heads in the NWB, BMP, and BMP+IB groups had a decrease of 20%, 14%, and 10%, respectively, in their mean epiphyseal quotient in comparison with the normal control group. Micro-CT analyses showed significantly higher femoral head bone volume in the BMP+IB group than in the BMP group (p = 0.02) and the NWB group (p < 0.001). BMP+IB and BMP groups had a significantly higher trabecular number (p < 0.01) and lower trabecular separation (p < 0.02) than the NWB group. In addition, the osteoclast number per bone surface was significantly lower in the BMP+IB group compared with the NWB group. Calcein labeling showed significantly higher bone formation in the BMP and BMP+IB groups than in the NWB group (p < 0.05). Heterotopic ossification was found in the capsule of four hips in the BMP+IB group but not in the BMP group. Administration of BMP-2 with bisphosphonate best decreased bone resorption and increased new bone formation during non-weight-bearing treatment of ischemic osteonecrosis in a pig model, but heterotopic ossification is a concern. This preclinical study provides new evidence that BMP-2 with bisphosphonate can effectively prevent the extreme bone loss associated with the non-weight-bearing treatment and increase new bone formation in the femoral head in this animal model of ischemic osteonecrosis. Copyright © 2014 by The Journal of Bone and Joint Surgery, Incorporated.

A novel registration-based methodology for prediction of trabecular bone fabric from clinical QCT: A comprehensive analysis

PubMed Central

Reyes, Mauricio; Zysset, Philippe

2017-01-01

Osteoporosis leads to hip fractures in aging populations and is diagnosed by modern medical imaging techniques such as quantitative computed tomography (QCT). Hip fracture sites involve trabecular bone, whose strength is determined by volume fraction and orientation, known as fabric. However, bone fabric cannot be reliably assessed in clinical QCT images of proximal femur. Accordingly, we propose a novel registration-based estimation of bone fabric designed to preserve tensor properties of bone fabric and to map bone fabric by a global and local decomposition of the gradient of a non-rigid image registration transformation. Furthermore, no comprehensive analysis on the critical components of this methodology has been previously conducted. Hence, the aim of this work was to identify the best registration-based strategy to assign bone fabric to the QCT image of a patient’s proximal femur. The normalized correlation coefficient and curvature-based regularization were used for image-based registration and the Frobenius norm of the stretch tensor of the local gradient was selected to quantify the distance among the proximal femora in the population. Based on this distance, closest, farthest and mean femora with a distinction of sex were chosen as alternative atlases to evaluate their influence on bone fabric prediction. Second, we analyzed different tensor mapping schemes for bone fabric prediction: identity, rotation-only, rotation and stretch tensor. Third, we investigated the use of a population average fabric atlas. A leave one out (LOO) evaluation study was performed with a dual QCT and HR-pQCT database of 36 pairs of human femora. The quality of the fabric prediction was assessed with three metrics, the tensor norm (TN) error, the degree of anisotropy (DA) error and the angular deviation of the principal tensor direction (PTD). The closest femur atlas (CTP) with a full rotation (CR) for fabric mapping delivered the best results with a TN error of 7.3 ± 0.9%, a DA error of 6.6 ± 1.3% and a PTD error of 25 ± 2°. The closest to the population mean femur atlas (MTP) using the same mapping scheme yielded only slightly higher errors than CTP for substantially less computing efforts. The population average fabric atlas yielded substantially higher errors than the MTP with the CR mapping scheme. Accounting for sex did not bring any significant improvements. The identified fabric mapping methodology will be exploited in patient-specific QCT-based finite element analysis of the proximal femur to improve the prediction of hip fracture risk. PMID:29176881

Influence of lactation and pregnancy + lactation on mechanical properties and mineral content of the rat femur.

PubMed

Peng, T C; Kusy, R P; Garner, S C; Hirsch, P F; De Blanco, M C

1987-06-01

The quality of bone was assessed from femurs of rats both during lactation and after pregnancy + lactation. Mechanical properties of stiffness, strength, toughness, and ductility were measured, along with standard measurements of dry weight, ash weight, and total bone mineral. No changes occurred during the first week of lactation. During the second and third weeks of lactation all bone parameters except ductility decreased significantly. These data are consistent with bone losing mineral in order to supplement the dietary calcium intake necessary for milk production. In other experiments, femurs were collected from nulliparous rats and from rats that had previously undergone 1-3 pregnancy + lactations. The largest changes in bone mineral and mechanical properties occurred after a single pregnancy + lactation period, although significant further decreases in stiffness and strength occurred after the second pregnancy + lactation. No additional losses occurred following the third pregnancy + lactation. Even 5 months after only one pregnancy + lactation period, the bone quality was still impaired as all bone properties were lower than in nulliparous controls. Because the changes, especially stiffness and strength, were relatively larger than the changes in dry and ash weights of bone, measurements of these mechanical properties provide a more sensitive method to evaluate the quality of bone.

Non-invasive assessment of bone quantity and quality in human trabeculae using scanning ultrasound imaging

NASA Astrophysics Data System (ADS)

Xia, Yi

Fractures and associated bone fragility induced by osteoporosis and osteopenia are widespread health threat to current society. Early detection of fracture risk associated with bone quantity and quality is important for both the prevention and treatment of osteoporosis and consequent complications. Quantitative ultrasound (QUS) is an engineering technology for monitoring bone quantity and quality of humans on earth and astronauts subjected to long duration microgravity. Factors currently limiting the acceptance of QUS technology involve precision, accuracy, single index and standardization. The objective of this study was to improve the accuracy and precision of an image-based QUS technique for non-invasive evaluation of trabecular bone quantity and quality by developing new techniques and understanding ultrasound/tissue interaction. Several new techniques have been developed in this dissertation study, including the automatic identification of irregular region of interest (iROI) in bone, surface topology mapping (STM) and mean scattering spacing (MSS) estimation for evaluating trabecular bone structure. In vitro results have shown that (1) the inter- and intra-observer errors in QUS measurement were reduced two to five fold by iROI compared to previous results; (2) the accuracy of QUS parameter, e.g., ultrasound velocity (UV) through bone, was improved 16% by STM; and (3) the averaged trabecular spacing can be estimated by MSS technique (r2=0.72, p<0.01). The measurement errors of BUA and UV introduced by the soft tissue and cortical shells in vivo can be quantified by developed foot model and simplified cortical-trabecular-cortical sandwich model, which were verified by the experimental results. The mechanisms of the errors induced by the cortical and soft tissues were revealed by the model. With developed new techniques and understanding of sound-tissue interaction, in vivo clinical trail and bed rest study were preformed to evaluate the performance of QUS in clinical applications. It has been demonstrated that the QUS has similar performance for in vivo bone density measurement compared to current gold-standard method, i.e., DXA, while additional information are obtained by the QUS for predicting fracture risk by monitoring of bone's quality. The developed QUS imaging technique can be used to assess bone's quantity and quality with improved accuracy and precision.

Short term effects on bone quality associated with consumption of soy protein isolate and other dietary protein sources in rapidly growing female rats

USDA-ARS?s Scientific Manuscript database

Beneficial effects of soy protein consumption on bone quality have been reported. The effects of other dietary protein sources such as whey protein hydrolysate (WPH) and rice protein isolate (RPI) on bone growth has been less well examined. The current study compared effects of feeding soy protein i...

Drilling force and temperature of bone under dry and physiological drilling conditions

NASA Astrophysics Data System (ADS)

Xu, Linlin; Wang, Chengyong; Jiang, Min; He, Huiyu; Song, Yuexian; Chen, Hanyuan; Shen, Jingnan; Zhang, Jiayong

2014-11-01

Many researches on drilling force and temperature have been done with the aim to reduce the labour intensiveness of surgery, avoid unnecessary damage and improve drilling quality. However, there has not been a systematic study of mid- and high-speed drilling under dry and physiological conditions(injection of saline). Furthermore, there is no consensus on optimal drilling parameters. To study these parameters under dry and physiological drilling conditions, pig humerus bones are drilled with medical twist drills operated using a wide range of drilling speeds and feed rates. Drilling force and temperature are measured using a YDZ-II01W dynamometer and a NEC TVS-500EX thermal infrared imager, respectively, to evaluate internal bone damage. To evaluate drilling quality, bone debris and hole morphology are observed by SEM(scanning electron microscopy). Changes in drilling force and temperature give similar results during drilling such that the value of each parameter peaks just before the drill penetrates through the osteon of the compact bone into the trabeculae of the spongy bone. Drilling temperatures under physiological conditions are much lower than those observed under dry conditions, while a larger drilling force occurs under physiological conditions than dry conditions. Drilling speed and feed rate have a significant influence on drilling force, temperature, bone debris and hole morphology. The investigation of the effect of drilling force and temperature on internal bone damage reveals that a drilling speed of 4500 r/min and a feed rate of 50 mm/min are recommended for bone drilling under physiological conditions. Drilling quality peaks under these optimal parameter conditions. This paper proposes the optimal drilling parameters under mid- and high-speed surgical drilling, considering internal bone damage and drilling quality, which can be looked as a reference for surgeons performing orthopedic operations.

Fourier Transform Infrared Imaging Microspectroscopy and Tissue-Level Mechanical Testing Reveal Intraspecies Variation in Mouse Bone Mineral and Matrix Composition

PubMed Central

Courtland, Hayden-William; Nasser, Philip; Goldstone, Andrew B.; Spevak, Lyudmila; Boskey, Adele L.; Jepsen, Karl J.

2009-01-01

Fracture susceptibility is heritable and dependent upon bone morphology and quality. However, studies of bone quality are typically overshadowed by emphasis on bone geometry and bone mineral density. Given that differences in mineral and matrix composition exist in a variety of species, we hypothesized that genetic variation in bone quality and tissue-level mechanical properties would also exist within species. Sixteen-week-old female A/J, C57BL/6J (B6), and C3H/HeJ (C3H) inbred mouse femora were analyzed using Fourier transform infrared imaging and tissue-level mechanical testing for variation in mineral composition, mineral maturity, collagen cross-link ratio, and tissue-level mechanical properties. A/J femora had an increased mineral-to-matrix ratio compared to B6. The C3H mineral-to-matrix ratio was intermediate of A/J and B6. C3H femora had reduced acid phosphate and carbonate levels and an increased collagen cross-link ratio compared to A/J and B6. Modulus values paralleled mineral-to-matrix values, with A/J femora being the most stiff, B6 being the least stiff, and C3H having intermediate stiffness. In addition, work-to-failure varied among the strains, with the highly mineralized and brittle A/J femora performing the least amount of work-to-failure. Inbred mice are therefore able to differentially modulate the composition of their bone mineral and the maturity of their bone matrix in conjunction with tissue-level mechanical properties. These results suggest that specific combinations of bone quality and morphological traits are genetically regulated such that mechanically functional bones can be constructed in different ways. PMID:18855037

Fourier transform infrared imaging microspectroscopy and tissue-level mechanical testing reveal intraspecies variation in mouse bone mineral and matrix composition.

PubMed

Courtland, Hayden-William; Nasser, Philip; Goldstone, Andrew B; Spevak, Lyudmila; Boskey, Adele L; Jepsen, Karl J

2008-11-01

Fracture susceptibility is heritable and dependent upon bone morphology and quality. However, studies of bone quality are typically overshadowed by emphasis on bone geometry and bone mineral density. Given that differences in mineral and matrix composition exist in a variety of species, we hypothesized that genetic variation in bone quality and tissue-level mechanical properties would also exist within species. Sixteen-week-old female A/J, C57BL/6J (B6), and C3H/HeJ (C3H) inbred mouse femora were analyzed using Fourier transform infrared imaging and tissue-level mechanical testing for variation in mineral composition, mineral maturity, collagen cross-link ratio, and tissue-level mechanical properties. A/J femora had an increased mineral-to-matrix ratio compared to B6. The C3H mineral-to-matrix ratio was intermediate of A/J and B6. C3H femora had reduced acid phosphate and carbonate levels and an increased collagen cross-link ratio compared to A/J and B6. Modulus values paralleled mineral-to-matrix values, with A/J femora being the most stiff, B6 being the least stiff, and C3H having intermediate stiffness. In addition, work-to-failure varied among the strains, with the highly mineralized and brittle A/J femora performing the least amount of work-to-failure. Inbred mice are therefore able to differentially modulate the composition of their bone mineral and the maturity of their bone matrix in conjunction with tissue-level mechanical properties. These results suggest that specific combinations of bone quality and morphological traits are genetically regulated such that mechanically functional bones can be constructed in different ways.

Image Guidance in External Beam Accelerated Partial Breast Irradiation: Comparison of Surrogates for the Lumpectomy Cavity

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

Hasan, Yasmin; Kim, Leonard; Martinez, Alvaro

Purpose: To compare localization of the lumpectomy cavity by using breast surface matching vs. clips for image-guided external beam accelerated partial breast irradiation. Methods and Materials: Twenty-seven patients with breast cancer with two computed tomography (CT) scans each had three CT registrations performed: (1) to bony anatomy, (2) to the center of mass (COM) of surgical clips, and (3) to the breast surface. The cavity COM was defined in both the initial and second CT scans after each type of registration, and distances between COMs ({delta}COM{sub Bone}, {delta}COM{sub Clips}, and {delta}COM{sub Surface}) were determined. Smaller {delta}COMs were interpreted as bettermore » localizations. Correlation coefficients were calculated for {delta}COM vs. several variables. Results: The {delta}COM{sub Bone} (mean, 7 {+-} 2 [SD] mm) increased with breast volume (r = 0.4; p = 0.02) and distance from the chest wall (r = 0.5; p = 0.003). Relative to bony registration, clip registration provided better localization ({delta}COM{sub Clips} < {delta}COM{sub Bone}) in 25 of 27 cases. Breast surface matching improved cavity localization ({delta}COM{sub Surface} < {delta}COM{sub Bone}) in 19 of 27 cases. Mean improvements ({delta}COM{sub Bone} - {delta}COM{sub ClipsorSurface}) were 4 {+-} 3 and 2 {+-} 4 mm, respectively. In terms of percentage of improvement ([{delta}COM{sub Bone} - {delta}COM{sub ClipsorSurface}]/{delta}COM{sub Bone}), only surface matching showed a correlation with breast volume. Clip localization outperformed surface registration for cavities located superior to the breast COM. Conclusions: Use of either breast surface or surgical clips as surrogates for the cavity results in improved localization in most patients compared with bony registration and may allow smaller planning target volume margins for external beam accelerated partial breast irradiation. Compared with surface registration, clip registration may be less sensitive to anatomic characteristics and therefore more broadly applicable.« less

Effect of hot-boned pork on the keeping quality of fresh pork sausage.

PubMed

Guerrero Legarreta, I; Usborne, W R; Ashton, G C

1987-01-01

The first experiment evaluated the effect of solid carbon dioxide (dry ice) addition to hot-boned meat, in different proportions, upon the keeping quality of fresh pork sausage patties. Dry ice had some negative effects at levels of 20% to 40%, such as hardening and colour fading of samples, although it increased water-holding capacity of the sausage. In the second experiment three proportions of hot-boned meat and chilled meat were evaluated as a means to extend the retail storage time of fresh pork sausage links. Hot-boned pork was treated by three methods: freezing the meat before grinding, salting and freezing, and salting plus dry ice addition. The results favoured the use of 50% hot-boned meat and 50% chilled meat, for which the lowest hardness and oxidation values were obtained. Microbial counts and hue values showed no significant variation among the three treatments. Salting and freezing hot-boned meat before grinding was the method which produced the best overall quality. Copyright © 1987. Published by Elsevier Ltd.

Evidence for the Adverse Effect of Starvation on Bone Quality: A Review of the Literature

PubMed Central

Kueper, Janina; Beyth, Shaul; Liebergall, Meir; Kaplan, Leon; Schroeder, Josh E.

2015-01-01

Malnutrition and starvation's possible adverse impacts on bone health and bone quality first came into the spotlight after the horrors of the Holocaust and the ghettos of World War II. Famine and food restrictions led to a mean caloric intake of 200–800 calories a day in the ghettos and concentration camps, resulting in catabolysis and starvation of the inhabitants and prisoners. Severely increased risks of fracture, poor bone mineral density, and decreased cortical strength were noted in several case series and descriptive reports addressing the medical issues of these individuals. A severe effect of severely diminished food intake and frequently concomitant calcium- and Vitamin D deficiencies was subsequently proven in both animal models and the most common cause of starvation in developed countries is anorexia nervosa. This review attempts to summarize the literature available on the impact of the metabolic response to Starvation on overall bone health and bone quality. PMID:25810719

Minimally Invasive Transforaminal Lumbar Interbody Fusion: Meta-analysis of the Fusion Rates. What is the Optimal Graft Material?

PubMed

Parajón, Avelino; Alimi, Marjan; Navarro-Ramirez, Rodrigo; Christos, Paul; Torres-Campa, Jose M; Moriguchi, Yu; Lang, Gernot; Härtl, Roger

2017-12-01

Minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) is an increasingly popular procedure with several potential advantages over traditional open TLIF. The current study aimed to compare fusion rates of different graft materials used in MIS-TLIF, via meta-analysis of the published literature. A Medline search was performed and a database was created including patient's type of graft, clinical outcome, fusion rate, fusion assessment modality, and duration of follow-up. Meta-analysis of the fusion rate was performed using StatsDirect software (StatsDirect Ltd, Cheshire, United Kingdom). A total of 1533 patients from 40 series were included. Fusion rates were high, ranging from 91.8% to 99%. The imaging modalities used to assess fusion were computed tomography scans (30%) and X-rays (70%). Comparison of all recombinant human bone morphogenetic protein (rhBMP) series with all non-rhBMP series showed fusion rates of 96.6% and 92.5%, respectively. The lowest fusion rate was seen with isolated use of autologous local bone (91.8%). The highest fusion rate was observed with combination of autologous local bone with bone extender and rhBMP (99.1%). The highest fusion rate without the use of BMP was seen with autologous local bone + bone extender (93.1%). The reported complication rate ranged from 0% to 35.71%. Clinical improvement was observed in all studies. Fusion rates are generally high with MIS-TLIF regardless of the graft material used. Given the potential complications of iliac bone harvesting and rhBMP, use of other bone graft options for MIS-TLIF is reasonable. The highest fusion rate without the use of rhBMP was seen with autologous local bone plus bone extender (93.1%). Published by Oxford University Press on behalf of Congress of Neurological Surgeons 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

[Dual energy CT angiography of the carotid arteries: quality, bone subtraction, and radiation dosage using tube voltage 80/140 kV versus 100/140 kV].

PubMed

Santos Armentia, E; Tardáguila de la Fuente, G; Castellón Plaza, D; Delgado Sánchez-Gracián, C; Prada González, R; Fernández Fernández, L; Tardáguila Montero, F

2014-01-01

To study the differences in vascular image quality, bone subtraction, and dose of radiation of dual energy CT angiography of the supraaortic trunks using different tube voltages. We reviewed the CT angiograms of the supraaortic trunks in 46 patients acquired with a 128-slice dual source CT scanner using two voltage protocols (80/140 kV and 100/140 kV). The "head bone removal" tool was used for postprocessing. We divided the arteries into 15 segments. In each segment, we evaluated the image quality of the vessels and the effectiveness of bone removal in multiplanar reconstructions (MPR) and in maximum intensity projections (MIP) with each protocol, analyzing the trabecular and cortical bones separately. We also evaluated the dose of radiation received. Of the 46 patients, 13 were studied using 80/140 kV and 33 with 100/140 kV. There were no significant differences between the two groups in age or sex. Image quality in four segments was better in the group examined with 100/140 kV. Cortical bone removal in MPR and MIP and trabecular bone removal in MIP were also better in the group examined with 100/140 kV. The dose of radiation received was significantly higher in the group examined with 100/140 kV (1.16 mSv with 80/140 kV vs. 1.59 mSv with 100/140 kV). Using 100/140 kV increases the dose of radiation but improves the quality of the study of arterial segments and bone subtraction. Copyright © 2011 SERAM. Published by Elsevier Espana. All rights reserved.

Legumain Regulates Differentiation Fate of Human Bone Marrow Stromal Cells and Is Altered in Postmenopausal Osteoporosis.

PubMed

Jafari, Abbas; Qanie, Diyako; Andersen, Thomas L; Zhang, Yuxi; Chen, Li; Postert, Benno; Parsons, Stuart; Ditzel, Nicholas; Khosla, Sundeep; Johansen, Harald Thidemann; Kjærsgaard-Andersen, Per; Delaisse, Jean-Marie; Abdallah, Basem M; Hesselson, Daniel; Solberg, Rigmor; Kassem, Moustapha

2017-02-14

Secreted factors are a key component of stem cell niche and their dysregulation compromises stem cell function. Legumain is a secreted cysteine protease involved in diverse biological processes. Here, we demonstrate that legumain regulates lineage commitment of human bone marrow stromal cells and that its expression level and cellular localization are altered in postmenopausal osteoporotic patients. As shown by genetic and pharmacological manipulation, legumain inhibited osteoblast (OB) differentiation and in vivo bone formation through degradation of the bone matrix protein fibronectin. In addition, genetic ablation or pharmacological inhibition of legumain activity led to precocious OB differentiation and increased vertebral mineralization in zebrafish. Finally, we show that localized increased expression of legumain in bone marrow adipocytes was inversely correlated with adjacent trabecular bone mass in a cohort of patients with postmenopausal osteoporosis. Our data suggest that altered proteolytic activity of legumain in the bone microenvironment contributes to decreased bone mass in postmenopausal osteoporosis. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Atomic scale chemical tomography of human bone

NASA Astrophysics Data System (ADS)

Langelier, Brian; Wang, Xiaoyue; Grandfield, Kathryn

2017-01-01

Human bone is a complex hierarchical material. Understanding bone structure and its corresponding composition at the nanometer scale is critical for elucidating mechanisms of biomineralization under healthy and pathological states. However, the three-dimensional structure and chemical nature of bone remains largely unexplored at the nanometer scale due to the challenges associated with characterizing both the structural and chemical integrity of bone simultaneously. Here, we use correlative transmission electron microscopy and atom probe tomography for the first time, to our knowledge, to reveal structures in human bone at the atomic level. This approach provides an overlaying chemical map of the organic and inorganic constituents of bone on its structure. This first use of atom probe tomography on human bone reveals local gradients, trace element detection of Mg, and the co-localization of Na with the inorganic-organic interface of bone mineral and collagen fibrils, suggesting the important role of Na-rich organics in the structural connection between mineral and collagen. Our findings provide the first insights into the hierarchical organization and chemical heterogeneity in human bone in three-dimensions at its smallest length scale - the atomic level. We demonstrate that atom probe tomography shows potential for new insights in biomineralization research on bone.

Optimal bone strength and mineralization requires the type 2 iodothyronine deiodinase in osteoblasts

PubMed Central

Bassett, J. H. Duncan; Boyde, Alan; Howell, Peter G. T.; Bassett, Richard H.; Galliford, Thomas M.; Archanco, Marta; Evans, Holly; Lawson, Michelle A.; Croucher, Peter; St. Germain, Donald L.; Galton, Valerie Anne; Williams, Graham R.

2010-01-01

Hypothyroidism and thyrotoxicosis are each associated with an increased risk of fracture. Although thyroxine (T4) is the predominant circulating thyroid hormone, target cell responses are determined by local intracellular availability of the active hormone 3,5,3′-L-triiodothyronine (T3), which is generated from T4 by the type 2 deiodinase enzyme (D2). To investigate the role of locally produced T3 in bone, we characterized mice deficient in D2 (D2KO) in which the serum T3 level is normal. Bones from adult D2KO mice have reduced toughness and are brittle, displaying an increased susceptibility to fracture. This phenotype is characterized by a 50% reduction in bone formation and a generalized increase in skeletal mineralization resulting from a local deficiency of T3 in osteoblasts. These data reveal an essential role for D2 in osteoblasts in the optimization of bone strength and mineralization. PMID:20368437

The effect of rigid fixation on growth of the neurocranium.

PubMed

Wong, L; Dufresne, C R; Richtsmeier, J T; Manson, P N

1991-09-01

The effects on skull growth of plating the coronal suture and frontal bone were studied in New Zealand White rabbits. Three-dimensional coordinate landmarks were digitized and analyzed to determine the differences in form between operated and unoperated animals using Euclidian distance matrix analysis. This method compares sets of interlandmark distances in three dimensions and was used to demonstrate changes induced by plating. We interpret these changes in morphology to be the result of differences in growth between the operated and unoperated groups. Periosteal elevation alone (n = 6) resulted in a minimal local growth increase. Coronal suture plating (n = 8) resulted in local growth restriction with contralateral and adjacent size increases. Frontal bone plating (n = 6) without crossing a suture line also resulted in local growth restriction and adjacent bone size increases. The timing of intervention in relation to the completion of bone growth may explain the magnitude of clinically apparent effects. Changes in bones adjacent to those directly manipulated may be an attempt to maintain a normal skull volume.

3D Reconstruction of human bones based on dictionary learning.

PubMed

Zhang, Binkai; Wang, Xiang; Liang, Xiao; Zheng, Jinjin

2017-11-01

An effective method for reconstructing a 3D model of human bones from computed tomography (CT) image data based on dictionary learning is proposed. In this study, the dictionary comprises the vertices of triangular meshes, and the sparse coefficient matrix indicates the connectivity information. For better reconstruction performance, we proposed a balance coefficient between the approximation and regularisation terms and a method for optimisation. Moreover, we applied a local updating strategy and a mesh-optimisation method to update the dictionary and the sparse matrix, respectively. The two updating steps are iterated alternately until the objective function converges. Thus, a reconstructed mesh could be obtained with high accuracy and regularisation. The experimental results show that the proposed method has the potential to obtain high precision and high-quality triangular meshes for rapid prototyping, medical diagnosis, and tissue engineering. Copyright © 2017 IPEM. Published by Elsevier Ltd. All rights reserved.

Bone mineral density in relation to efficacy and side effects of budesonide and prednisolone in Crohn's disease.

PubMed

Schoon, Erik J; Bollani, Simona; Mills, Peter R; Israeli, Eran; Felsenberg, Dieter; Ljunghall, Sverker; Persson, Tore; Haptén-White, Louise; Graffner, Hans; Bianchi Porro, Gabriele; Vatn, Morten; Stockbrügger, Reinhold W

2005-02-01

Osteoporosis frequently occurs in Crohn's disease, often because of corticosteroids. Budesonide as controlled release capsules is a locally acting corticosteroid with low systemic bioavailability. We investigated its effects on bone compared with prednisolone. In 34 international centers, 272 patients with Crohn's disease involving ileum and/or colon ascendens were randomized to once daily treatment with budesonide or prednisolone for 2 years at doses adapted to disease activity. One hundred eighty-one corticosteroid-free patients had active disease (98 had never received corticosteroids, corticosteroid naive; 83 had received corticosteroids previously, corticosteroid exposed), and 90 had quiescent disease, receiving long-term low doses of corticosteroids, corticosteroid-dependent; in 1 patient, no efficacy data were obtained. Bone mineral density and fractures were assessed in a double-blinded fashion; disease activity, side effects, and quality of life were monitored. Neither the corticosteroid-free nor the corticosteroid-dependent patients treated with budesonide differed significantly in bone mineral density from those receiving prednisolone. However, corticosteroid-naive patients receiving budesonide had smaller reductions in bone mineral density than those on prednisolone (mean, -1.04% vs -3.84%; P = .0084). Treatment-emergent corticosteroid side effects were less frequent with budesonide. Efficacy was similar in both groups. Treatment with budesonide is associated with better preserved bone mass compared with prednisolone in only the corticosteroid-naive patients with active ileocecal Crohn's disease. In both the corticosteroid-free and corticosteroid-dependent groups, budesonide and prednisolone were equally effective for up to 2 years, but budesonide caused fewer corticosteroid side effects.

Evaluation of the pain and local tenderness in bone metastasis treated with magnetic resonance-guided focused ultrasound surgery (MRgFUS)

NASA Astrophysics Data System (ADS)

Namba, Hirofumi; Kawasaki, Motohiro; Kato, Tomonari; Tani, Toshikazu; Ushida, Takahiro; Koizumi, Norihiro

2017-03-01

It has been reported that MRgFUS has pain palliative effects on the local pain in patients with bone metastasis. In general, a severity of pain has been evaluated using only subjective method with numerical rating scale (NRS) or visual analogue scale (VAS). It is important to evaluate local pain-palliative effects of MRgFUS treatment with objective and quantitative method. The aim of this study is to investigate changes in the severity of local pain of bone metastasis before and after MRgFUS treatments, measuring pressure pain threshold (PPT) using pressure algometer, and pain intensity using electrical stimulation device (the Pain Vision system) at most painful site of bone metastasis. We have conducted MRgFUS for pain palliation of bone metastasis for 8 patients, and evaluated the local tenderness quantitatively for 8 patients, and evaluated local pain intensity for 7 patients. Before the treatments, PPTs were 106.3kPa [40.0-431.5] at metastatic site and 344.8 kPa [206.0-667.0] at normal control site, which showed a significant difference. The PPTs at metastatic site shows a significant increase from 106.3 kPa [40.0-431.5] at the baseline to 270.5 kPa [93.5-533.5] at 3 months after the treatment. The NRS score shows a significant decrease from 6.0 [4-8] at baseline to 1 [0-3] at 3 months after the treatment. Similarly, the pain intensity shows a significant decrease 245 [96.3-888.7] at baseline to 55.9 [2.8-292] at 3 months after the treatment. The results of our study illustrate the pain-relieving effects of MRgFUS for the treatment of painful bone metastasis. PPT might be a useful parameter not only for assessing a treatment's effect, but also for the decision of the painful area to treat with MRgFUS. Pain Vision seems to be useful for quantitative and objective evaluation of local pain of painful bone metastasis.

A CAD system and quality assurance protocol for bone age assessment utilizing digital hand atlas

NASA Astrophysics Data System (ADS)

Gertych, Arakadiusz; Zhang, Aifeng; Ferrara, Benjamin; Liu, Brent J.

2007-03-01

Determination of bone age assessment (BAA) in pediatric radiology is a task based on detailed analysis of patient's left hand X-ray. The current standard utilized in clinical practice relies on a subjective comparison of the hand with patterns in the book atlas. The computerized approach to BAA (CBAA) utilizes automatic analysis of the regions of interest in the hand image. This procedure is followed by extraction of quantitative features sensitive to skeletal development that are further converted to a bone age value utilizing knowledge from the digital hand atlas (DHA). This also allows providing BAA results resembling current clinical approach. All developed methodologies have been combined into one CAD module with a graphical user interface (GUI). CBAA can also improve the statistical and analytical accuracy based on a clinical work-flow analysis. For this purpose a quality assurance protocol (QAP) has been developed. Implementation of the QAP helped to make the CAD more robust and find images that cannot meet conditions required by DHA standards. Moreover, the entire CAD-DHA system may gain further benefits if clinical acquisition protocol is modified. The goal of this study is to present the performance improvement of the overall CAD-DHA system with QAP and the comparison of the CAD results with chronological age of 1390 normal subjects from the DHA. The CAD workstation can process images from local image database or from a PACS server.

Variability of morphometric parameters of human trabecular tissue from coxo-arthritis and osteoporotic samples.

PubMed

Marinozzi, Franco; Marinozzi, Andrea; Bini, Fabiano; Zuppante, Francesca; Pecci, Raffaella; Bedini, Rossella

2012-01-01

Morphometric and architectural bone parameters change in diseases such as osteoarthritis and osteoporosis. The mechanical strength of bone is primarily influenced by bone quantity and quality. Bone quality is defined by parameters such as trabecular thickness, trabecular separation, trabecular density and degree of anisotropy that describe the micro-architectural structure of bone. Recently, many studies have validated microtomography as a valuable investigative technique to assess bone morphometry, thanks to micro-CT non-destructive, non-invasive and reliability features, in comparison to traditional techniques such as histology. The aim of this study is the analysis by micro-computed tomography of six specimens, extracted from patients affected by osteoarthritis and osteoporosis, in order to observe the tridimensional structure and calculate several morphometric parameters.

[Benign bone tumors. General principles].

PubMed

Hillmann, A; Gösling, T

2014-10-01

Benign bone tumors and tumor-like lesions are much more frequent than malignant bone tumors among the total number of tumors of the skeleton. This article gives a presentation of the characteristics and treatment modalities of benign bone tumors. In this article in-house treatment principles are compared with those in the currently available literature. Benign bone tumors are frequently found incidentally; however, the term benign does not always signify that a purely observational role is needed. Benign bone tumors differ in their biological behavior and can be latent, active or aggressive which determines the treatment approach. Some benign bone tumors are just as aggressive locally as malignant tumors. The most important diagnostic feature is still conventional radiography and a thorough systematic analysis is necessary. Therapy options range from ignore, wait and see up to wide resection. In contrast to malignant tumors the radicalism of resection can be weighed against the accompanying local control and loss of function. The treatment of benign bone tumors depends on the histological type and the biological activity. Most benign bone tumors are diagnosed incidentally and do not necessitate any treatment.

Prediction of local proximal tibial subchondral bone structural stiffness using subject-specific finite element modeling: Effect of selected density-modulus relationship.

PubMed

Nazemi, S Majid; Amini, Morteza; Kontulainen, Saija A; Milner, Jaques S; Holdsworth, David W; Masri, Bassam A; Wilson, David R; Johnston, James D

2015-08-01

Quantitative computed tomography based subject-specific finite element modeling has potential to clarify the role of subchondral bone alterations in knee osteoarthritis initiation, progression, and pain initiation. Calculation of bone elastic moduli from image data is a basic step when constructing finite element models. However, different relationships between elastic moduli and imaged density (known as density-modulus relationships) have been reported in the literature. The objective of this study was to apply seven different trabecular-specific and two cortical-specific density-modulus relationships from the literature to finite element models of proximal tibia subchondral bone, and identify the relationship(s) that best predicted experimentally measured local subchondral structural stiffness with highest explained variance and least error. Thirteen proximal tibial compartments were imaged via quantitative computed tomography. Imaged bone mineral density was converted to elastic moduli using published density-modulus relationships and mapped to corresponding finite element models. Proximal tibial structural stiffness values were compared to experimentally measured stiffness values from in-situ macro-indentation testing directly on the subchondral bone surface (47 indentation points). Regression lines between experimentally measured and finite element calculated stiffness had R(2) values ranging from 0.56 to 0.77. Normalized root mean squared error varied from 16.6% to 337.6%. Of the 21 evaluated density-modulus relationships in this study, Goulet combined with Snyder and Schneider or Rho appeared most appropriate for finite element modeling of local subchondral bone structural stiffness. Though, further studies are needed to optimize density-modulus relationships and improve finite element estimates of local subchondral bone structural stiffness. Copyright © 2015 Elsevier Ltd. All rights reserved.

Bone quality changes associated with aging and disease: a review.

PubMed

Boskey, Adele L; Imbert, Laurianne

2017-12-01

Bone quality encompasses all the characteristics of bone that, in addition to density, contribute to its resistance to fracture. In this review, we consider changes in architecture, porosity, and composition, including collagen structure, mineral composition, and crystal size. These factors all are known to vary with tissue and animal ages, and health status. Bone morphology and presence of microcracks, which also contribute to bone quality, will not be discussed in this review. Correlations with mechanical performance for collagen cross-linking, crystallinity, and carbonate content are contrasted with mineral content. Age-dependent changes in humans and rodents are discussed in relation to rodent models of disease. Examples are osteoporosis, osteomalacia, osteogenesis imperfecta (OI), and osteopetrosis in both humans and animal models. Each of these conditions, along with aging, is associated with increased fracture risk for distinct reasons. © 2017 New York Academy of Sciences.

Dynamic hydraulic fluid stimulation regulated intramedullary pressure.

PubMed

Hu, Minyi; Serra-Hsu, Frederick; Bethel, Neville; Lin, Liangjun; Ferreri, Suzanne; Cheng, Jiqi; Qin, Yi-Xian

2013-11-01

Physical signals within the bone, i.e. generated from mechanical loading, have the potential to initiate skeletal adaptation. Strong evidence has pointed to bone fluid flow (BFF) as a media between an external load and the bone cells, in which altered velocity and pressure can ultimately initiate the mechanotransduction and the remodeling process within the bone. Load-induced BFF can be altered by factors such as intramedullary pressure (ImP) and/or bone matrix strain, mediating bone adaptation. Previous studies have shown that BFF induced by ImP alone, with minimum bone strain, can initiate bone remodeling. However, identifying induced ImP dynamics and bone strain factor in vivo using a non-invasive method still remains challenging. To apply ImP as a means for alteration of BFF, it was hypothesized that non-invasive dynamic hydraulic stimulation (DHS) can induce local ImP with minimal bone strain to potentially elicit osteogenic adaptive responses via bone-muscle coupling. The goal of this study was to evaluate the immediate effects on local and distant ImP and strain in response to a range of loading frequencies using DHS. Simultaneous femoral and tibial ImP and bone strain values were measured in three 15-month-old female Sprague Dawley rats during DHS loading on the tibia with frequencies of 1Hz to 10Hz. DHS showed noticeable effects on ImP induction in the stimulated tibia in a nonlinear fashion in response to DHS over the range of loading frequencies, where they peaked at 2Hz. DHS at various loading frequencies generated minimal bone strain in the tibiae. Maximal bone strain measured at all loading frequencies was less than 8με. No detectable induction of ImP or bone strain was observed in the femur. This study suggested that oscillatory DHS may regulate the local fluid dynamics with minimal mechanical strain in the bone, which serves critically in bone adaptation. These results clearly implied DHS's potential as an effective, non-invasive intervention for osteopenia and osteoporosis treatments. © 2013. Published by Elsevier Inc. All rights reserved.

Adaptation of bone to physiological stimuli.

PubMed

Judex, S; Gross, T S; Bray, R C; Zernicke, R F

1997-05-01

The ability of bone to alter its morphology in response to local physical stimuli is predicated upon the appropriate recruitment of bone cell populations. In turn, the ability to initiate cellular recruitment is influenced by numerous local and systemic factors. In this paper, we discuss data from three ongoing projects from our laboratory that examine how physiological processes influence adaptation and growth in the skeleton. In the first study, we recorded in vivo strains to quantify the locomotion-induced distribution of two parameters closely related to bone fluid flow strain rate and strain gradients. We found that the magnitude of these parameters (and thus the implied fluid flow) varies substantially within a given cross-section, and that while strain rate magnitude increases uniformly with elevated speed, strain gradients increase focally as gait speed is increased. Secondly, we examined the influence of vascular alterations on bone adaptation by assessing bone blood flow and bone mechanical properties in an in vivo model of trauma-induced joint laxity. A strong negative correlation (r2 = 0.8) was found between increased blood flow (76%) in the primary and secondary spongiosa and decreased stiffness (-34%) following 14 weeks of joint laxity. These data suggest that blood flow and/or vascular adaptation may interact closely with bone adaptation initiated by trauma. Thirdly, we examined the effect of a systemic influence upon skeletal health. After 4 weeks old rats were fed high fat-sucrose diets for 2 yr, their bone mechanical properties were significantly reduced. These changes were primarily due to interference with normal calcium absorption. In the aggregate, these studies emphasize the complexity of bone's normal physical environment, and also illustrate the potential interactions of local and systemic factors upon the process by which bone adapts to physical stimuli.

Understanding bone responses in B-mode ultrasound images and automatic bone surface extraction using a Bayesian probabilistic framework

NASA Astrophysics Data System (ADS)

Jain, Ameet K.; Taylor, Russell H.

2004-04-01

The registration of preoperative CT to intra-operative reality systems is a crucial step in Computer Assisted Orthopedic Surgery (CAOS). The intra-operative sensors include 3D digitizers, fiducials, X-rays and Ultrasound (US). Although US has many advantages over others, tracked US for Orthopedic Surgery has been researched by only a few authors. An important factor limiting the accuracy of tracked US to CT registration (1-3mm) has been the difficulty in determining the exact location of the bone surfaces in the US images (the response could range from 2-4mm). Thus it is crucial to localize the bone surface accurately from these images. Moreover conventional US imaging systems are known to have certain inherent inaccuracies, mainly due to the fact that the imaging model is assumed planar. This creates the need to develop a bone segmentation framework that can couple information from various post-processed spatially separated US images (of the bone) to enhance the localization of the bone surface. In this paper we discuss the various reasons that cause inherent uncertainties in the bone surface localization (in B-mode US images) and suggest methods to account for these. We also develop a method for automatic bone surface detection. To do so, we account objectively for the high-level understanding of the various bone surface features visible in typical US images. A combination of these features would finally decide the surface position. We use a Bayesian probabilistic framework, which strikes a fair balance between high level understanding from features in an image and the low level number crunching of standard image processing techniques. It also provides us with a mathematical approach that facilitates combining multiple images to augment the bone surface estimate.

Nerve growth factor and associated nerve sprouting contribute to local mechanical hyperalgesia in a rat model of bone injury.

PubMed

Yasui, M; Shiraishi, Y; Ozaki, N; Hayashi, K; Hori, K; Ichiyanagi, M; Sugiura, Y

2012-08-01

To clarify the mechanism of tenderness after bone injury, we investigated changes in the withdrawal threshold to mechanical stimuli, nerve distribution and nerve growth factor (NGF)-expression in a rat model of bone injury without immobilization for bone injury healing. Rats were divided into three groups as follows: (1) rats incised in the skin and periosteum, followed by drilling a hole in the tibia [bone lesion group (BLG)]; (2) those incised in the skin and periosteum without bone drilling [periosteum lesion group (PLG)]; and (3) those incised in the skin [skin lesion group (SLG)]. Mechanical hyperalgesia continued for 28 days at a lesion in the BLG, 21 days in PLG and 5 days in SLG after treatments, respectively. Endochondral ossification was observed on days 5-28 in BLG and on days 5-21 in PLG. Nerve growth appeared in deep connective tissue (DCT) at day 28 in BLG. Nerve fibres increased in both cutaneous tissue and DCT at day 7 in PLG, but they were not found at day 28. Mechanical hyperalgesia accompanied with endochondral ossification and nerve fibres increasing at the lesion in both BLG and PLG. NGF was expressed in bone-regenerating cells during the bone injury healing. Anti-NGF and trk inhibitor K252a inhibited hyperalgesia in the different time course. This study shows that localized tenderness coincides with the bone healing and involves NGF expression and nerve sprouting after bone injury. The findings present underlying mechanisms and provide pathophysiological relevance of local tenderness to determination of bone fracture and its healing. © 2011 European Federation of International Association for the Study of Pain Chapters.

Locally limited inhibition of bone resorption and orthodontic relapse by recombinant osteoprotegerin protein.

PubMed

Schneider, D A; Smith, S M; Campbell, C; Hayami, T; Kapila, S; Hatch, N E

2015-04-01

To determine minimal dose levels required for local inhibition of orthodontic relapse by recombinant OPG protein (OPG-Fc), while also determining effects of injected OPG-Fc on alveolar bone and long bone. The Department of Orthodontics and Pediatric Dentistry at the University of Michigan. Eighteen male Sprague Dawley rats. Maxillary molars were moved with nickel-titanium springs and then allowed to relapse in Sprague Dawley rats. Upon appliance removal, animals were injected with a single dose of 1.0 mg/kg OPG-Fc, 0.1 mg/kg OPG-Fc, or phosphate-buffered saline (vehicle) just distal to the molar teeth. Tooth movement measurements were made from stone casts, which were scanned and digitally measured. Alveolar tissues were examined by histology. Micro-computed tomography was used to quantify changes in alveolar and femur bone. Local injection of OPG-Fc inhibited molar but not incisor relapse, when compared to vehicle-injected animals. No significant differences in alveolar or femur bone were seen between the three treatment groups after 24 days of relapse. Our results demonstrate that a single local injection of OPG-Fc effectively inhibits orthodontic relapse, with minimal systemic bone metabolic effects. Our results also show that a single injection of OPG-Fc will influence tooth movement only in teeth close to the injection site. These findings indicate that OPG-Fc has potential as a safe and effective pharmacological means to locally control osteoclasts, for uses such as maintaining anchorage during orthodontic tooth movement and preventing orthodontic relapse in humans. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The mechanical heterogeneity of the hard callus influences local tissue strains during bone healing: a finite element study based on sheep experiments.

PubMed

Vetter, A; Liu, Y; Witt, F; Manjubala, I; Sander, O; Epari, D R; Fratzl, P; Duda, G N; Weinkamer, R

2011-02-03

During secondary fracture healing, various tissue types including new bone are formed. The local mechanical strains play an important role in tissue proliferation and differentiation. To further our mechanobiological understanding of fracture healing, a precise assessment of local strains is mandatory. Until now, static analyses using Finite Elements (FE) have assumed homogenous material properties. With the recent quantification of both the spatial tissue patterns (Vetter et al., 2010) and the development of elastic modulus of newly formed bone during healing (Manjubala et al., 2009), it is now possible to incorporate this heterogeneity. Therefore, the aim of this study is to investigate the effect of this heterogeneity on the strain patterns at six successive healing stages. The input data of the present work stemmed from a comprehensive cross-sectional study of sheep with a tibial osteotomy (Epari et al., 2006). In our FE model, each element containing bone was described by a bulk elastic modulus, which depended on both the local area fraction and the local elastic modulus of the bone material. The obtained strains were compared with the results of hypothetical FE models assuming homogeneous material properties. The differences in the spatial distributions of the strains between the heterogeneous and homogeneous FE models were interpreted using a current mechanobiological theory (Isakson et al., 2006). This interpretation showed that considering the heterogeneity of the hard callus is most important at the intermediate stages of healing, when cartilage transforms to bone via endochondral ossification. Copyright © 2010 Elsevier Ltd. All rights reserved.

[Issues related to secondary osteoporosis associated with growth hormone deficiency in adulthood].

PubMed

Kužma, Martin; Jackuliak, Peter; Killinger, Zdenko; Vaňuga, Peter; Payer, Juraj

Growth hormone (GH) increases linear bone growth through complex hormonal reactions, mainly mediated by insulin like growth factor 1 (IGF1) that is produced mostly by hepatocytes under influence of GH and stimulates differentiation of epiphyseal prechondrocytes. IGF1 and GH play a key role in the linear bone growth after birth and regulation of bone remodelation during the entire lifespan. It is known that adult GH deficient (GHD) patients have decreased BMD and increased risk of low-impact fractures. Most data gathered thus far on the effect of GH replacement on bone status comprise the measurement of quantitative changes of bone mass. Some animal studies with GHD showed that the bone microarchitecture, measured using computed tomography methods, is significantly compromised and improve after GH replacement. However, human studies did not show significantly decreased bone microarchitecture, but limited methodological quality does not allow firm conclusions on this subject.Key words: bone mass - bone quality - fracture - growth hormone - IGF1.

Lack of deleterious effect of slow-release sodium fluoride treatment on cortical bone histology and quality in osteoporotic patients

NASA Technical Reports Server (NTRS)

Zerwekh, J. E.; Antich, P. P.; Sakhaee, K.; Prior, J.; Gonzales, J.; Gottschalk, F.; Pak, C. Y.

1992-01-01

We evaluated the effects of intermittent slow-release sodium fluoride (SRNaF) and continuous calcium citrate therapy on cortical bone histology, reflection ultrasound velocity (material strength) and back-scattered electron image analysis (BEI) in 26 osteoporotic patients before and following therapy. All measurements were made on transiliac crest bone biopsies obtained before and following 2 years of therapy in each patient. For all 26 patients there were no significant changes in cortical bone histomorphometric parameters. In 15 patients in whom bone material quality was assessed by reflection ultrasound, there was no change in velocity (4000 +/- 227 SD to 4013 +/- 240 m/s). BEI disclosed no mineralization defects or the presence of woven bone. Mean atomic number (density) of bone increased slightly, but significantly (9.261 +/- 0.311 to 9.457 +/- 0.223, P = 0.031). While these changes are less marked than those observed for cancellous bone, they indicate that this form of therapy does not adversely affect cortical bone remodelling.

Osteoporosis, Fractures, and Diabetes

PubMed Central

2014-01-01

It is well established that osteoporosis and diabetes are prevalent diseases with significant associated morbidity and mortality. Patients with diabetes mellitus have an increased risk of bone fractures. In type 1 diabetes, the risk is increased by ∼6 times and is due to low bone mass. Despite increased bone mineral density (BMD), in patients with type 2 diabetes the risk is increased (which is about twice the risk in the general population) due to the inferior quality of bone. Bone fragility in type 2 diabetes, which is not reflected by bone mineral density, depends on bone quality deterioration rather than bone mass reduction. Thus, surrogate markers and examination methods are needed to replace the insensitivity of BMD in assessing fracture risks of T2DM patients. One of these methods can be trabecular bone score. The aim of the paper is to present the present state of scientific knowledge about the osteoporosis risk in diabetic patient. The review also discusses the possibility of problematic using the study conclusions in real clinical practice. PMID:25050121

Reducing the radiation sterilization dose improves mechanical and biological quality while retaining sterility assurance levels of bone allografts.

PubMed

Nguyen, Huynh; Cassady, Alan I; Bennett, Michael B; Gineyts, Evelyne; Wu, Andy; Morgan, David A F; Forwood, Mark R

2013-11-01

Bone allografts carry a risk of infection, so terminal sterilization by gamma irradiation at 25kGy is recommended; but is deleterious to bone quality. Contemporary bone banking significantly reduces initial allograft bioburden, questioning the need to sterilize at 25kGy. We inoculated allograft bone with Staphylococcus epidermidis and Bacillus pumilus, then exposed them to gamma irradiation at 0, 5, 10, 15, 20 and 25kGy. Mechanical and biological properties of allografts were also assessed. Our aim was to determine an optimal dose that achieves sterility assurance while minimizing deleterious effects on allograft tissue. 20-25kGy eliminated both organisms at concentrations from 10(1) to 10(3)CFU, while 10-15kGy sterilized bone samples to a bioburden concentration of 10(2)CFU. Irradiation did not generate pro-inflammatory bone surfaces, as evidenced by macrophage activation, nor did it affect attachment or proliferation of osteoblasts. At doses ≥10kGy, the toughness of cortical bone was reduced (P<0.05), and attachment and fusion of osteoclasts onto irradiated bone declined at 20 and 25kGy (P<0.05). There was no change in collagen cross-links, but a significant dose-response increase in denatured collagen (P<0.05). Our mechanical and cell biological data converge on 15kGy as a threshold for radiation sterilization of bone allografts. Between 5 and 15kGy, bone banks can undertake validation that provides allografts with an acceptable sterility assurance level, improving their strength and biocompatibility significantly. The application of radiation sterilization doses between 5 and 15kGy will improve bone allograft mechanical performance and promote integration, while retaining sterility assurance levels. Improved quality of allograft bone will promote superior clinical outcomes. © 2013.

Aging Versus Postmenopausal Osteoporosis: Bone Composition and Maturation Kinetics at Actively-Forming Trabecular Surfaces of Female Subjects Aged 1 to 84 Years.

PubMed

Paschalis, Eleftherios P; Fratzl, Peter; Gamsjaeger, Sonja; Hassler, Norbert; Brozek, Wolfgang; Eriksen, Erik F; Rauch, Frank; Glorieux, Francis H; Shane, Elizabeth; Dempster, David; Cohen, Adi; Recker, Robert; Klaushofer, Klaus

2016-02-01

Bone strength depends on the amount of bone, typically expressed as bone mineral density (BMD), determined by dual-energy X-ray absorptiometry (DXA), and on bone quality. Bone quality is a multifactorial entity including bone structural and material compositional properties. The purpose of the present study was to examine whether bone material composition properties at actively-forming trabecular bone surfaces in health are dependent on subject age, and to contrast them with postmenopausal osteoporosis patients. To achieve this, we analyzed by Raman microspectroscopy iliac crest biopsy samples from healthy subjects aged 1.5 to 45.7 years, paired biopsy samples from females before and immediately after menopause aged 46.7 to 53.6 years, and biopsy samples from placebo-treated postmenopausal osteoporotic patients aged 66 to 84 years. The monitored parameters were as follows: the mineral/matrix ratio; the mineral maturity/crystallinity (MMC); nanoporosity; the glycosaminoglycan (GAG) content; the lipid content; and the pyridinoline (Pyd) content. The results indicate that these bone quality parameters in healthy, actively-forming trabecular bone surfaces are dependent on subject age at constant tissue age, suggesting that with advancing age the kinetics of maturation (either accumulation, or posttranslational modifications, or both) change. For most parameters, the extrapolation of models fitted to the individual age dependence of bone in healthy individuals was in rough agreement with their values in postmenopausal osteoporotic patients, except for MMC, lipid, and Pyd content. Among these three, Pyd content showed the greatest deviation between healthy aging and disease, highlighting its potential to be used as a discriminating factor. © 2015 American Society for Bone and Mineral Research.

Markers of Bone Health, Bone-Specific Physical Activities, Nutritional Intake, and Quality of Life of Professional Jockeys in Hong Kong.

PubMed

Poon, Eric Tsz-Chun; O'Reilly, John; Sheridan, Sinead; Cai, Michelle Mingjing; Wong, Stephen Heung-Sang

2018-04-28

Weight-making practices, regularly engaged in by horse racing jockeys, have been suggested to impair both physiological and mental health. This study aimed to assess bone health markers, nutritional intake, bone-specific physical activity (PA) habits, and quality of life of professional jockeys in Hong Kong (n = 14), with gender-, age-, and body mass index-matched controls (n = 14). Anthropometric measurements, serum hormonal biomarkers, bone mineral density, bone-specific PA habits, nutritional intake, and quality of life were assessed in all participants. The jockey group displayed significantly lower bone mineral density at both calcanei than the control group (left: 0.50 ± 0.06 vs. 0.63 ± 0.07 g/cm 2 ; right: 0.51 ± 0.07 vs. 0.64 ± 0.10 g/cm 2 , both ps < .01). Thirteen of the 14 jockeys (93%) showed either osteopenia or osteoporosis in at least one of their calcanei. No significant difference in bone mineral density was detected for either forearm between the groups. The current bone-specific PA questionnaire score was lower in the jockey group than the control group (5.61 ± 1.82 vs. 8.27 ± 2.91, p < .05). Daily energy intake was lower in the jockeys than the controls (1,360 ± 515 vs. 1,985 ± 1,046 kcal/day, p < .01). No significant group difference was found for micronutrient intake assessed by the bone-specific food frequency questionnaire, blood hormonal markers, and quality of life scores. Our results revealed suboptimal bone conditions at calcanei and insufficient energy intake and bone-loading PAs among professional jockeys in Hong Kong compared with healthy age-, gender-, and body mass index-matched controls. Further research is warranted to examine the effect of improved bone-loading PAs and nutritional habits on the musculoskeletal health of professional jockeys.

Dose and diagnostic image quality in digital tomosynthesis imaging of facial bones in pediatrics

NASA Astrophysics Data System (ADS)

King, J. M.; Hickling, S.; Elbakri, I. A.; Reed, M.; Wrogemann, J.

2011-03-01

The purpose of this study was to evaluate the use of digital tomosynthesis (DT) for pediatric facial bone imaging. We compared the eye lens dose and diagnostic image quality of DT facial bone exams relative to digital radiography (DR) and computed tomography (CT), and investigated whether we could modify our current DT imaging protocol to reduce patient dose while maintaining sufficient diagnostic image quality. We measured the dose to the eye lens for all three modalities using high-sensitivity thermoluminescent dosimeters (TLDs) and an anthropomorphic skull phantom. To assess the diagnostic image quality of DT compared to the corresponding DR and CT images, we performed an observer study where the visibility of anatomical structures in the DT phantom images were rated on a four-point scale. We then acquired DT images at lower doses and had radiologists indicate whether the visibility of each structure was adequate for diagnostic purposes. For typical facial bone exams, we measured eye lens doses of 0.1-0.4 mGy for DR, 0.3-3.7 mGy for DT, and 26 mGy for CT. In general, facial bone structures were visualized better with DT then DR, and the majority of structures were visualized well enough to avoid the need for CT. DT imaging provides high quality diagnostic images of the facial bones while delivering significantly lower doses to the lens of the eye compared to CT. In addition, we found that by adjusting the imaging parameters, the DT effective dose can be reduced by up to 50% while maintaining sufficient image quality.

Correlation between gamma glutamyltransferase fractions and bone quality.

PubMed

Franzini, M; Nesti, A; Panetta, D; Fierabracci, V; Marchetti, S; Parchi, P D; Caponi, L; Paolicchi, A; Musetti, V; Salvadori, P; Edmin, M; Pucci, A; Bonicoli, E; Scaglione, M; Piolanti, N

Gamma-glutamyltransferase (GGT) has been recently identified as a bone-resorbing factor. The aim of this study was to investigate the association between plasma GGT fractions levels and bone quality. Plasma GGT fractions were analysed by gel-filtration chromatography. Bone quality was established quantitatively by two micro-CT derived microarchitectural parameters: the BV/TV (mineralised bone volume/total volume), and the SMI (structure model index) that describes the rod-like (low resistant) or plate-like (high-resistant) shape of bone trabeculae. We enrolled 93 patients hospitalised for elective total hip replacement (group Arthrosis, n=46) or for proximal femoral fracture (group Fracture, n=47). Patients within the first quartile of BV/TV (Q1, osteoporotic patients, n=6) showed higher levels of b-GGT fraction [median (min-max): 3.37 (1.42–6.81)] compared to patients with normal bone density (fourth quartile Q4, n=10; 1.40 (0.83–4.36); p=0.0393]. Also, according to SMI, b-GGT value was higher in the subgroup with bone fragility [Q1, n=8: 1.36 (0.43–4.36); Q4, n=8: 5.10 (1.4 –7.60); p=0.0117]. In conclusion, patients characterised by fragile bone structure showed specifically higher levels of plasma b-GGT activity thus suggesting fractional GGT analysis as a possible biomarker in the diagnosis of osteoporosis.

Intrinsic qualities of primate bones as predictors of skeletal element representation in modern and fossil carnivore feeding assemblages.

PubMed

Carlson, Kristian J; Pickering, Travis Rayne

2003-04-01

Plio-Pleistocene faunal assemblages from Swartkrans Cave (South Africa) preserve large numbers of primate remains. Brain, C.K., 1981. The Hunters or the Hunted? An Introduction to African Cave Taphonomy. University of Chicago Press, Chicago suggested that these primate subassemblages might have resulted from a focus by carnivores on primate predation and bone accumulation. Brain's hypothesis prompted us to investigate, in a previous study, this taphonomic issue as it relates to density-mediated destruction of primate bones (J. Archaeol. Sci. 29, 2002, 883). Here we extend our investigation of Brain's hypothesis by examining additional intrinsic qualities of baboon bones and their role as mediators of skeletal element representation in carnivore-created assemblages. Using three modern adult baboon skeletons, we collected data on four intrinsic bone qualities (bulk bone mineral density, maximum length, volume, and cross-sectional area) for approximately 81 bones per baboon skeleton. We investigated the relationship between these intrinsic bone qualities and a measure of skeletal part representation (the percentage minimum animal unit) for baboon bones in carnivore refuse and scat assemblages. Refuse assemblages consist of baboon bones not ingested during ten separate experimental feeding episodes in which individual baboon carcasses were fed to individual captive leopards and a spotted hyena. Scat assemblages consist of those baboon bones recovered in carnivore regurgitations and feces resulting from the feeding episodes. In refuse assemblages, volume (i.e., size) was consistently the best predictor of element representation, while cross-sectional area was the poorest predictor in the leopard refuse assemblage and bulk bone mineral density (i.e., a measure of the proportion of cortical to trabecular bone) was the poorest predictor in the hyena refuse assemblage. In light of previous documentation of carnivore-induced density-mediated destruction to bone assemblages, we interpret the current findings as suggestive of the secondary importance of bulk bone mineral density to other intrinsic qualities of skeletal elements (e.g., size, maximum dimension, and average cross-sectional area). It is only when skeletal elements are too large for consumption (e.g., many long bones) that they are fragmented following intra-element patterns of density-mediated carnivore destruction. There appears to be a size threshold beneath which bulk bone mineral density contributes little to mediating carnivore destruction of carcasses. Thus, depending on body size of the predator, body size of the prey, and specific size of the element, bulk bone mineral density may play little or no role of primary importance in mediating the destruction of skeletal elements. We compare patterns in modern comparative assemblages to patterns in primate fossil assemblages from Swartkrans. One of the fossil assemblages, Swartkrans Member 1, Hanging Remnant, most closely approximates a hyena (possibly refuse) assemblage pattern, while the Swartkrans Member 2 assemblage most closely approximates a leopard (possibly scat) assemblage pattern. The Swartkrans Member 1, Lower Bank, assemblage does not closely approximate any of our modern comparative assemblage patterns.

Does bone debris in anterior cruciate ligament reconstruction really matter? A cohort study of a protocol for bone debris debridement

PubMed Central

Imam, Mohamed A.; Abdelkafy, Ashraf; Dinah, Feroz; Adhikari, Ajeya

2015-01-01

Background: The purpose of the current study was to determine whether a systematic five-step protocol for debridement and evacuation of bone debris during anterior cruciate ligament reconstruction (ACLR) reduces the presence of such debris on post-operative radiographs. Methods: A five-step protocol for removal of bone debris during arthroscopic assisted ACLR was designed. It was applied to 60 patients undergoing ACLR (Group 1), and high-quality digital radiographs were taken post-operatively in each case to assess for the presence of intra-articular bone debris. A control group of 60 consecutive patients in whom no specific bone debris protocol was applied (Group 2) and their post-operative radiographs were also checked for the presence of intra-articular bone debris. Results: In Group 1, only 15% of post-operative radiographs showed residual bone debris, compared to 69% in Group 2 (p < 0.001). Conclusion: A five-step systematic protocol for bone debris removal during arthroscopic assisted ACLR resulted in a significant decrease in residual bone debris seen on high-quality post-operative radiographs. PMID:27163060

Biodegradable Scaffolds for Bone Regeneration Combined with Drug-Delivery Systems in Osteomyelitis Therapy

PubMed Central

Dorati, Rossella; DeTrizio, Antonella; Modena, Tiziana; Conti, Bice; Benazzo, Francesco; Gastaldi, Giulia; Genta, Ida

2017-01-01

A great deal of research is ongoing in the area of tissue engineering (TE) for bone regeneration. A possible improvement in restoring damaged tissues involves the loading of drugs such as proteins, genes, growth factors, antibiotics, and anti-inflammatory drugs into scaffolds for tissue regeneration. This mini-review is focused on the combination of the local delivery of antibiotic agents with bone regenerative therapy for the treatment of a severe bone infection such as osteomyelitis. The review includes a brief explanation of scaffolds for bone regeneration including scaffolds characteristics and types, a focus on severe bone infections (especially osteomyelitis and its treatment), and a literature review of local antibiotic delivery by the combination of scaffolds and drug-delivery systems. Some examples related to published studies on gentamicin sulfate-loaded drug-delivery systems combined with scaffolds are discussed, and future perspectives are highlighted. PMID:29231857

Osteogenic Activity of Locally Applied Small Molecule Drugs in a Rat Femur Defect Model

PubMed Central

Cottrell, Jessica A.; Vales, Francis M.; Schachter, Deborah; Wadsworth, Scott; Gundlapalli, Rama; Kapadia, Rasesh; O'Connor, J. Patrick

2010-01-01

The long-term success of arthroplastic joints is dependent on the stabilization of the implant within the skeletal site. Movement of the arthroplastic implant within the bone can stimulate osteolysis, and therefore methods which promote rigid fixation or bone growth are expected to enhance implant stability and the long-term success of joint arthroplasty. In the present study, we used a simple bilateral bone defect model to analyze the osteogenic activity of three small-molecule drug implants via microcomputerized tomography (micro-CT) and histomorphometry. In this study, we show that local delivery of alendronate, but not lovastatin or omeprazole, led to significant new bone formation at the defect site. Since alendronate impedes osteoclast-development, it is theorized that alendronate treatment results in a net increase in bone formation by preventing osteoclast mediated remodeling of the newly formed bone and upregulating osteoblasts. PMID:20625499

Pharmacotherapy of bone metastases in breast cancer patients.

PubMed

Petrut, Bianca; Simmons, Christine; Broom, Reuben; Trinkaus, Mateya; Clemons, Mark

2008-04-01

A diagnosis of bone metastases is often a devastating occurrence in breast cancer patients. Bone metastases are associated with increased morbidity as reflected through pain, reduced quality of life and skeletal-related events. This paper reviews the role of different pharmacotherapeutic agents in the treatment of bone metastases from breast cancer. Randomised controlled trials of osteoclast-inhibiting agents, that is the bisphosphonates, have shown significant patient benefit. The aims of bisphosphonates are to prevent and delay skeletal-related events, reduce bone pain and improve quality of life. However, there are some limitations with bisphosphonate treatment. Biochemical markers of bone turnover seem to be a promising tool in guiding bisphosphonate treatment and future research directions. Hopefully, patient management will be further improved as new agents become available such as denosumab, osteoprotegerin analogues and anti-angiogenic agents.

Chondromyxoid fibroma of the pubic ramus: a case report and literature review.

PubMed

Arıkan, Murat; Toğral, Güray; Yıldırım, Ahmet; Aktaş, Erdem

2016-01-01

Chondromyxoid fibromas (CMF) are benign cartilaginous bone tumors which are found most frequently in the metaphyses of long bones. They comprise less than 1% of primary bone neoplasms. We report an interesting incidental case of a 43-year-old woman with a CMF of the left pubic ramus, presenting with complaints of gradual onset of left groin pain over a period of 2 years. According to radiological examination, a malign chondroid bone tumor was excluded, and histopathological examination confirmed the diagnosis of CMF. The patient underwent aggressive curettage and bone grafting 6 years ago. Pelvic bones are encountered as rare localizations for CMFs. Pubic ramus is accepted as an exceptional site for this benign bone tumor of cartilaginous origin. To our knowledge, no any other CMF case in this localization has been reported in the literature. In atypical regions such as the pelvis and pubic ramus, CMF must be considered for differential diagnosis of malign tumors.

Image analysis for dental bone quality assessment using CBCT imaging

NASA Astrophysics Data System (ADS)

Suprijanto; Epsilawati, L.; Hajarini, M. S.; Juliastuti, E.; Susanti, H.

2016-03-01

Cone beam computerized tomography (CBCT) is one of X-ray imaging modalities that are applied in dentistry. Its modality can visualize the oral region in 3D and in a high resolution. CBCT jaw image has potential information for the assessment of bone quality that often used for pre-operative implant planning. We propose comparison method based on normalized histogram (NH) on the region of inter-dental septum and premolar teeth. Furthermore, the NH characteristic from normal and abnormal bone condition are compared and analyzed. Four test parameters are proposed, i.e. the difference between teeth and bone average intensity (s), the ratio between bone and teeth average intensity (n) of NH, the difference between teeth and bone peak value (Δp) of NH, and the ratio between teeth and bone of NH range (r). The results showed that n, s, and Δp have potential to be the classification parameters of dental calcium density.

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

PubMed

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

2017-05-01

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

Effectiveness of mathematics education in secondary schools to meet the local universities missions in producing quality engineering and science undergraduates

NASA Astrophysics Data System (ADS)

Bakar Hasan, Abu; Fatah Abdul, Abdul; Selamat, Zalilah

2018-01-01

Critical claims by certain quarters that our local undergraduates are not performing well in Mathematics, Statistics and Numerical Methods needs a serious thinking and actions. Yearly examinations results from the Sijil Pelajaran Malaysia (SPM equivalent to A-Level) and Sijil Tinggi Pelajaran Malaysia (STPM equivalent to O-Level) levels have been splendid whereby it is either increasing or decreasing in a very tight range. A good foundation in mathematics and additional mathematics will tremendously benefit these students when they enter their university education especially in engineering and science courses. This paper uses SPM results as the primary data, questionnaires as secondary, and apply the Fish Bones technique for analysis. The outcome shows that there is a clear correlation between the causes and effect.

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.

The role of bone marrow evaluation in the staging of patients with otherwise localized, low-risk neuroblastoma.

PubMed

Russell, Heidi V; Golding, Laurie A; Suell, Mary Nell; Nuchtern, Jed G; Strother, Douglas R

2005-12-01

Bone marrow aspirations and biopsies are standard staging procedures for neuroblastoma because the tumor frequently metastasizes to the bone marrow. The presence of bone marrow metastases indicates stage 4 or 4S neuroblastoma by International Neuroblastoma Staging System (INSS) criteria; these stages are also associated with other metastatic sites of disease. We questioned whether bone marrow studies changed the staging or treatment of children with localized, completely resected tumors if there was no other evidence of metastatic spread. If stage of disease rarely changed with bone marrow results, it might be possible to avoid this procedure in a subset of patients with neuroblastoma. The staging studies of patients with INSS stage 1 (n = 29), 4 (n = 60), and 4S (n = 13) neuroblastoma from two institutions were reviewed. There were no patients upstaged from stage 1 to 4 or 4S by bone marrow metastases alone. Fifty-nine of 60 stage 4 patients had other sites of metastases on imaging studies, the remaining patient had an unresectable primary tumor and marrow disease. All subjects with stage 4S disease had liver metastases. Bone marrow studies did not contribute data that changed the stage of patients who had surgically resectable tumors and no evidence of metastatic spread on imaging studies. When present, metastatic spread to the marrow was associated with advanced local tumors or other sites of metastatic disease. Given the relatively small size of our study population, further studies are warranted that investigate the utility of bone marrow studies for patients who otherwise have INSS stage 1 neuroblastoma. 2005 Wiley-Liss, Inc.

A systematic review of optimal treatment strategies for localized Ewing's sarcoma of bone after neo-adjuvant chemotherapy.

PubMed

Werier, Joel; Yao, Xiaomei; Caudrelier, Jean-Michel; Di Primio, Gina; Ghert, Michelle; Gupta, Abha A; Kandel, Rita; Verma, Shailendra

2016-03-01

To perform a systematic review to investigate the optimal treatment strategy among the options of surgery alone, radiotherapy (RT) alone, and the combination of RT plus surgery in the management of localized Ewing's sarcoma of bone following neo-adjuvant chemotherapy. MEDLINE and EMBASE (1999 to February 2015), the Cochrane Library, and relevant conferences were searched. Two systematic reviews and eight full texts met the pre-planned study selection criteria. When RT was compared with surgery, a meta-analysis combining two papers showed that surgery resulted in a higher event-free survival (EFS) than RT in any location (HR = 1.50, 95% CI 1.12-2.00; p = 0.007). However another paper did not find a statistically significant difference in patients with pelvic disease, and no papers identified a significant difference in overall survival. When surgery plus RT was compared with surgery alone, a meta-analysis did not demonstrate a statistically significant difference for EFS between the two groups (HR = 1.21, 95% CI 0.90-1.63). Both surgical morbidities and radiation toxicities were reported. The existing evidence is based on very low aggregate quality as assessed by the GRADE approach. In patients with localized Ewing's sarcoma, either surgery alone (if complete surgical excision with clear margin can be achieved) or RT alone may be a reasonable treatment option. The optimal local treatment for an individual patient should be decided through consideration of patient characteristics, the potential benefit and harm of the treatment options, and patient preference. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Radiation dose optimization in pediatric temporal bone computed tomography: influence of tube tension on image contrast and image quality.

PubMed

Nauer, Claude Bertrand; Zubler, Christoph; Weisstanner, Christian; Stieger, Christof; Senn, Pascal; Arnold, Andreas

2012-03-01

The purpose of this experimental study was to investigate the effect of tube tension reduction on image contrast and image quality in pediatric temporal bone computed tomography (CT). Seven lamb heads with infant-equivalent sizes were scanned repeatedly, using four tube tensions from 140 to 80 kV while the CT-Dose Index (CTDI) was held constant. Scanning was repeated with four CTDI values from 30 to 3 mGy. Image contrast was calculated for the middle ear as the Hounsfield unit (HU) difference between bone and air and for the inner ear as the HU difference between bone and fluid. The influence of tube tension on high-contrast detail delineation was evaluated using a phantom. The subjective image quality of eight middle and inner ear structures was assessed using a 4-point scale (scores 1-2 = insufficient; scores 3-4 = sufficient). Middle and inner ear contrast showed a near linear increase with tube tension reduction (r = -0.94/-0.88) and was highest at 80 kV. Tube tension had no influence on spatial resolution. Subjective image quality analysis showed significantly better scoring at lower tube tensions, with highest image quality at 80 kV. However, image quality improvement was most relevant for low-dose scans. Image contrast in the temporal bone is significantly higher at low tube tensions, leading to a better subjective image quality. Highest contrast and best quality were found at 80 kV. This image quality improvement might be utilized to further reduce the radiation dose in pediatric low-dose CT protocols.

The Use of Lead Isotope and Rare Earth Element Geochemistry for Forensic Geographic Provenancing

NASA Astrophysics Data System (ADS)

Carey, A.; Darrah, T.; Harrold, Z.; Prutsman-Pfeiffer, J.; Poreda, R.

2008-12-01

Lead isotope and rare earth element composition of modern human bones are analyzed to explore their utility for geographical provenancing. DNA analysis is the standard for identification of individuals. DNA analysis requires a DNA match for comparison. Thus, DNA analysis is of limited use in cases involving unknown remains. Trace elements are incorporated into bones and teeth during biomineralization, recording the characteristics of an individual's geochemical environment. Teeth form during adolescence, recording the geochemical environment of an individual's youth. Bones remodel throughout an individual's lifetime. Bones consist of two types of bone tissue (cortical and trabecular) that remodel at different rates, recording the geochemical environment at the time of biomineralization. Cortical bone tissue, forming the outer surface of bones, is dense, hard tissue that remodels in 25-30 yrs. Conversely, trabecular bone tissue, the inner cavity of bones, is low density, porous and remodels in 2-5 years. Thus, analyzing teeth and both bone tissues allows for the development of a geographical time line capable of tracking immigration patterns through time instead of only an individual's youth. Geochemical isotopic techniques (Sr, O, C, N) have been used for geographical provenancing in physical anthropology. The isotopic values of Sr, C, O, N are predominantly a function of soil compositions in areas where food is grown or water is consumed. Application of these provenancing techniques has become difficult as an individual's diet may reflect the isotopic composition of foods obtained at the local grocer as opposed to local soil compositions. Thus, we explore the use of REEs and Pb isotopes for geographical provenancing. Pb and REEs are likely more reliable indicators of modern geographical location as their composition are high in bio-available sources such as local soils, atmospheric aerosols, and dust as opposed to Sr, C, O, N that are controlled by food and drinking water. Lead isotope and REE analysis of trabecular and cortical bone tissue of 60 femoral heads resected during hip replacement surgery at the Univ. of Roch. Medical Center were analyzed by a combination of TIMS and ICP-MS. Results show that Pb compositions are consistent with local soil with variable inputs from known environmental sources. Several samples demonstrate inputs from known environmental sources (e.g. Mississippi Valley ore) that was used in paint, solder, and US gasoline. Additionally, results suggest bioincorporation of Pb with isotopic composition consistent with that observed for Canadian gasoline aerosols. Immigrants included in the study show Pb compositions distinctly different than local residents.

Ultrastructure Organization of Human Trabeculae Assessed by 3D sSAXS and Relation to Bone Microarchitecture

PubMed Central

Guizar-Sicairos, Manuel; Gschwend, Oliver; Hangartner, Peter; Bunk, Oliver; Müller, Ralph; Schneider, Philipp

2016-01-01

Although the organization of bone ultrastructure, i.e. the orientation and arrangement of the mineralized collagen fibrils, has been in the focus of research for many years for cortical bone, and many models on the osteonal arrangement have been proposed, limited attention has been paid to trabecular bone ultrastructure. This is surprising because trabeculae play a crucial role for the mechanical strength of several bone sites, including the vertebrae and the femoral head. On this account, we first validated a recently developed method (3D sSAXS or 3D scanning small-angle X-ray scattering) for investigating bone ultrastructure in a quantitative and spatially resolved way, using conventional linearly polarized light microscopy as a gold standard. While both methods are used to analyze thin tissue sections, in contrast to polarized light microscopy, 3D sSAXS has the important advantage that it provides 3D information on the orientation and arrangement of bone ultrastructure. In this first study of its kind, we used 3D sSAXS to investigate the ultrastructural organization of 22 vertebral trabeculae of different alignment, types and sizes, obtained from 4 subjects of different ages. Maps of ultrastructure orientation and arrangement of the trabeculae were retrieved by stacking information from consecutive 20-μm-thick bone sections. The organization of the ultrastructure was analyzed in relation to trabecular microarchitecture obtained from computed tomography and to relevant parameters such as distance to trabecular surface, local curvature or local bone mineralization. We found that (i) ultrastructure organization is similar for all investigated trabeculae independent of their particular characteristics, (ii) bone ultrastructure exhibiting a high degree of orientation was arranged in domains, (iii) highly oriented ultrastructural areas were located closer to the bone surface, (iv) the ultrastructure of the human trabecular bone specimens followed the microarchitecture, being oriented mostly parallel to bone surface, and (v) local surface curvature seems to have an effect on the ultrastructure organization. Further studies that investigate bone ultrastructure orientation and arrangement are needed in order to understand its organization and consequently its relation to bone biology and mechanics. PMID:27547973

[Bone quantitative ultrasound].

PubMed

Matsukawa, Mami

2016-01-01

The conventional ultrasonic bone densitometry system can give us information of bone as ultrasonic wave velocity and attenuation. However, the data reflect both structural and material properties of bone. In order to focus only on the bone matrix properties without the effect of bone structure, studies of microscopic Brillouin scattering technique are introduced. The wave velocity in a trabecula was anisotropic and depended on the position and structure of the cancellous bone. The glycation also affected on the wave velocities in bone. As a new bone quality, the piezoelectricity of bone is also discussed.

Capturing microscopic features of bone remodeling into a macroscopic model based on biological rationales of bone adaptation.

PubMed

Kim, Young Kwan; Kameo, Yoshitaka; Tanaka, Sakae; Adachi, Taiji

2017-10-01

To understand Wolff's law, bone adaptation by remodeling at the cellular and tissue levels has been discussed extensively through experimental and simulation studies. For the clinical application of a bone remodeling simulation, it is significant to establish a macroscopic model that incorporates clarified microscopic mechanisms. In this study, we proposed novel macroscopic models based on the microscopic mechanism of osteocytic mechanosensing, in which the flow of fluid in the lacuno-canalicular porosity generated by fluid pressure gradients plays an important role, and theoretically evaluated the proposed models, taking biological rationales of bone adaptation into account. The proposed models were categorized into two groups according to whether the remodeling equilibrium state was defined globally or locally, i.e., the global or local uniformity models. Each remodeling stimulus in the proposed models was quantitatively evaluated through image-based finite element analyses of a swine cancellous bone, according to two introduced criteria associated with the trabecular volume and orientation at remodeling equilibrium based on biological rationales. The evaluation suggested that nonuniformity of the mean stress gradient in the local uniformity model, one of the proposed stimuli, has high validity. Furthermore, the adaptive potential of each stimulus was discussed based on spatial distribution of a remodeling stimulus on the trabecular surface. The theoretical consideration of a remodeling stimulus based on biological rationales of bone adaptation would contribute to the establishment of a clinically applicable and reliable simulation model of bone remodeling.

Are serial bone scans useful for the follow-up of clinically localized, low to intermediate grade prostate cancer managed with watchful observation alone?

PubMed

Yap, B K; Choo, R; Deboer, G; Klotz, L; Danjoux, C; Morton, G

2003-05-01

To assess the predictive value of serial bone scans as a surveillance tool for bone metastasis in men with clinically localized prostate cancer and managed with watchful observation. A prospective single-arm study was conducted to assess the feasibility of a watchful observation protocol with selective delayed intervention for patients with clinically localized prostate cancer, i.e. T1b-T2bN0M0, a Gleason score of 15 ng/mL the patient underwent bone scintigraphy every year. In all, 244 eligible patients were enrolled into the study. With a median follow-up of 30 months, 449 bone scans were taken (150 at baseline and 299 in follow-up evaluations); all 299 follow-up scans were negative for bone metastasis. Hence, the true rate of positive follow-up bone scans was estimated to be 0-1.0% (95% confidence). In all, 171 patients had at least one follow-up bone scan; of these, the number (%) of patients who had 1, 2, 3, 4 and >or= 5 follow-up scans was 89 (52), 53 (31), 17 (10), eight (4.7) and four (2.3), respectively. The PSA levels (ng/mL) corresponding to all follow-up bone scans were: 214 scans at PSA < 10, 61 at 10-14.9, 18 at 15-19.9 and six at >or= 20 (range 20.2-24.9). The probability of a negative bone scan was estimated to be 88-100% (95% confidence interval) when a PSA threshold of 15 ng/mL was used. The probability of positive findings in serial bone scans in untreated, localized, low to intermediate grade prostate cancer was low when the follow-up PSA level remained < 15 ng/mL. Avoiding bone scans in this group of patients would translate into a significant cost saving and reduction in their psychological and physical burden. As for those with a follow-up PSA of> 15 ng/mL, the role of serial bone scintigraphy remains undefined, as a longer follow-up and a larger sample are needed.

Effect of Anti-Sclerostin Therapy and Osteogenesis Imperfecta on Tissue-level Properties in Growing and Adult Mice While Controlling for Tissue Age

PubMed Central

Sinder, Benjamin P.; Lloyd, William R.; Salemi, Joseph D.; Marini, Joan C.; Caird, Michelle S.; Morris, Michael D.; Kozloff, Kenneth M.

2016-01-01

Bone composition and biomechanics at the tissue-level are important contributors to whole bone strength. Sclerostin antibody (Scl-Ab) is a candidate anabolic therapy for the treatment of osteoporosis that increases bone formation, bone mass, and bone strength in animal studies, but its effect on bone quality at the tissue-level has received little attention. Pre-clinical studies of Scl-Ab have recently expanded to include diseases with altered collagen and material properties such as Osteogenesis Imperfecta (OI). The purpose of this study was to investigate the role of Scl-Ab on bone quality by determining bone material composition and tissue-level mechanical properties in normal wild type (WT) tissue, as well as mice with a typical OI Gly→Cys mutation (Brtl/+) in type I collagen. Rapidly growing (3-week-old) and adult (6-month-old) WT and Brtl/+ mice were treated for 5 weeks with Scl-Ab. Fluorescent guided tissue-level bone composition analysis (Raman spectroscopy) and biomechanical testing (nanoindentation) were performed at multiple tissue ages. Scl-Ab increased mineral to matrix in adult WT and Brtl/+ at tissue ages of 2–4wks. However, no treatment related changes were observed in mineral to matrix levels at mid-cortex, and elastic modulus was not altered by Scl-Ab at any tissue age. Increased mineral-to-matrix was phenotypically observed in adult Brtl/+ OI mice (at tissue ages >3wk) and rapidly growing Brtl/+ (at tissue ages > 4wk) mice compared to WT. At identical tissue ages defined by fluorescent labels adult mice had generally lower mineral to matrix ratios and a greater elastic modulus than rapidly growing mice, demonstrating that bone matrix quality can be influenced by animal age and tissue age alike. In summary, these data suggest that Scl-Ab alters the matrix chemistry of newly formed bone while not affecting the elastic modulus, induces similar changes between Brtl/+ and WT mice, and provides new insight into the interaction between tissue age and animal age on bone quality. PMID:26769006

Effect of anti-sclerostin therapy and osteogenesis imperfecta on tissue-level properties in growing and adult mice while controlling for tissue age.

PubMed

Sinder, Benjamin P; Lloyd, William R; Salemi, Joseph D; Marini, Joan C; Caird, Michelle S; Morris, Michael D; Kozloff, Kenneth M

2016-03-01

Bone composition and biomechanics at the tissue-level are important contributors to whole bone strength. Sclerostin antibody (Scl-Ab) is a candidate anabolic therapy for the treatment of osteoporosis that increases bone formation, bone mass, and bone strength in animal studies, but its effect on bone quality at the tissue-level has received little attention. Pre-clinical studies of Scl-Ab have recently expanded to include diseases with altered collagen and material properties such as osteogenesis imperfecta (OI). The purpose of this study was to investigate the role of Scl-Ab on bone quality by determining bone material composition and tissue-level mechanical properties in normal wild type (WT) tissue, as well as mice with a typical OI Gly➔Cys mutation (Brtl/+) in type I collagen. Rapidly growing (3-week-old) and adult (6-month-old) WT and Brtl/+ mice were treated for 5weeks with Scl-Ab. Fluorescent guided tissue-level bone composition analysis (Raman spectroscopy) and biomechanical testing (nanoindentation) were performed at multiple tissue ages. Scl-Ab increased mineral to matrix in adult WT and Brtl/+ at tissue ages of 2-4wks. However, no treatment related changes were observed in mineral to matrix levels at mid-cortex, and elastic modulus was not altered by Scl-Ab at any tissue age. Increased mineral-to-matrix was phenotypically observed in adult Brtl/+ OI mice (at tissue ages>3wks) and rapidly growing Brtl/+ (at tissue ages>4wks) mice compared to WT. At identical tissue ages defined by fluorescent labels, adult mice had generally lower mineral to matrix ratios and a greater elastic modulus than rapidly growing mice, demonstrating that bone matrix quality can be influenced by animal age and tissue age alike. In summary, these data suggest that Scl-Ab alters the matrix chemistry of newly formed bone while not affecting the elastic modulus, induces similar changes between Brtl/+ and WT mice, and provides new insight into the interaction between tissue age and animal age on bone quality. Copyright © 2016 Elsevier Inc. All rights reserved.

One year of abaloparatide, a selective peptide activator of the PTH1 receptor, increased bone mass and strength in ovariectomized rats.

PubMed

Varela, Aurore; Chouinard, Luc; Lesage, Elisabeth; Guldberg, Robert; Smith, Susan Y; Kostenuik, Paul J; Hattersley, Gary

2017-02-01

Abaloparatide is a novel 34 amino acid peptide selected to be a potent and selective activator of the parathyroid hormone receptor 1 (PTHR1) signaling pathway. The effects of 12months of abaloparatide treatment on bone mass, bone strength and bone quality was assessed in osteopenic ovariectomized (OVX) rats. SD rats were subjected to OVX or sham surgery at 6months of age and left untreated for 3months to allow OVX-induced bone loss. Eighteen OVX rats were sacrificed after this bone depletion period, and the remaining OVX rats received daily s.c. injections of vehicle (n=18) or abaloparatide at 1, 5 or 25μg/kg/d (n=18/dose level) for 12months. Sham controls (n=18) received vehicle daily. Bone changes were assessed by DXA and pQCT after 0, 3, 6 or 12months of treatment, and destructive biomechanical testing was conducted at month 12 to assess bone strength and bone quality. Abaloparatide dose-dependently increased bone mass at the lumbar spine and at the proximal and diaphyseal regions of the tibia and femur. pQCT revealed that increased cortical bone volume at the tibia was a result of periosteal expansion and endocortical bone apposition. Abaloparatide dose-dependently increased structural strength of L4-L5 vertebral bodies, the femur diaphysis, and the femur neck. Increments in peak load for lumbar spine and the femur diaphysis of abaloparatide-treated rats persisted even after adjusting for treatment-related increments in BMC, and estimated material properties were maintained or increased at the femur diaphysis with abaloparatide. The abaloparatide groups also exhibited significant and positive correlations between bone mass and bone strength at these sites. These data indicate that gains in cortical and trabecular bone mass with abaloparatide are accompanied by and correlated with improvements in bone strength, resulting in maintenance or improvement in bone quality. Thus, this study demonstrated that long-term daily administration of abaloparatide to osteopenic OVX rats led to dose-dependent improvements in bone mass, geometry and strength. Copyright © 2016. Published by Elsevier Inc.

[Effect of milk product with soy isoflavones on quality of life and bone metabolism in postmenopausal Spanish women: randomized trial].

PubMed

García-Martín, Antonia; Quesada Charneco, Miguel; Alvárez Guisado, Alejandro; Jiménez Moleón, José Juan; Fonollá Joya, Juristo; Muñoz-Torres, Manuel

2012-02-04

To analyze the effects of nutritional intervention with a milk product enriched with soy isoflavones on quality of life and bone metabolism in postmenopausal Spanish women. We performed a double-blind controlled randomized trial in ninety-nine postmenopausal women. Group S women (n=48) were randomized to consume milk product enriched with soy isoflavone (50 mg/day) while group C (n=51) consumed product control for 12 months. Parameters of quality of life (Cervantes scale), markers of bone metabolism and bone mass estimated by ultrasound of the calcaneus (QUS) were evaluated. Overall, there was an improvement in the domains menopause (P=.015) and vasomotor symptoms (P<.001). S group emphasized the assessment of vasomotor symptoms (P=.001) and differed positively from group C in health (P=.019), sex (P=.021) and partner (P=.002). Serum levels TRAP (P<.001) and OPG (P=.007) decreased and concentrations of 25-OH-vitamin D increased (P<.001) without differences between groups. In the assessment of QUS, there was an increase in estimated bone mineral density in group S (P=.040), whereas in group C there were no significant differences. Daily consumption of these milk products increases levels of 25-OH-vitamin D and decreases bone metabolism markers. Additional supplementation with soy isoflavones seems to improve quality of life and bone mass in Spanish postmenopausal women. Copyright © 2010 Elsevier España, S.L. All rights reserved.

Assessment of bone quality within the tuberosities of the osteoporotic humeral head: relevance for anchor positioning in rotator cuff repair.

PubMed

Kirchhoff, Chlodwig; Braunstein, Volker; Milz, Stefan; Sprecher, Christoph M; Fischer, Florian; Tami, Andrea; Ahrens, Philipp; Imhoff, Andreas B; Hinterwimmer, Stefan

2010-03-01

Tears of the rotator cuff are highly prevalent in patients older than 60 years, thereby presenting a population also suffering from osteopenia or osteoporosis. Suture fixation in the bone depends on the holding strength of the anchoring technique, whether a bone tunnel or suture anchor is selected. Because of osteopenic or osteoporotic bone changes, suture anchors in the older patient might pull out, resulting in failure of repair. The aim of our study was to analyze the bone quality within the tuberosities of the osteoporotic humeral head using high-resolution quantitative computed tomography (HR-pQCT). Descriptive laboratory study. Thirty-six human cadaveric shoulders were analyzed using HR-pQCT. The mean bone volume to total volume (BV/TV) as well as trabecular bone mineral densities (trabBMDs) of the greater tuberosity (GT) and the lesser tuberosity (LT) were determined. Within the GT, 6 volumes of interest (VOIs) within the LT, and 2 VOIs and 1 control volume within the subchondral area beyond the articular surface were set. Comparing BV/TV of the medial and the lateral row, significantly higher values were found medially (P < .001). The highest BV/TV, 0.030% + or - 0.027%, was found in the posteromedial portion of the GT (P < .05). Regarding the analysis of the LT, no difference was found comparing the superior (BV/TV: 0.024% + or - 0.022%) and the inferior (BV/TV: 0.019% + or - 0.016%) portion. Analyzing trabBMD, equal proportions were found. An inverse correlation with a correlation coefficient of -0.68 was found regarding BV/TV of the posterior portion of the GT and age (P < .05). Significant regional differences of trabecular microarchitecture were found in our HR-pQCT study. The volume of highest bone quality resulted for the posteromedial aspect of the GT. Moreover, a significant correlation of bone quality within the GT and age was found, while the bone quality within the LT seems to be independent from it. The shape of the rotator cuff tear largely determines the bony site of tendon reattachment, although the surgeon has distinct options to modify anchor positioning. According to our results, placement of suture anchors in a medialized way at the border to the articular surface might guarantee a better structural bone stock.

Intra-operatively customized implant coating strategies for local and controlled drug delivery to bone.

PubMed

Trajkovski, Branko; Petersen, Ansgar; Strube, Patrick; Mehta, Manav; Duda, Georg N

2012-09-01

Bone is one of the few tissues in the human body with high endogenous healing capacity. However, failure of the healing process presents a significant clinical challenge; it is a tremendous burden for the individual and has related health and economic consequences. To overcome such healing deficits, various concepts for a local drug delivery to bone have been developed during the last decades. However, in many cases these concepts do not meet the specific requirements of either surgeons who must use these strategies or individual patients who might benefit from them. We describe currently available methods for local drug delivery and their limitations in therapy. Various solutions for drug delivery to bone focusing on clinical applications and intra-operative constraints are discussed and drug delivery by implant coating is highlighted. Finally, a new set of design and performance requirements for intra-operatively customized implant coatings for controlled drug delivery is proposed. In the future, these requirements may improve approaches for local and intra-operative treatment of patients. Copyright © 2012 Elsevier B.V. All rights reserved.

Osteoclast inhibition impairs chondrosarcoma growth and bone destruction.

PubMed

Otero, Jesse E; Stevens, Jeff W; Malandra, Allison E; Fredericks, Douglas C; Odgren, Paul R; Buckwalter, Joseph A; Morcuende, Jose

2014-12-01

Because Chondrosarcoma is resistant to available chemotherapy and radiation regimens, wide resection is the mainstay in treatment, which frequently results in high morbidity and which may not prevent local recurrence. There is a clear need for improved adjuvant treatment of this malignancy. We have observed the presence of osteoclasts in the microenvironment of chondrosarcoma in human pathological specimens. We utilized the Swarm rat chondrosarcoma (SRC) model to test the hypothesis that osteoclasts affect chondrosarcoma pathogenesis. We implanted SRC tumors in tibia of Sprague-Dawley rats and analyzed bone histologically and radiographically for bone destruction and tumor growth. At three weeks, tumors invaded local bone causing cortical disruption and trabecular resorption. Bone destruction was accompanied by increased osteoclast number and resorbed bone surface. Treatment of rats with the zoledronic acid prevented cortical destruction, inhibited trabecular resorption, and resulted in decreased tumor volume in bone. To confirm that inhibition of osteoclasts per se, and not off-target effects of drug, was responsible for the prevention of tumor growth and bone destruction, we implanted SRC into osteopetrotic rat tibia. SRC-induced bone destruction and tumor growth were impaired in osteopetrotic bone compared with control bone. The results from our animal model demonstrate that osteoclasts contribute to chondrosarcoma-mediated bone destruction and tumor growth and may represent a therapeutic target in particular chondrosarcoma patients. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Radiographic absorptiometry method in measurement of localized alveolar bone density changes.

PubMed

Kuhl, E D; Nummikoski, P V

2000-03-01

The objective of this study was to measure the accuracy and precision of a radiographic absorptiometry method by using an occlusal density reference wedge in quantification of localized alveolar bone density changes. Twenty-two volunteer subjects had baseline and follow-up radiographs taken of mandibular premolar-molar regions with an occlusal density reference wedge in both films and added bone chips in the baseline films. The absolute bone equivalent densities were calculated in the areas that contained bone chips from the baseline and follow-up radiographs. The differences in densities described the masses of the added bone chips that were then compared with the true masses by using regression analysis. The correlation between the estimated and true bone-chip masses ranged from R = 0.82 to 0.94, depending on the background bone density. There was an average 22% overestimation of the mass of the bone chips when they were in low-density background, and up to 69% overestimation when in high-density background. The precision error of the method, which was calculated from duplicate bone density measurements of non-changing areas in both films, was 4.5%. The accuracy of the intraoral radiographic absorptiometry method is low when used for absolute quantification of bone density. However, the precision of the method is good and the correlation is linear, indicating that the method can be used for serial assessment of bone density changes at individual sites.

Quantitative computed tomography and cranial burr holes: a model to evaluate the quality of cranial reconstruction in humans.

PubMed

Worm, Paulo Valdeci; Ferreira, Nelson Pires; Ferreira, Marcelo Paglioli; Kraemer, Jorge Luiz; Lenhardt, Rene; Alves, Ronnie Peterson Marcondes; Wunderlich, Ricardo Castilho; Collares, Marcus Vinicius Martins

2012-05-01

Current methods to evaluate the biologic development of bone grafts in human beings do not quantify results accurately. Cranial burr holes are standardized critical bone defects, and the differences between bone powder and bone grafts have been determined in numerous experimental studies. This study evaluated quantitative computed tomography (QCT) as a method to objectively measure cranial bone density after cranial reconstruction with autografts. In each of 8 patients, 2 of 4 surgical burr holes were reconstructed with autogenous wet bone powder collected during skull trephination, and the other 2 holes, with a circular cortical bone fragment removed from the inner table of the cranial bone flap. After 12 months, the reconstructed areas and a sample of normal bone were studied using three-dimensional QCT; bone density was measured in Hounsfield units (HU). Mean (SD) bone density was 1535.89 (141) HU for normal bone (P < 0.0001), 964 (176) HU for bone fragments, and 453 (241) HU for bone powder (P < 0.001). As expected, the density of the bone fragment graft was consistently greater than that of bone powder. Results confirm the accuracy and reproducibility of QCT, already demonstrated for bone in other locations, and suggest that it is an adequate tool to evaluate cranial reconstructions. The combination of QCT and cranial burr holes is an excellent model to accurately measure the quality of new bone in cranial reconstructions and also seems to be an appropriate choice of experimental model to clinically test any cranial bone or bone substitute reconstruction.

Impact of implant design on primary stability of orthodontic mini-implants.

PubMed

Wilmes, Benedict; Ottenstreuer, Stephanie; Su, Yu-Yu; Drescher, Dieter

2008-01-01

Skeletal anchorage with mini-implants has greatly broadened the treatment possibilities in orthodontics over the last few years. To reduce implant failure rates, it is advisable to obtain adequate primary stability. The aim of this study was to quantitatively analyze the impact of implant design and dimension on primary stability. Forty-two porcine iliac bone segments were prepared and embedded in resin. To evaluate the primary stability, we documented insertion torques of the following mini-implants: Aarhus Screw, AbsoAnchor, LOMAS, Micro-Anchorage-System, ORLUS and Spider Screw. In each bone, five Dual Top Screws were inserted for reference purposes to achieve comparability among the specimens. We observed wide variation in insertion torques and hence primary stability, depending on mini-implant design and dimension; the great impact that mini-implant diameter has on insertion torques was particularly conspicuous. Conical mini-implants achieved higher primary stabilities than cylindrical designs. The diameter and design of the mini-implant thread have a distinctive impact on primary stability. Depending on the region of insertion and local bone quality, the choice of the mini-implant design and size is crucial to establish sufficient primary stability.

Stem cells and other innovative intra-articular therapies for osteoarthritis: what does the future hold?

PubMed Central

2012-01-01

Osteoarthritis (OA), the most common type of arthritis in the world, is associated with suffering due to pain, productivity loss, decreased mobility and quality of life. Systemic therapies available for OA are mostly symptom modifying and have potential gastrointestinal, renal, hepatic, and cardiac side effects. BMC Musculoskeletal Disorders recently published a study showing evidence of reparative effects demonstrated by homing of intra-articularly injected autologous bone marrow stem cells in damaged cartilage in an animal model of OA, along with clinical and radiographic benefit. This finding adds to the growing literature showing the potential benefit of intra-articular (IA) bone marrow stem cells. Other emerging potential IA therapies include IL-1 receptor antagonists, conditioned autologous serum, botulinum toxin, and bone morphogenetic protein-7. For each of these therapies, trial data in humans have been published, but more studies are needed to establish that they are safe and effective. Several additional promising new OA treatments are on the horizon, but challenges remain to finding safe and effective local and systemic therapies for OA. Please see related article: http://www.biomedcentral.com/1471-2474/12/259 PMID:22551396

Tin-117m-labeled stannic (Sn.sup.4+) chelates

DOEpatents

Srivastava, Suresh C.; Meinken, George E.; Richards, Powell

1985-01-01

The radiopharmaceutical reagents of this invention and the class of Tin-117m radiopharmaceuticals are therapeutic and diagnostic agents that incorporate gamma-emitting nuclides that localize in bone after intravenous injection in mammals (mice, rats, dogs, and rabbits). Images reflecting bone structure or function can then be obtained by a scintillation camera that detects the distribution of ionizing radiation emitted by the radioactive agent. Tin-117m-labeled chelates of stannic tin localize almost exclusively in cortical bone. Upon intravenous injection of the reagent, the preferred chelates are phosphonate compounds, preferable, PYP, MDP, EHDP, and DTPA. This class of reagents is therapeutically and diagnostically useful in skeletal scintigraphy and for the radiotherapy of bone tumors and other disorders.

Systemic Mesenchymal Stromal Cell Transplantation Prevents Functional Bone Loss in a Mouse Model of Age-Related Osteoporosis.

PubMed

Kiernan, Jeffrey; Hu, Sally; Grynpas, Marc D; Davies, John E; Stanford, William L

2016-05-01

Age-related osteoporosis is driven by defects in the tissue-resident mesenchymal stromal cells (MSCs), a heterogeneous population of musculoskeletal progenitors that includes skeletal stem cells. MSC decline leads to reduced bone formation, causing loss of bone volume and the breakdown of bony microarchitecture crucial to trabecular strength. Furthermore, the low-turnover state precipitated by MSC loss leads to low-quality bone that is unable to perform remodeling-mediated maintenance--replacing old damaged bone with new healthy tissue. Using minimally expanded exogenous MSCs injected systemically into a mouse model of human age-related osteoporosis, we show long-term engraftment and markedly increased bone formation. This led to improved bone quality and turnover and, importantly, sustained microarchitectural competence. These data establish proof of concept that MSC transplantation may be used to prevent or treat human age-related osteoporosis. This study shows that a single dose of minimally expanded mesenchymal stromal cells (MSCs) injected systemically into a mouse model of human age-related osteoporosis display long-term engraftment and prevent the decline in bone formation, bone quality, and microarchitectural competence. This work adds to a growing body of evidence suggesting that the decline of MSCs associated with age-related osteoporosis is a major transformative event in the progression of the disease. Furthermore, it establishes proof of concept that MSC transplantation may be a viable therapeutic strategy to treat or prevent human age-related osteoporosis. ©AlphaMed Press.

Systemic Mesenchymal Stromal Cell Transplantation Prevents Functional Bone Loss in a Mouse Model of Age-Related Osteoporosis

PubMed Central

Kiernan, Jeffrey; Hu, Sally; Grynpas, Marc D.

2016-01-01

Age-related osteoporosis is driven by defects in the tissue-resident mesenchymal stromal cells (MSCs), a heterogeneous population of musculoskeletal progenitors that includes skeletal stem cells. MSC decline leads to reduced bone formation, causing loss of bone volume and the breakdown of bony microarchitecture crucial to trabecular strength. Furthermore, the low-turnover state precipitated by MSC loss leads to low-quality bone that is unable to perform remodeling-mediated maintenance—replacing old damaged bone with new healthy tissue. Using minimally expanded exogenous MSCs injected systemically into a mouse model of human age-related osteoporosis, we show long-term engraftment and markedly increased bone formation. This led to improved bone quality and turnover and, importantly, sustained microarchitectural competence. These data establish proof of concept that MSC transplantation may be used to prevent or treat human age-related osteoporosis. Significance This study shows that a single dose of minimally expanded mesenchymal stromal cells (MSCs) injected systemically into a mouse model of human age-related osteoporosis display long-term engraftment and prevent the decline in bone formation, bone quality, and microarchitectural competence. This work adds to a growing body of evidence suggesting that the decline of MSCs associated with age-related osteoporosis is a major transformative event in the progression of the disease. Furthermore, it establishes proof of concept that MSC transplantation may be a viable therapeutic strategy to treat or prevent human age-related osteoporosis. PMID:26987353

Effect on Bone Architecture of Marginal Grooves in Dental Implants Under Occlusal Loaded Conditions in Beagle Dogs.

PubMed

Kato, Hatsumi; Kuroshima, Shinichiro; Inaba, Nao; Uto, Yusuke; Sawase, Takashi

2018-02-01

The aim of this study was to clarify whether marginal grooves on dental implants affect osseointegration, bone structure, and the alignment of collagen fibers to determine bone quality under loaded conditions. Anodized Ti-6Al-4V alloy dental implants, with and without marginal grooves (test and control implants, respectively), were used (3.7 × 8.0 mm). Fourth premolars and first molars of 6 beagle mandibles were extracted. Two control and test implants were placed in randomly selected healed sites at 12 weeks after tooth extraction. Screw-retained single crowns for first molars were fabricated. Euthanasia was performed at 8 weeks after the application of occlusal forces. Implant marginal bone level, bone to implant contact (BIC), bone structure around dental implants, and the alignment of collagen fibers determining bone quality were analyzed. The marginal bone level in test implants was significantly higher than that in control implants. Occlusal forces significantly increased BIC in test implants ( P = .007), whereas BIC did not change in control implants, irrespective of occlusal forces ( P = .303). Moreover, occlusal forces significantly increased BIC in test implants compared with control implants ( P = .032). Additionally, occlusal forces preferentially aligned collagen fibers in test implants, but not control implants. Hence, marginal grooves on dental implants have positive effects on increased osseointegration and adapted bone quality based on the preferential alignment of collagen fibers around dental implants under loaded conditions.

Radionuclide bone scan SPECT-CT: lowering the dose of CT significantly reduces radiation dose without impacting CT image quality

PubMed Central

Gupta, Sandeep Kumar; Trethewey, Scott; Brooker, Bree; Rutherford, Natalie; Diffey, Jenny; Viswanathan, Suresh; Attia, John

2017-01-01

The CT component of SPECT-CT is required for attenuation correction and anatomical localization of the uptake on SPECT but there is no guideline about the optimal CT acquisition parameters. In our department, a standard CT acquisition protocol was changed in 2013 to give lower radiation dose to the patient. In this study, we retrospectively compared the effects on patient dose as well as the CT image quality with current versus older CT protocols. Ninety nine consecutive patients [n=51 Standard dose ‘old’ protocol (SDP); n=48 lower dose ‘new’ protocol (LDP)] with lumbar spine SPECT-CT for bone scan were examined. The main differences between the two protocols were that SDP used 130 kVp tube voltage and reference current-time product of 70 mAs whereas the LDP used 110 kVp and 40 mAs respectively. Various quantitative parameters from the CT images were obtained and the images were also rated blindly by two experienced nuclear medicine physicians for bony definition and noise. The mean calculated dose length product of the LDP group (121.5±39.6 mGy.cm) was significantly lower compared to the SDP group patients (266.9±96.9 mGy.cm; P<0.0001). This translated into a significant reduction in the mean effective dose to 1.8 mSv from 4.0 mSv. The physicians reported better CT image quality for the bony structures in LDP group although for soft tissue structures, the SDP group had better image quality. The optimized new CT acquisition protocol significantly reduced the radiation dose to the patient and in-fact improved CT image quality for the assessment of bony structures. PMID:28533938

Planning, guidance, and quality assurance of pelvic screw placement using deformable image registration

NASA Astrophysics Data System (ADS)

Goerres, J.; Uneri, A.; Jacobson, M.; Ramsay, B.; De Silva, T.; Ketcha, M.; Han, R.; Manbachi, A.; Vogt, S.; Kleinszig, G.; Wolinsky, J.-P.; Osgood, G.; Siewerdsen, J. H.

2017-12-01

Percutaneous pelvic screw placement is challenging due to narrow bone corridors surrounded by vulnerable structures and difficult visual interpretation of complex anatomical shapes in 2D x-ray projection images. To address these challenges, a system for planning, guidance, and quality assurance (QA) is presented, providing functionality analogous to surgical navigation, but based on robust 3D-2D image registration techniques using fluoroscopy images already acquired in routine workflow. Two novel aspects of the system are investigated: automatic planning of pelvic screw trajectories and the ability to account for deformation of surgical devices (K-wire deflection). Atlas-based registration is used to calculate a patient-specific plan of screw trajectories in preoperative CT. 3D-2D registration aligns the patient to CT within the projective geometry of intraoperative fluoroscopy. Deformable known-component registration (dKC-Reg) localizes the surgical device, and the combination of plan and device location is used to provide guidance and QA. A leave-one-out analysis evaluated the accuracy of automatic planning, and a cadaver experiment compared the accuracy of dKC-Reg to rigid approaches (e.g. optical tracking). Surgical plans conformed within the bone cortex by 3-4 mm for the narrowest corridor (superior pubic ramus) and  >5 mm for the widest corridor (tear drop). The dKC-Reg algorithm localized the K-wire tip within 1.1 mm and 1.4° and was consistently more accurate than rigid-body tracking (errors up to 9 mm). The system was shown to automatically compute reliable screw trajectories and accurately localize deformed surgical devices (K-wires). Such capability could improve guidance and QA in orthopaedic surgery, where workflow is impeded by manual planning, conventional tool trackers add complexity and cost, rigid tool assumptions are often inaccurate, and qualitative interpretation of complex anatomy from 2D projections is prone to trial-and-error with extended fluoroscopy time.

Interventions for treating simple bone cysts in the long bones of children.

PubMed

Zhao, Jia-Guo; Wang, Jia; Huang, Wan-Jie; Zhang, Peng; Ding, Ning; Shang, Jian

2017-02-04

Simple bone cysts, also known as a unicameral bone cysts or solitary bone cysts, are the most common type of benign bone lesion in growing children. Cysts may lead to repeated pathological fracture (fracture that occurs in an area of bone weakened by a disease process). Occasionally, these fractures may result in symptomatic malunion. The main goals of treatment are to decrease the risk of pathological fracture, enhance cyst healing and resolve pain. Despite the numerous treatment methods that have been used for simple bone cysts in long bones of children, there is no consensus on the best procedure. This is an update of a Cochrane review first published in 2014. To assess the effects (benefits and harms) of interventions for treating simple bone cysts in the long bones of children, including adolescents.We intended the following main comparisons: invasive (e.g. injections, curettage, surgical fixation) versus non-invasive interventions (e.g. observation, plaster cast, restricted activity); different categories of invasive interventions (i.e. injections, curettage, drilling holes and decompression, surgical fixation and continued decompression); different variations of each category of invasive intervention (e.g. different injection substances: autologous bone marrow versus steroid). We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, the China National Knowledge Infrastructure Platform, trial registers, conference proceedings and reference lists. Date of last search: April 2016. Randomised and quasi-randomised controlled trials evaluating methods for treating simple bone cysts in the long bones of children. Two review authors independently screened search results and performed study selection. We resolved differences in opinion between review authors by discussion and by consulting a third review author. Two review authors independently assessed risk of bias and data extraction. We summarised data using risk ratios (RRs) or mean differences (MDs), as appropriate, and 95% confidence intervals (CIs). We used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the overall quality of the evidence. In this update in 2017, we did not identify any new randomised controlled trials (RCT) for inclusion. We identified one ongoing trial that we are likely to include in a future update. Accordingly, our results are unchanged. The only included trial is a multicentre RCT conducted at 24 locations in North America and India that compared bone marrow injection with steroid (methylprednisolone acetate) injection for treating simple bone cysts. Up to three injections were planned for participants in each group. The trial involved 90 children (mean age 9.5 years) and presented results for 77 children at two-year follow-up. Although the trial had secure allocation concealment, it was at high risk of performance bias and from major imbalances in baseline characteristics. Reflecting these study limitations, we downgraded the quality of evidence by two levels to 'low' for most outcomes, meaning that we are unsure about the estimates of effect. For outcomes where there was serious imprecision, we downgraded the quality of evidence by a further level to 'very low'.The trial provided very low quality evidence that fewer children in the bone marrow injection group had radiographically assessed healing of bone cysts at two years than in the steroid injection group (9/39 versus 16/38; RR 0.55 favouring steroid injection, 95% CI 0.28 to 1.09). However, the result was uncertain and may be compatible with no difference or small benefit favouring bone marrow injection. Based on an illustrative success rate of 421 children with healed bone cysts per 1000 children treated with steroid injections, this equates to 189 fewer (95% CI 303 fewer to 38 more) children with healed bone cysts per 1000 children treated with bone marrow injections. There was low quality evidence of a lack of difference between the two interventions at two years in functional outcome, based on the Activity Scale for Kids function score (0 to 100; higher scores equate to better outcome: MD -0.90; 95% CI -4.26 to 2.46) or in pain assessed using the Oucher pain score. There was very low quality evidence of a lack of differences between the two interventions for adverse events: subsequent pathological fracture (9/39 versus 11/38; RR 0.80, 95% CI 0.37 to 1.70) or superficial infection (two cases in the bone marrow group). Recurrence of bone cyst, unacceptable malunion, return to normal activities, and participant satisfaction were not reported. The available evidence is insufficient to determine the relative effects of bone marrow versus steroid injections, although the bone marrow injections are more invasive. Noteably, the rate of radiographically assessed healing of the bone cyst at two years was well under 50% for both interventions. Overall, there is a lack of evidence to determine the best method for treating simple bone cysts in the long bones of children. Further RCTs of sufficient size and quality are needed to guide clinical practice.

Comparisons of bone mineral density and bone quality in adult rock climbers, resistance-trained men, and untrained men.

PubMed

Sherk, Vanessa D; Bemben, Michael G; Bemben, Debra A

2010-09-01

The nature of muscular contractions and episodes of impact loading during technical rock climbing are often varied and complex, and the resulting effects on bone health are unclear. The purpose of this study was to compare total body, lumbar spine, proximal femur, and forearm areal bone mineral density (aBMD) and tibia and forearm bone quality in male rock climbers (RC) (n = 15), resistance trained men (RT) (n = 16), and untrained male controls (CTR) (n = 16). Total body, anteroposterior (AP) lumbar spine, proximal femur, and forearm aBMD and body composition were measured using dual-energy X-ray absorptiometry (DXA) (Lunar Prodigy, v. 10.50.086; GE Healthcare, Waukesha, Wisconsin, U.S.A.). Volumetric BMD (vBMD), bone content, bone area, and muscle cross-sectional area (MCSA) of the tibia and forearm were measured using pQCT (peripheral quantitative computed tomography; Stratec XCT 3000, Pforzheim, Germany). No significant group differences were seen in bone-free lean body mass. CTR had significantly (p < 0.05) greater body fat % than RC and RT and significantly (p < 0.05) greater fat mass than RC. Lumbar spine and femoral neck aBMD were significantly (p < 0.05) greater in RT compared to both RC and CTR. RC had significantly (p < 0.05) lower aBMD at the 33% radius site than CTR. Forearm MCSA was significantly (p < 0.05) lower in CTR than in the other groups. No significant differences were seen between groups for vBMD or bone area of the tibia and forearm. In conclusion, resistance-trained men had higher bone density at the central skeletal sites than rock climbers; however, bone quality variables of the peripheral limbs were similar in rock climber and resistance-trained groups.

EVALUATION OF CALCIUM 47 IN NORMAL MAN AND ITS USE IN THE EVALUATION OF BONE HEALING FOLLOWING RADIATION THERAPY IN METASTATIC DESEASE

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

Brady, L.W.; Croll, M.N.; Stanton, L.

1962-02-01

It was concluded that radioactlve Ca/sup 47/ is an isotope suitable for the study of calcium metabolism in the body. It is easily traced by external counting technics. Local uptake measurements as well as ratios over various areas of the skeleton can be determined, thus yielding useful diagnostic information. It is a safe agent for use. It is possible to differentiate normal bone from areas of diseased bone using it. It is not useful for scintiscanning. It is grossly applicable in the evaluation of effects of radiation therapy to local metastatic lesions in bone. These observations support the fact thatmore » bone- seeking isotopes may well be useful as diagnostic agents for the evaluation of subradiographic metastases. (auth)« less

[Scintigraphic findings in a patient with sickle-cell thalassemia and recurrent pain attacks].

PubMed

Mikosch, Peter; Jauk, Barbara; Kaulfersch, Wilhelm; Gallowitsch, Hans-Jürgen; Lind, Peter

2003-01-01

The case of an eight years old African boy who suffers from sickle cell-thalassemia is presented. In the course of the disease frequent pain attacks occurred within the abdomen and extremities, recently also within the trunk. Local pain, at some occasions in combination with local swelling and always positive laboratory parameters for inflammation, hindered a solely clinical differentiation between bone infarcts and osteomyelitis. Bone scintigraphy, eventually in combination with bone marrow scintigraphy, can assist the clinician in the differentiation of aseptic bone infarcts versus secondary osteomyelitis. Based on the presented case scintigraphic results for bone infarcts, osteomyelitis and special scintigraphic pattern seen in sickle cell disease are presented. Furthermore, problems regarding the interpretation of the scintigraphies in relation to the delayed time after the beginning of pain attacks are discussed.

Bone remodelling: its local regulation and the emergence of bone fragility.

PubMed

Martin, T John; Seeman, Ego

2008-10-01

Bone modelling prevents the occurrence of damage by adapting bone structure - and hence bone strength - to its loading circumstances. Bone remodelling removes damage, when it inevitably occurs, in order to maintain bone strength. This cellular machinery is successful during growth, but fails during advancing age because of the development of a negative balance between the volumes of bone resorbed and formed during remodelling by the basic multicellular unit (BMU), high rates of remodelling during midlife in women and late in life in both sexes, and a decline in periosteal bone formation. together resulting in bone loss and structural decay each time a remodelling event occurs. The two steps in remodelling - resorption of a volume of bone by osteoclasts and formation of a comparable volume by osteoblasts - are sequential, but the regulatory events leading to these two fully differentiated functions are not. Reparative remodelling is initiated by damage producing osteocyte apoptosis, which signals the location of damage via the osteocyte canalicular system to endosteal lining cells which forms the canopy of a bone-remodelling compartment (BRC). Within the BRC, local recruitment of osteoblast precursors from the lining cells, the marrow and circulation, direct contact with osteoclast precursors, osteoclastogenesis and molecular cross-talk between precursors, mature cells, cells of the immune system, and products of the resorbed matrix, titrate the birth, work and lifespan of the cells of this multicellular remodelling machinery to either remove or form a net volume of bone appropriate to the mechanical requirements.

Nandrolone decanoate appears to increase bone callus formation in young adult rats after a complete femoral fracture.

PubMed

Guimarães, Ana Paula Franttini Garcia Moreno; Butezloff, Mariana Maloste; Zamarioli, Ariane; Issa, João Paulo Mardegan; Volpon, José Batista

2017-11-01

To evaluate the influence of nandrolone decanoate on fracture healing and bone quality in normal rats. Male rats were assigned to four groups (n=28/group): Control group consisting of animals without any intervention, Nandrolone decanoate (DN) group consisting of animals that received intramuscular injection of nandrolone decanoate, Fracture group consisting of animals with a fracture at the mid-diaphysis of the femur, and Fracture and nandrolone decanoate group consisting of animals with a femur fracture and treatment with nandrolone decanoate. Fractures were created at the mid-diaphysis of the right femur by a blunt trauma and internally fixed using an intramedullary steel wire. The DN was injected intramuscularly twice per week (10 mg/kg of body mass). The femurs were measured and evaluated by densitometry and mechanical resistance after animal euthanasia. The newly formed bone and collagen type I levels were quantified in the callus. The treated animals had longer femurs after 28 days. The quality of the intact bone was not significantly different between groups. The bone callus did show a larger mass in the treated rats. The administration of nandrolone decanoate did not affect the quality of the intact bone, but might have enhanced the bone callus formation.

Preservation and promotion of bone formation in the mandible as a response to a novel calcium-phosphate based biomaterial in mineral deficiency induced low bone mass male versus female rats

PubMed Central

Srinivasan, Kritika; Naula, Diana P.; Mijares, Dindo Q.; Janal, Malvin N.; LeGeros, Raquel Z.; Zhang, Yu

2016-01-01

Calcium and other trace mineral supplements have previously demonstrated to safely improve bone quality. We hypothesize that our novel calcium-phosphate based biomaterial (SBM) preserves and promotes mandibular bone formation in male and female rats on mineral deficient diet (MD). Sixty Sprague-Dawley rats were randomly assigned to receive one of three diets (n = 10): basic diet (BD), MD or mineral deficient diet with 2% SBM. Rats were sacrificed after 6 months. Micro-Computed Tomography (μCT) was used to evaluate bone volume and 3D-microarchitecture while microradiography (Faxitron) was used to measure bone mineral density from different sections of the mandible. Results showed that bone quality varied with region, gender and diet. MD reduced bone mineral density (BMD) and volume and increased porosity. SBM preserved BMD and bone mineral content (BMC) in the alveolar bone and condyle in both genders. In the alveolar crest and mandibular body, while preserving more bone in males, SBM also significantly supplemented female bone. Results indicate that mineral deficiency leads to low bone mass in skeletally immature rats, comparatively more in males. Furthermore, SBM administered as a dietary supplement was effective in preventing mandibular bone loss in all subjects. This study suggests that the SBM preparation has potential use in minimizing low peak bone mass induced by mineral deficiency and related bone loss irrespective of gender. PMID:26914814

Increased physical activity ameliorates high fat diet-induced bone resorption in mice

USDA-ARS?s Scientific Manuscript database

It has been recognized that mechanical stresses associated with physical activity (PA) have beneficial effects on increasing bone mineral density (BMD) and improving bone quality. On the other hand, high fat diet (HFD) and obesity increase bone marrow adiposity leading to increased excretion of pro-...

Mechanical Vibration Mitigates the Decrease of Bone Quantity and Bone Quality of Leptin Receptor-Deficient Db/Db Mice by Promoting Bone Formation and Inhibiting Bone Resorption.

PubMed

Jing, Da; Luo, Erping; Cai, Jing; Tong, Shichao; Zhai, Mingming; Shen, Guanghao; Wang, Xin; Luo, Zhuojing

2016-09-01

Leptin, a major hormonal product of adipocytes, is involved in regulating appetite and energy metabolism. Substantial studies have revealed the anabolic actions of leptin on skeletons and bone cells both in vivo and in vitro. Growing evidence has substantiated that leptin receptor-deficient db/db mice exhibit decreased bone mass and impaired bone microstructure despite several conflicting results previously reported. We herein systematically investigated bone microarchitecture, mechanical strength, bone turnover and its potential molecular mechanisms in db/db mice. More importantly, we also explored an effective approach for increasing bone mass in leptin receptor-deficient animals in an easy and noninvasive manner. Our results show that deterioration of trabecular and cortical bone microarchitecture and decreases of skeletal mechanical strength-including maximum load, yield load, stiffness, energy, tissue-level modulus and hardness-in db/db mice were significantly ameliorated by 12-week, whole-body vibration (WBV) with 0.5 g, 45 Hz via micro-computed tomography (μCT), three-point bending, and nanoindentation examinations. Serum biochemical analysis shows that WBV significantly decreased serum tartrate-resistant acid phosphatase 5b (TRACP5b) and CTx-1 levels and also mitigated the reduction of serum osteocalcin (OCN) in db/db mice. Bone histomorphometric analysis confirmed that decreased bone formation-lower mineral apposition rate, bone formation rate, and osteoblast numbers in cancellous bone-in db/db mice were suppressed by WBV. Real-time PCR assays show that WBV mitigated the reductions of tibial alkaline phosphatase (ALP), OCN, Runt-related transcription factor 2 (RUNX2), type I collagen (COL1), BMP2, Wnt3a, Lrp6, and β-catenin mRNA expression, and prevented the increases of tibial sclerostin (SOST), RANK, RANKL, RANL/osteoprotegerin (OPG) gene levels in db/db mice. Our results show that WBV promoted bone quantity and quality in db/db mice with obvious anabolic and anticatabolic effects. This study not only enriches our basic knowledge about bone quality and bone turnover mechanisms in leptin receptor-deficient animals, but also advances our understanding of the skeletal sensitivity of leptin-resistant db/db mice in response to external mechanical stimulation. © 2016 American Society for Bone and Mineral Research. © 2016 American Society for Bone and Mineral Research.

Reduced bone mineral density is not associated with significantly reduced bone quality in men and women practicing long-term calorie restriction with adequate nutrition.

PubMed

Villareal, Dennis T; Kotyk, John J; Armamento-Villareal, Reina C; Kenguva, Venkata; Seaman, Pamela; Shahar, Allon; Wald, Michael J; Kleerekoper, Michael; Fontana, Luigi

2011-02-01

Calorie restriction (CR) reduces bone quantity but not bone quality in rodents. Nothing is known regarding the long-term effects of CR with adequate intake of vitamin and minerals on bone quantity and quality in middle-aged lean individuals. In this study, we evaluated body composition, bone mineral density (BMD), and serum markers of bone turnover and inflammation in 32 volunteers who had been eating a CR diet (approximately 35% less calories than controls) for an average of 6.8 ± 5.2 years (mean age 52.7 ± 10.3 years) and 32 age- and sex-matched sedentary controls eating Western diets (WD). In a subgroup of 10 CR and 10 WD volunteers, we also measured trabecular bone (TB) microarchitecture of the distal radius using high-resolution magnetic resonance imaging. We found that the CR volunteers had significantly lower body mass index than the WD volunteers (18.9 ± 1.2 vs. 26.5 ± 2.2 kg m(-2) ; P = 0.0001). BMD of the lumbar spine (0.870 ± 0.11 vs. 1.138 ± 0.12 g cm(-2) , P = 0.0001) and hip (0.806 ± 0.12 vs. 1.047 ± 0.12 g cm(-2) , P = 0.0001) was also lower in the CR than in the WD group. Serum C-terminal telopeptide and bone-specific alkaline phosphatase concentration were similar between groups, while serum C-reactive protein (0.19 ± 0.26 vs. 1.46 ± 1.56 mg L(-1) , P = 0.0001) was lower in the CR group. Trabecular bone microarchitecture parameters such as the erosion index (0.916 ± 0.087 vs. 0.877 ± 0.088; P = 0.739) and surface-to-curve ratio (10.3 ± 1.4 vs. 12.1 ± 2.1, P = 0.440) were not significantly different between groups. These findings suggest that markedly reduced BMD is not associated with significantly reduced bone quality in middle-aged men and women practicing long-term calorie restriction with adequate nutrition.

Alcohol: A Simple Nutrient with Complex Actions on Bone in the Adult Skeleton

PubMed Central

Gaddini, Gino W.; Turner, Russell T.; Grant, Kathleen A.; Iwaniec, Urszula T.

2016-01-01

Background Alcohol is an important nonessential component of diet, but the overall impact of drinking on bone health, especially at moderate levels, is not well understood. Bone health is important because fractures greatly reduce quality of life and are a major cause of morbidity and mortality in the elderly. Regular alcohol consumption is most common following skeletal maturity, emphasizing the importance of understanding the skeletal consequences of drinking in adults. Method This review focuses on describing the complex effects of alcohol on the adult skeleton. Studies assessing the effects of alcohol on bone in adult humans as well as skeletally-mature animal models published since the year 2000 are emphasized. Results Light to moderate alcohol consumption is generally reported to be beneficial, resulting in higher bone mineral density (BMD) and reduced age-related bone loss, whereas heavy alcohol consumption is generally associated with decreased BMD, impaired bone quality and increased fracture risk. Bone remodeling is the principle mechanism for maintaining a healthy skeleton in adults and dysfunction in bone remodeling can lead to bone loss and/or decreased bone quality. Light to moderate alcohol may exert beneficial effects in older individuals by slowing the rate of bone remodeling but the impact of light to moderate alcohol on bone remodeling in younger individuals is less certain. The specific effects of alcohol on bone remodeling in heavy drinkers is even less certain because the effects are often obscured by unhealthy lifestyle choices, alcohol-associated disease, and altered endocrine signaling. Conclusions Although there have been advances in understanding the complex actions of alcohol on bone, much remains to be determined. Limited evidence implicates age, skeletal site evaluated, duration and pattern of drinking as important variables. Few studies systematically evaluating the impact of these factors have been conducted and should be made a priority for future research. In addition, studies performed in skeletally mature animals have potential to reveal mechanistic insights into the precise actions of alcohol and associated co-morbidity factors on bone remodeling. PMID:26971854

Comparison of Bone Grafts From Various Donor Sites in Human Bone Specimens.

PubMed

Kamal, Mohammad; Gremse, Felix; Rosenhain, Stefanie; Bartella, Alexander K; Hölzle, Frank; Kessler, Peter; Lethaus, Bernd

2018-05-14

The objective of the current study was to compare the three-dimensional (3D) morphometric microstructure in human cadaveric bone specimens taken from various commonly utilized donor sites for autogenous bone grafting. Autogenous bone grafts can be harvested from various anatomic sites and express heterogeneous bone quality with a specific 3D microstructure for each site. The long-term structural integrity and susceptibility to resorption of the graft depend on the selected donor bone. Micro-computed tomography generates high-resolution datasets of bone structures and calcifications making this modality versatile for microarchitecture analysis and quantification of the bone. Six bone specimens, 10 mm in length, where anatomically possible, were obtained from various anatomical sites from 10 human dentate cadavers (4 men, 6 women, mean age 69.5 years). Specimens were scanned using a micro-computed tomography device and volumetrically reconstructed. A virtual cylindrical inclusion was reconstructed to analyze the bone mineral density and structural morphometric analysis using bone indices: relative bone volume, surface density, trabecular thicknesses, and trabecular separation. Calvarial bone specimens showed the highest mineral density, followed by the chin, then mandibular ramus then the tibia, whereas iliac crest and maxillary tuberosity had lower bone mineral densities. The pairwise comparison revealed statistically significant differences in the bone mineral density and relative bone volume index in the calvaria, mandibular ramus, mandibular symphysis groups when compared with those in the iliac crest and maxillary tuberosity, suggesting higher bone quality in the former groups than in the latter; tibial specimens expressed variable results.

The Local Pharmacokinetics of 3H-Ropivacaine and 14C-Lidocaine After Maxillary Infiltration Anesthesia in Rats

PubMed Central

Kimi, Hiromi; Yamashiro, Mikiko; Hashimoto, Shuichi

2012-01-01

The effects of infiltration anesthesia with ropivacaine on the dental pulp are considered to be weak. This may be partly associated with its permeation into the oral tissue. With the objective of investigating the local pharmacokinetics of ropivacaine and lidocaine following infiltration anesthesia, we injected 3H-ropivacaine or 14C-lidocaine to the palatal mucosa in rats, measured distributions of radioactivity in the maxilla, and compared the local pharmacokinetics of these agents. The animals were sacrificed at various times and the maxillas were removed. The palatal mucosa and maxillary nerve were resected, and the bone was divided into 6 portions. We measured radioactivity in each tissue and calculated the level of each local anesthetic (n  =  8). Lidocaine diffused to the surrounding tissue immediately after the injection, whereas ropivacaine tended to remain in the palatal mucosa for a longer period. Lidocaine showed a higher affinity for the maxillary bone than ropivacaine. There was a correlation between the distribution level of local anesthetics in the maxillary bone and that in the maxillary nerve. The lower-level effects of infiltration anesthesia with ropivacaine on the dental pulp may be because ropivacaine has a high affinity for soft tissue, and its transfer to bone is slight. PMID:22822994

Cisplatin loaded PMMA: mechanical properties, surface analysis and effects on Saos-2 cell culture.

PubMed

Özben, Hakan; Eralp, Levent; Baysal, Gökhan; Cort, Ayşegül; Sarkalkan, Nazli; Özben, Tomris

2013-01-01

Despite wide resection and systemic chemotherapy, bone tumors may present with local recurrences, metastases and pathological fractures. Application of bone cement containing antineoplastic drug to fill the defect after resection of metastatic lesions and to support implants has been suggested to prevent local tumor growth and implant failures. In this study, we aimed to demonstrate the effects of the addition of cisplatin which is a widely used antineoplastic drug for osteosarcoma, on the mechanical properties of bone cement, and to evaluate the cytotoxic effects of eluted cisplatin on Saos-2 cell culture. Two cement samples were prepared by mixing 100 mg and 300 mg of cisplatin powder with 40 g cement powder. The bone cement of the control group did not contain cisplatin. Mechanical analyses included 4-point bending, compression and shear testing. For cytotoxicity analysis, samples were incubated in Dulbecco's Modified Eagle's medium for 15 days. Mediums were applied to Saos-2 cell culture and cell viability was measured. Surface analyses were performed by scanning electron microscope (SEM). The addition of cisplatin did not alter the mechanical properties of bone cement. It was observed that the eluted cisplatin had cytotoxic effects on Saos-2 cells. SEM analyses demonstrated cisplatin granules on the surface of cement samples. Cisplatin maintains its cytotoxic property when released from bone cement without compromising the mechanical stability. Application of cisplatin loaded bone cement may help local control of tumor growth. We believe that our study will shed light on to these new practices for the treatment of bone cancers and will encourage future studies.

Diagnosing and discriminating between primary and secondary aneurysmal bone cysts

PubMed Central

Sasaki, Hiromi; Nagano, Satoshi; Shimada, Hirofumi; Yokouchi, Masahiro; Setoguchi, Takao; Ishidou, Yasuhiro; Kunigou, Osamu; Maehara, Kosuke; Komiya, Setsuro

2017-01-01

Aneurysmal bone cysts (ABCs) are benign bony lesions frequently accompanied by multiple cystic lesions and aggressive bone destruction. They are relatively rare lesions, representing only 1% of bone tumors. The pathogenesis of ABCs has yet to be elucidated. In the present study, a series of 22 cases of primary and secondary ABC from patients treated in Department of Orthopedic Surgery, Kagoshima University Hospital (Kagoshima, Japan) from 2001–2015 were retrospectively analyzed. The average age at the time of diagnosis of primary ABC was 17.9 years. Intralesional curettage and artificial bone grafting were performed in the majority of the patients with primary ABC. The local recurrence rate following curettage for primary ABC was 18%, and the cause of local recurrence was considered to be insufficient curettage. Although no adjuvant therapy was administered during the surgeries, it may assist the prevention of local recurrence in certain cases. The cases of secondary ABC were preceded by benign bone tumors, including fibrous dysplasia, giant cell tumors, chondroblastoma and non-ossifying fibroma. The features of the secondary ABC typically reflected those of the preceding bone tumor. In the majority of cases, distinguishing the primary ABC from the secondary ABC was possible based on characteristic features, including age of the patient at diagnosis and the tumor location. In cases that exhibit ambiguous features, including a soft tissue mass or a thick septal enhancement on the preoperative magnetic resonance images, a biopsy must be obtained in order to exclude other types of aggressive bone tumors, including giant cell tumor, osteosarcoma and telangiectatic osteosarcoma. PMID:28454393

Fine mapping of the human bone morphogenetic protein-4 gene (BMP4) to chromosome 14q22-q23 by in situ hybridization

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

Wijngaard, A. van den; Boersma, C.J.C.; Olijve, W.

Bone morphogenetic protein-4 (BMP-4) is a member of the transforming growth factor-{beta} (TGF-{beta}) superfamily and is involved in morphogenesis and bone cell differentiation. Recombinant BMP-4 can induce ectopic cartilage and bone formation when implanted subcutaneously or intramuscularly in rodents. This ectopic bone formation process resembles the process of bone formation during embryogenesis and fracture healing. A cosmid clone containing the complete human bone morphogenetic protein-4 gene (BMP4) was isolated (details to be published elsewhere) and used as a probe to determine the precise chromosomal localization of the human BMP4 gene. This cosmid clone was labeled with biotin-14-dATP and hybridized inmore » situ to chromosomal preparations of metaphase cells as described previously. In 20 metaphase preparations, an intense and specific fluorescence signal (FITC) was detected on the q arm of chromosome 14. The DAPI-counterstained chromosomes were computer-converted into GTG-like banding patterns, allowing the regional localization of BMP4 within 14q22-q23. 10 refs., 1 fig.« less

Diagnostic imaging of trabecular bone microstructure for oral implants: a literature review.

PubMed

Ibrahim, N; Parsa, A; Hassan, B; van der Stelt, P; Wismeijer, D

2013-01-01

Several dental implant studies have reported that radiographic evaluation of bone quality can aid in reducing implant failure. Bone quality is assessed in terms of its quantity, density, trabecular characteristics and cells. Current imaging modalities vary widely in their efficiency in assessing trabecular structures, especially in a clinical setting. Most are very costly, require an extensive scanning procedure coupled with a high radiation dose and are only partially suitable for patient use. This review examines the current literature regarding diagnostic imaging assessment of trabecular microstructure prior to oral implant placement and suggests cone beam CT as a method of choice for evaluating trabecular bone microstructure.

Osteoporosis Imaging: State of the Art and Advanced Imaging

PubMed Central

2012-01-01

Osteoporosis is becoming an increasingly important public health issue, and effective treatments to prevent fragility fractures are available. Osteoporosis imaging is of critical importance in identifying individuals at risk for fractures who would require pharmacotherapy to reduce fracture risk and also in monitoring response to treatment. Dual x-ray absorptiometry is currently the state-of-the-art technique to measure bone mineral density and to diagnose osteoporosis according to the World Health Organization guidelines. Motivated by a 2000 National Institutes of Health consensus conference, substantial research efforts have focused on assessing bone quality by using advanced imaging techniques. Among these techniques aimed at better characterizing fracture risk and treatment effects, high-resolution peripheral quantitative computed tomography (CT) currently plays a central role, and a large number of recent studies have used this technique to study trabecular and cortical bone architecture. Other techniques to analyze bone quality include multidetector CT, magnetic resonance imaging, and quantitative ultrasonography. In addition to quantitative imaging techniques measuring bone density and quality, imaging needs to be used to diagnose prevalent osteoporotic fractures, such as spine fractures on chest radiographs and sagittal multidetector CT reconstructions. Radiologists need to be sensitized to the fact that the presence of fragility fractures will alter patient care, and these fractures need to be described in the report. This review article covers state-of-the-art imaging techniques to measure bone mineral density, describes novel techniques to study bone quality, and focuses on how standard imaging techniques should be used to diagnose prevalent osteoporotic fractures. © RSNA, 2012 PMID:22438439

Unusual localizations of unicameral bone cysts and aneurysmal bone cysts: A retrospective review of 451 cases.

PubMed

Aycan, Osman Emre; Çamurcu, İsmet Yalkın; Özer, Devrim; Arıkan, Yavuz; Kabukçuoğlu, Yavuz Selim

2015-06-01

Unicameral bone cysts (UBC) and aneurysmal bone cysts (ABC) are benign cystic lesions of bone which are easily diagnosed. However, unusual locations may lead to a false diagnosis. Therefore the aim of this retrospective study was to determine the frequency of unusual localizations. The authors studied 451 cases with histopathologically confirmed diagnosis of UBC or ABC, seen between 1981 and 2012. In the UBC group (352 cases) humerus, femur and calcaneus were found to be the most common sites, while acetabulum, scapula, scaphoid, lunatum, metacarpals, metatarsals, toe phalanges and ulna each accounted for less than 1%. In the ABC group (99 cases) the most common sites of involvement were femur, humerus and tibia, while finger phalanges, ilium, acetabulum, pubis, calcaneus, cuboid, and toe phalanges each accounted for only 1%. The differential diagnosis of cystic bone lesions should include both UBC and ABC. Pain complaints plead for the latter, except in case of fracture.

Decrease in local volumetric bone mineral density (vBMD) in osteoarthritic joints is associated with the increase in cartilage damage: a pQCT study

NASA Astrophysics Data System (ADS)

Tamaddon, Maryam; Chen, Shen Mao; Vanaclocha, Leyre; Hart, Alister; El-Husseiny, Moataz; Henckel, Johann; Liu, Chaozong

2017-11-01

Osteoarthritis (OA) is the most common type of arthritis and a major cause of disability in the adult population. It affects both cartilage and subchondral bone in the joints. There has been some progress in understanding the changes in subchondral bone with progression of osteoarthritis. However, local changes in subchondral bone such as microstructure or volumetric bone mineral density in connection with the defect in cartilage are relatively unexplored. To develop an effective treatment for progression of OA, it is important to understand how the physical environment provided by the subchondral bone affects the overlying cartilage. In this study we examined the volumetric bone mineral density (vBMD) distribution in the osteoarthritic joint tissues obtained from total hip replacement surgeries due to osteoarthritis, using peripheral quantitative CT (pQCT). It was found that there is a significant decrease in volumetric bone mineral density, which co-localises with the damage in the overlying cartilage. This was not limited to the subchondral bone immediately adjacent to the cartilage defect but continued in the layers below. Bone resorption and cyst formation in the OA tissues were also detected. We observed that the bone surrounding subchondral bone cysts exhibited much higher volumetric bone mineral density than that of the surrounding bones. PQCT was able to detect significant changes in vBMD between OA and non-OA samples, as well as between areas of different cartilage degeneration, which points to its potential as a technique for detection of early OA.

Comparison of six bone-graft substitutes regarding to cell seeding efficiency, metabolism and growth behaviour of human mesenchymal stem cells (MSC) in vitro.

PubMed

Seebach, Caroline; Schultheiss, Judith; Wilhelm, Kerstin; Frank, Johannes; Henrich, Dirk

2010-07-01

Various synthetic bone-graft substitutes are used commercially as osteoconductive scaffolds in the treatment of bone defects and fractures. The role of bone-graft substitutes is changing from osteoconductive conduits for growth to an delivery system for biologic fracture treatments. Achieving optimal bone regeneration requires biologics (e.g. MSC) and using the correct scaffold incorporated into a local environment for bone regeneration. The need for an unlimited supply with high quality bone-graft substitutes continue to find alternatives for bone replacement surgery. This in vitro study investigates cell seeding efficiency, metabolism, gene expression and growth behaviour of MSC sown on six commercially clinical available bone-graft substitutes in order to define their biological properties: synthetic silicate-substituted porous hydroxyapatite (Actifuse ABX), synthetic alpha-TCP (Biobase), synthetic beta-TCP (Vitoss), synthetic beta-TCP (Chronos), processed human cancellous allograft (Tutoplast) and processed bovines hydroxyapatite ceramic (Cerabone). 250,000 MSC derived from human bone marrow (n=4) were seeded onto the scaffolds, respectively. On days 2, 6 and 10 the adherence of MSC (fluorescence microscopy) and cellular activity (MTT assay) were analysed. Osteogenic gene expression (cbfa-1) was analysed by RT-PCR and scanning electron microscopy was performed. The highest number of adhering cells was found on Tutoplast (e.g. day 6: 110.0+/-24.0 cells/microscopic field; p<0.05) followed by Chronos (47.5+/-19.5, p<0.05), Actifuse ABX (19.1+/-4.4), Biobase (15.7+/-9.9), Vitoss (8.8+/-8.7) and Cerabone (8.1+/-2.2). MSC seeded onto Tutoplast showed highest metabolic activity and gene expression of cbfa-1. These data are confirmed by scanning electron microscopy. The cell shapes varied from round-shaped cells to wide spread cells and cell clusters, depending on the bone-graft substitutes. Processed human cancellous allograft is a well-structured and biocompatible scaffold for ingrowing MSC in vitro. Of all other synthetical scaffolds, beta-tricalcium phosphate (Chronos) have shown the best growth behaviour for MSC. Our results indicate that various bone-graft substitutes influence cell seeding efficiency, metabolic activity and growth behaviour of MSC in different manners. We detected a high variety of cellular integration of MSC in vitro, which may be important for bony integration in the clinical setting. 2010 Elsevier Ltd. All rights reserved.

Non-destructive and non-invasive observation of friction and wear of human joints and of fracture initiation by acoustic emission.

PubMed

Schwalbe, H J; Bamfaste, G; Franke, R P

1999-01-01

Quality control in orthopaedic diagnostics according to DIN EN ISO 9000ff requires methods of non-destructive process control, which do not harm the patient by radiation or by invasive examinations. To obtain an improvement in health economy, quality-controlled and non-destructive measurements have to be introduced into the diagnostics and therapy of human joints and bones. A non-invasive evaluation of the state of wear of human joints and of the cracking tendency of bones is, as of today's point of knowledge, not established. The analysis of acoustic emission signals allows the prediction of bone rupture far below the fracture load. The evaluation of dry and wet bone samples revealed that it is possible to conclude from crack initiation to the bone strength and thus to predict the probability of bone rupture.

In vivo outcomes of tissue-engineered osteochondral grafts.

PubMed

Bal, B Sonny; Rahaman, Mohamed N; Jayabalan, Prakash; Kuroki, Keiichi; Cockrell, Mary K; Yao, Jian Q; Cook, James L

2010-04-01

Tissue-engineered osteochondral grafts have been synthesized from a variety of materials, with some success at repairing chondral defects in animal models. We hypothesized that in tissue-engineered osteochondral grafts synthesized by bonding mesenchymal stem cell-loaded hydrogels to a porous material, the choice of the porous scaffold would affect graft healing to host bone, and the quality of cell restoration at the hyaline cartilage surface. Bone marrow-derived allogeneic mesenchymal stem cells were suspended in hydrogels that were attached to cylinders of porous tantalum metal, allograft bone, or a bioactive glass. The tissue-engineered osteochondral grafts, thus created were implanted into experimental defects in rabbit knees. Subchondral bone restoration, defect fill, bone ingrowth-implant integration, and articular tissue quality were compared between the three subchondral materials at 6 and 12 weeks. Bioactive glass and porous tantalum were superior to bone allograft in integrating to adjacent host bone, regenerating hyaline-like tissue at the graft surface, and expressing type II collagen in the articular cartilage.

High doses of ionizing radiation on bone repair: is there effect outside the irradiated site?

PubMed

Rocha, Flaviana Soares; Dias, Pâmella Coelho; Limirio, Pedro Henrique Justino Oliveira; Lara, Vitor Carvalho; Batista, Jonas Dantas; Dechichi, Paula

2017-03-01

Local ionizing radiation causes damage to bone metabolism, it reduces blood supply and cellularity over time. Recent studies indicate that radiation promotes biological response outside the treatment field. The aim of this study was to investigate the effects of ionizing radiation on bone repair outside the irradiated field. Ten healthy male Wistar rats were used; and five animals were submitted to radiotherapy on the left femur. After 4 weeks, in all animals were created bone defects in the right and left femurs. Seven days after surgery, animals were euthanized. The femurs were removed and randomly divided into 3 groups (n=5): Control (C) (right femur of the non-irradiated animals); Local ionizing radiation (IR) (left femur of the irradiated animals); Contralateral ionizing radiation (CIR) (right femur of the irradiated animals). The femurs were processed and embedded in paraffin; and bone histologic sections were evaluated to quantify the bone neoformation. Histomorphometric analysis showed that there was no significant difference between groups C (24.6±7.04) and CIR (25.3±4.31); and IR group not showed bone neoformation. The results suggest that ionizing radiation affects bone repair, but does not interfere in bone repair distant from the primary irradiated site. Copyright © 2016 Elsevier Ltd. All rights reserved.

Tissue engineering skeletal muscle for orthopaedic applications

NASA Technical Reports Server (NTRS)

Payumo, Francis C.; Kim, Hyun D.; Sherling, Michael A.; Smith, Lee P.; Powell, Courtney; Wang, Xiao; Keeping, Hugh S.; Valentini, Robert F.; Vandenburgh, Herman H.

2002-01-01

With current technology, tissue-engineered skeletal muscle analogues (bioartificial muscles) generate too little active force to be clinically useful in orthopaedic applications. They have been engineered genetically with numerous transgenes (growth hormone, insulinlike growth factor-1, erythropoietin, vascular endothelial growth factor), and have been shown to deliver these therapeutic proteins either locally or systemically for months in vivo. Bone morphogenetic proteins belonging to the transforming growth factor-beta superfamily are osteoinductive molecules that drive the differentiation pathway of mesenchymal cells toward the chondroblastic or osteoblastic lineage, and stimulate bone formation in vivo. To determine whether skeletal muscle cells endogenously expressing bone morphogenetic proteins might serve as a vehicle for systemic bone morphogenetic protein delivery in vivo, proliferating skeletal myoblasts (C2C12) were transduced with a replication defective retrovirus containing the gene for recombinant human bone morphogenetic protein-6 (C2BMP-6). The C2BMP-6 cells constitutively expressed recombinant human bone morphogenetic protein-6 and synthesized bioactive recombinant human bone morphogenetic protein-6, based on increased alkaline phosphatase activity in coincubated mesenchymal cells. C2BMP-6 cells did not secrete soluble, bioactive recombinant human bone morphogenetic protein-6, but retained the bioactivity in the cell layer. Therefore, genetically-engineered skeletal muscle cells might serve as a platform for long-term delivery of osteoinductive bone morphogenetic proteins locally.

Strontium enhances osseointegration of calcium phosphate cement: a histomorphometric pilot study in ovariectomized rats.

PubMed

Baier, Martin; Staudt, Patric; Klein, Roman; Sommer, Ulrike; Wenz, Robert; Grafe, Ingo; Meeder, Peter Jürgen; Nawroth, Peter P; Kasperk, Christian

2013-06-07

Calcium phosphate cements are used frequently in orthopedic and dental surgeries. Strontium-containing drugs serve as systemic osteoblast-activating medication in various clinical settings promoting mechanical stability of the osteoporotic bone. Strontium-containing calcium phosphate cement (SPC) and calcium phosphate cement (CPC) were compared regarding their local and systemic effects on bone tissue in a standard animal model for osteoporotic bone. A bone defect was created in the distal femoral metaphysis of 60 ovariectomized Sprague-Dawley rats. CPC and SPC were used to fill the defects in 30 rats in each group. Local effects were assessed by histomorphometry at the implant site. Systemic effects were assessed by bone mineral density (BMD) measurements at the contralateral femur and the spine. Faster osseointegration and more new bone formation were found for SPC as compared to CPC implant sites. SPC implants exhibited more cracks than CPC implants, allowing more bone formation within the implant. Contralateral femur BMD and spine BMD did not differ significantly between the groups. The addition of strontium to calcium phosphate stimulates bone formation in and around the implant. Systemic release of strontium from the SPC implants did not lead to sufficiently high serum strontium levels to induce significant systemic effects on bone mass in this rat model.

Effect of odanacatib on root resorption and alveolar bone metabolism during orthodontic tooth movement.

PubMed

Wei, X X; Chu, J P; Zou, Y Z; Ru, N; Cui, S X; Bai, Y X

2015-12-22

The aim of this study was to investigate the effect of local administration of odanacatib (ODN) on orthodontic root resorption and the status of alveolar bone metabolism in rat molars. All specimens were scanned using microcomputed tomography and then the raw images were reconstructed. The total volume of the root resorption craters of the 60 g-NS (normal saline) group was higher than in the 60 g-ODN group and the control group. In the 60 g-NS group, the bone volume fraction values of alveolar bone were significantly decreased compared with the other 2 groups. There were no significant differences in the bone volume fraction values of the tibiae among the 3 groups. The results of tartrate-resistant acid phosphatase-positive (TRAP+) numbers showed that there was no difference between the 60 g-NS group and the 60 g-ODN group. The expression of cathepsin K was decreased significantly in the 60 g-ODN group. These results indicate that ODN reduces orthodontics-induced external root resorption and increases alveolar bone metabolism. This may be because ODN inhibits the activity of odontoclasts, but maintains the quantity of odontoclasts and enhances bone formation. ODN promotes local alveolar bone metabolism, but does not affect systemic bone metabolism.

Overexpression of TIMP-3 in Chondrocytes Produces Transient Reduction in Growth Plate Length but Permanently Reduces Adult Bone Quality and Quantity

PubMed Central

Plumb, Darren; Vo, Phoung; Shah, Mittal; Staines, Katherine; Sampson, Alexandra; Shefelbine, Sandra; Pitsillides, Andrew A.; Bou-Gharios, George

2016-01-01

Bone development and length relies on the growth plate formation, which is dependent on degradative enzymes such as MMPs. Indeed, deletion of specific members of this enzyme family in mice results in important joint and bone abnormalities, suggesting a role in skeletal development. As such, the control of MMP activity is vital in the complex process of bone formation and growth. We generated a transgenic mouse line to overexpress TIMP3 in mouse chondrocytes using the Col2a1-chondrocyte promoter. This overexpression in cartilage resulted in a transient shortening of growth plate in homozygote mice but bone length was restored at eight weeks of age. However, tibial bone structure and mechanical properties remained compromised. Despite no transgene expression in adult osteoblasts from transgenic mice in vitro, their differentiation capacity was decreased. Neonates, however, did show transgene expression in a subset of bone cells. Our data demonstrate for the first time that transgene function persists in the chondro-osseous lineage continuum and exert influence upon bone quantity and quality. PMID:28002442

The local administration of parathyroid hormone encourages the healing of bone defects in the rat calvaria: Micro-computed tomography, histological and histomorphometric evaluation.

PubMed

Auersvald, Caroline Moreira; Santos, Felipe Rychuv; Nakano, Mayara Mytie; Leoni, Graziela Bianchi; de Sousa Neto, Manoel Damião; Scariot, Rafaela; Giovanini, Allan Fernando; Deliberador, Tatiana Miranda

2017-07-01

To evaluate the effect of a single-dose local administration of PTH on bone healing in rat calvarial bone defects by means of micro-computed tomography, histological and histomorphometric analysis. Critical-size cranial osteotomy defects were created in 42 male rats. The animals were randomly divided into 3 groups. In the C Group, the bone defect was only filled with a blood clot. In the S Group, it was filled with a collagen sponge and covered with bovine cortical membrane. In the PTH Group, the defect was filled with a collagen sponge soaked with PTH and covered with bovine cortical membrane. The groups were further split in two for euthanasia 15 and 60days post-surgery. Data was statistically analyzed with t-tests for independent samples or the nonparametric Mann-Whitney test when applicable. Intragroup comparisons were analyzed with paired t-tests (p<0.05). Micro-CT analysis results did not demonstrate statistically significant intergroup differences. At 15days post-surgery, the histomorphometric analysis showed that the PTH Group exhibited a significantly higher percentage of bone formation compared with the S Group. At 60days post-surgery, a higher percentage of new bone was observed in the PTH group. The results suggest that the local administration of PTH encouraged the bone healing in critical-size calvarial defects in rats. Copyright © 2017 Elsevier Ltd. All rights reserved.

Oxygen isotope variations in phosphate of deer bones

NASA Astrophysics Data System (ADS)

Luz, Boaz; Cormie, Allison B.; Schwarcz, Henry P.

1990-06-01

Variations of δ 18O of bone phosphate (δ p) of white tailed deer were studied in samples with wide geographic distribution in North America. Bones from the same locality have similar isotopic values, and the difference between specimens (0.4‰) is not large relative to the measurement error (0.3‰). The total range of δ p values is about 12‰. This indicates that deer use water from a relatively small area, and thus their δ p indicates local environmental conditions. Multiple regression analysis between oxygen isotope composition of deer bone phosphate and of local relative humidity and precipitation (δ w) yields a high correlation coefficient (0.95). This correlation is significantly better than the linear correlation (0.81) between δ p and δ w of precipitation alone. Thus δ p depends on both isotopic composition of precipitation and on relative humidity. This is because deer obtain most of their water from leaves, the isotopic composition of which is partly controlled by relative humidity through evaporation/transpiration.

A Novel Videography Method for Generating Crack-Extension Resistance Curves in Small Bone Samples

PubMed Central

Katsamenis, Orestis L.; Jenkins, Thomas; Quinci, Federico; Michopoulou, Sofia; Sinclair, Ian; Thurner, Philipp J.

2013-01-01

Assessment of bone quality is an emerging solution for quantifying the effects of bone pathology or treatment. Perhaps one of the most important parameters characterising bone quality is the toughness behaviour of bone. Particularly, fracture toughness, is becoming a popular means for evaluating bone quality. The method is moving from a single value approach that models bone as a linear-elastic material (using the stress intensity factor, K) towards full crack extension resistance curves (R-curves) using a non-linear model (the strain energy release rate in J-R curves). However, for explanted human bone or small animal bones, there are difficulties in measuring crack-extension resistance curves due to size constraints at the millimetre and sub-millimetre scale. This research proposes a novel “whitening front tracking” method that uses videography to generate full fracture resistance curves in small bone samples where crack propagation cannot typically be observed. Here we present this method on sharp edge notched samples (<1 mm×1 mm×Length) prepared from four human femora tested in three-point bending. Each sample was loaded in a mechanical tester with the crack propagation recorded using videography and analysed using an algorithm to track the whitening (damage) zone. Using the “whitening front tracking” method, full R-curves and J-R curves could be generated for these samples. The curves for this antiplane longitudinal orientation were similar to those found in the literature, being between the published longitudinal and transverse orientations. The proposed technique shows the ability to generate full “crack” extension resistance curves by tracking the whitening front propagation to overcome the small size limitations and the single value approach. PMID:23405186

A neural network technique for remeshing of bone microstructure.

PubMed

Fischer, Anath; Holdstein, Yaron

2012-01-01

Today, there is major interest within the biomedical community in developing accurate noninvasive means for the evaluation of bone microstructure and bone quality. Recent improvements in 3D imaging technology, among them development of micro-CT and micro-MRI scanners, allow in-vivo 3D high-resolution scanning and reconstruction of large specimens or even whole bone models. Thus, the tendency today is to evaluate bone features using 3D assessment techniques rather than traditional 2D methods. For this purpose, high-quality meshing methods are required. However, the 3D meshes produced from current commercial systems usually are of low quality with respect to analysis and rapid prototyping. 3D model reconstruction of bone is difficult due to the complexity of bone microstructure. The small bone features lead to a great deal of neighborhood ambiguity near each vertex. The relatively new neural network method for mesh reconstruction has the potential to create or remesh 3D models accurately and quickly. A neural network (NN), which resembles an artificial intelligence (AI) algorithm, is a set of interconnected neurons, where each neuron is capable of making an autonomous arithmetic calculation. Moreover, each neuron is affected by its surrounding neurons through the structure of the network. This paper proposes an extension of the growing neural gas (GNN) neural network technique for remeshing a triangular manifold mesh that represents bone microstructure. This method has the advantage of reconstructing the surface of a genus-n freeform object without a priori knowledge regarding the original object, its topology, or its shape.

The relative contributions of non-enzymatic glycation and cortical porosity on the fracture toughness of aging bone

PubMed Central

Tang, S.Y.; Vashishth, D.

2010-01-01

The risk of fracture increases with age due to the decline of bone mass and bone quality. One of the age-related changes in bone quality occurs through the formation and accumulation of advanced glycation end-products (AGEs) due to non-enzymatic glycation (NEG). However as a number of other changes including increased porosity occur with age and affect bone fragility, the relative contribution of AGEs on the fracture resistance of aging bone is unknown. Using a high-resolution nonlinear finite element model that incorporate cohesive elements and micro-computed tomography-based 3d meshes, we investigated the contribution of AGEs and cortical porosity on the fracture toughness of human bone. The results show that NEG caused a 52% reduction in propagation fracture toughness (R-curve slope). The combined effects of porosity and AGEs resulted in an 88% reduction in propagation toughness. These findings are consistent with previous experimental results. The model captured the age-related changes in the R-curve toughening by incorporating bone quantity and bone quality changes, and these simulations demonstrate the ability of the cohesive models to account for the irreversible dynamic crack growth processes affected by the changes in post-yield material behavior. By decoupling the matrix-level effects due to NEG and intracortical porosity, we are able to directly determine the effects of NEG on fracture toughness. The outcome of this study suggests that it may be important to include the age-related changes in the material level properties by using finite element analysis towards the prediction of fracture risk. PMID:21056419

A novel treatment approach to infected nonunion of long bones without systemic antibiotics.

PubMed

Masrouha, Karim Z; Raad, Michael E; Saghieh, Said S

2018-04-01

Infected nonunion of long bones may require intravenous antibiotics over a lengthy period which may result in a high rate of complications. This study aims to assess the efficacy of local antibiotics used as a replacement to prolonged intravenous therapy. Thirteen patients with infected nonunion of long bones who failed at least one previous surgery were included. The infection was treated through extensive debridement, application of antibiotic-impregnated calcium sulphate pellets and the bone stabilized with external fixation. These patients were monitored for union and infection by clinical signs, laboratory values, and radiographs over a period of 24 months. The results support an eradication of infection and union in all patients with no antibiotic-associated complications. Local antibiotic delivery using calcium sulphate pellets provides an effective method for treatment of nonunion in long bones and is free of the complications from the intravenous route.

Hydrogeochemistry of the drinking water sources of Derebogazi Village (Kahramanmaras) and their effects on human health.

PubMed

Uras, Yusuf; Uysal, Yagmur; Arikan, Tugba Atilan; Kop, Alican; Caliskan, Mustafa

2015-06-01

The aim of this study was to investigate the sources of drinking water for Derebogazi Village, Kahramanmaras Province, Turkey, in terms of hydrogeochemistry, isotope geochemistry, and medical geology. Water samples were obtained from seven different water sources in the area, all of which are located within quartzite units of Paleozoic age, and isotopic analyses of (18)O and (2)H (deuterium) were conducted on the samples. Samples were collected from the region for 1 year. Water quality of the samples was assessed in terms of various water quality parameters, such as temperature, pH, conductivity, alkalinity, trace element concentrations, anion-cation measurements, and metal concentrations, using ion chromatography, inductively coupled plasma (ICP) mass spectrometry, ICP-optical emission spectrometry techniques. Regional health surveys had revealed that the heights of local people are significantly below the average for the country. In terms of medical geology, the sampled drinking water from the seven sources was deficient in calcium and magnesium ions, which promote bone development. Bone mineral density screening tests were conducted on ten females using dual energy X-ray absorptiometry to investigate possible developmental disorder(s) and potential for mineral loss in the region. Of these ten women, three had T-scores close to the osteoporosis range (T-score < -2.5).

Quality standards for bone conduction implants.

PubMed

Gavilan, Javier; Adunka, Oliver; Agrawal, Sumit; Atlas, Marcus; Baumgartner, Wolf-Dieter; Brill, Stefan; Bruce, Iain; Buchman, Craig; Caversaccio, Marco; De Bodt, Marc T; Dillon, Meg; Godey, Benoit; Green, Kevin; Gstoettner, Wolfgang; Hagen, Rudolf; Hagr, Abdulrahman; Han, Demin; Kameswaran, Mohan; Karltorp, Eva; Kompis, Martin; Kuzovkov, Vlad; Lassaletta, Luis; Li, Yongxin; Lorens, Artur; Martin, Jane; Manoj, Manikoth; Mertens, Griet; Mlynski, Robert; Mueller, Joachim; O'Driscoll, Martin; Parnes, Lorne; Pulibalathingal, Sasidharan; Radeloff, Andreas; Raine, Christopher H; Rajan, Gunesh; Rajeswaran, Ranjith; Schmutzhard, Joachim; Skarzynski, Henryk; Skarzynski, Piotr; Sprinzl, Georg; Staecker, Hinrich; Stephan, Kurt; Sugarova, Serafima; Tavora, Dayse; Usami, Shin-Ichi; Yanov, Yuri; Zernotti, Mario; Zorowka, Patrick; de Heyning, Paul Van

2015-01-01

Bone conduction implants are useful in patients with conductive and mixed hearing loss for whom conventional surgery or hearing aids are no longer an option. They may also be used in patients affected by single-sided deafness. To establish a consensus on the quality standards required for centers willing to create a bone conduction implant program. To ensure a consistently high level of service and to provide patients with the best possible solution the members of the HEARRING network have established a set of quality standards for bone conduction implants. These standards constitute a realistic minimum attainable by all implant clinics and should be employed alongside current best practice guidelines. Fifteen items are thoroughly analyzed. They include team structure, accommodation and clinical facilities, selection criteria, evaluation process, complete preoperative and surgical information, postoperative fitting and assessment, follow-up, device failure, clinical management, transfer of care and patient complaints.

7 Tesla MRI of bone microarchitecture discriminates between women without and with fragility fractures who do not differ by bone mineral density.

PubMed

Chang, Gregory; Honig, Stephen; Liu, Yinxiao; Chen, Cheng; Chu, Kevin K; Rajapakse, Chamith S; Egol, Kenneth; Xia, Ding; Saha, Punam K; Regatte, Ravinder R

2015-05-01

Osteoporosis is a disease of poor bone quality. Bone mineral density (BMD) has limited ability to discriminate between subjects without and with poor bone quality, and assessment of bone microarchitecture may have added value in this regard. Our goals were to use 7 T MRI to: (1) quantify and compare distal femur bone microarchitecture in women without and with poor bone quality (defined clinically by presence of fragility fractures); and (2) determine whether microarchitectural parameters could be used to discriminate between these two groups. This study had institutional review board approval, and we obtained written informed consent from all subjects. We used a 28-channel knee coil to image the distal femur of 31 subjects with fragility fractures and 25 controls without fracture on a 7 T MRI scanner using a 3-D fast low angle shot sequence (0.234 mm × 0.234 mm × 1 mm, parallel imaging factor = 2, acquisition time = 7 min 9 s). We applied digital topological analysis to quantify parameters of bone microarchitecture. All subjects also underwent standard clinical BMD assessment in the hip and spine. Compared to controls, fracture cases demonstrated lower bone volume fraction and markers of trabecular number, plate-like structure, and plate-to-rod ratio, and higher markers of trabecular isolation, rod disruption, and network resorption (p < 0.05 for all). There were no differences in hip or spine BMD T-scores between groups (p > 0.05). In receiver-operating-characteristics analyses, microarchitectural parameters could discriminate cases and controls (AUC = 0.66-0.73, p < 0.05). Hip and spine BMD T-scores could not discriminate cases and controls (AUC = 0.58-0.64, p ≥ 0.08). We conclude that 7 T MRI can detect bone microarchitectural deterioration in women with fragility fractures who do not differ by BMD. Microarchitectural parameters might some day be used as an additional tool to detect patients with poor bone quality who cannot be detected by dual-energy X-ray absorptiometry (DXA).

Low bone mineral density in ambulatory persons with cerebral palsy? A systematic review.

PubMed

Mus-Peters, Cindy T R; Huisstede, Bionka M A; Noten, Suzie; Hitters, Minou W M G C; van der Slot, Wilma M A; van den Berg-Emons, Rita J G

2018-05-22

Non-ambulatory persons with cerebral palsy are prone to low bone mineral density. In ambulatory persons with cerebral palsy, bone mineral density deficits are expected to be small or absent, but a consensus conclusion is lacking. In this systematic review bone mineral density in ambulatory persons with cerebral palsy (Gross Motor Function Classification Scales I-III) was studied. Medline, Embase, and Web of Science were searched. According to international guidelines, low bone mineral density was defined as Z-score ≤ -2.0. In addition, we focused on Z-score ≤ -1.0 because this may indicate a tendency towards low bone mineral density. We included 16 studies, comprising 465 patients aged 1-65 years. Moderate and conflicting evidence for low bone mineral density (Z-score ≤ -2.0) was found for several body parts (total proximal femur, total body, distal femur, lumbar spine) in children with Gross Motor Function Classification Scales II and III. We found no evidence for low bone mineral density in children with Gross Motor Function Classification Scale I or adults, although there was a tendency towards low bone mineral density (Z-score ≤ -1.0) for several body parts. Although more high-quality research is needed, results indicate that deficits in bone mineral density are not restricted to non-ambulatory people with cerebral palsy. Implications for Rehabilitation Although more high-quality research is needed, including adults and fracture risk assessment, the current study indicates that deficits in bone mineral density are not restricted to non-ambulatory people with CP. Health care professionals should be aware that optimal nutrition, supplements on indication, and an active lifestyle, preferably with weight-bearing activities, are important in ambulatory people with CP, also from a bone quality point-of-view. If indicated, medication and fall prevention training should be prescribed.

Bone regeneration: Biomaterials as local delivery systems with improved osteoinductive properties.

PubMed

Martin, Victor; Bettencourt, Ana

2018-01-01

Bone is a mineralized conjunctive tissue, with a unique trauma healing capability. However, the replacement or regeneration of lost bone is not always successful and becomes more difficult the wider the bone defect. A significant growth in the demand for orthopedic and maxillofacial surgical procedures as a result of population aging and increase in chronic diseases as diabetes is a fact and successful approaches for bone regeneration are still needed. Until today, autogenous bone graft continues to be the best solution even with important limitations, as quantity and the requirement of a donator area. Alternatively, local delivery systems combining an osteoconductive biomaterial with osteoinductive compounds as hormones, growth factors or drugs is a popular approach aiming to replace the need for autogenous bone grafts. Nevertheless, in spite of the intense research in the area, presently there is no system that can mimic all the biological functions of the autogenous bone grafts. In this context, the present work provides an overview of the most recent advances in the field of synthetic bone grafts. The opportunities and limitations are detailed along with the remaining gaps in the research that are still preventing the successful translation of more products into the market able to be a valuable option in comparison to the autogenous bone grafts. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of boning method and postmortem aging on meat quality characteristics of pork loin.

PubMed

Li, Chunbao; Wu, Juqing; Zhang, Nan; Zhang, Song; Liu, Juan; Li, Jinping; Li, Hongmin; Feng, Xianchao; Han, Yanqing; Zhu, Zhiyuan; Xu, Xinglian; Zhou, Guanghong

2009-10-01

This work investigated the effects of boning method and postmortem aging on pork loin color, shearing value and sensory attributes. Two experiments were assigned. In Experiment I, 30 Chinese native black pigs were slaughtered and their carcasses were divided into three groups: (i) hot-boning: carcasses were fabricated within 45 min postmortem just after dressing; (ii) cold boning at 24 h: carcasses were fabricated after chilling at 0 degrees C for 24 h; (iii) cold boning at 36 h: carcasses were fabricated after chilling at 0 degrees C for 36 h. In Experiment II, right sides of the second group in Experiment I were used and primal cuts were vacuum packed and aged for 1 day, 8 days and 16 days. Pork loins (Longissimus lumborum) were used for color measurement, shearing test, and sensory evaluation. Among three boning methods, cold-boning at 36 h postmortem had the advantages of giving muscles a better color, the lowest cooking loss and cooked shearing value, and the highest sensory tenderness, juiciness, flavor and overall liking. Postmortem aging could improve pork quality characteristics, but it is not the fact that the longer aging time is, the better pork quality would be. Eight days may be enough to obtain an acceptable sensory attribute. These results are meaningful for pork processing and pork consumption.

Finite element analysis of a pseudoelastic compression-generating intramedullary ankle arthrodesis nail.

PubMed

Anderson, Ryan T; Pacaccio, Douglas J; Yakacki, Christopher M; Carpenter, R Dana

2016-09-01

Tibio-talo-calcaneal (TTC) arthrodesis is an end-stage treatment for patients with severe degeneration of the ankle joint. This treatment consists of using an intramedullary nail (IM) to fuse the calcaneus, talus, and tibia bones together into one construct. Poor bone quality within the joint prior to surgery is common and thus the procedure has shown complications due to non-union. However, a new FDA-approved IM nail has been released that houses a nickel titanium (NiTi) rod that uses its inherent pseudoelastic material properties to apply active compression across the fusion site. Finite element analysis was performed to model the mechanical response of the NiTi within the device. A bone model was then developed based on a quantitative computed tomography (QCT) image for anatomical geometry and bone material properties. A total bone and device system was modeled to investigate the effect of bone quality change and gather load-sharing properties during gait loading. It was found that during the highest magnitude loading of gait, the load taken by the bone was more than 50% higher than the load taken by the nail. When comparing the load distribution during gait, results from this study would suggest that the device helps to prevent stress shielding by allowing a more even distribution of load between bone and nail. In conditions where bone quality may vary patient-to-patient, the model indicates that a 10% decrease in overall bone modulus (i.e. material stiffness) due to reduced bone mineral density would result in higher stresses in the nail (3.4%) and a marginal decrease in stress for the bone (0.5%). The finite element model presented in this study can be used as a quantitative tool to further understand the stress environment of both bone and device for a TTC fusion. Furthermore, the methodology presented gives insight on how to computationally program and use the unique material properties of NiTi in an active compression state useful for bone fracture healing or fusion treatments. Copyright © 2016 Elsevier Ltd. All rights reserved.

Development and testing of texture discriminators for the analysis of trabecular bone in proximal femur radiographs

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

Huber, M. B.; Carballido-Gamio, J.; Fritscher, K.

2009-11-15

Purpose: Texture analysis of femur radiographs may serve as a potential low cost technique to predict osteoporotic fracture risk and has received considerable attention in the past years. A further application of this technique may be the measurement of the quality of specific bone compartments to provide useful information for treatment of bone fractures. Two challenges of texture analysis are the selection of the best suitable texture measure and reproducible placement of regions of interest (ROIs). The goal of this in vitro study was to automatically place ROIs in radiographs of proximal femur specimens and to calculate correlations between variousmore » different texture analysis methods and the femurs' anchorage strength. Methods: Radiographs were obtained from 14 femoral specimens and bone mineral density (BMD) was measured in the femoral neck. Biomechanical testing was performed to assess the anchorage strength in terms of failure load, breakaway torque, and number of cycles. Images were segmented using a framework that is based on the usage of level sets and statistical in-shape models. Five ROIs were automatically placed in the head, upper and lower neck, trochanteric, and shaft compartment in an atlas subject. All other subjects were registered rigidly, affinely, and nonlinearly, and the resulting transformation was used to map the five ROIs onto the individual femora. Results: In each ROI, texture features were extracted using gray level co-occurence matrices (GLCM), third-order GLCM, morphological gradients (MGs), Minkowski dimensions (MDs), Minkowski functionals (MFs), Gaussian Markov random fields, and scaling index method (SIM). Coefficients of determination for each texture feature with parameters of anchorage strength were computed. In a stepwise multiregression analysis, the most predictive parameters were identified in different models. Texture features were highly correlated with anchorage strength estimated by the failure load of up to R{sup 2}=0.61 (MF and MG features, p<0.01) and were partially independent of BMD. The correlations were dependent on the choice of the ROI and the texture measure. The best predictive multiregression model for failure load R{sub adj}{sup 2}=0.86 (p<0.001) included a set of recently developed texture methods (MF and SIM) but excluded bone mineral density and commonly used texture measures. Conclusions: The results suggest that texture information contained in trabecular bone structure visualized on radiographs may predict whether an implant anchorage can be used and may determine the local bone quality from preoperative radiographs.« less

Cryoablation of Bone Metastases from Renal Cell Carcinoma for Local Tumor Control.

PubMed

Gardner, Carly S; Ensor, Joe E; Ahrar, Kamran; Huang, Steven Y; Sabir, Sharjeel H; Tannir, Nizar M; Lewis, Valerae O; Tam, Alda L

2017-11-15

Patients with bone metastases from renal cell carcinoma often are not surgical candidates and have a poor prognosis. There are limited data on the use of cryoablation as a locoregional therapy for bone metastases. Our objective was to assess the local tumor-control rate following cryoablation of bone metastases in the setting of renal cell carcinoma. We retrospectively reviewed the medical records of patients with metastatic renal cell carcinoma who underwent cryoablation for bone metastases between 2007 and 2014. We excluded patients if the intent of treatment was for pain palliation only, if cryoablation was performed without an attempt for complete tumor control (cytoreduction), or if the patient had no further follow-up beyond the cryoablation procedure. We recorded patient demographics, procedural variables, and complications. Cross-sectional imaging and clinical follow-up were reviewed to determine disease recurrence. The median overall survival and recurrence-free survival were determined using the Kaplan-Meier method. Forty patients (30 male and 10 female) with 50 bone metastases were included for analysis. The mean patient age was 62 years (range, 47 to 82 years). The median follow-up was 35 months (95% confidence interval [CI], 22.7 to 74.4 months). Twenty-five (62.5%) of the 40 patients had oligometastatic disease, defined as ≤5 metastases at the time of ablation. The mean tumor size was 3.4 ± 1.5 cm. Metastases in the pelvic region represented 68% of the treated tumors (34 of 50). The overall local tumor-control rate per lesion was 82% (41 of 50). Patients with oligometastatic disease experienced better local tumor control (96% [24 of 25]) compared with patients who had >5 metastases (53.3% [8 of 15]) (p = 0.001). The local tumor-control rate was better for lesions for which a larger mean difference between maximum ice-ball diameter and maximum lesion diameter was achieved (2.2 ± 0.9 cm for those without recurrence versus 1.35 ± 1.2 cm for those with recurrence; p = 0.005). There were 3 grade-3 complications and 1 grade-4 complication. Cryoablation can be effective for achieving local oncologic control in bone metastases from renal cell carcinoma and may represent a valuable alternative to surgical metastasectomy in select patients. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Erythroblast apoptosis and microenvironmental iron restriction trigger anemia in the VK*MYC model of multiple myeloma

PubMed Central

Bordini, Jessica; Bertilaccio, Maria Teresa Sabrina; Ponzoni, Maurilio; Fermo, Isabella; Chesi, Marta; Bergsagel, P. Leif; Camaschella, Clara; Campanella, Alessandro

2015-01-01

Multiple myeloma is a malignant disorder characterized by bone marrow proliferation of plasma cells and by overproduction of monoclonal immunoglobulin detectable in the sera (M-spike). Anemia is a common complication of multiple myeloma, but the underlying pathophysiological mechanisms have not been completely elucidated. We aimed to identify the different determinants of anemia using the Vk*MYC mouse, which spontaneously develops an indolent bone marrow localized disease with aging. Affected Vk*MYC mice develop a mild normochromic normocytic anemia. We excluded the possibility that anemia results from defective erythropoietin production, inflammation or increased hepcidin expression. Mature erythroid precursors are reduced in Vk*MYC bone marrow compared with wild-type. Malignant plasma cells express the apoptogenic receptor Fas ligand and, accordingly, active caspase 8 is detected in maturing erythroblasts. Systemic iron homeostasis is not compromised in Vk*MYC animals, but high expression of the iron importer CD71 by bone marrow plasma cells and iron accumulation in bone marrow macrophages suggest that iron competition takes place in the local multiple myeloma microenvironment, which might contribute to anemia. In conclusion, the mild anemia of the Vk*MYC model is mainly related to the local effect of the bone marrow malignant clone in the absence of an overt inflammatory status. We suggest that this reproduces the initial events triggering anemia in patients. PMID:25715406

Erythroblast apoptosis and microenvironmental iron restriction trigger anemia in the VK*MYC model of multiple myeloma.

PubMed

Bordini, Jessica; Bertilaccio, Maria Teresa Sabrina; Ponzoni, Maurilio; Fermo, Isabella; Chesi, Marta; Bergsagel, P Leif; Camaschella, Clara; Campanella, Alessandro

2015-06-01

Multiple myeloma is a malignant disorder characterized by bone marrow proliferation of plasma cells and by overproduction of monoclonal immunoglobulin detectable in the sera (M-spike). Anemia is a common complication of multiple myeloma, but the underlying pathophysiological mechanisms have not been completely elucidated. We aimed to identify the different determinants of anemia using the Vk*MYC mouse, which spontaneously develops an indolent bone marrow localized disease with aging. Affected Vk*MYC mice develop a mild normochromic normocytic anemia. We excluded the possibility that anemia results from defective erythropoietin production, inflammation or increased hepcidin expression. Mature erythroid precursors are reduced in Vk*MYC bone marrow compared with wild-type. Malignant plasma cells express the apoptogenic receptor Fas ligand and, accordingly, active caspase 8 is detected in maturing erythroblasts. Systemic iron homeostasis is not compromised in Vk*MYC animals, but high expression of the iron importer CD71 by bone marrow plasma cells and iron accumulation in bone marrow macrophages suggest that iron competition takes place in the local multiple myeloma microenvironment, which might contribute to anemia. In conclusion, the mild anemia of the Vk*MYC model is mainly related to the local effect of the bone marrow malignant clone in the absence of an overt inflammatory status. We suggest that this reproduces the initial events triggering anemia in patients. Copyright© Ferrata Storti Foundation.

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

PubMed

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

2017-01-01

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

Fixation of revision implants is improved by a surgical technique to crack the sclerotic bone rim.

PubMed

Kold, Søren; Bechtold, Joan E; Mouzin, Olivier; Elmengaard, Brian; Chen, Xinqian; Søballe, Kjeld

2005-03-01

Revision joint replacement has poorer outcomes compared with primary joint replacement, and these poor outcomes have been associated with poorer fixation. We investigated a surgical technique done during the revision operation to improve access from the marrow space to the implant interface by locally cracking the sclerotic bone rim that forms during aseptic loosening. Sixteen implants were inserted bilaterally by distal femur articulation of the knee joint of eight dogs, using our controlled experimental model that replicates the revision setting (sclerotic bone rim, dense fibrous tissue, macrophages, elevated cytokines) by pistoning a loaded 6.0-mm implant 500 microm into the distal femur with particulate PE. At 8 weeks, one of two revision procedures was done. Both revision procedures included complete removal of the membrane, scraping, lavaging, and inserting a revision plasma-spray Ti implant. The crack revision procedure also used a splined tool to circumferentially locally perforate the sclerotic bone rim before insertion of an identical revision implant. Superior fixation was achieved with the cracking procedure in this experimental model. Revision implants inserted with the rim cracking procedure had a significantly higher pushout strength (fivefold median increase) and energy to failure (sixfold median increase), compared with the control revision procedure. Additional evaluation is needed of local perforation of sclerotic bone rim as a simple bone-sparing means to improve revision implant fixation and thereby increase revision implant longevity.

Drug diffusion, integration, and stability of nanoengineered drug-releasing implants in bone ex-vivo.

PubMed

Rahman, Shafiur; Gulati, Karan; Kogawa, Masakazu; Atkins, Gerald J; Pivonka, Peter; Findlay, David M; Losic, Dusan

2016-03-01

To treat skeletal conditions such as bone infections, osteoporotic fractures, and osteosarcoma, it would be ideal to introduce drugs directly to the affected site. Localized drug delivery from the bone implants is a promising alternative to systemic drug administration. In this study we investigated electrochemically nanoengineered Ti wire implants with titania nanotubes (TNTs), as minimally invasive drug-releasing implants for the delivery of drugs directly into the bone tissue. Since trabecular bone in vivo contains a highly interconnected bone marrow, we sought to determine the influence of marrow on drug release and diffusion. Electrochemical anodization of Ti wires (length 10 mm) was performed to create an oxide layer with TNTs on the surface, followed by loading with a fluorescent model drug, Rhodamine B (RhB). Cores of bovine trabecular bone were generated from the sternum of a young steer, and were processed to have an intact bone marrow, or the marrow was removed. RhB-loaded TNTs/Ti wires were inserted into the bone cores, which were then cultured ex vivo using the ZetOS™ bioreactor system to maintain bone viability. Release and diffusion of RhB inside the bone was monitored using fluorescence imaging and different patterns of drug transport in the presence or absence of marrow were observed. Scanning electron microscopy of the implants after retrieval from bone cores confirmed survival of the TNTs structures. Histological investigation showed the presence of bone cells adherent on the implants. This study shows a potential of Ti drug-releasing implants based on TNTs technology towards localized bone therapy. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 714-725, 2016. © 2015 Wiley Periodicals, Inc.

Histologic Evaluation of Critical Size Defect Healing With Natural and Synthetic Bone Grafts in the Pigeon ( Columba livia ) Ulna.

PubMed

Tunio, Ahmed; Jalila, Abu; Goh, Yong Meng; Shameha-Intan; Shanthi, Ganabadi

2015-06-01

Fracture and bone segment loss are major clinical problems in birds. Achieving bone formation and clinical union in a fracture case is important for the survival of the bird. To evaluate the efficacy of bone grafts for defect healing in birds, 2 different bone grafts were investigated in the healing of a bone defect in 24 healthy pigeons ( Columba livia ). In each bird, a 1-cm critical size defect (CSD) was created in the left ulna, and the fracture was stabilized with external skeletal fixation (ESF). A graft of hydroxyapatite (HA) alone (n = 12 birds) or demineralized bone matrix (DBM) combined with HA (n = 12 birds) was implanted in the CSD. The CSD healing was evaluated at 3 endpoints: 3, 6, and 12 weeks after surgery. Four birds were euthanatized at each endpoint from each treatment group, and bone graft healing in the ulna CSD was evaluated by histologic examination. The CSD and graft implants were evaluated for quality of union, cortex development, and bone graft incorporation. Results showed no graft rejection in any bird, and all birds had connective tissue formation in the defect because of the bone graft application. These results suggest that bone defect healing can be achieved by a combination of osteoinductive and osteoconductive bone graft materials for clinical union and new bone regeneration in birds. The combination of DBM and HA resulted in a better quality bone graft (P < .05) than did HA alone, but there was no significant differences in cortex development or bone graft incorporation at 3, 6, or 12 weeks. From the results of this study, we conclude that HA bone grafts, alone or in combination with DBM, with external skeletal fixation is suitable and safe for bone defect and fracture treatment in pigeons.

Bone Balance within a Cortical BMU: Local Controls of Bone Resorption and Formation

PubMed Central

Smith, David W.; Gardiner, Bruce S.; Dunstan, Colin

2012-01-01

Maintaining bone volume during bone turnover by a BMU is known as bone balance. Balance is required to maintain structural integrity of the bone and is often dysregulated in disease. Consequently, understanding how a BMU controls bone balance is of considerable interest. This paper develops a methodology for identifying potential balance controls within a single cortical BMU. The theoretical framework developed offers the possibility of a directed search for biological processes compatible with the constraints of balance control. We first derive general control constraint equations and then introduce constitutive equations to identify potential control processes that link key variables that describe the state of the BMU. The paper describes specific local bone volume balance controls that may be associated with bone resorption and bone formation. Because bone resorption and formation both involve averaging over time, short-term fluctuations in the environment are removed, leaving the control systems to manage deviations in longer-term trends back towards their desired values. The length of time for averaging is much greater for bone formation than for bone resorption, which enables more filtering of variability in the bone formation environment. Remarkably, the duration for averaging of bone formation may also grow to control deviations in long-term trends of bone formation. Providing there is sufficient bone formation capacity by osteoblasts, this leads to an extraordinarily robust control mechanism that is independent of either osteoblast number or the cellular osteoid formation rate. A complex picture begins to emerge for the control of bone volume. Different control relationships may achieve the same objective, and the ‘integration of information’ occurring within a BMU may be interpreted as different sets of BMU control systems coming to the fore as different information is supplied to the BMU, which in turn leads to different observable BMU behaviors. PMID:22844401

Treatment of aneurysmal bone cysts of the pelvis and sacrum.

PubMed

Papagelopoulos, P J; Choudhury, S N; Frassica, F J; Bond, J R; Unni, K K; Sim, F H

2001-11-01

Aneurysmal bone cysts are benign, non-neoplastic, highly vascular bone lesions. The purpose of this study was to describe the prevalence, the clinical presentation, and the recurrence rate of aneurysmal bone cysts of the pelvis and sacrum and to examine the diagnostic and therapeutic options and prognosis for patients with this condition. Forty consecutive patients with an aneurysmal bone cyst of the pelvis and/or sacrum were treated from 1921 to 1996. Their medical records and radiographic and imaging studies were reviewed, and histological sections from the cysts were examined. Seventeen lesions were iliosacral, sixteen were acetabular, and seven were ischiopubic. Seven involved the hip joint, and two involved the sacroiliac joint. All twelve sacral lesions extended to more than one sacral segment and were associated with neurological signs and symptoms. Destructive acetabular lesions were associated with pathological fracture in five patients and with medial migration of the femoral head, hip subluxation, and hip dislocation in one patient each. The mean duration of follow-up was thirteen years (range, three to fifty-three years). Thirty-five patients who were initially treated for a primary lesion had surgical treatment (twenty-one had excision-curettage and fourteen had intralesional excision); two patients also had adjuvant radiation therapy. Of the thirty-five patients, five (14%) had a local recurrence noted less than eighteen months after the operation. Of five patients initially treated for a recurrent lesion, one had a local recurrence. At the latest follow-up examination, all forty patients were disease-free and twenty-eight (70%) were asymptomatic. There were two deep infections. Aneurysmal bone cysts of the pelvis and sacrum are usually aggressive lesions associated with substantial bone destruction, pathological fractures, and local recurrence. Current management recommendations include preoperative selective arterial embolization, excision-curettage, and bone-grafting.

Growth-dependent effects of dietary protein concentration and quality on the biomechanical properties of the diaphyseal rat femur.

PubMed

Alippi, Rosa M; Picasso, Emilio; Huygens, Patricia; Bozzini, Carlos E; Bozzini, Clarisa

2012-01-01

This study compares the effects of feeding growing rats with increasing concentrations of casein (C) and wheat gluten (G), proteins that show different biological qualities, on the morphometrical and biomechanical properties of the femoral diaphysis. Female rats were fed with one of ten diets containing different concentrations (5-30%) of C and G between the 30th and 90th days of life (Control=C-20%). Biomechanical structural properties of the right femur middiaphysis were estimated using a 3-point bending mechanical test with calculation of some indicators of bone material properties. Body weight and length were affected by treatments, values being highest in rats fed the C-20% diet. G diets affected negatively both parameters. Changes in cross-sectional geometry (mid-diaphyseal cross-sectional and cortical areas, femoral volume, and rectangular moment of inertia) were positively related to the C content of the diet, while they were severely and negatively affected by G diets. Similar behaviors were observed in the bone structural properties (fracture load, yielding load, diaphyseal stiffness and elastic energy absorption). When values of strength and stiffness were normalized for body weight, the differences disappeared. The bone material quality indicators (elastic modulus, yielding stress, elastic energy absorption/volume) did not differ significantly among all studied groups. Femoral calcium concentration in ashes was not significantly different among groups. The clear differences in strength and stiffness of bone beams induced by dietary protein concentration and quality seemed to be the result of an induced subnormal gain in bone structural properties as a consequence of a correlative subnormal gain in bone growth and mass, yet not in bone material properties. Copyright © 2011 SEEN. Published by Elsevier Espana. All rights reserved.

Direct bone morphogenetic protein 2 and Indian hedgehog gene transfer for articular cartilage repair using bone marrow coagulates.

PubMed

Sieker, J T; Kunz, M; Weißenberger, M; Gilbert, F; Frey, S; Rudert, M; Steinert, A F

2015-03-01

Bone morphogenetic protein 2 (BMP-2, encoded by BMP2) and Indian hedgehog protein (IHH, encoded by IHH) are well known regulators of chondrogenesis and chondrogenic hypertrophy. Despite being a potent chondrogenic factor BMP-2 was observed to induce chondrocyte hypertrophy in osteoarthritis (OA), growth plate cartilage and adult mesenchymal stem cells (MSCs). IHH might induce chondrogenic differentiation through different intracellular signalling pathways without inducing subsequent chondrocyte hypertrophy. The primary objective of this study is to test the efficacy of direct BMP2 and IHH gene delivery via bone marrow coagulates to influence histological repair cartilage quality in vivo. Vector-laden autologous bone marrow coagulates with 10(11) adenoviral vector particles encoding BMP2, IHH or the Green fluorescent protein (GFP) were delivered to 3.2 mm osteochondral defects in the trochlea of rabbit knees. After 13 weeks the histological repair cartilage quality was assessed using the ICRS II scoring system and the type II collagen positive area. IHH treatment resulted in superior histological repair cartilage quality than GFP controls in all of the assessed parameters (with P < 0.05 in five of 14 assessed parameters). Results of BMP2 treatment varied substantially, including severe intralesional bone formation in two of six joints after 13 weeks. IHH gene transfer is effective to improve repair cartilage quality in vivo, whereas BMP2 treatment, carried the risk intralesional bone formation. Therefore IHH protein can be considered as an attractive alternative candidate growth factor for further preclinical research and development towards improved treatments for articular cartilage defects. Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Tin-117m-labeled stannic (Sn/sup 4 +/) chelate of diethylenetriamine pentaacetic acid (DTPA) for application in diagnosis and therapy

DOEpatents

Srivastava, S.C.; Meinken, G.E.; Richards, P.

1983-08-25

The radiopharmaceutical reagents of this invention and the class of Tin-117m radiopharmaceuticals are therapeutic and diagnostic agents that incorporate gamma-emitting nuclides that localize in bone after intravenous injection in mammals (mice, rats, dogs, and rabbits). Images reflecting bone structure or function can then be obtained by a scintillation camera that detects the distribution of ionizing radiation emitted by the radioactive agent. Tin-117m-labeled chelates of stannic tin localize almost exclusively in cortical bone. Upon intravenous injection of the reagent, the preferred chelates are phosphonate compounds, preferable, PYP, MDP, EHDP, and DTPA. This class of reagents is therapeutically and diagnostically useful in skeletal scintigraphy and for the radiotherapy of bone tumors and other disorders.

[Vertebral aneurysmatic bone cyst: study of three cases].

PubMed

Vale, Benjamim Pessoa; Alencar, Francisco José; de Aguiar, Guilherme Brasileiro; de Almeida, Bruno Ribeiro

2005-12-01

Aneurysmatic bone cyst is a hypervascularized, benign lesion locally destructive by its progressive growth with greater incidence in the second decade of life. It lodges preferably in the long bones and vertebrae. The clinical picture varies from pain to local edema and even neurological symptoms when in vertebral location. Three cases of vertebral aneurysmatic bone cyst occurring in childhood and all with neurologic deficit symptoms are described. Computerized tomography and/or magnetic resonance imaging confirmed the diagnosis. Patients underwent surgery to remove the tumor. In one of the cases, pre-operative selective arterial embolization of the lesion was performed. The three patients progressed satisfactorily with neurological improvement, which demonstrated the efficiency of the microsurgical technique for the resection of the spinal tumor. The evolution of the cases and the current treatment are discussed.

About the inevitable compromise between spatial resolution and accuracy of strain measurement for bone tissue: a 3D zero-strain study.

PubMed

Dall'Ara, E; Barber, D; Viceconti, M

2014-09-22

The accurate measurement of local strain is necessary to study bone mechanics and to validate micro computed tomography (µCT) based finite element (FE) models at the tissue scale. Digital volume correlation (DVC) has been used to provide a volumetric estimation of local strain in trabecular bone sample with a reasonable accuracy. However, nothing has been reported so far for µCT based analysis of cortical bone. The goal of this study was to evaluate accuracy and precision of a deformable registration method for prediction of local zero-strains in bovine cortical and trabecular bone samples. The accuracy and precision were analyzed by comparing scans virtually displaced, repeated scans without any repositioning of the sample in the scanner and repeated scans with repositioning of the samples. The analysis showed that both precision and accuracy errors decrease with increasing the size of the region analyzed, by following power laws. The main source of error was found to be the intrinsic noise of the images compared to the others investigated. The results, once extrapolated for larger regions of interest that are typically used in the literature, were in most cases better than the ones previously reported. For a nodal spacing equal to 50 voxels (498 µm), the accuracy and precision ranges were 425-692 µε and 202-394 µε, respectively. In conclusion, it was shown that the proposed method can be used to study the local deformation of cortical and trabecular bone loaded beyond yield, if a sufficiently high nodal spacing is used. Copyright © 2014 Elsevier Ltd. All rights reserved.

Local transplantation is an effective method for cell delivery in the osteogenesis imperfecta murine model.

PubMed

Pauley, Penelope; Matthews, Brya G; Wang, Liping; Dyment, Nathaniel A; Matic, Igor; Rowe, David W; Kalajzic, Ivo

2014-09-01

Osteogenesis imperfecta is a serious genetic disorder that results from improper type I collagen production. We aimed to evaluate whether bone marrow stromal cells (BMSC) delivered locally into femurs were able to engraft, differentiate into osteoblasts, and contribute to formation of normal bone matrix in the osteogenesis imperfect murine (oim) model. Donor BMSCs from bone-specific reporter mice (Col2.3GFP) were expanded in vitro and transplanted into the femoral intramedullary cavity of oim mice. Engraftment was evaluated after four weeks. We detected differentiation of donor BMSCs into Col2.3GFP+ osteoblasts and osteocytes in cortical and trabecular bone of transplanted oim femurs. New bone formation was detected by deposition of dynamic label in the proximity to the Col2.3GFP+ osteoblasts, and new bone showed more organized collagen structure and expression of type I α2 collagen. Col2.3GFP cells were not found in the contralateral femur indicating that transplanted osteogenic cells did not disseminate by circulation. No osteogenic engraftment was observed following intravenous transplantation of BMSCs. BMSC cultures derived from transplanted femurs showed numerous Col2.3GFP+ colonies, indicating the presence of donor progenitor cells. Secondary transplantation of cells recovered from recipient femurs and expanded in vitro also showed Col2.3GFP+ osteoblasts and osteocytes confirming the persistence of donor stem/progenitor cells. We show that BMSCs delivered locally in oim femurs are able to engraft, differentiate into osteoblasts and osteocytes and maintain their progenitor potential in vivo. This suggests that local delivery is a promising approach for introduction of autologous MSC in which mutations have been corrected.

Influence of press-fit parameters on the primary stability of uncemented femoral resurfacing implants.

PubMed

Gebert, A; Peters, J; Bishop, N E; Westphal, F; Morlock, M M

2009-01-01

Primary stability is essential to the success of uncemented prostheses. It is strongly influenced by implantation technique, implant design and bone quality. The goal of this study was to investigate the effect of press-fit parameters on the primary stability of uncemented femoral head resurfacing prostheses. An in vitro study with human specimens and prototype implants (nominal radial interference 170 and 420 microm) was used to investigate the effect of interference on primary stability. A finite element model was used to assess the influence of interference, friction between implant and bone, and bone quality. Primary stability was represented by the torque capacity of the implant. The model predicted increasing stability with actual interference, bone quality and friction coefficient; plastic deformation of the bone began at interferences of less than 100 microm. Experimentally, however, stability was not related to interference. This may be due to abrasion or the collapse of trabecular bone structures at higher interferences, which could not be captured by the model. High nominal interferences as tested experimentally appear unlikely to result in improved stability clinically. An implantation force of about 2,500 N was estimated to be sufficient to achieve a torque capacity of about 30 N m with a small interference (70 microm).

Removal of bone in CT angiography by multiscale matched mask bone elimination.

PubMed

Gratama van Andel, H A F; Venema, H W; Streekstra, G J; van Straten, M; Majoie, C B L M; den Heeten, G J; Grimbergen, C A

2007-10-01

For clear visualization of vessels in CT angiography (CTA) images of the head and neck using maximum intensity projection (MIP) or volume rendering (VR) bone has to be removed. In the past we presented a fully automatic method to mask the bone [matched mask bone elimination (MMBE)] for this purpose. A drawback is that vessels adjacent to bone may be partly masked as well. We propose a modification, multiscale MMBE, which reduces this problem by using images at two scales: a higher resolution than usual for image processing and a lower resolution to which the processed images are transformed for use in the diagnostic process. A higher in-plane resolution is obtained by the use of a sharper reconstruction kernel. The out-of-plane resolution is improved by deconvolution or by scanning with narrower collimation. The quality of the mask that is used to remove bone is improved by using images at both scales. After masking, the desired resolution for the normal clinical use of the images is obtained by blurring with Gaussian kernels of appropriate widths. Both methods (multiscale and original) were compared in a phantom study and with clinical CTA data sets. With the multiscale approach the width of the strip of soft tissue adjacent to the bone that is masked can be reduced from 1.0 to 0.2 mm without reducing the quality of the bone removal. The clinical examples show that vessels adjacent to bone are less affected and therefore better visible. Images processed with multiscale MMBE have a slightly higher noise level or slightly reduced resolution compared with images processed by the original method and the reconstruction and processing time is also somewhat increased. Nevertheless, multiscale MMBE offers a way to remove bone automatically from CT angiography images without affecting the integrity of the blood vessels. The overall image quality of MIP or VR images is substantially improved relative to images processed with the original MMBE method.

Antibiotic-loaded bone void filler accelerates healing in a femoral condylar rat model.

PubMed

Shiels, S M; Cobb, R R; Bedigrew, K M; Ritter, G; Kirk, J F; Kimbler, A; Finger Baker, I; Wenke, J C

2016-08-01

Demineralised bone matrix (DBM) is rarely used for the local delivery of prophylactic antibiotics. Our aim, in this study, was to show that a graft with a bioactive glass and DBM combination, which is currently available for clinical use, can be loaded with tobramycin and release levels of antibiotic greater than the minimum inhibitory concentration for Staphylococcus aureus without interfering with the bone healing properties of the graft, thus protecting the graft and surrounding tissues from infection. Antibiotic was loaded into a graft and subsequently evaluated for drug elution kinetics and the inhibition of bacterial growth. A rat femoral condylar plug model was used to determine the effect of the graft, loaded with antibiotic, on bone healing. We found that tobramycin loaded into a graft composed of bioglass and DBM eluted antibiotic above the minimum inhibitory concentration for three days in vitro. It was also found that the antibiotic loaded into the graft produced no adverse effects on the bone healing properties of the DBM at a lower level of antibiotic. This antibiotic-loaded bone void filler may represent a promising option for the delivery of local antibiotics in orthopaedic surgery. Cite this article: Bone Joint J 2016;98-B:1126-31. ©2016 The British Editorial Society of Bone & Joint Surgery.

Development of a novel method for surgical implant design optimization through noninvasive assessment of local bone properties.

PubMed

Schiuma, D; Brianza, S; Tami, A E

2011-03-01

A method was developed to improve the design of locking implants by finding the optimal paths for the anchoring elements, based on a high resolution pQCT assessment of local bone mineral density (BMD) distribution and bone micro-architecture (BMA). The method consists of three steps: (1) partial fixation of the implant to the bone and creation of a reference system, (2) implant removal and pQCT scan of the bone, and (3) determination of BMD and BMA of all implant-anchoring locations along the actual and alternative directions. Using a PHILOS plate, the method uncertainty was tested on an artificial humerus bone model. A cadaveric humerus was used to quantify how the uncertainty of the method affects the assessment of bone parameters. BMD and BMA were determined along four possible alternative screw paths as possible criteria for implant optimization. The method is biased by a 0.87 ± 0.12 mm systematic uncertainty and by a 0.44 ± 0.09 mm random uncertainty in locating the virtual screw position. This study shows that this method can be used to find alternative directions for the anchoring elements, which may possess better bone properties. This modification will thus produce an optimized implant design. Copyright © 2010 IPEM. Published by Elsevier Ltd. All rights reserved.

Osteoclastogenesis in Local Alveolar Bone in Early Decortication-Facilitated Orthodontic Tooth Movement

PubMed Central

Liu, Chang; Jiang, Yu-Xi; Qu, Hong; Li, Cui-Ying; Jiang, Jiu-Hui

2016-01-01

Objective In the current study, we aimed to investigate the effects of alveolar decortication on local bone remodeling, and to explore the possible mechanism by which decortication facilitates tooth movement. Materials and Methods Forty rabbits were included in the experiment. The left mandible was subjected to decortication-facilitated orthodontics, and the right mandible underwent traditional orthodontics as a control. The animals were sacrificed on the days 1, 3, 5, 7 and 14, after undergoing orthodontic procedures. Tooth movement was measured by Micro-CT, and the local periodontal tissues were investigated using H&E, Masson's trichrome and tartrate-resistant acid phosphatase (TRAP) staining. The mRNA levels of genes related to bone remodeling in the alveolar bone were analyzed using real-time PCR. Result On days 3, 5, 7 and 14, tooth movement was statistically accelerated by decortication (P < 0.05) and was accompanied by increased hyperemia. Despite the lack of new bone formation in both groups, more osteoclasts were noted in the decorticated group, with two peak counts (P < 0.05). The first peak count was consistent with the maximum values of ctsk and TRAP expression, and the second peak counts accompanied the maximum nfatc1 and jdp2 expression. The increased fra2 expression and the ratio of rankl/opg also accompanied the second peak counts. Conclusions Following alveolar decortication, osteoclastogenesis was initially induced to a greater degree than the new bone formation which was thought to have caused a regional acceleratory phenomenon (RAP). The amount of steoclastogenesis in the decorticated alveolar bone was found to have two peaks, perhaps due to attenuated local resistance. The first peak count in osteoclasts may have been due to previously existing osteoclast precursors, whereas the second may represent the differentiation of peripheral blood mononuclear cells which came from circulation as the result of hyperemia. PMID:27096621

[Subchondral bone in osteoarthritis: a review].

PubMed

Pang, Jian; Cao, Yue-long; Shi, Yin-yu

2011-08-01

Osteoarthritis (OA) is the most prevalent of joint diseases,and its pathology is characterized by the degeneration of cartilage, sclerosis of subchondral bone, and osteophyte formation. Localization of the early lesions of OA has not been clarified, but many researchers have focused on cartilage and have considered that changes in subchondral bone occur subsequently to the degeneration of cartilage. However, a low bone mineral density, particularly in the knee joint with OA, high bone turnover, and efficacy of bone resorption inhibitors for OA have recently been reported, suggesting that subchondral bone plays an important role in the pathogenesis of OA. This review aims to make a conclusion about advancement in research of subchondral bone in osteoarthritis.

Micro-computed tomography assessment of human alveolar bone: bone density and three-dimensional micro-architecture.

PubMed

Kim, Yoon Jeong; Henkin, Jeffrey

2015-04-01

Micro-computed tomography (micro-CT) is a valuable means to evaluate and secure information related to bone density and quality in human necropsy samples and small live animals. The aim of this study was to assess the bone density of the alveolar jaw bones in human cadaver, using micro-CT. The correlation between bone density and three-dimensional micro architecture of trabecular bone was evaluated. Thirty-four human cadaver jaw bone specimens were harvested. Each specimen was scanned with micro-CT at resolution of 10.5 μm. The bone volume fraction (BV/TV) and the bone mineral density (BMD) value within a volume of interest were measured. The three-dimensional micro architecture of trabecular bone was assessed. All the parameters in the maxilla and the mandible were subject to comparison. The variables for the bone density and the three-dimensional micro architecture were analyzed for nonparametric correlation using Spearman's rho at the significance level of p < .05. A wide range of bone density was observed. There was a significant difference between the maxilla and mandible. All micro architecture parameters were consistently higher in the mandible, up to 3.3 times greater than those in the maxilla. The most linear correlation was observed between BV/TV and BMD, with Spearman's rho = 0.99 (p = .01). Both BV/TV and BMD were highly correlated with all micro architecture parameters with Spearman's rho above 0.74 (p = .01). Two aspects of bone density using micro-CT, the BV/TV and BMD, are highly correlated with three-dimensional micro architecture parameters, which represent the quality of trabecular bone. This noninvasive method may adequately enhance evaluation of the alveolar bone. © 2013 Wiley Periodicals, Inc.

Premature Osteoblast Clustering by Enamel Matrix Proteins Induces Osteoblast Differentiation through Up-Regulation of Connexin 43 and N-Cadherin

PubMed Central

Miron, Richard J.; Hedbom, Erik; Ruggiero, Sabrina; Bosshardt, Dieter D.; Zhang, Yufeng; Mauth, Corinna; Gemperli, Anja C.; Iizuka, Tateyuki; Buser, Daniel; Sculean, Anton

2011-01-01

In recent years, enamel matrix derivative (EMD) has garnered much interest in the dental field for its apparent bioactivity that stimulates regeneration of periodontal tissues including periodontal ligament, cementum and alveolar bone. Despite its widespread use, the underlying cellular mechanisms remain unclear and an understanding of its biological interactions could identify new strategies for tissue engineering. Previous in vitro research has demonstrated that EMD promotes premature osteoblast clustering at early time points. The aim of the present study was to evaluate the influence of cell clustering on vital osteoblast cell-cell communication and adhesion molecules, connexin 43 (cx43) and N-cadherin (N-cad) as assessed by immunofluorescence imaging, real-time PCR and Western blot analysis. In addition, differentiation markers of osteoblasts were quantified using alkaline phosphatase, osteocalcin and von Kossa staining. EMD significantly increased the expression of connexin 43 and N-cadherin at early time points ranging from 2 to 5 days. Protein expression was localized to cell membranes when compared to control groups. Alkaline phosphatase activity was also significantly increased on EMD-coated samples at 3, 5 and 7 days post seeding. Interestingly, higher activity was localized to cell cluster regions. There was a 3 fold increase in osteocalcin and bone sialoprotein mRNA levels for osteoblasts cultured on EMD-coated culture dishes. Moreover, EMD significantly increased extracellular mineral deposition in cell clusters as assessed through von Kossa staining at 5, 7, 10 and 14 days post seeding. We conclude that EMD up-regulates the expression of vital osteoblast cell-cell communication and adhesion molecules, which enhances the differentiation and mineralization activity of osteoblasts. These findings provide further support for the clinical evidence that EMD increases the speed and quality of new bone formation in vivo. PMID:21858092

Precision of DVC approaches for strain analysis in bone imaged with μCT at different dimensional levels.

NASA Astrophysics Data System (ADS)

Dall'Ara, Enrico; Peña-Fernández, Marta; Palanca, Marco; Giorgi, Mario; Cristofolini, Luca; Tozzi, Gianluca

2017-11-01

Accurate measurement of local strain in heterogeneous and anisotropic bone tissue is fundamental to understand the pathophysiology of musculoskeletal diseases, to evaluate the effect of interventions from preclinical studies, and to optimize the design and delivery of biomaterials. Digital volume correlation (DVC) can be used to measure the three-dimensional displacement and strain fields from micro-Computed Tomography (µCT) images of loaded specimens. However, this approach is affected by the quality of the input images, by the morphology and density of the tissue under investigation, by the correlation scheme, and by the operational parameters used in the computation. Therefore, for each application the precision of the method should be evaluated. In this paper we present the results collected from datasets analyzed in previous studies as well as new data from a recent experimental campaign for characterizing the relationship between the precision of two different DVC approaches and the spatial resolution of the outputs. Different bone structures scanned with laboratory source µCT or Synchrotron light µCT (SRµCT) were processed in zero-strain tests to evaluate the precision of the DVC methods as a function of the subvolume size that ranged from 8 to 2500 micrometers. The results confirmed that for every microstructure the precision of DVC improves for larger subvolume size, following power laws. However, for the first time large differences in the precision of both local and global DVC approaches have been highlighted when SRµCT or in vivo µCT images were used instead of conventional ex vivo µCT. These findings suggest that in situ mechanical testing protocols applied in SRµCT facilities should be optimized in order to allow DVC analyses of localized strain measurements. Moreover, for in vivo µCT applications DVC analyses should be performed only with relatively course spatial resolution for achieving a reasonable precision of the method. In conclusion, we have extensively shown that the precision of both tested DVC approaches is affected by different bone structures, different input image resolution and different subvolume sizes. Before each specific application DVC users should always apply a similar approach to find the best compromise between precision and spatial resolution of the measurements.

CD133: Enhancement of Bone Healing by Local Transplantation of Peripheral Blood Cells in a Biologically Delayed Rat Osteotomy Model

PubMed Central

Preininger, Bernd; Duda, Georg; Gerigk, Hinnerk; Bruckner, Jonas; Ellinghaus, Agnes; Sass, F. Andrea; Perka, Carsten; Schmidt-Bleek, Katharina; Dienelt, Anke

2013-01-01

Sufficient angiogenesis is crucial during tissue regeneration and therefore also pivotal in bone defect healing. Recently, peripheral blood derived progenitor cells have been identified to have in addition to their angiogenic potential also osteogenic characteristics, leading to the hypothesis that bone regeneration could be stimulated by local administration of these cells. The aim of this study was to evaluate the angiogenic potential of locally administered progenitor cells to improve bone defect healing. Cells were separated from the peripheral blood of donor animals using the markers CD34 and CD133. Results of the in vitro experiments confirmed high angiogenic potential in the CD133(+) cell group. CD34(+) and CD133(+) cells were tested in an in vivo rat femoral defect model of delayed healing for their positive effect on the healing outcome. An increased callus formation and higher bone mineral density of callus tissue was found after the CD133(+) cell treatment compared to the group treated with CD34(+) cells and the control group without cells. Histological findings confirmed an increase in vessel formation and mineralization at day 42 in the osteotomy gap after CD133(+) cell transplantation. The higher angiogenic potential of CD133(+) cells from the in vitro experients therefore correlates with the in vivo data. This study demonstrates the suitability of angiogenic precursors to further bone healing and gives an indication that peripheral blood is a promising source for progenitor cells circumventing the problems associated with bone marrow extraction. PMID:23457441

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.

Segmentation of knee MRI using structure enhanced local phase filtering

NASA Astrophysics Data System (ADS)

Lim, Mikhiel; Hacihaliloglu, Ilker

2016-03-01

The segmentation of bone surfaces from magnetic resonance imaging (MRI) data has applications in the quanti- tative measurement of knee osteoarthritis, surgery planning for patient specific total knee arthroplasty and its subsequent fabrication of artificial implants. However, due to the problems associated with MRI imaging such as low contrast between bone and surrounding tissues, noise, bias fields, and the partial volume effect, segmentation of bone surfaces continues to be a challenging operation. In this paper, a new framework is presented for the enhancement of knee MRI scans prior to segmentation in order to obtain high contrast bone images. During the first stage, a new contrast enhanced relative total variation (RTV) regularization method is used in order to remove textural noise from the bone structures and surrounding soft tissue interface. This salient bone edge information is further enhanced using a sparse gradient counting method based on L0 gradient minimization, which globally controls how many non-zero gradients are resulted in order to approximate prominent bone structures in a structure-sparsity-management manner. The last stage of the framework involves incorporation of local phase bone boundary information in order to provide an intensity invariant enhancement of contrast between the bone and surrounding soft tissue. The enhanced images are segmented using a fast random walker algorithm. Validation against expert segmentation was performed on 10 clinical knee MRI images, and achieved a mean dice similarity coefficient (DSC) of 0.975.

Fixation of Hydroxyapatite-Coated Revision Implants Is Improved by the Surgical Technique of Cracking the Sclerotic Bone Rim

PubMed Central

Elmengaard, Brian; Bechtold, Joan E.; Chen, Xinqian; Søballe, Kjeld

2013-01-01

Revision joint replacement has poorer outcomes that have been associated with poorer mechanical fixation. We investigate a new bone-sparing surgical technique that locally cracks the sclerotic bone rim formed during aseptic loosening. We inserted 16 hydroxyapatite-coated implants bilaterally in the distal femur of eight dogs, using a controlled weight-bearing experimental model that replicates important features of a typical revision setting. At 8 weeks, a control revision procedure and a crack revision procedure were performed on contralateral implants. The crack procedure used a splined tool to perform a systematic local perforation of the sclerotic bone rim of the revision cavity. After 4 weeks, the hydroxyapatite-coated implants were evaluated for mechanical fixation by a push-out test and for tissue distribution by histomorphometry. The cracking revision procedure resulted in significantly improved mechanical fixation, significantly more bone ongrowth and bone volume in the gap, and reduced fibrous tissue compared to the control revision procedure. The study demonstrates that the sclerotic bone rim prevents bone ingrowth and promotes fixation by fibrous tissue. The effect of the cracking technique may be due to improved access to the vascular compartment of the bone. The cracking technique is a simple surgical method that potentially can improve the fixation of revision implants in sclerotic regions important for obtaining the fixation critical for overall implant stability. PMID:19148940

CERAMENT treatment of fracture defects (CERTiFy): protocol for a prospective, multicenter, randomized study investigating the use of CERAMENT™ BONE VOID FILLER in tibial plateau fractures

PubMed Central

2014-01-01

Background Bone graft substitutes are widely used for reconstruction of posttraumatic bone defects. However, their clinical significance in comparison to autologous bone grafting, the gold-standard in reconstruction of larger bone defects, still remains under debate. This prospective, randomized, controlled clinical study investigates the differences in pain, quality of life, and cost of care in the treatment of tibia plateau fractures-associated bone defects using either autologous bone grafting or bioresorbable hydroxyapatite/calcium sulphate cement (CERAMENT™|BONE VOID FILLER (CBVF)). Methods/Design CERTiFy (CERament™ Treatment of Fracture defects) is a prospective, multicenter, controlled, randomized trial. We plan to enroll 136 patients with fresh traumatic depression fractures of the proximal tibia (types AO 41-B2 and AO 41-B3) in 13 participating centers in Germany. Patients will be randomized to receive either autologous iliac crest bone graft or CBVF after reduction and osteosynthesis of the fracture to reconstruct the subchondral bone defect and prevent the subsidence of the articular surface. The primary outcome is the SF-12 Physical Component Summary at week 26. The co-primary endpoint is the pain level 26 weeks after surgery measured by a visual analog scale. The SF-12 Mental Component Summary after 26 weeks and costs of care will serve as key secondary endpoints. The study is designed to show non-inferiority of the CBVF treatment to the autologous iliac crest bone graft with respect to the physical component of quality of life. The pain level at 26 weeks after surgery is expected to be lower in the CERAMENT bone void filler treatment group. Discussion CERTiFy is the first randomized multicenter clinical trial designed to compare quality of life, pain, and cost of care in the use of the CBVF and the autologous iliac crest bone graft in the treatment of tibia plateau fractures. The results are expected to influence future treatment recommendations. Trial registration number ClinicalTrials.gov: NCT01828905 PMID:24606670

Paleontologic investigations at Big Bone Lick State Park, Kentucky: A preliminary report

USGS Publications Warehouse

Schultz, C.B.; Tanner, L.G.; Whitmore, F.C.; Ray, L.L.; Crawford, E.C.

1963-01-01

The Big Bone Lick area in Kentucky, the first widely known collecting locality for vertebrate fossils in North America, is being investigated for further faunal and geologic evidence. Mammal bones, ranging in age from Wisconsin (Tazewell?) to Recent, were recovered in 1962 from four different faunal zones in two terrace fills.

Nano-engineered titanium for enhanced bone therapy

NASA Astrophysics Data System (ADS)

Gulati, Karan; Atkins, Gerald J.; Findlay, David M.; Losic, Dusan

2013-09-01

Current treatment of a number of orthopaedic conditions, for example fractures, bone infection, joint replacement and bone cancers, could be improved if mechanical support could be combined with drug delivery. A very challenging example is that of infection following joint replacement, which is very difficult to treat, can require multiple surgeries and compromises both the implant and the patient's wellbeing. An implant capable of providing appropriate biomechanics and releasing drugs/proteins locally might ensure improved healing of the traumatized bone. We propose fabrication of nanoengineered titanium bone implants using bioinert titanium wires in order to achieve this goal. Titanium in the form of flat foils and wires were modified by fabrication of titania nanotubes (TNTs), which are hollow self-ordered cylindrical tubes capable of accommodating substantial drug amounts and releasing them locally. To further control the release of drug to over a period of months, a thin layer of biodegradable polymer PLGA poly(lactic-coglycolic acid) was coated onto the drug loaded TNTs. This delayed release of drug and additionally the polymer enhanced bone cell adhesion and proliferation.

An ultrastructural and immunogold localization study of proteoglycans associated with the osteocytes of fetal bone in osteogenesis imperfecta.

PubMed

Sarathchandra, P; Pope, F M; Ali, S Y

1996-06-01

Osteogenesis imperfecta (OI) is a rare, heterogeneous, inherited connective tissue disorder frequently caused by abnormalities of type I collagen. It is characterized by bone fragility, osteopenia, and progressive skeletal deformities. Electron microscopy of three OI type II fetal bone samples revealed numerous large osteocyte lacunae. In addition, there was a perilacunar osteoid-like band of collagen surrounding the osteocytes, which was unmineralized and morphologically unusual. Furthermore, large osteocyte lacunae contained fine particles and filamentous material similar to the expected ultrastructural appearance of proteoglycans. More detailed examination was carried out using histochemical and immunogold localization of proteoglycans at light and ultrastructural levels. These tests and the use of electron probe X-ray microanalysis confirmed that the material in the osteocyte lacunae was proteoglycan. In contrast, in the age- and site-matched normal fetal bone, all the osteocyte lacunae appeared negative for proteoglycan. Proteoglycans are regarded as inhibitors of calcification. Our observation of substantial amounts of proteoglycan in abnormally enlarged osteocytic lacunae of some OI fetal bone suggests association with the abnormal bone of this particular subtype of OI type II.

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

Contemporary adjuvant polymethyl methacrylate cementation optimally limits recurrence in primary giant cell tumor of bone patients compared to bone grafting: a systematic review and meta-analysis

PubMed Central

2013-01-01

Background Reports of recurrence following restructuring of primary giant cell tumor (GCT) defects using polymethyl methacrylate (PMMA) bone cementation or allogeneic bone graft with and without adjuvants for intralesional curettage vary widely. Systematic review and meta-analysis were conducted to investigate efficacy of PMMA bone cementation and allogeneic bone grafting following intralesional curettage for GCT. Methods Medline, EMBASE, Google Scholar, and Cochrane databases were searched for studies reporting GCT of bone treatment with PMMA cementation and/or bone grafting with or without adjuvant therapy following intralesional curettage of primary GCTs. Pooled risk ratios and 95% confidence intervals (CIs) for local recurrence risks were calculated by fixed-effects methods. Results Of 1,690 relevant titles, 6 eligible studies (1,293 patients) spanning March 2008 to December 2011 were identified in published data. Treatment outcomes of PMMA-only (n = 374), bone graft-only (n = 436), PMMA with or without adjuvant (PMMA + adjuvant; n = 594), and bone graft filling with or without adjuvant (bone graft + adjuvant; n = 699) were compared. Bone graft-only patients exhibited higher recurrence rates than PMMA-treated patients (RR 2.09, 95% CI (1.64, 2.66), Overall effect: Z = 6.00; P <0.001), and bone graft + adjuvant patients exhibited higher recurrence rates than PMMA + adjuvant patients (RR 1.66, 95% CI (1.21, 2.28), Overall effect: Z = 3.15, P = 0.002). Conclusions Local recurrence was minimal in PMMA cementation patients, suggesting that PMMA is preferable for routine clinical restructuring in eligible GCT patients. Relationships between tumor characteristics, other modern adjuvants, and recurrence require further exploration. PMID:23866921

Optimal parameters to avoid thermal necrosis during bone drilling: A finite element analysis.

PubMed

Mediouni, Mohamed; Schlatterer, Daniel R; Khoury, Amal; Von Bergen, Tobias; Shetty, Sunil H; Arora, Manit; Dhond, Amit; Vaughan, Neil; Volosnikov, Alexander

2017-11-01

The drilling bone may potentially cause excessive frictional heat, which can lead to local bone necrosis. This heat generation and local necrosis has been suggested to contribute to the resorption of bone around the placed screws, ending in loss of screw purchase in the bone and inadvertent loosening and/or the bone-implant construct. In vivo studies on this subject have inherent obstacles not the least of which is controlling the variables and real time bone temperature data acquisition. Theoretical models can be generated using computer software and the inclusion of known constants for the mechanical properties of metal and bone. These known Data points for the variables (drill bit and bone) enables finite element analysis of various bone drilling scenarios. An elastic-plastic three-dimensional (3D) acetabular bone mode was developed and finite element model analysis (FEA) was applied to various simulated drilling procedures. The FEA results clearly indicate that the depth of drilling and the drill speed both have a significant effect on the temperature during drilling procedures. The reduction of the feeding speed leads to a reduction in bone temperature. Our data suggests that reducing the feeding speed regardless of RPMs and pressure applied could be a simple useful and effective way to reduce drilling temperatures. This study is the first step in helping any surgeon who drills bone and places screws to better understand the ideal pressure to apply and drill speed to employ and advance rate to avoid osteonecrosis. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2386-2391, 2017. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Medicarpin, a Natural Pterocarpan, Heals Cortical Bone Defect by Activation of Notch and Wnt Canonical Signaling Pathways

PubMed Central

Gupta, Chandra Prakash; Kureel, Jyoti; Mansoori, Mohd Nizam; Shukla, Priyanka; John, Aijaz A.; Singh, Kavita; Purohit, Dipak; Awasthi, Pallavi; Singh, Divya; Goel, Atul

2015-01-01

We evaluated the bone regeneration and healing effect of Medicarpin (med) in cortical bone defect model that heals by intramembranous ossification. For the study, female Sprague–Dawley rats were ovariectomized and rendered osteopenic. A drill hole injury was generated in mid femoral bones of all the animals. Med treatment was commenced the day after and continued for 15 days. PTH was taken as a reference standard. Fifteen days post-treatment, animals were sacrificed. Bones were collected for histomorphometry studies at the injury site by micro-computed tomography (μCT) and confocal microscopy. RNA and protein was harvested from newly generated bone. For immunohistochemistry, 5μm sections of decalcified femur bone adjoining the drill hole site were cut. By μCT analysis and calcein labeling of newly generated bone it was found that med promotes bone healing and new bone formation at the injury site and was comparable to PTH in many aspects. Med treatment led to increase in the Runx-2 and osteocalcin signals indicating expansion of osteoprogenitors at the injury site as evaluated by qPCR and immunohistochemical localization. It was observed that med promoted bone regeneration by activating canonical Wnt and notch signaling pathway. This was evident by increased transcript and protein levels of Wnt and notch signaling components in the defect region. Finally, we confirmed that med treatment leads to elevated bone healing in pre-osteoblasts by co localization of beta catenin with osteoblast marker alkaline phosphatase. In conclusion, med treatment promotes new bone regeneration and healing at the injury site by activating Wnt/canonical and notch signaling pathways. This study also forms a strong case for evaluation of med in delayed union and non-union fracture cases. PMID:26657206

Medicarpin, a Natural Pterocarpan, Heals Cortical Bone Defect by Activation of Notch and Wnt Canonical Signaling Pathways.

PubMed

Dixit, Manisha; Raghuvanshi, Ashutosh; Gupta, Chandra Prakash; Kureel, Jyoti; Mansoori, Mohd Nizam; Shukla, Priyanka; John, Aijaz A; Singh, Kavita; Purohit, Dipak; Awasthi, Pallavi; Singh, Divya; Goel, Atul

2015-01-01

We evaluated the bone regeneration and healing effect of Medicarpin (med) in cortical bone defect model that heals by intramembranous ossification. For the study, female Sprague-Dawley rats were ovariectomized and rendered osteopenic. A drill hole injury was generated in mid femoral bones of all the animals. Med treatment was commenced the day after and continued for 15 days. PTH was taken as a reference standard. Fifteen days post-treatment, animals were sacrificed. Bones were collected for histomorphometry studies at the injury site by micro-computed tomography (μCT) and confocal microscopy. RNA and protein was harvested from newly generated bone. For immunohistochemistry, 5μm sections of decalcified femur bone adjoining the drill hole site were cut. By μCT analysis and calcein labeling of newly generated bone it was found that med promotes bone healing and new bone formation at the injury site and was comparable to PTH in many aspects. Med treatment led to increase in the Runx-2 and osteocalcin signals indicating expansion of osteoprogenitors at the injury site as evaluated by qPCR and immunohistochemical localization. It was observed that med promoted bone regeneration by activating canonical Wnt and notch signaling pathway. This was evident by increased transcript and protein levels of Wnt and notch signaling components in the defect region. Finally, we confirmed that med treatment leads to elevated bone healing in pre-osteoblasts by co localization of beta catenin with osteoblast marker alkaline phosphatase. In conclusion, med treatment promotes new bone regeneration and healing at the injury site by activating Wnt/canonical and notch signaling pathways. This study also forms a strong case for evaluation of med in delayed union and non-union fracture cases.

Accelerated and enhanced bone formation on novel simvastatin-loaded porous titanium oxide surfaces.

PubMed

Nyan, Myat; Hao, Jia; Miyahara, Takayuki; Noritake, Kanako; Rodriguez, Reena; Kasugai, Shohei

2014-10-01

With increasing application of dental implants in poor-quality bones, the need for implant surfaces ensuring accelerated osseointegration and enhanced peri-implant bone regeneration is increased. A study was performed to evaluate the osseointegration and bone formation on novel simvastatin-loaded porous titanium oxide surface. Titanium screws were treated by micro-arc oxidation to form porous oxide surface and 25 or 50 μg of simvastatin was loaded. The nontreated control, micro-arc oxidized, and simvastatin-loaded titanium screws were surgically implanted into the proximal tibia of 16-week-old male Wistar rats (n = 36). Peri-implant bone volume, bone-implant contact, and mineral apposition rates were measured at 2 and 4 weeks. Data were analyzed by one-way analysis of variance followed by Tukey's post hoc test. New bone was formed directly on the implant surface in the bone marrow cavity in simvastatin-loaded groups since 2 weeks. Bone-implant contact values were significantly higher in simvastatin-loaded groups than control and micro-arc oxidized groups at both time points (p < .05). Peri-implant bone volume and mineral apposition rate of simvastatin-loaded groups were significantly higher than control and micro-arc oxidized groups at 2 weeks (p < .05). These data suggested that simvastatin-loaded porous titanium oxide surface provides faster osseointegration and peri-implant bone formation and it would be potentially applicable in poor-quality bones. © 2013 Wiley Periodicals, Inc.

Vitamin E and the Healing of Bone Fracture: The Current State of Evidence

PubMed Central

Borhanuddin, Boekhtiar; Mohd Fozi, Nur Farhana; Naina Mohamed, Isa

2012-01-01

Background. The effect of vitamin E on health-related conditions has been extensively researched, with varied results. However, to date, there was no published review of the effect of vitamin E on bone fracture healing. Purpose. This paper systematically audited past studies of the effect of vitamin E on bone fracture healing. Methods. Related articles were identified from Medline, CINAHL, and Scopus databases. Screenings were performed based on the criteria that the study must be an original study that investigated the independent effect of vitamin E on bone fracture healing. Data were extracted using standardised forms, followed by evaluation of quality of reporting using ARRIVE Guidelines, plus recalculation procedure for the effect size and statistical power of the results. Results. Six animal studies fulfilled the selection criteria. The study methods were heterogeneous with mediocre reporting quality and focused on the antioxidant-related mechanism of vitamin E. The metasynthesis showed α-tocopherol may have a significant effect on bone formation during the normal bone remodeling phase of secondary bone healing. Conclusion. In general, the effect of vitamin E on bone fracture healing remained inconclusive due to the small number of heterogeneous and mediocre studies included in this paper. PMID:23304211

Healing in the new millennium: bone stimulators: an overview of where we've been and where we may be heading.

PubMed

Cook, Jeremy J; Summers, N Jake; Cook, Emily A

2015-01-01

Electromagnetic fields and their uses in bone healing have been fairly well studied, with most results showing improvement in healing of both bone and cartilage. Most supportive data are found in relation to the spine, femur, and tibia, but there is increasing evidence for its use in the foot and ankle for treatment of nonunions and as an adjunctive device in arthrodeses, particularly in high-risk populations. There are varying data and a significant variety of quality in the current research and publications concerning the use of electrical bone stimulation in the treatment of the foot and ankle. Thus, there is a definite need for further investigation and high-quality study designs to determine the most effective treatment modalities and pathologies best used with bone stimulation. Bone stimulation should be viewed as an adjunctive procedure in which the surgeon optimizes the high-risk patient both medically or surgically whenever possible. But when used appropriately, bone stimulation has the potential to influence outcomes and aid in bone healing when complications arise and in high-risk populations. Copyright © 2015 Elsevier Inc. All rights reserved.

Solitary pancreatic head metastasis from tibial adamantinoma: a rare indication to pancreaticoduodenectomy

PubMed Central

Silvestri, S; Sandrucci, S; Comandone, A; Molinaro, L; Chiusa, L; Fronda, G R; Franchello, A

2018-01-01

Abstract Pancreatic metastases are rare, <2% of all pancreatic neoplasia. This is the first case of pancreatic metastasis from adamantinoma, a rare, low grade and slow growing tumor which is frequently localized in long bones. We describe a case of a 45-year-old woman presenting with increased bilirubin level. Computed tomography and ecoendoscopic ultra sonography revealed a pancreatic head mass. Fine-needle aspiration biopsy was consistent with metastatic adamantinoma. The patient was submitted to a standard pancreaticoduodenectomy. As in the case presented, standard pancreatic resections are safe and feasible options to treat non-pancreatic primary tumor improving patient’s survival and quality of life. PMID:29479415

Local plate/rod descriptors of 3D trabecular bone micro-CT images from medial axis topologic analysis

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

Peyrin, Francoise; Attali, Dominique; Chappard, Christine

Purpose: Trabecular bone microarchitecture is made of a complex network of plate and rod structures evolving with age and disease. The purpose of this article is to propose a new 3D local analysis method for the quantitative assessment of parameters related to the geometry of trabecular bone microarchitecture. Methods: The method is based on the topologic classification of the medial axis of the 3D image into branches, rods, and plates. Thanks to the reversibility of the medial axis, the classification is next extended to the whole 3D image. Finally, the percentages of rods and plates as well as their meanmore » thicknesses are calculated. The method was applied both to simulated test images and 3D micro-CT images of human trabecular bone. Results: The classification of simulated phantoms made of plates and rods shows that the maximum error in the quantitative percentages of plate and rods is less than 6% and smaller than with the structure model index (SMI). Micro-CT images of human femoral bone taken in osteoporosis and early or advanced osteoarthritis were analyzed. Despite the large physiological variability, the present method avoids the underestimation of rods observed with other local methods. The relative percentages of rods and plates were not significantly different between osteoarthritis and osteoporotic groups, whereas their absolute percentages were in relation to an increase of rod and plate thicknesses in advanced osteoarthritis with also higher relative and absolute number of nodes. Conclusions: The proposed method is model-independent, robust to surface irregularities, and enables geometrical characterization of not only skeletal structures but entire 3D images. Its application provided more accurate results than the standard SMI on simple simulated phantoms, but the discrepancy observed on the advanced osteoarthritis group raises questions that will require further investigations. The systematic use of such a local method in the characterization of trabecular bone samples could provide new insight in bone microarchitecture changes related to bone diseases or to those induced by drugs or therapy.« less

A piezoelectric bone-conduction bending hearing actuator.

PubMed

Adamson, R B A; Bance, M; Brown, J A

2010-10-01

A prototype of a novel bone-conduction hearing actuator based on a piezoelectric bending actuator is presented. The device lies flat against the skull which would allow it to form the basis of a subcutaneous bone-anchored hearing aid. The actuator excites bending in bone through a local bending moment rather than the application of a point force as with conventional bone-anchored hearing aids. Through measurements of the cochlear velocity created by the actuator in embalmed human heads, the device is shown to exhibit high efficiency, making it a possible alternative to present-day electromagnetic bone-vibration actuators.

Added Value of SPECT/CT in the Evaluation of Benign Bone Diseases of the Appendicular Skeleton.

PubMed

Abikhzer, Gad; Srour, Saher; Keidar, Zohar; Bar-Shalom, Rachel; Kagna, Olga; Israel, Ora; Militianu, Daniela

2016-04-01

Bone scintigraphy is a sensitive technique to detect altered bone mineralization but has limited specificity. The use of SPECT/CT has improved significantly the diagnostic accuracy of bone scintigraphy, in patients with cancer as well as in evaluation of benign bone disease. It provides precise localization and characterization of tracer-avid foci, shortens the diagnostic workup, and decreases patient anxiety. Through both the SPECT and the CT components, SPECT/CT has an incremental value in characterizing benign bone lesions, specifically in the appendicular skeleton, as illustrated by present case series.

Is Surgical Navigation Useful During Closed Reduction of Nasal Bone Fractures?

PubMed

Kim, Seon Tae; Jung, Joo Hyun; Kang, Il Gyu

2017-05-01

To report the case of a 42-year-old woman with a nasal bone fracture that was easily treated using a surgical navigation system. In this clinical report, the authors suggest that intraoperative surgical navigation systems are useful diagnostically and for localizing sites of nasal bone fractures exactly. The patient underwent successful closed reduction of the nasal bone fracture. Surgical navigation is a useful tool for identifying nasal bone fracture locations and for guiding closed reduction. Surgical navigation is recommended when nasal bone fractures are complicated or not well reduced using the ordinary method.

[Bone remodeling and modeling/mini-modeling.

PubMed

Hasegawa, Tomoka; Amizuka, Norio

Modeling, adapting structures to loading by changing bone size and shapes, often takes place in bone of the fetal and developmental stages, while bone remodeling-replacement of old bone into new bone-is predominant in the adult stage. Modeling can be divided into macro-modeling(macroscopic modeling)and mini-modeling(microscopic modeling). In the cellular process of mini-modeling, unlike bone remodeling, bone lining cells, i.e., resting flattened osteoblasts covering bone surfaces will become active form of osteoblasts, and then, deposit new bone onto the old bone without mediating osteoclastic bone resorption. Among the drugs for osteoporotic treatment, eldecalcitol(a vitamin D3 analog)and teriparatide(human PTH[1-34])could show mini-modeling based bone formation. Histologically, mature, active form of osteoblasts are localized on the new bone induced by mini-modeling, however, only a few cell layer of preosteoblasts are formed over the newly-formed bone, and accordingly, few osteoclasts are present in the region of mini-modeling. In this review, histological characteristics of bone remodeling and modeling including mini-modeling will be introduced.

Opportunities for exercise during pullet rearing, Part II: Long-term effects on bone characteristics of adult laying hens at the end-of-lay.

PubMed

Casey-Trott, T M; Korver, D R; Guerin, M T; Sandilands, V; Torrey, S; Widowski, T M

2017-08-01

Osteoporosis in laying hens has been a production and welfare concern for several decades. The objective of this study was to determine whether differing opportunities for exercise during pullet rearing influences long-term bone quality characteristics in end-of-lay hens. A secondary objective was to assess whether differing opportunities for exercise in adult housing systems alters bone quality characteristics in end-of-lay hens. Four flock replicates of 588 Lohmann Selected Leghorn-Lite pullets were reared in either conventional cages (Conv) or an aviary rearing system (Avi) and placed into conventional cages (CC), 30-bird furnished cages (FC-S), or 60-bird furnished cages (FC-L) for adult housing. Wing and leg bones were collected at the end-of-lay to quantify bone composition and strength using quantitative computed tomography and bone breaking strength (BBS). At the end-of-lay, Avi hens had greater total and cortical cross-sectional area (P < 0.05) for the radius and tibia, greater total bone mineral content of the radius (P < 0.001), and greater tibial cortical bone mineral content (P = 0.029) than the Conv hens; however, total bone mineral density of the radius (P < 0.001) and cortical bone mineral density of the radius and tibia (P < 0.001) were greater in the Conv hens. Hens in the FC-L had greater total bone mineral density for the radius and tibia (P < 0.05) and greater trabecular bone mineral density for the radius (P = 0.027), compared to hens in the FC-S and CC. Total bone mineral content of the tibia (P = 0.030) and cortical bone mineral content of the radius (P = 0.030) and tibia (P = 0.013) were greater in the FC-L compared to the CC. The humerus of Conv hens had greater BBS than the Avi hens (P < 0.001), and the tibiae of FC-L and FC-S hens had greater BBS than CC hens (P = 0.006). Increased opportunities for exercise offered by the aviary rearing system provided improved bone quality characteristics lasting through to the end-of-lay. © The Author 2017. Published by Oxford University Press on behalf of Poultry Science Association.

[Application of acupoint anatomy localization method with colorful tube in education of acupoint anatomy].

PubMed

Song, Shi-Lin

2013-04-01

To seek a precise and simple method for localization of acupoint in anatomical experiment teaching. Medical bone needles were inserted into acupoints. Then, self-mode copper probe needles were thrust along the center of the bone needles to open the inner structures of acuppoints. And probe needles were replaced by colored plastic tubes. Finally, bone needles were withdrawn so as to fix the plastic tubes into the acupoints to facilitate the later cutting. This method for acupoint anatomic positioning is of low cost with accurate positioning and simple manipulation, which has advantages in strong experimental and innovative values.

Optimising antiresorptive therapies in postmenopausal women: why do we need to give due consideration to the degree of suppression?

PubMed

Karsdal, Morten A; Qvist, Per; Christiansen, Claus; Tankó, László B

2006-01-01

Accelerated bone turnover with bone resorption exceeding bone formation is a major mechanism underlying postmenopausal bone loss and hence the development of osteoporosis. Accordingly, inhibition of bone resorption is a rational approach for the prevention of osteoporosis. In this context, the most logical option, hormone replacement therapy, reverses the rate of bone turnover to premenopausal levels, whereas the magnitude of inhibition by amino-bisphosphonates and the recently introduced anti-receptor activator of NFkappaB ligand (RANKL) antibody often exceeds this. As bone turnover has crucial implications for the continuous renewal of bone tissue, the over-suppression of bone turnover has potential consequences for bone quality and strength. Long-term treatment with potent bisphosphonates has recently been associated with osteonecrosis of the jaw and dose-dependent increases in micro-crack accumulation in animals. Although these observations are the subject of ongoing discussions, it is timely to discuss whether the over-suppression of bone turnover below premenopausal levels is really our ultimate goal when defining the success criteria for antiresorptive agents. In this review, the implications of high and excessively low bone turnover of endogenous origin for bone quality, fracture risk and integrity of the jaw are discussed. In addition, animal and clinical research revealing initial findings regarding the potential adverse effects of drug-induced suppression of bone remodeling are summarised. The inhibition of bone resorption, which is either transient between doses (e.g. with calcitonin) or does not exceed premenopausal levels (with hormone replacement therapy or selective estrogen receptor modulators), is preferable because it not only provides similar antifracture efficacy but can also assist in the maintenance of the dynamic repair of micro-cracks/micro-fractures.

[LOCAL ANTIBIOTIC THERAPY OF OSTEOMYELITIS USING NONABSORBABLE IMPLANT (REVIEW)].

PubMed

Tuleubaev, B; Saginova, D; Abiyev, T; Davletbaev, M; Koshanova, A

2016-06-01

Despite the variety of treatments available, including surgical procedures and antimicrobial therapy, bone infections is still a medical problem, because they are difficult to treat. Optimal treatment should stabilize the bone, promote the biological recovery of bone defects and destroy bacterial infection. Systemic antibiotics are part of the standard therapy after surgical treatment of infected bone, but their effectiveness is limited due to malnutrition and low absorption at the site of infection. Moreover, long-term treatment and higher doses are associated with serious side effects. In contrast, the antibiotic impregnated bone cements or fillers can act as a local anti-infective drug delivery system, which not only fills the dead space after debridement, but also provide high concentrations of antibiotics in a potential site of infection, no increase levels of antibiotics in serum. The review analyzed the use of antibiotic-impregnated cement as local delivery of antibiotics systems. Gentamycin impregnated polymethylmethacrylate (PMMA) beads, for the topical treatment of orthopedic infections clinically used for over 30 years. Application of antibiotic delivery systems using cement in the infected region is common method of treatment that continues to improve. On the downside of PMMA is that the material does not biodegradable requires subsequent invasive procedures necessary to remove the implant.

CD146 expression on primary nonhematopoietic bone marrow stem cells is correlated with in situ localization

PubMed Central

Tormin, Ariane; Li, Ou; Brune, Jan Claas; Walsh, Stuart; Schütz, Birgit; Ehinger, Mats; Ditzel, Nicholas; Kassem, Moustapha

2011-01-01

Nonhematopoietic bone marrow mesenchymal stem cells (BM-MSCs) are of central importance for bone marrow stroma and the hematopoietic environment. However, the exact phenotype and anatomical distribution of specified MSC populations in the marrow are unknown. We characterized the phenotype of primary human BM-MSCs and found that all assayable colony-forming units-fibroblast (CFU-Fs) were highly and exclusively enriched not only in the lin−/CD271+/CD45−/CD146+ stem-cell fraction, but also in lin−/CD271+/CD45−/CD146−/low cells. Both populations, regardless of CD146 expression, shared a similar phenotype and genotype, gave rise to typical cultured stromal cells, and formed bone and hematopoietic stroma in vivo. Interestingly, CD146 was up-regulated in normoxia and down-regulated in hypoxia. This was correlated with in situ localization differences, with CD146 coexpressing reticular cells located in perivascular regions, whereas bone-lining MSCs expressed CD271 alone. In both regions, CD34+ hematopoietic stem/progenitor cells were located in close proximity to MSCs. These novel findings show that the expression of CD146 differentiates between perivascular versus endosteal localization of non-hematopoietic BM-MSC populations, which may be useful for the study of the hematopoietic environment. PMID:21415267

Bone volume fraction and structural parameters for estimation of mechanical stiffness and failure load of human cancellous bone samples; in-vitro comparison of ultrasound transit time spectroscopy and X-ray μCT.

PubMed

Alomari, Ali Hamed; Wille, Marie-Luise; Langton, Christian M

2018-02-01

Conventional mechanical testing is the 'gold standard' for assessing the stiffness (N mm -1 ) and strength (MPa) of bone, although it is not applicable in-vivo since it is inherently invasive and destructive. The mechanical integrity of a bone is determined by its quantity and quality; being related primarily to bone density and structure respectively. Several non-destructive, non-invasive, in-vivo techniques have been developed and clinically implemented to estimate bone density, both areal (dual-energy X-ray absorptiometry (DXA)) and volumetric (quantitative computed tomography (QCT)). Quantitative ultrasound (QUS) parameters of velocity and attenuation are dependent upon both bone quantity and bone quality, although it has not been possible to date to transpose one particular QUS parameter into separate estimates of quantity and quality. It has recently been shown that ultrasound transit time spectroscopy (UTTS) may provide an accurate estimate of bone density and hence quantity. We hypothesised that UTTS also has the potential to provide an estimate of bone structure and hence quality. In this in-vitro study, 16 human femoral bone samples were tested utilising three techniques; UTTS, micro computed tomography (μCT), and mechanical testing. UTTS was utilised to estimate bone volume fraction (BV/TV) and two novel structural parameters, inter-quartile range of the derived transit time (UTTS-IQR) and the transit time of maximum proportion of sonic-rays (TTMP). μCT was utilised to derive BV/TV along with several bone structure parameters. A destructive mechanical test was utilised to measure the stiffness and strength (failure load) of the bone samples. BV/TV was calculated from the derived transit time spectrum (TTS); the correlation coefficient (R 2 ) with μCT-BV/TV was 0.885. For predicting mechanical stiffness and strength, BV/TV derived by both μCT and UTTS provided the strongest correlation with mechanical stiffness (R 2 =0.567 and 0.618 respectively) and mechanical strength (R 2 =0.747 and 0.736 respectively). When respective structural parameters were incorporated to BV/TV, multiple regression analysis indicated that none of the μCT histomorphometric parameters could improve the prediction of mechanical stiffness and strength, while for UTTS, adding TTMP to BV/TV increased the prediction of mechanical stiffness to R 2 =0.711 and strength to R 2 =0.827. It is therefore envisaged that UTTS may have the ability to estimate BV/TV along with providing an improved prediction of osteoporotic fracture risk, within routine clinical practice in the future. Copyright © 2017 Elsevier Inc. All rights reserved.

[New methods for the evaluation of bone quality. Assessment of bone structural property using imaging.

PubMed

Ito, Masako

Structural property of bone includes micro- or nano-structural property of the trabecular and cortical bone, and macroscopic geometry. Radiological technique is useful to analyze the bone structural property;multi-detector row CT(MDCT)or high-resolution peripheral QCT(HR-pQCT)is available to analyze human bone in vivo . For the analysis of hip geometry, CT-based hip structure analysis(HSA)is available as well as DXA-based HSA. These structural parameters are related to biomechanical property, and these assessment tools provide information of pathological changes or the effects of anti-osteoporotic agents on bone.

Associations Between Plasma Chemerin Concentrations and Bone Quality in Adults From the General Population.

PubMed

Kadric, Lejla; Zylla, Stephanie; Nauck, Matthias; Völzke, Henry; Friedrich, Nele; Hannemann, Anke

2018-06-01

Chemerin is an adipokine associated with parameters of inflammation and the metabolic syndrome. Small observational studies suggested that high circulating chemerin levels are also related to bone erosion. We aimed to determine whether plasma chemerin levels are related to bone quality in the general population and to investigate the influence of body mass index (BMI) on that relation. For our analyses, we obtained data from 3583 adults who participated in the population-based Study of Health in Pomerania-Trend. The participants were divided into three groups according to their BMI: lean (<25 kg/m2), overweight (25 to 30 kg/m2), and obese (≥30 kg/m2). Chemerin concentrations were determined in EDTA plasma. Bone quality was assessed using quantitative ultrasound at the heel. Broadband ultrasound attenuation (BUA), speed of sound (SOS), stiffness index, and osteoporotic fracture risk were derived from this measurement. Sex- and BMI-specific linear regression models revealed inverse associations between chemerin levels and BUA in obese men. In obese women, inverse relations between chemerin levels and SOS or stiffness index were found. Logistic regression models revealed positive associations between chemerin levels and osteoporotic fracture risk. In lean or overweight subjects, no statistically significant associations were found. Our sex- and BMI-specific analyses showed that inverse associations between chemerin levels and bone quality are restricted to obese men and women. The observed association may be due to a chemerin-induced negative affect on bone metabolism, possibly due to abrogation of osteoblastogenesis or stimulation of adipogenesis.

Peri-implant and systemic effects of high-/low-affinity bisphosphonate-hydroxyapatite composite coatings in a rabbit model with peri-implant high bone turnover

PubMed Central

2012-01-01

Background Hydroxyapatite (HA) coatings composed with bisphosphonates (BPs) which have high mineral-binding affinities have been confirmed to successfully enhance implant stability. However, few previous studies focused on HA coatings composed with low-affinity BPs or on systemic effects of locally released BPs. Methods In this long-term study, we developed two kinds of BP-HA composite coatings using either high-affinity BP (alendronate, ALN) or low-affinity BP (risedronate, RIS). Thirty-six rabbits were divided into three groups according to different coating applications (group I: HA, group II: ALN-HA, and group III: RIS-HA). Implants were inserted into the proximal region of the medullary cavity of the left tibiay. At insertion, 2 × 108 wear particles were injected around implants to induce a peri-implant high bone turnover environment. Both local (left tibias) and systemic (right tibias and lumbar vertebrae) inhibitory effect on bone resorption were compared, including bone-implant integration, bone architecture, bone mineral density (BMD), implant stability, and serum levels of bone turnover markers. Results The results indicated that ALN-HA composite coating, which could induce higher bone-implant contact (BIC) ratio, bone mass augmentation, BMD, and implant stability in the peri-implant region, was more potent on peri-implant bone, while RIS-HA composite coating, which had significant systemic effect, was more potent on non-peri-implant bone, especially lumbar vertebrae. Conclusions It is instructive and meaningful to further clinical studies that we could choose different BP-HA composite coatings according to the patient’s condition. PMID:22686414

2D FEA of evaluation of micromovements and stresses at bone-implant interface in immediately loaded tapered implants in the posterior maxilla.

PubMed

Desai, Shrikar R; Singh, Rika; Karthikeyan, I

2013-09-01

The aim of the study is to evaluate the influence implant length on stress distribution at bone implant interface in single immediately loaded implants when placed in D4 bone quality. A 2-dimensional finite element models were developed to simulate two types of implant designs, standard 3.75 mm-diameter tapered body implants of 6 and 10 mm lengths. The implants were placed in D4 bone quality with a cortical bone thickness of 0.5 mm. The implant design incorporated microthreads at the crestal part and the rest of the implant body incorporated Acme threads. The Acme thread form has a 29° thread angle with a thread height half of the pitch; the apex and valley are flat. A 100 N of force was applied vertically and in the oblique direction (at an angle of 45°) to the long axis of the implants. The respective material properties were assigned. Micro-movements and stresses at the bone implant interface were evaluated. The results of total deformation (micro-movement) and Von mises stress were found to be lower for tapered long implant (10 mm) than short implant (6 mm) while using both vertical as well as oblique loading. Short implants can be successfully placed in poor bone quality under immediate loading protocol. The novel approach of the combination of microthreads at the crestal portion and acme threads for body portion of implant fixture gave promising results.

Impact of radiation history, gender and age on bone quality in sites for orthodontic skeletal anchorage device placement.

PubMed

Konermann, A; Appel, T; Wenghoefer, M; Sirokay, S; Dirk, C; Jäger, A; Götz, W

2015-05-01

Stability of orthodontic miniscrew implants is prerequisite to their success and durability in orthodontic treatment. As investigations revealed a positive correlation of miniscrew stability to periimplant bone quality, it has been the aim of this study to analyze the bone structure of resection preparations of human mandibles histologically by investigating the samples according to age, gender and exposure to radiotherapy. Inflammation- and tumor-free alveolar bone sections from human mandibles (n = 31) with previously diagnosed carcinoma, chronic osteomyelitis or cysts were analyzed histomorphologically and histomorphometrically as to the dimension of trabeculae in cancellous areas. Group A investigated the impact of a history of radiation therapy, group B of gender and group C contrasted biopsies from individuals aging under 60 or over 60 years. Statistics were performed using the Kruskal-Wallis-test. Radiation, gender and age did not significantly influence bone density. The mean bone density averaged 40.7 ± 15.0% of spongiosa for the total collective with a median age of 58.4 years ± 14.7 years. Our findings provide new information on bone quality, thus contributing to a more precise evaluation of the parameters affecting and those not affecting miniscrew implant stability. On the basis of these results, the formulation of clinical guidelines for risk assessment of therapeutic approaches in patients prior to insertion of orthodontic skeletal anchorage devices seems to be conceivable. Copyright © 2014 Elsevier GmbH. All rights reserved.

The QUALYOR (QUalité Osseuse LYon Orléans) study: a new cohort for non invasive evaluation of bone quality in postmenopausal osteoporosis. Rationale and study design.

PubMed

Chapurlat, Roland; Pialat, Jean-Baptiste; Merle, Blandine; Confavreux, Elisabeth; Duvert, Florence; Fontanges, Elisabeth; Khacef, Farida; Peres, Sylvie Loiseau; Schott, Anne-Marie; Lespessailles, Eric

2017-12-27

The diagnostic performance of densitometry is inadequate. New techniques of non-invasive evaluation of bone quality may improve fracture risk prediction. Testing the value of these techniques is the goal of the QUALYOR cohort. The bone mineral density (BMD) of postmenopausal women who sustain osteoporotic fracture is generally above the World Health Organization definition for osteoporosis. Therefore, new approaches to improve the detection of women at high risk for fracture are warranted. We have designed and recruited a new cohort to assess the predictive value of several techniques to assess bone quality, including high-resolution peripheral quantitative computerized tomography (HRpQCT), hip QCT, calcaneus texture analysis, and biochemical markers. We have enrolled 1575 postmenopausal women, aged at least 50, with an areal BMD femoral neck or lumbar spine T-score between - 1.0 and - 3.0. Clinical risk factors for fracture have been collected along with serum and blood samples. We describe the design of the QUALYOR study. Among these 1575 women, 80% were aged at least 60. The mean femoral neck T-score was - 1.6 and the mean lumbar spine T-score was -1.2. This cohort is currently being followed up. QUALYOR will provide important information on the relationship between bone quality variables and fracture risk in women with moderately decreased BMD.

[Growing up with bone marrow transplantation: repercussions for the quality of life of children and adolescents].

PubMed

Anders, Jane Cristina; Lima, Regina Aparecida Garcia de

2004-01-01

Nowadays, various knowledge areas take an increasing interest in the discussion about the quality of life of people submitted to bone marrow transplantation-BMT. This study aims to describe the experiences of children and adolescents who survived this kind of transplantation and to discover how this therapy mode influenced their quality of life. Study participants were 14 children/adolescents who survived BMT. In this qualitative research, data were collected by means of interviews, which were held at the participants' homes or when they returned to hospital. We identified their life as permeated by insecurity, changed body image, physical and emotional problems. These data indicate the importance of understanding the experience of children/adolescents living with bone marrow transplantation, seeking to identify aspects for the intervention and planning of nursing care, so as to contribute to their reinsertion and a better quality of life.

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

PubMed Central

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

2014-01-01

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

Molecular mechanisms underlying the actions of dietary factors on the skeleton

USDA-ARS?s Scientific Manuscript database

This book chapter summarizes the current state of knowledge on molecular mechanisms whereby nutritional status and dietary factors found in fruits, vegetables, and grains affect bone turnover and skeletal quality. The Wnt-beta catenin and bone morphogenic protein (BMP) pathways in osteoblast bone ce...

The Biomechanical Testing for the Assessment of Bone Quality in an Experimental Model of Chronic Kidney Disease.

PubMed

Oksztulska-Kolanek, Ewa; Znorko, Beata; Michałowska, Małgorzata; Pawlak, Krystyna

2016-01-01

Mineral metabolism disturbances are common in chronic kidney disease (CKD) and have been classified as a new clinical entity, also known as CKD-mineral and bone disorders (CKD-MBD). A decrease in the bone strength, whose clinical manifestation is a tendency for fracture, has been recognized as an important component of CKD-MBD. Because of ethical issues, measurements of the bone strength in the human body are usually limited to noninvasive techniques, such as radiography, dual-energy X-ray absorptiometry and the assays of bone turnover biomarkers. However, it has been postulated recently that the evidence concerning bone strength based solely on the determination of the bone quantity may be insufficient and that bone quality should also be examined. In this regard, an animal model of CKD can represent an experimental tool to test the effectiveness of new therapeutic strategies. Despite the many available methods that are used to diagnose metabolic bone disorders and predict fracture risk especially in small rodents with CKD, it turns out that the most appropriate are biomechanical tests, which can provide information about the structural and material properties of bone. The present review summarizes and discusses the principles for carrying out selected biomechanical tests (3-point bending test and compression test) and their application in clinical practice. © 2015 S. Karger AG, Basel.

Bone surface enhancement in ultrasound images using a new Doppler-based acquisition/processing method.

PubMed

Yang, Xu; Tang, Songyuan; Tasciotti, Ennio; Righetti, Raffaella

2018-01-17

Ultrasound (US) imaging has long been considered as a potential aid in orthopedic surgeries. US technologies are safe, portable and do not use radiations. This would make them a desirable tool for real-time assessment of fractures and to monitor fracture healing. However, image quality of US imaging methods in bone applications is limited by speckle, attenuation, shadow, multiple reflections and other imaging artifacts. While bone surfaces typically appear in US images as somewhat 'brighter' than soft tissue, they are often not easily distinguishable from the surrounding tissue. Therefore, US imaging methods aimed at segmenting bone surfaces need enhancement in image contrast prior to segmentation to improve the quality of the detected bone surface. In this paper, we present a novel acquisition/processing technique for bone surface enhancement in US images. Inspired by elastography and Doppler imaging methods, this technique takes advantage of the difference between the mechanical and acoustic properties of bones and those of soft tissues to make the bone surface more easily distinguishable in US images. The objective of this technique is to facilitate US-based bone segmentation methods and improve the accuracy of their outcomes. The newly proposed technique is tested both in in vitro and in vivo experiments. The results of these preliminary experiments suggest that the use of the proposed technique has the potential to significantly enhance the detectability of bone surfaces in noisy ultrasound images.

Precision of pQCT-measured total, trabecular and cortical bone area, content, density and estimated bone strength in children

PubMed Central

Duff, W.R.D.; Björkman, K.M.; Kawalilak, C.E.; Kehrig, A.M.; Wiebe, S.; Kontulainen, S.

2017-01-01

Objectives: To define pQCT precision errors, least-significant-changes, and identify associated factors for bone outcomes at the radius and tibia in children. Methods: We obtained duplicate radius and tibia pQCT scans from 35 children (8-14yrs). We report root-mean-squared coefficient of variation (CV%RMS) and 95% limits-of-agreement to characterize repeatability across scan quality and least-significant-changes for bone outcomes at distal (total and trabecular area, content and density; and compressive bone strength) and shaft sites (total area and content; cortical area content, density and thickness; and torsional bone strength). We used Spearman’s rho to identify associations between CV% and time between measurements, child’s age or anthropometrics. Results: After excluding unanalyzable scans (6-10% of scans per bone site), CV%RMS ranged from 4% (total density) to 19% (trabecular content) at the distal radius, 4% (cortical content) to 8% (cortical thickness) at the radius shaft, 2% (total density) to 14% (trabecular content) at the distal tibia and from 2% (cortical content) to 6% (bone strength) at the tibia shaft. Precision errors were within 95% limits-of-agreement across scan quality. Age was associated (rho -0.4 to -0.5, p <0.05) with CV% at the tibia. Conclusion: Bone density outcomes and cortical bone properties appeared most precise (CV%RMS <5%) in children. PMID:28574412

Bone surface enhancement in ultrasound images using a new Doppler-based acquisition/processing method

NASA Astrophysics Data System (ADS)

Yang, Xu; Tang, Songyuan; Tasciotti, Ennio; Righetti, Raffaella

2018-01-01

Ultrasound (US) imaging has long been considered as a potential aid in orthopedic surgeries. US technologies are safe, portable and do not use radiations. This would make them a desirable tool for real-time assessment of fractures and to monitor fracture healing. However, image quality of US imaging methods in bone applications is limited by speckle, attenuation, shadow, multiple reflections and other imaging artifacts. While bone surfaces typically appear in US images as somewhat ‘brighter’ than soft tissue, they are often not easily distinguishable from the surrounding tissue. Therefore, US imaging methods aimed at segmenting bone surfaces need enhancement in image contrast prior to segmentation to improve the quality of the detected bone surface. In this paper, we present a novel acquisition/processing technique for bone surface enhancement in US images. Inspired by elastography and Doppler imaging methods, this technique takes advantage of the difference between the mechanical and acoustic properties of bones and those of soft tissues to make the bone surface more easily distinguishable in US images. The objective of this technique is to facilitate US-based bone segmentation methods and improve the accuracy of their outcomes. The newly proposed technique is tested both in in vitro and in vivo experiments. The results of these preliminary experiments suggest that the use of the proposed technique has the potential to significantly enhance the detectability of bone surfaces in noisy ultrasound images.

Mitigation of bone loss with ultrasound induced dynamic mechanical signals in an OVX induced rat model of osteopenia.

PubMed

Ferreri, Suzanne L; Talish, Roger; Trandafir, Titi; Qin, Yi-Xian

2011-05-01

This study tests the hypothesis that an ultrasound generated dynamic mechanical signal can attenuate bone loss in an estrogen deficient model of osteopenia. Eighty-four 16-week-old Sprague-Dawley rats were divided into six groups: baseline control, age-matched control, ovariectomy (OVX) control, OVX+5mW/cm(2) ultrasound (US), OVX+30mW/cm(2) US and OVX+100mW/cm(2) US. Low intensity pulsed ultrasound (LIPUS) was delivered transdermally at the L4/L5 vertebrae, using gel-coupled plane wave US transducers. The signal, characterized by 200μs pulses of 1.5MHz sine waves repeating at 1kHz with spatial-averaged temporal-averaged (SATA) intensities of 5, 30 or 100mW/cm(2), was applied 20 min/day, 5 days/week for 4 weeks. OVX treatment reduced bone volume fraction 40% and compromised microstructure at 4 weeks. LIPUS treatment, however, significantly increased BV/TV (+33%) compared to OVX controls for the 100mW/cm(2) treated group. SMI and Tb.N showed significant improvements compared with OVX for the 100mW/cm(2) treated group and Tb.Th was significantly improved in the 30 and 100mW/cm(2) treated groups. Improvements in bone's microstructural characteristics with 100mW/cm(2) US treatment translated into improved load bearing characteristics, including a significant 42% increase in apparent level elastic modulus compared to OVX controls. Significant improvement of trabecular mechanical strength was also observed in the treated animals, e.g., principal compressive stress (represent bone's ability to resist loads) was significantly higher compared to OVX controls. Histomorphometric analysis also showed that treatment with 100mW/cm(2) US resulted in a 76% improvement in MS/BS. In addition, measures of bone quantity and quality at the femoral metaphysis suggest that LIPUS is site specific. This study indicates that localized ultrasound treatment, delivered at specific intensities, has beneficial effects on intact bone and may represent a novel intervention for bone loss. Copyright © 2011 Elsevier Inc. All rights reserved.

The impact of the International Atomic Energy Agency (IAEA) program on radiation and tissue banking in Indonesia.

PubMed

Hilmy, Nazly; Manjas, Menkher; Ferdiansyah; Abbas, Basril; Morales Pedraza, Jorge

2009-05-01

In 1986, the National Nuclear Energy Agency (Batan) in Jakarta started the research and development for the setting up of a tissue bank (Batan Research Tissue Bank/BRTB) by preserving fresh amnion or fetal membranes by lyophilisation and then sterilising by gamma irradiation. During the period of 1990 and 2000, three more tissue banks were set up, i.e., Biomaterial Centre in Surabaya, Jamil Tissue Bank in Padang, and Sitanala Tissue Bank in Tangerang. In 1994, BRTB produced bone allografts. The banks established under the IAEA program concentrated its work on the production of amnion, bone and soft tissues allografts, as well as bone xenografts. These tissues (allografts and xenografts) were sterilised using gamma irradiation (about 90%) and the rest were sterilized by ETO and those products have been used in the treatment of patients at more than 50 hospitals in Indonesia. In 2004, those tissue banks produced 8,500 grafts and 5,000 of them were amnion grafts for eye treatment and wound dressing. All of those grafts were used for patients as well as for research. In 2006, the production increased to 9,000 grafts. Although the capacity of those banks can produce more grafts, we are facing problems on getting raw materials from suitable donors. To fulfill the demand of bone grafts we also produced bone xenografts. The impact of the IAEA program in tissue banking activities in Indonesia can be summarised as follows: to support the national program on importing substitutes for medical devices. The price of imported tissues are between US$ 50 and US$ 6,000 per graft. Local tissue bank can produce tissues with the same quality with the price for about 10-30% of the imported tissues.

Assessment of the Breakaway Torque at the Posterior Pelvic Ring in Human Cadavers.

PubMed

Bastian, Johannes Dominik; Bergmann, Mathias; Schwyn, Ronald; Keel, Marius Johann Baptist; Benneker, Lorin Michael

2015-01-01

To enhance the diminished screw purchase in cancellous, osteoporotic bone following the fixation of posterior pelvic ring injuries by iliosacral screws an increased bone-implant contact area using modificated screws, techniques or bone cement may become necessary. The aim of the study was to identify sites within the pathway of iliosacral screws requiring modifications of the local bone or the design of instrumentations placed at this site. The breakaway torque was measured mechanically at the iliosacral joint ("ISJ"), the sacral lateral mass ("SLM") and the center of the S1 ("CS1"), at a superior and an inferior site under fluoroscopic control on five human cadaveric specimens (3 female; mean age 87 years, range: 76-99) using the DensiProbe™Spine device. The measured median (range) breakaway torque was 0.63 Nm (0.31-2.52) at the "iliosacral joint", 0.14 Nm (0.05-1.22) at the "sacral lateral mass", 0.57 Nm (0.05-1.42) at the "S1 center." The "sacral lateral mass" breakaway torque was lower than compared to that at the "iliosacral joint" (p < .001) or "S1 center" (p < .001). The median (range) breakaway torque measured at all superior measurement points was 0.52 Nm (0.10-2.52), and 0.48 Nm (0.05-1.18) at all inferior sites. The observed difference was statistically significant (p < .05). The lateral mass of the sacrum provides the lowest bone quality for implant anchorage. Iliosacral screws should be placed as superior as safely possible, should bridge the iliosacral joint and may allow for cement application at the lateral mass of the sacrum through perforations.

Bone and glucocorticoids.

PubMed

Briot, Karine

2018-06-01

Corticosteroid-induced osteoporosis is the most common form of secondary osteoporosis and the most frequent cause of osteoporosis in young people. Bone loss and fracture risk increase rapidly after the initiation of corticosteroid therapy and are proportional to dose and treatment duration. The increase in fracture risk is not fully assessed by bone mineral density measurement, as it is also related to impaired bone quality and increased risk of falls. Prevention should be considered in all patients beginning corticosteroid therapy, especially as the underlying inflammation in itself impairs bone quality. Bisphosphonates and teriparatide have shown efficacy in the treatment of corticosteroid-induced osteoporosis. Several national and international guidelines are available to improve management of corticosteroid-induced osteoporosis, which remains inadequate. Duration of anti-osteoporotic treatment should be discussed at the individual level, depending on the subject's characteristics and on the progression of the underlying inflammation. Copyright © 2018. Published by Elsevier Masson SAS.

The effect of intramedullary bone endoscopy on the endosteal blood supply in long bones. An experimental study in sheep.

PubMed

Herget, Georg W; Haberstroh, Jörg; Südkamp, Norbert; Riede, Ursus; Oberst, Michael

2011-02-01

This study investigated whether the Intramedullary Bone Endoscopy (IBE) procedure within the cavity of an intact long bone will interfere with the local endosteal blood supply. In a sheep model, 10 animals underwent the IBE procedure with complete perioperative anaesthesiology monitoring. After the femora were harvested, histological analysis was performed to examine destruction of the endosteum and consecutive reduction in perfusion. Only one animal showed evidence of detachment of the endosteum with destruction of several microns of the endosteum, although this did not interfere with the cortical perfusion. None of the vessels were occluded by fat or other causes of occlusion, e.g. blood coagulation. Our findings indicate that with the IBE procedure under visual control there is a potential risk to damage the endosteum. However, the interference was limited to a small part of the endosteum and did not lead to a reduction in the cortical perfusion. Clinical use could be in localized intramedullary lesions such as osteomyelitis or benign bone tumours.

Study on osteogenesis promoted by low sound pressure level infrasound in vivo and some underlying mechanisms.

PubMed

Long, Hua; Zheng, Liheng; Gomes, Fernando Cardoso; Zhang, Jinhui; Mou, Xiang; Yuan, Hua

2013-09-01

To clarify the effects of low sound pressure level (LSPL) infrasound on local bone turnover and explore its underlying mechanisms, femoral defected rats were stabilized with a single-side external fixator. After exposure to LSPL infrasound for 30min twice everyday for 6 weeks, the pertinent features of bone healing were assessed by radiography, peripheral quantitative computerized tomography (pQCT), histology and immunofluorescence assay. Infrasound group showed a more consecutive and smoother process of fracture healing and modeling in radiographs and histomorphology. It also showed significantly higher average bone mineral content (BMC) and bone mineral density (BMD). Immunofluorescence showed increased expression of calcitonin gene related peptide (CGRP) and decreased Neuropeptide Y (NPY) innervation in microenvironment. The results suggested the osteogenesis promotion effects of LSPL infrasound in vivo. Neuro-osteogenic network in local microenvironment was probably one target mediating infrasonic osteogenesis, which might provide new strategy to accelerate bone healing and remodeling. Copyright © 2013 Elsevier B.V. All rights reserved.

Carbon nanotubes with high bone-tissue compatibility and bone-formation acceleration effects.

PubMed

Usui, Yuki; Aoki, Kaoru; Narita, Nobuyo; Murakami, Narumichi; Nakamura, Isao; Nakamura, Koichi; Ishigaki, Norio; Yamazaki, Hiroshi; Horiuchi, Hiroshi; Kato, Hiroyuki; Taruta, Seiichi; Kim, Yoong Ahm; Endo, Morinobu; Saito, Naoto

2008-02-01

Carbon nanotubes (CNTs) have been used in various fields as composites with other substances or alone to develop highly functional materials. CNTs hold great interest with respect to biomaterials, particularly those to be positioned in contact with bone such as prostheses for arthroplasty, plates or screws for fracture fixation, drug delivery systems, and scaffolding for bone regeneration. Accordingly, bone-tissue compatibility of CNTs and CNT influence on bone formation are important issues, but the effects of CNTs on bone have not been delineated. Here, it is found that multi-walled CNTs adjoining bone induce little local inflammatory reaction, show high bone-tissue compatibility, permit bone repair, become integrated into new bone, and accelerate bone formation stimulated by recombinant human bone morphogenetic protein-2 (rhBMP-2). This study provides an initial investigational basis for CNTs in biomaterials that are used adjacent to bone, including uses to promote bone regeneration. These findings should encourage development of clinical treatment modalities involving CNTs.

Cretaceous Small Scavengers: Feeding Traces in Tetrapod Bones from Patagonia, Argentina

PubMed Central

de Valais, Silvina; Apesteguía, Sebastián; Garrido, Alberto C.

2012-01-01

Ecological relationships among fossil vertebrate groups are interpreted based on evidence of modification features and paleopathologies on fossil bones. Here we describe an ichnological assemblage composed of trace fossils on reptile bones, mainly sphenodontids, crocodyliforms and maniraptoran theropods. They all come from La Buitrera, an early Late Cretaceous locality in the Candeleros Formation of northwestern Patagonia, Argentina. This locality is significant because of the abundance of small to medium-sized vertebrates. The abundant ichnological record includes traces on bones, most of them attributable to tetrapods. These latter traces include tooth marks that provde evidence of feeding activities made during the sub-aerial exposure of tetrapod carcasses. Other traces are attributable to arthropods or roots. The totality of evidence provides an uncommon insight into paleoecological aspects of a Late Cretaceous southern ecosystem. PMID:22253800

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

PubMed Central

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

2017-01-01

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

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

PubMed

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

2017-05-01

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

Comparison of Piezosurgery and Conventional Rotary Instruments for Removal of Impacted Mandibular Third Molars: A Randomized Controlled Clinical and Radiographic Trial

PubMed Central

Shokry, Mohamed; Aboelsaad, Nayer

2016-01-01

The purpose of this study was to test the effect of the surgical removal of impacted mandibular third molars using piezosurgery versus the conventional surgical technique on postoperative sequelae and bone healing. Material and Methods. This study was carried out as a randomized controlled clinical trial: split mouth design. Twenty patients with bilateral mandibular third molar mesioangular impaction class II position B indicated for surgical extraction were treated randomly using either the piezosurgery or the conventional bur technique on each site. Duration of the procedure, postoperative edema, trismus, pain, healing, and bone density and quantity were evaluated up to 6 months postoperatively. Results. Test and control sites were compared using paired t-test. There was statistical significance in reduction of pain and swelling in test sites, where the time of the procedure was statistically increased in test site. For bone quantity and quality, statistical difference was found where test site showed better results. Conclusion. Piezosurgery technique improves quality of patient's life in form of decrease of postoperative pain, trismus, and swelling. Furthermore, it enhances bone quality within the extraction socket and bone quantity along the distal aspect of the mandibular second molar. PMID:27597866

Dietary protein level and source differentially affect bone metabolism, strength, and intestinal calcium transporter expression during ad libitum and food-restricted conditions in male rats

USDA-ARS?s Scientific Manuscript database

High protein diets may attenuate bone loss during energy restriction (ER). The objective of the current study was to determine whether high protein diets suppress bone turnover and improve bone quality in rats during ER and whether dietary protein source affects this relationship. Eighty 12-week o...

[Long-term effects of 7-year growth hormone substitution on bone metabolism, bone density, and bone quality in growth hormone-deficient adults].

PubMed

Wilhelm, Birgit; Kann, Peter Herbert

2004-10-15

Subnormal bone mineral density (BMD) and increased fracture risk are described in patients with growth hormone deficiency (GHD). Growth hormone (GH) has been reported to have beneficial effects on bone in GHD. The aim of this study was to investigate the long-term effects of GH replacement therapy on bone metabolism, BMD, and bone quality in patients with GHD. 20 adult patients with GHD (eleven male, nine female, mean age 42.5 years) were included in the study and randomized to either GH or placebo in a dose of 0.25 U/kg body weight/week. After 6 months all patients received GH. After a 1-year double-blind, placebo-controlled study the patients were followed for another 72 months in an open study. The patients were compared to 20 age- und sex-matched healthy controls. Bone turnover was determined by ICTP (type I collagen carboxyterminal cross-linked telopeptide) as parameter of bone resorption and PICP (carboxyterminal propeptide of type I procollagen) as marker of bone formation. BMD was measured at the lumbar spine by dual-photon absorptiometry (DPA) and at the forearm by single-photon absorptiometry (SPA). Apparent phalangeal ultrasound transmission velocity (APU) was assessed as parameter of bone quality independent of BMD. At the beginning of the study BMD at both measuring sites was lower in patients with GHD than in healthy controls. During the 1st year of GH replacement therapy BMD decreased, followed by a continuous increase in BMD (about 12%) up to 60 months which remained unchanged thereafter, building up a plateau. After 72 months no significant difference between the patients and the healthy controls could be detected. Concerning parameters of bone turnover, first ICTP as marker of bone resorption showed a significant increase, later on the marker of bone formation increased as well. APU decreased during the first 6 months of treatment, but had returned to its baseline value after 24 months and remained unchanged throughout the rest of the study. BMD is subnormal in adults with GHD. GH replacement therapy stimulates bone turnover in patients with GHD and in the long term such stimulation results in an increased BMD. Thereby, GH shows a triphasic action on BMD: an initial decrease in BMD during the 1st year, followed by a continuous increase in BMD with buildup of a stable plateau after 60 months. The newly formed bone seems to have normal bone elasticity.

Hyperthermia in bone generated with MR imaging-controlled focused ultrasound: control strategies and drug delivery.

PubMed

Staruch, Robert; Chopra, Rajiv; Hynynen, Kullervo

2012-04-01

To evaluate the feasibility of achieving image-guided drug delivery in bone by using magnetic resonance (MR) imaging-controlled focused ultrasound hyperthermia and temperature-sensitive liposomes. Experiments were approved by the institutional animal care committee. Hyperthermia (43°C, 20 minutes) was generated in 10-mm-diameter regions at a muscle-bone interface in nine rabbit thighs by using focused ultrasound under closed-loop temperature control with MR thermometry. Thermosensitive liposomal doxorubicin was administered systemically during heating. Heating uniformity and drug delivery were evaluated for control strategies with the temperature control image centered 10 mm (four rabbits) or 0 mm (five rabbits) from the bone. Simulations estimated temperature elevations in bone. Drug delivery was quantified by using the fluorescence of doxorubicin extracted from bone marrow and muscle and was compared between treated and untreated thighs by using the one-sided Wilcoxon signed rank test. With ultrasound focus and MR temperature control plane 0 mm and 10 mm from the bone interface, average target region temperatures were 43.1°C and 43.3°C, respectively; numerically estimated bone temperatures were 46.8°C and 78.1°C. The 10-mm offset resulted in thermal ablation; numerically estimated muscle temperature was 66.1°C at the bone interface. Significant increases in doxorubicin concentration occurred in heated versus unheated marrow (8.2-fold, P = .002) and muscle (16.8-fold, P = .002). Enhancement occurred for 0- and 10-mm offsets, which suggests localized drug delivery in bone is possible with both hyperthermia and thermal ablation. MR imaging-controlled focused ultrasound can achieve localized hyperthermia in bone for image-guided drug delivery in bone with temperature-sensitive drug carriers. © RSNA, 2012.

Immunology of Gut-Bone Signaling.

PubMed

Collins, Fraser L; Schepper, Jonathan D; Rios-Arce, Naiomy Deliz; Steury, Michael D; Kang, Ho Jun; Mallin, Heather; Schoenherr, Daniel; Camfield, Glen; Chishti, Saima; McCabe, Laura R; Parameswaran, Narayanan

2017-01-01

In recent years a link between the gastrointestinal tract and bone health has started to gain significant attention. Dysbiosis of the intestinal microbiota has been linked to the pathology of a number of diseases which are associated with bone loss. In addition modulation of the intestinal microbiota with probiotic bacteria has revealed to have both beneficial local and systemic effects. In the present chapter, we discuss the intestinal and bone immune systems, explore how intestinal disease affects the immune system, and examine how these pathologic changes could adversely impact bone health.

Immunology of Gut Bone Signaling

PubMed Central

Collins, Fraser L.; Schepper, Jonathan; Rios-Arce, Naiomy Deliz; Steury, Michael; Kang, Ho Jun; Mallin, Heather; Schoenherr, Daniel; Camfield, Glen; Chishti, Saima; McCabe, Laura R; Parameswaran, Narayanan

2017-01-01

In recent years a link between the gastro-intestinal tract and bone health has started to gain significant attention. Dysbiosis of the intestinal microbiota has been linked to the pathology of a number of diseases which are associated with bone loss. In addition modulation of the intestinal microbiota with probiotic bacteria has revealed to have both beneficial local and systemic effects. In the present chapter we discuss the intestinal and bone immune systems, explore how intestinal disease affects the immune system and examine how these pathologic changes could adversely impact bone health. PMID:29101652

Investigating the Role of Global Histogram Equalization Technique for 99mTechnetium-Methylene diphosphonate Bone Scan Image Enhancement.

PubMed

Pandey, Anil Kumar; Sharma, Param Dev; Dheer, Pankaj; Parida, Girish Kumar; Goyal, Harish; Patel, Chetan; Bal, Chandrashekhar; Kumar, Rakesh

2017-01-01

99m Technetium-methylene diphosphonate ( 99m Tc-MDP) bone scan images have limited number of counts per pixel, and hence, they have inferior image quality compared to X-rays. Theoretically, global histogram equalization (GHE) technique can improve the contrast of a given image though practical benefits of doing so have only limited acceptance. In this study, we have investigated the effect of GHE technique for 99m Tc-MDP-bone scan images. A set of 89 low contrast 99m Tc-MDP whole-body bone scan images were included in this study. These images were acquired with parallel hole collimation on Symbia E gamma camera. The images were then processed with histogram equalization technique. The image quality of input and processed images were reviewed by two nuclear medicine physicians on a 5-point scale where score of 1 is for very poor and 5 is for the best image quality. A statistical test was applied to find the significance of difference between the mean scores assigned to input and processed images. This technique improves the contrast of the images; however, oversaturation was noticed in the processed images. Student's t -test was applied, and a statistically significant difference in the input and processed image quality was found at P < 0.001 (with α = 0.05). However, further improvement in image quality is needed as per requirements of nuclear medicine physicians. GHE techniques can be used on low contrast bone scan images. In some of the cases, a histogram equalization technique in combination with some other postprocessing technique is useful.

Lactation-Induced Changes in the Volume of Osteocyte Lacunar-Canalicular Space Alter Mechanical Properties in Cortical Bone Tissue.

PubMed

Kaya, Serra; Basta-Pljakic, Jelena; Seref-Ferlengez, Zeynep; Majeska, Robert J; Cardoso, Luis; Bromage, Timothy G; Zhang, Qihong; Flach, Carol R; Mendelsohn, Richard; Yakar, Shoshana; Fritton, Susannah P; Schaffler, Mitchell B

2017-04-01

Osteocytes can remove and remodel small amounts of their surrounding bone matrix through osteocytic osteolysis, which results in increased volume occupied by lacunar and canalicular space (LCS). It is well established that cortical bone stiffness and strength are strongly and inversely correlated with vascular porosity, but whether changes in LCS volume caused by osteocytic osteolysis are large enough to affect bone mechanical properties is not known. In the current studies we tested the hypotheses that (1) lactation and postlactation recovery in mice alter the elastic modulus of bone tissue, and (2) such local changes in mechanical properties are related predominantly to alterations in lacunar and canalicular volume rather than bone matrix composition. Mechanical testing was performed using microindentation to measure modulus in regions containing solely osteocytes and no vascular porosity. Lactation caused a significant (∼13%) reduction in bone tissue-level elastic modulus (p < 0.001). After 1 week postweaning (recovery), bone modulus levels returned to control levels and did not change further after 4 weeks of recovery. LCS porosity tracked inversely with changes in cortical bone modulus. Lacunar and canalicular void space increased 7% and 15% with lactation, respectively (p < 0.05), then returned to control levels at 1 week after weaning. Neither bone mineralization (assessed by high-resolution backscattered scanning electron microscopy) nor mineral/matrix ratio or crystallinity (assessed by Raman microspectroscopy) changed with lactation. Thus, changes in bone mechanical properties induced by lactation and recovery appear to depend predominantly on changes in osteocyte LCS dimensions. Moreover, this study demonstrates that tissue-level cortical bone mechanical properties are rapidly and reversibly modulated by osteocytes in response to physiological challenge. These data point to a hitherto unappreciated role for osteocytes in modulating and maintaining local bone mechanical properties. © 2016 American Society for Bone and Mineral Research. © 2016 American Society for Bone and Mineral Research.

Evaluation of implants coated with rhBMP-2 using two different coating strategies: a critical-size supraalveolar peri-implant defect study in dogs.

PubMed

Lee, Jaebum; Decker, John F; Polimeni, Giuseppe; Cortella, Carlo Alberto; Rohrer, Michael D; Wozney, John M; Hall, Jan; Susin, Cristiano; Wikesjö, Ulf M E

2010-06-01

Implants coated with recombinant human bone morphogenetic protein-2 (rhBMP-2) induce relevant bone formation but also resident bone remodelling. To compare the effect of implants fully or partially coated with rhBMP-2 on new bone formation and resident bone remodelling. Twelve, male, adult, Hound Labrador mongrel dogs were used. Critical-size, supraalveolar, peri-implant defects received titanium porous oxide surface implants coated in their most coronal aspect with rhBMP-2 (coronal-load/six animals) or by immersion of the entire implant in an rhBMP-2 solution (soak-load/six animals) for a total of 30 mug rhBMP-2/implant. All implants were air-dried. The animals were euthanized at 8 weeks for histometric evaluation. Clinical healing was uneventful. Supraalveolar bone formation was not significantly affected by the rhBMP-2 application protocol. New bone height and area averaged (+/- SE) 3.4 +/- 0.2 versus 3.5 +/- 0.4 mm and 2.6 +/- 0.4 versus 2.5 +/- 0.7 mm(2) for coronal-load and soak-load implants, respectively (p>0.05). The corresponding bone density and bone-implant contact (BIC) recordings averaged 38.0 +/- 3.8%versus 34.4 +/- 5.6% and 25.0 +/- 3.8%versus 31.2 +/- 3.3% (p>0.05). In contrast, resident bone remodelling was significantly influenced by the rhBMP-2 application protocol. Bone density outside the implants threads averaged 74.7 +/- 3.8% and 50.8 +/- 4.1% for coronal-load and soak-load implants, respectively (p<0.05); bone density within the thread area averaged 51.8 +/- 1.2% and 37.8 +/- 2.9%, and BIC 70.1 +/- 6.7% and 43.3 +/- 3.9% (p<0.05). Local application of rhBMP-2 appears to be a viable technology to support local bone formation and osseointegration. Coronal-load implants obviate resident bone remodelling without compromising new bone formation.

[Osteostimulating effect of bone xenograft on bone tissue regeneration].

PubMed

Balin, V N; Balin, D V; Iordanishvili, A K; Musikin, M I

2015-01-01

The aim of experimental case-control study performed in 28 dogs divided in 2 groups was to assess local tissue reactions on bone xenograft transplantation; dynamics of bone remodeling and formation at the site of bone defect wall contacting with bone xenograft; dynamics and mechanisms of xenograft remodeling. Transplantation of xenograft in conventional bone defects did not cause inflammatory of destructive reactions because of high biocompatibility of the material. At transplantation site active fibrous bone trabeculae formation filling the spaces between xenograft participles was observed. On the 90th day newly formed bone showed lammelar structure. Simultaneously from the 42d day the invasion of cell elements from recipient bed into the material was seen leading to xenograft resorption. The observed dynamics may be assessed as gradual substitution of xenograft with newly formed host bone structures.

Bone Regeneration Using Bone Morphogenetic Proteins and Various Biomaterial Carriers

PubMed Central

Sheikh, Zeeshan; Javaid, Mohammad Ahmad; Hamdan, Nader; Hashmi, Raheel

2015-01-01

Trauma and disease frequently result in fractures or critical sized bone defects and their management at times necessitates bone grafting. The process of bone healing or regeneration involves intricate network of molecules including bone morphogenetic proteins (BMPs). BMPs belong to a larger superfamily of proteins and are very promising and intensively studied for in the enhancement of bone healing. More than 20 types of BMPs have been identified but only a subset of BMPs can induce de novo bone formation. Many research groups have shown that BMPs can induce differentiation of mesenchymal stem cells and stem cells into osteogenic cells which are capable of producing bone. This review introduces BMPs and discusses current advances in preclinical and clinical application of utilizing various biomaterial carriers for local delivery of BMPs to enhance bone regeneration. PMID:28788032

Influence of bone density on the cement fixation of femoral hip resurfacing components.

PubMed

Bitsch, Rudi G; Jäger, Sebastian; Lürssen, Marcus; Loidolt, Travis; Schmalzried, Thomas P; Clarius, Michael

2010-08-01

In clinical outcome studies, small component sizes, female gender, femoral shape, focal bone defects, bad bone quality, and biomechanics have been associated with failures of resurfacing arthroplasties. We used a well-established experimental setup and human bone specimens to analyze the effects of bone density on cement fixation of femoral hip resurfacing components. Thirty-one fresh frozen femora were prepared for resurfacing using the original instruments. ASR resurfacing prostheses were implanted after dual-energy X-ray densitometer scans. Real-time measurements of pressure and temperature during implantation, analyses of cement penetration, and measurements of micro motions under torque application were performed. The associations of bone density and measurement data were examined calculating regression lines and multiple correlation coefficients; acceptability was tested with ANOVA. We found significant relations between bone density and micro motion, cement penetration, cement mantle thickness, cement pressure, and interface temperature. Mean bone density of the femora was 0.82 +/- 0.13 g/cm(2), t-score was -0.7 +/- 1.0, and mean micro motion between bone and femoral resurfacing component was 17.5 +/- 9.1 microm/Nm. The regression line between bone density and micro motion was equal to -56.7 x bone density + 63.8, R = 0.815 (p < 0.001). Bone density scans are most helpful for patient selection in hip resurfacing, and a better bone quality leads to higher initial component stability. A sophisticated cementing technique is recommended to avoid vigorous impaction and incomplete seating, since increasing bone density also results in higher cement pressures, lower cement penetration, lower interface temperatures, and thicker cement mantles. Copyright 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Myostatin deficiency partially rescues the bone phenotype of osteogenesis imperfecta model mice.

PubMed

Oestreich, A K; Carleton, S M; Yao, X; Gentry, B A; Raw, C E; Brown, M; Pfeiffer, F M; Wang, Y; Phillips, C L

2016-01-01

Mice with osteogenesis imperfecta (+/oim), a disorder of bone fragility, were bred to mice with muscle over growth to test whether increasing muscle mass genetically would improve bone quality and strength. The results demonstrate that femora from mice carrying both mutations have greater mechanical integrity than their +/oim littermates. Osteogenesis imperfecta is a heritable connective tissue disorder due primarily to mutations in the type I collagen genes resulting in skeletal deformity and fragility. Currently, there is no cure, and therapeutic strategies encompass the use of antiresorptive pharmaceuticals and surgical bracing, with limited success and significant potential for adverse effects. Bone, a mechanosensing organ, can respond to high mechanical loads by increasing new bone formation and altering bone geometry to withstand increased forces. Skeletal muscle is a major source of physiological loading on bone, and bone strength is proportional to muscle mass. To test the hypothesis that congenic increases in muscle mass in the osteogenesis imperfecta murine model mouse (oim) will improve their compromised bone quality and strength, heterozygous (+/oim) mice were bred to mice deficient in myostatin (+/mstn), a negative regulator of muscle growth. The resulting adult offspring were evaluated for hindlimb muscle mass, and bone microarchitecture, physiochemistry, and biomechanical integrity. +/oim mice deficient in myostatin (+/mstn +/oim) were generated and demonstrated that myostatin deficiency increased body weight, muscle mass, and biomechanical strength in +/mstn +/oim mice as compared to +/oim mice. Additionally, myostatin deficiency altered the physiochemical properties of the +/oim bone but did not alter bone remodeling. Myostatin deficiency partially improved the reduced femoral bone biomechanical strength of adult +/oim mice by increasing muscle mass with concomitant improvements in bone microarchitecture and physiochemical properties.

Customized a Ti6Al4V Bone Plate for Complex Pelvic Fracture by Selective Laser Melting.

PubMed

Wang, Di; Wang, Yimeng; Wu, Shibiao; Lin, Hui; Yang, Yongqiang; Fan, Shicai; Gu, Cheng; Wang, Jianhua; Song, Changhui

2017-01-04

In pelvic fracture operations, bone plate shaping is challenging and the operation time is long. To address this issue, a customized bone plate was designed and produced using selective laser melting (SLM) technology. The key steps of this study included designing the customized bone plate, metal 3D printing, vacuum heat treatment, surface post-processing, operation rehearsal, and clinical application and evaluation. The joint surface of the bone plate was placed upwards with respect to the build platform to keep it away from the support and to improve the quality of the joint surface. Heat conduction was enhanced by adding a cone-type support beneath the bone plate to prevent low-quality fabrication due to poor heat conductivity of the Ti-6Al-4V powder. The residual stress was eliminated by exposing the SLM-fabricated titanium-alloy bone plate to a vacuum heat treatment. Results indicated that the bone plate has a hardness of HV1 360-HV1 390, an ultimate tensile strength of 1000-1100 MPa, yield strength of 900-950 MPa, and an elongation of 8%-10%. Pre-operative experiments and operation rehearsal were performed using the customized bone plate and the ABC-made pelvic model. Finally, the customized bone plate was clinically applied. The intraoperative C-arm and postoperative X-ray imaging results indicated that the customized bone plate matched well to the damaged pelvis. The customized bone plate fixed the broken bone and guides pelvis restoration while reducing operation time to about two hours. The customized bone plate eliminated the need for preoperative titanium plate pre-bending, thereby greatly reducing surgical wounds and operation time.

Customized a Ti6Al4V Bone Plate for Complex Pelvic Fracture by Selective Laser Melting

PubMed Central

Wang, Di; Wang, Yimeng; Wu, Shibiao; Lin, Hui; Yang, Yongqiang; Fan, Shicai; Gu, Cheng; Wang, Jianhua; Song, Changhui

2017-01-01

In pelvic fracture operations, bone plate shaping is challenging and the operation time is long. To address this issue, a customized bone plate was designed and produced using selective laser melting (SLM) technology. The key steps of this study included designing the customized bone plate, metal 3D printing, vacuum heat treatment, surface post-processing, operation rehearsal, and clinical application and evaluation. The joint surface of the bone plate was placed upwards with respect to the build platform to keep it away from the support and to improve the quality of the joint surface. Heat conduction was enhanced by adding a cone-type support beneath the bone plate to prevent low-quality fabrication due to poor heat conductivity of the Ti-6Al-4V powder. The residual stress was eliminated by exposing the SLM-fabricated titanium-alloy bone plate to a vacuum heat treatment. Results indicated that the bone plate has a hardness of HV1 360–HV1 390, an ultimate tensile strength of 1000–1100 MPa, yield strength of 900–950 MPa, and an elongation of 8%–10%. Pre-operative experiments and operation rehearsal were performed using the customized bone plate and the ABC-made pelvic model. Finally, the customized bone plate was clinically applied. The intraoperative C-arm and postoperative X-ray imaging results indicated that the customized bone plate matched well to the damaged pelvis. The customized bone plate fixed the broken bone and guides pelvis restoration while reducing operation time to about two hours. The customized bone plate eliminated the need for preoperative titanium plate pre-bending, thereby greatly reducing surgical wounds and operation time. PMID:28772395

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

PubMed

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

2017-04-03

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

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

PubMed Central

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

2017-01-01

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

[Adapted physical activity in the prevention and therapy of osteoporosis].

PubMed

Bosković, Ksenija; Gava, Branka Protić; Grajić, Mirko; Madić, Dejan; Obradović, Borislav; Todorović, Snezana Tomasević

2013-01-01

Osteoporosis, a disease characterized by the progressive loss of bone tissue, is one of the most common complications of aging. According to some calculations, there were 25% of women and 4% of men older than 50 years with osteoporosis in the world in 2010. It is assumed that the number of patients with osteoporosis will increase by 30% in every 10 years in the 21st century. There are many reasons for that: the world's population is growing older, diet is getting poorer in vitamins and minerals and physical activity is decreasing. THE QUALITY AND QUANTITY OF BONE TISSUE: Developing bones are much more responsive to mechanical loading and physical activity than mature bones. This suggests that training in early childhood may be an important factor in the prevention of osteoporosis in later life. It is important to note that the quality of bone achieved by training at younger age cannot be maintained permanently if it is not supported by physical activity later in life. Adapted physical activity represents physical activity individually tailored according to the psychosomatic capabilities of a person and the goal to be achieved. It can be applied at any age in order to maintain strong bones and reduce the risk of fracture. Adapted physical activity is different for men and women, for different age, as well as for the individuals. Aerobic exercises, which lead to an acceleration of breathing, increased heart rate and mild perspiration, as well as resistance exercises and exercises against resistance done by stretching elastic bands, for hands, legs and torso have been proven to increase bone density and improve bone strength. Coordination and balance exercises are important in an individual workout program. An explanation of the action of adapted physical activity is the basis for the theory of control and modulation of bone loss, muscle strength, coordination and balance. Physical activity is very effective in reducing sclerostin, which is known to inhibit bone formation. In addition, physical training enhances the levels of insulinlike growth factor, which has a very positive effect on bone formation. The aim of adapted physical activity is to improve bone formation in youngsters, to preserve the bone mass in adults and to prevent the bone loss in the elderly thus reducing the risk of falls and resulting fractures; in other words, to minimize the disability caused by fractures and improve the quality of life.

A comparative study of zirconium and titanium implants in rat: osseointegration and bone material quality.

PubMed

Hoerth, Rebecca M; Katunar, María R; Gomez Sanchez, Andrea; Orellano, Juan C; Ceré, Silvia M; Wagermaier, Wolfgang; Ballarre, Josefina

2014-02-01

Permanent metal implants are widely used in human medical treatments and orthopedics, for example as hip joint replacements. They are commonly made of titanium alloys and beyond the optimization of this established material, it is also essential to explore alternative implant materials in view of improved osseointegration. The aim of our study was to characterize the implant performance of zirconium in comparison to titanium implants. Zirconium implants have been characterized in a previous study concerning material properties and surface characteristics in vitro, such as oxide layer thickness and surface roughness. In the present study, we compare bone material quality around zirconium and titanium implants in terms of osseointegration and therefore characterized bone material properties in a rat model using a multi-method approach. We used light and electron microscopy, micro Raman spectroscopy, micro X-ray fluorescence and X-ray scattering techniques to investigate the osseointegration in terms of compositional and structural properties of the newly formed bone. Regarding the mineralization level, the mineral composition, and the alignment and order of the mineral particles, our results show that the maturity of the newly formed bone after 8 weeks of implantation is already very high. In conclusion, the bone material quality obtained for zirconium implants is at least as good as for titanium. It seems that the zirconium implants can be a good candidate for using as permanent metal prosthesis for orthopedic treatments.

Bone mass improved effect of icariin for postmenopausal osteoporosis in ovariectomy-induced rats: a meta-analysis and systematic review.

PubMed

Xu, Jin-Hai; Yao, Min; Ye, Jie; Wang, Guo-Dong; Wang, Jing; Cui, Xue-Jun; Mo, Wen

2016-10-01

Ovariectomy (OVX)-induced rats are the most frequently used animal model to research postmenopausal osteoporosis. Our objective was to summarize and critically assess the bone mass improved effect of icariin (ICA) for treatment of postmenopausal osteoporosis in an OVX-induced rat model. The PUBMED, EMBASE, and Chinese databases were searched from their inception date to February 2015. Two reviewers independently selected animal studies that evaluated the bone mass improved effect of ICA compared with control in OVX-induced rats. Extracted data were analyzed by RevMan statistical software, and the methodological quality of each study was assessed. Seven studies with adequate randomization were included in the systematic review. Overall, ICA seemed to significantly improve bone mass as assessed using the bone mineral density (seven studies, n = 169; weighted mean difference, 0.02; 95% CI, 0.01-0.02, I = 77%, P < 0.00001) using a random-effects model. There is no significant difference between ICA and estrogen (E) (six studies, n = 128; weighted mean difference, 0.00; 95% CI, -0.00 to 0.01, I = 54%, P = 0.01). Bone mass improved effect of ICA for postmenopausal osteoporosis was observed in OVX-induced rats. Assessment of the methodological quality of studies involving OVX-induced animal models is required, and good methodological quality should be valued in systematic reviews of animal studies.

Expression of extracellular calcium (Ca2+o)-sensing receptor in human peripheral blood monocytes

NASA Technical Reports Server (NTRS)

Yamaguchi, T.; Olozak, I.; Chattopadhyay, N.; Butters, R. R.; Kifor, O.; Scadden, D. T.; Brown, E. M.; O'Malley, B. W. (Principal Investigator)

1998-01-01

The calcium-sensing receptor (CaR) is a G protein-coupled receptor playing key roles in extracellular calcium ion (Ca2+o) homeostasis in parathyroid gland and kidney. Macrophage-like mononuclear cells appear at sites of osteoclastic bone resorption during bone turnover and may play a role in the "reversal" phase of skeletal remodeling that follows osteoclastic resorption and precedes osteoblastic bone formation. Bone resorption produces substantial local increases in Ca2+o that could provide a signal for such mononuclear cells present locally within the bone marrow microenvironment. Indeed, previous studies by other investigators have shown that raising Ca2+o either in vivo or in vitro stimulated the release of interleukin-6 (IL-6) from human peripheral blood monocytes, suggesting that these cells express a Ca2+o-sensing mechanism. In these earlier studies, however, the use of reverse transcription-polymerase chain reaction (RT-PCR) failed to detect transcripts for the CaR previously cloned from parathyroid and kidney in peripheral blood monocytes. Since we recently found that non-specific esterase-positive, putative monocytes isolated from murine bone marrow express the CaR, we reevaluated the expression of this receptor in human peripheral blood monocytes. Immunocytochemistry, flow cytometry, and Western blot analysis, performed using a polyclonal antiserum specific for the CaR, detected CaR protein in human monocytes. In addition, the use of RT-PCR with CaR-specific primers, followed by nucleotide sequencing of the amplified products, identified CaR transcripts in the cells. Therefore, taken together, our data show that human peripheral blood monocytes possess both CaR protein and mRNA very similar if not identical to those expressed in parathyroid and kidney that could mediate the previously described, direct effects of Ca2+o on these cells. Furthermore, since mononuclear cells isolated from bone marrow also express the CaR, the latter might play some role in the "reversal" phase of bone remodeling, sensing local changes in Ca2+o resulting from osteoclastic bone resorption and secreting osteotropic cytokines or performing other Ca2+o-regulated functions that contribute to the control of bone turnover.

Application of quality by design for 3D printed bone prostheses and scaffolds

PubMed Central

Martinez-Marquez, Daniel; Mirnajafizadeh, Ali; Carty, Christopher P.

2018-01-01

3D printing is an emergent manufacturing technology recently being applied in the medical field for the development of custom bone prostheses and scaffolds. However, successful industry transformation to this new design and manufacturing approach requires technology integration, concurrent multi-disciplinary collaboration, and a robust quality management framework. This latter change enabler is the focus of this study. While a number of comprehensive quality frameworks have been developed in recent decades to ensure that the manufacturing of medical devices produces reliable products, they are centred on the traditional context of standardised manufacturing techniques. The advent of 3D printing technologies and the prospects for mass customisation provides significant market opportunities, but also presents a serious challenge to regulatory bodies tasked with managing and assuring product quality and safety. Before 3D printing bone prostheses and scaffolds can gain traction, industry stakeholders, such as regulators, clients, medical practitioners, insurers, lawyers, and manufacturers, would all require a high degree of confidence that customised manufacturing can achieve the same quality outcomes as standardised manufacturing. A Quality by Design (QbD) approach to custom 3D printed prostheses can help to ensure that products are designed and manufactured correctly from the beginning without errors. This paper reports on the adaptation of the QbD approach for the development process of 3D printed custom bone prosthesis and scaffolds. This was achieved through the identification of the Critical Quality Attributes of such products, and an extensive review of different design and fabrication methods for 3D printed bone prostheses. Research outcomes include the development of a comprehensive design and fabrication process flow diagram, and categorised risks associated with the design and fabrication processes of such products. An extensive systematic literature review and post-hoc evaluation survey with experts was completed to evaluate the likely effectiveness of the herein suggested QbD framework. PMID:29649231

Application of quality by design for 3D printed bone prostheses and scaffolds.

PubMed

Martinez-Marquez, Daniel; Mirnajafizadeh, Ali; Carty, Christopher P; Stewart, Rodney A

2018-01-01

3D printing is an emergent manufacturing technology recently being applied in the medical field for the development of custom bone prostheses and scaffolds. However, successful industry transformation to this new design and manufacturing approach requires technology integration, concurrent multi-disciplinary collaboration, and a robust quality management framework. This latter change enabler is the focus of this study. While a number of comprehensive quality frameworks have been developed in recent decades to ensure that the manufacturing of medical devices produces reliable products, they are centred on the traditional context of standardised manufacturing techniques. The advent of 3D printing technologies and the prospects for mass customisation provides significant market opportunities, but also presents a serious challenge to regulatory bodies tasked with managing and assuring product quality and safety. Before 3D printing bone prostheses and scaffolds can gain traction, industry stakeholders, such as regulators, clients, medical practitioners, insurers, lawyers, and manufacturers, would all require a high degree of confidence that customised manufacturing can achieve the same quality outcomes as standardised manufacturing. A Quality by Design (QbD) approach to custom 3D printed prostheses can help to ensure that products are designed and manufactured correctly from the beginning without errors. This paper reports on the adaptation of the QbD approach for the development process of 3D printed custom bone prosthesis and scaffolds. This was achieved through the identification of the Critical Quality Attributes of such products, and an extensive review of different design and fabrication methods for 3D printed bone prostheses. Research outcomes include the development of a comprehensive design and fabrication process flow diagram, and categorised risks associated with the design and fabrication processes of such products. An extensive systematic literature review and post-hoc evaluation survey with experts was completed to evaluate the likely effectiveness of the herein suggested QbD framework.

Correction of metabolic acidosis with potassium citrate in renal transplant patients and its effect on bone quality.

PubMed

Starke, Astrid; Corsenca, Alf; Kohler, Thomas; Knubben, Johannes; Kraenzlin, Marius; Uebelhart, Daniel; Wüthrich, Rudolf P; von Rechenberg, Brigitte; Müller, Ralph; Ambühl, Patrice M

2012-09-01

Acidosis and transplantation are associated with increased risk of bone disturbances. This study aimed to assess bone morphology and metabolism in acidotic patients with a renal graft, and to ameliorate bone characteristics by restoration of acid/base homeostasis with potassium citrate. This was a 12-month controlled, randomized, interventional trial that included 30 renal transplant patients with metabolic acidosis (S-[HCO(3)(-)] <24 mmol/L) undergoing treatment with either potassium citrate to maintain S-[HCO(3)(-)] >24 mmol/L, or potassium chloride (control group). Iliac crest bone biopsies and dual-energy X-ray absorptiometry were performed at baseline and after 12 months of treatment. Bone biopsies were analyzed by in vitro micro-computed tomography and histomorphometry, including tetracycline double labeling. Serum biomarkers of bone turnover were measured at baseline and study end. Twenty-three healthy participants with normal kidney function comprised the reference group. Administration of potassium citrate resulted in persisting normalization of S-[HCO(3)(-)] versus potassium chloride. At 12 months, bone surface, connectivity density, cortical thickness, and cortical porosity were better preserved with potassium citrate than with potassium chloride, respectively. Serological biomarkers and bone tetracycline labeling indicate higher bone turnover with potassium citrate versus potassium chloride. In contrast, no relevant changes in bone mineral density were detected by dual-energy X-ray absorptiometry. Treatment with potassium citrate in renal transplant patients is efficient and well tolerated for correction of metabolic acidosis and may be associated with improvement in bone quality. This study is limited by the heterogeneity of the investigated population with regard to age, sex, and transplant vintage.

Raman spectroscopy of bone metastasis

NASA Astrophysics Data System (ADS)

Esmonde-White, Karen A.; Sottnik, Joseph; Morris, Michael; Keller, Evan

2012-02-01

Raman spectroscopy of bone has been used to characterize chemical changes occurring in diseases such as osteoporosis, osteoarthritis and osteomyelitis. Metastasis of cancer into bone causes changes to bone quality that are similar to those observed in osteoporosis, such as decreased bone strength, but with an accelerated timeframe. In particular, osteolytic (bone degrading) lesions in bone metastasis have a marked effect on patient quality of life because of increased risk of fractures, pain, and hypercalcemia. We use Raman spectroscopy to examine bone from two different mouse models of osteolytic bone metastasis. Raman spectroscopy measures physicochemical information which cannot be obtained through standard biochemical and histological measurements. This study was reviewed and approved by the University of Michigan University Committee on the Care and Use of Animals. Two mouse models of prostate cancer bone metastasis, RM1 (n=3) and PC3-luc (n=4) were examined. Tibiae were injected with RM1 or PC3-luc cancer cells, while the contralateral tibiae received a placebo injection for use as controls. After 2 weeks of incubation, the mice were sacrificed and the tibiae were examined by Raman microspectroscopy (λ=785 nm). Spectroscopic markers corresponding to mineral stoichiometry, bone mineralization, and mineral crystallinity were compared in spectra from the cancerous and control tibiae. X-ray imaging of the tibia confirmed extensive osteolysis in the RM1 mice, with tumor invasion into adjoining soft tissue and moderate osteolysis in the PC3-luc mice. Raman spectroscopic markers indicate that osteolytic lesions are less mineralized than normal bone tissue, with an altered mineral stoichiometry and crystallinity.

Evidence for a Role for Nanoporosity and Pyridinoline Content in Human Mild Osteogenesis Imperfecta.

PubMed

Paschalis, Eleftherios P; Gamsjaeger, Sonja; Fratzl-Zelman, Nadja; Roschger, Paul; Masic, Admir; Brozek, Wolfgang; Hassler, Norbert; Glorieux, Francis H; Rauch, Frank; Klaushofer, Klaus; Fratzl, Peter

2016-05-01

Osteogenesis imperfecta (OI) is a clinically and genetically heterogeneous connective tissue disorder characterized by bone fragility that arises from decreased bone mass and abnormalities in bone material quality. OI type I represents the milder form of the disease and according to the original Sillence classification is characterized by minimal skeletal deformities and near-normal stature. Raman microspectroscopy is a vibrational spectroscopic technique that allows the determination of bone material properties in bone biopsy blocks with a spatial resolution of ∼1 µm, as a function of tissue age. In the present study, we used Raman microspectroscopy to evaluate bone material quality in transiliac bone biopsies from children with a mild form of OI, either attributable to collagen haploinsufficiency OI type I (OI-Quant; n = 11) or aberrant collagen structure (OI-Qual; n = 5), as a function of tissue age, and compared it against the previously published values established in a cohort of biopsies from healthy children (n = 54, ages 1 to 23 years). The results indicated significant differences in bone material compositional characteristics between OI-Quant patients and healthy controls, whereas fewer were evident in the OI-Qual patients. Differences in both subgroups of OI compared with healthy children were evident for nanoporosity, mineral maturity/crystallinity as determined by maxima of the v1 PO4 Raman band, and pyridinoline (albeit in different direction) content. These alterations in bone material compositional properties most likely contribute to the bone fragility characterizing this disease. © 2016 American Society for Bone and Mineral Research. © 2016 American Society for Bone and Mineral Research.

Constitutional bone impairment in Noonan syndrome.

PubMed

Baldassarre, Giuseppina; Mussa, Alessandro; Carli, Diana; Molinatto, Cristina; Ferrero, Giovanni Battista

2017-03-01

Noonan syndrome (NS) is an autosomal dominant trait characterized by genotypic and phenotypic variability. It belongs to the Ras/MAPK pathway disorders collectively named Rasopathies or neurocardiofaciocutaneous syndromes. Phenotype is characterized by short stature, congenital heart defects, facial dysmorphisms, skeletal and ectodermal anomalies, cryptorchidism, mild to moderate developmental delay/learning disability, and tumor predisposition. Short stature and skeletal dysmorphisms are almost constant and several studies hypothesized a role for the RAS pathway in regulating bone metabolism. In this study, we investigated the bone quality assessed by phalangeal quantitative ultrasound (QUS) and the metabolic bone profiling in a group of patients with NS, to determine whether low bone mineralization is primary or secondary to NS characteristics. Thirty-five patients were enrolled, including 20 males (55.6%) and 15 females (44.5%) aged 1.0-17.8 years (mean 6.4 ± 4.5, median 4.9 years). Each patients was submitted to clinical examination, estimation of the bone age, laboratory assays, and QUS assessment. Twenty-five percent of the cohort shows reduced QUS values for their age based on bone transmission time. Bone measurement were adjusted for multiple factors frequently observed in NS patients, such as growth retardation, delayed bone age, retarded puberty, and reduced body mass index, potentially affecting bone quality or its appraisal. In spite of the correction attempts, QUS measurement indicates that bone impairment persists in nearly 15% of the cohort studied. Our results indicate that bone impairment in NS is likely primary and not secondary to any of the phenotypic traits of NS, nor consistent with metabolic disturbances. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Mineral & Bone Disorder in Chronic Kidney Disease

MedlinePlus

... stages of CKD. Slowed bone growth leads to short stature, which may remain with a child into adulthood. ... and local anesthetic. The health care provider uses imaging techniques such as ultrasound or a computerized tomography ...

Safety profile and long-term engraftment of human CD31+ blood progenitors in bone tissue engineering.

PubMed

Zigdon-Giladi, Hadar; Elimelech, Rina; Michaeli-Geller, Gal; Rudich, Utai; Machtei, Eli E

2017-07-01

Endothelial progenitor cells (EPCs) participate in angiogenesis and induce favorable micro-environments for tissue regeneration. The efficacy of EPCs in regenerative medicine is extensively studied; however, their safety profile remains unknown. Therefore, our aims were to evaluate the safety profile of human peripheral blood-derived EPCs (hEPCs) and to assess the long-term efficacy of hEPCs in bone tissue engineering. hEPCs were isolated from peripheral blood, cultured and characterized. β tricalcium phosphate scaffold (βTCP, control) or 10 6 hEPCs loaded onto βTCP were transplanted in a nude rat calvaria model. New bone formation and blood vessel density were analyzed using histomorphometry and micro-computed tomography (CT). Safety of hEPCs using karyotype analysis, tumorigenecity and biodistribution to target organs was evaluated. On the cellular level, hEPCs retained their karyotype during cell expansion (seven passages). Five months following local hEPC transplantation, on the tissue and organ level, no inflammatory reaction or dysplastic change was evident at the transplanted site or in distant organs. Direct engraftment was evident as CD31 human antigens were detected lining vessel walls in the transplanted site. In distant organs human antigens were absent, negating biodistribution. Bone area fraction and bone height were doubled by hEPC transplantation without affecting mineral density and bone architecture. Additionally, local transplantation of hEPCs increased blood vessel density by nine-fold. Local transplantation of hEPCs showed a positive safety profile. Furthermore, enhanced angiogenesis and osteogenesis without mineral density change was found. These results bring us one step closer to first-in-human trials using hEPCs for bone regeneration. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Optimizing finite element predictions of local subchondral bone structural stiffness using neural network-derived density-modulus relationships for proximal tibial subchondral cortical and trabecular bone.

PubMed

Nazemi, S Majid; Amini, Morteza; Kontulainen, Saija A; Milner, Jaques S; Holdsworth, David W; Masri, Bassam A; Wilson, David R; Johnston, James D

2017-01-01

Quantitative computed tomography based subject-specific finite element modeling has potential to clarify the role of subchondral bone alterations in knee osteoarthritis initiation, progression, and pain. However, it is unclear what density-modulus equation(s) should be applied with subchondral cortical and subchondral trabecular bone when constructing finite element models of the tibia. Using a novel approach applying neural networks, optimization, and back-calculation against in situ experimental testing results, the objective of this study was to identify subchondral-specific equations that optimized finite element predictions of local structural stiffness at the proximal tibial subchondral surface. Thirteen proximal tibial compartments were imaged via quantitative computed tomography. Imaged bone mineral density was converted to elastic moduli using multiple density-modulus equations (93 total variations) then mapped to corresponding finite element models. For each variation, root mean squared error was calculated between finite element prediction and in situ measured stiffness at 47 indentation sites. Resulting errors were used to train an artificial neural network, which provided an unlimited number of model variations, with corresponding error, for predicting stiffness at the subchondral bone surface. Nelder-Mead optimization was used to identify optimum density-modulus equations for predicting stiffness. Finite element modeling predicted 81% of experimental stiffness variance (with 10.5% error) using optimized equations for subchondral cortical and trabecular bone differentiated with a 0.5g/cm 3 density. In comparison with published density-modulus relationships, optimized equations offered improved predictions of local subchondral structural stiffness. Further research is needed with anisotropy inclusion, a smaller voxel size and de-blurring algorithms to improve predictions. Copyright © 2016 Elsevier Ltd. All rights reserved.

Three-dimensional Characterization of Resorption Cavity Size and Location in Human Vertebral Trabecular Bone

PubMed Central

Goff, M.G.; Slyfield, C.R.; Kummari, S.R.; Tkachenko, E.V.; Fischer, S. E.; Yi, Y.H.; Jekir, M.; Keaveny, T.M.; Hernandez, C.J.

2012-01-01

The number and size of resorption cavities in cancellous bone are believed to influence rates of bone loss, local tissue stress and strain and potentially whole bone strength. Traditional two-dimensional approaches to measuring resorption cavities in cancellous bone report the percent of the bone surface covered by cavities or osteoclasts, but cannot measure cavity number or size. Here we use three-dimensional imaging (voxel size 0.7 × 0.7 × 5.0 μm) to characterize resorption cavity location, number and size in human vertebral cancellous bone from nine elderly donors (7 male, 2 female, ages 47–80 years). Cavities were 30.10 ± 8.56 μm in maximum depth, 80.60 ± 22.23 *103 μm2 in surface area and 614.16 ± 311.93 *103 μm3 in volume (mean ± SD). The average number of cavities per unit tissue volume (N.Cv/TV) was 1.25 ± 0.77 mm−3. The ratio of maximum cavity depth to local trabecular thickness was 30.46 ± 7.03 % and maximum cavity depth was greater on thicker trabeculae (p < 0.05, r2 = 0.14). Half of the resorption cavities were located entirely on nodes (the intersection of two or more trabeculae) within the trabecular structure. Cavities that were not entirely on nodes were predominately on plate-like trabeculae oriented in the cranial-caudal (longitudinal) direction. Cavities on plate-like trabeculae were larger in maximum cavity depth, cavity surface area and cavity volume than cavities on rod-like trabeculae (p < 0.05). We conclude from these findings that cavity size and location are related to local trabecular microarchitecture. PMID:22507299

Local electronic structure and nanolevel hierarchical organization of bone tissue: theory and NEXAFS study

NASA Astrophysics Data System (ADS)

Pavlychev, A. A.; Avrunin, A. S.; Vinogradov, A. S.; Filatova, E. O.; Doctorov, A. A.; Krivosenko, Yu S.; Samoilenko, D. O.; Svirskiy, G. I.; Konashuk, A. S.; Rostov, D. A.

2016-12-01

Theoretical and experimental investigations of native bone are carried out to understand relationships between its hierarchical organization and local electronic and atomic structure of the mineralized phase. The 3D superlattice model of a coplanar assembly of the hydroxyapatite (HAP) nanocrystallites separated by the hydrated nanolayers is introduced to account the interplay of short-, long- and super-range order parameters in bone tissue. The model is applied to (i) predict and rationalize the HAP-to-bone spectral changes in the electronic structure and (ii) describe the mechanisms ensuring the link of the hierarchical organization with the electronic structure of the mineralized phase in bone. To check the predictions the near-edge x-ray absorption fine structure (NEXAFS) at the Ca 2p, P 2p and O 1s thresholds is measured for native bone and compared with NEXAFS for reference compounds. The NEXAFS analysis has demonstrated the essential hierarchy induced HAP-to-bone red shifts of the Ca and P 2p-to-valence transitions. The lowest O 1s excitation line at 532.2 eV in bone is assigned with superposition of core transitions in the hydroxide OH-(H2O) m anions, Ca2+(H2O) n cations, the carboxyl groups inside the collagen and [PO4]2- and [PO4]- anions with unsaturated P-O bonds.

Local strain and damage mapping in single trabeculae during three-point bending tests

PubMed Central

Jungmann, R.; Szabo, M.E.; Schitter, G.; Tang, Raymond Yue-Sing; Vashishth, D.; Hansma, P.K.; Thurner, P.J.

2012-01-01

The use of bone mineral density as a surrogate to diagnose bone fracture risk in individuals is of limited value. However, there is growing evidence that information on trabecular microarchitecture can improve the assessment of fracture risk. One current strategy is to exploit finite element analysis (FEA) applied to 3D image data of several mm-sized trabecular bone structures obtained from non-invasive imaging modalities for the prediction of apparent mechanical properties. However, there is a lack of FE damage models, based on solid experimental facts, which are needed to validate such approaches and to provide criteria marking elastic–plastic deformation transitions as well as microdamage initiation and accumulation. In this communication, we present a strategy that could elegantly lead to future damage models for FEA: direct measurements of local strains involved in microdamage initiation and plastic deformation in single trabeculae. We use digital image correlation to link stress whitening in bone, reported to be correlated to microdamage, to quantitative local strain values. Our results show that the whitening zones, i.e. damage formation, in the presented loading case of a three-point bending test correlate best with areas of elevated tensile strains oriented parallel to the long axis of the samples. The average local strains along this axis were determined to be (1.6 ± 0.9)% at whitening onset and (12 ± 4)% just prior to failure. Overall, our data suggest that damage initiation in trabecular bone is asymmetric in tension and compression, with failure originating and propagating over a large range of tensile strains. PMID:21396601

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

PubMed Central

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

2007-01-01

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

The effect of phytase and fructooligosaccharide supplementation on growth performance, bone quality, and phosphorus utilization in broiler chickens.

PubMed

Shang, Y; Rogiewicz, A; Patterson, R; Slominski, B A; Kim, W K

2015-05-01

An experiment was conducted to investigate the effects of phytase and 2 levels of fructooligosaccharide (FOS) supplementation on growth performance, bone mineralization, and P utilization of broiler chickens. A total of 210 day-old male broiler chickens (Ross) were randomly placed into 7 dietary treatments consisting of 6 replicates with 5 birds per pen. The experiment was designed as an augmented 2 × 3 factorial arrangement with 0 or 500 U/kg of phytase and 0, 0.5% or 1% of FOS added to a reduced Ca (0.8%) and available P (0.25%) negative control diet (NC). A positive control diet (PC) that contained 1% Ca and 0.45% available P was also included. During the entire experimental period, phytase supplementation significantly improved (P < 0.05) the feed conversion ratio (FCR), BW gain (BWG), and feed intake. Birds fed the PC diet showed significantly higher bone mineral density (BMD) and bone mineral content (BMC) in both femur and tibia bones (P < 0.0001) than those fed the NC diet. Phytase supplementation increased femur BMD (P < 0.05), whereas FOS decreased femur BMD and BMC (P < 0.05). Phosphorus utilization was significantly higher for the NC diet (P < 0.0001). Phytase alone and in combination with 0.5% FOS increased P utilization significantly when compared with other treatments (P < 0.05). Fructooligosaccharides, especially at the level of 0.5%, increased P retention. In conclusion, phytase supplementation in low Ca and P diets improved growth performance, bone quality, and P utilization. However, supplementing NC diets with phytase and FOS did not result in bone mineralization values comparable with that of the PC diet. The application of dietary FOS alone had a negative effect on broiler bone quality. © 2015 Poultry Science Association Inc.

Template-based automatic extraction of the joint space of foot bones from CT scan

NASA Astrophysics Data System (ADS)

Park, Eunbi; Kim, Taeho; Park, Jinah

2016-03-01

Clean bone segmentation is critical in studying the joint anatomy for measuring the spacing between the bones. However, separation of the coupled bones in CT images is sometimes difficult due to ambiguous gray values coming from the noise and the heterogeneity of bone materials as well as narrowing of the joint space. For fine reconstruction of the individual local boundaries, manual operation is a common practice where the segmentation remains to be a bottleneck. In this paper, we present an automatic method for extracting the joint space by applying graph cut on Markov random field model to the region of interest (ROI) which is identified by a template of 3D bone structures. The template includes encoded articular surface which identifies the tight region of the high-intensity bone boundaries together with the fuzzy joint area of interest. The localized shape information from the template model within the ROI effectively separates the bones nearby. By narrowing the ROI down to the region including two types of tissue, the object extraction problem was reduced to binary segmentation and solved via graph cut. Based on the shape of a joint space marked by the template, the hard constraint was set by the initial seeds which were automatically generated from thresholding and morphological operations. The performance and the robustness of the proposed method are evaluated on 12 volumes of ankle CT data, where each volume includes a set of 4 tarsal bones (calcaneus, talus, navicular and cuboid).

Ewing's sarcoma of the cranial vault: a case report.

PubMed

Feki, Jihene; Guermazi, Zeineb; Kammoun, Brahim; Khanfir, Afef; Toumi, Nabil; Boudawara, Tahiya; Boudawara, Zaher; Daoud, Jamel; Frikha, Mounir

2017-12-01

Ewing's sarcoma is a malignant tumor that mainly affects young patients. It represents 10% of primary malignant tumors of the bone and 3% of malignant tumors of the child. Cranial localization is extremely rare representing less than 1% of all the localizations. We report a case of a 10-year-old girl who presented with an intracranial hypertension syndrome with left parietal mass of progressive installation. The X-ray skull showed a lytic lesion with irregular margins involving the left parietal bone. Brain magnetic resonance imaging revealed extensive parietal bone destruction involving both the inner and outer tables. The girl was operated in emergency. Histological examination concluded to Ewing's Sarcoma. The resection was incomplete (R1). The girl received induction's chemotherapy. The cerebral scanner evaluation showed no abnormalities. Then, she received consolidation's chemotherapy with concomitant local radiation therapy. Currently, the girl is in complete remission with a seven-month decline.

A new approach to depict bone surfaces in finger imaging using photoacoustic tomography

NASA Astrophysics Data System (ADS)

Biswas, S. K.; van Es, P.; Steenbergen, W.; Manohar, S.

2015-03-01

Imaging the vasculature close around the finger joints is of interest in the field of rheumatology. Locally increased vasculature in the synovial membrane of these joints can be a marker for rheumatoid arthritis. In previous work we showed that part of the photoacoustically induced ultrasound from the epidermis reflects on the bone surface within the finger. These reflected signals could be wrongly interpreted as new photoacoustic sources. In this work we show that a conventional ultrasound reconstruction algorithm, that considers the skin as a collection of ultrasound transmitters and the PA tomography probe as the detector array, can be used to delineate bone surfaces of a finger. This can in the future assist in the localization of the joint gaps. This can provide us with a landmark to localize the region of the inflamed synovial membrane. We test the approach on finger mimicking phantoms.

Synthesis and Characterization of Poly(lactic-co-glycolic) Acid Nanoparticles-Loaded Chitosan/Bioactive Glass Scaffolds as a Localized Delivery System in the Bone Defects

PubMed Central

Nazemi, K.; Moztarzadeh, F.; Jalali, N.; Asgari, S.; Mozafari, M.

2014-01-01

The functionality of tissue engineering scaffolds can be enhanced by localized delivery of appropriate biological macromolecules incorporated within biodegradable nanoparticles. In this research, chitosan/58S-bioactive glass (58S-BG) containing poly(lactic-co-glycolic) acid (PLGA) nanoparticles has been prepared and then characterized. The effects of further addition of 58S-BG on the structure of scaffolds have been investigated to optimize the characteristics of the scaffolds for bone tissue engineering applications. The results showed that the scaffolds had high porosity with open pores. It was also shown that the porosity decreased with increasing 58S-BG content. Furthermore, the PLGA nanoparticles were homogenously distributed within the scaffolds. According to the obtained results, the nanocomposites could be considered as highly bioactive bone tissue engineering scaffolds with the potential of localized delivery of biological macromolecules. PMID:24949477

Bone geometry, structure and mineral distribution using Dual energy X ray Absorptiometry (DXA)

NASA Technical Reports Server (NTRS)

Whalen, Robert; Cleek, Tammy

1993-01-01

Dual energy x-ray absorptiometry (DXA) is currently the most widely used method of analyzing regional and whole body changes in bone mineral content (BMC) and areal (g/sq cm) bone mineral density (BMD). However, BMC and BMD do not provide direct measures of long bone geometry, structure, or strength nor do regional measurements detect localized changes in other regions of the same bone. The capabilities of DXA can be enhanced significantly by special processing of pixel BMC data which yields cross-sectional geometric and structural information. We have extended this method of analysis in order to develop non-uniform structural beam models of long bones.

Alteration of the bone tissue material properties in type 1 diabetes mellitus: A Fourier transform infrared microspectroscopy study.

PubMed

Mieczkowska, Aleksandra; Mansur, Sity Aishah; Irwin, Nigel; Flatt, Peter R; Chappard, Daniel; Mabilleau, Guillaume

2015-07-01

Type 1 diabetes mellitus (T1DM) is a severe disorder characterized by hyperglycemia and hypoinsulinemia. A higher occurrence of bone fractures has been reported in T1DM, and although bone mineral density is reduced in this disorder, it is also thought that bone quality may be altered in this chronic pathology. Vibrational microscopies such as Fourier transform infrared microspectroscopy (FTIRM) represent an interesting approach to study bone quality as they allow investigation of the collagen and mineral compartment of the extracellular matrix in a specific bone location. However, as spectral feature arising from the mineral may overlap with those of the organic component, the demineralization of bone sections should be performed for a full investigation of the organic matrix. The aims of the present study were to (i) develop a new approach, based on the demineralization of thin bone tissue section to allow a better characterization of the bone organic component by FTIRM, (ii) to validate collagen glycation and collagen integrity in bone tissue and (iii) to better understand what alterations of tissue material properties in newly forming bone occur in T1DM. The streptozotocin-injected mouse (150 mg/kg body weight, injected at 8 weeks old) was used as T1DM model. Animals were randomly allocated to control (n = 8) or diabetic (n = 10) groups and were sacrificed 4 weeks post-STZ injection. Bones were collected at necropsy, embedded in polymethylmethacrylate and sectioned prior to examination by FTIRM. FTIRM collagen parameters were collagen maturity (area ratio between 1660 and 1690 cm(-1) subbands), collagen glycation (area ratio between the 1032 cm(-1) subband and amide I) and collagen integrity (area ratio between the 1338 cm(-1) subband and amide II). No significant differences in the mineral compartment of the bone matrix could be observed between controls and STZ-injected animals. On the other hand, as compared with controls, STZ-injected animals presented with significant higher value for collagen maturity (17%, p = 0.0048) and collagen glycation (99%, p = 0.0121), while collagen integrity was significantly lower by 170% (p = 0.0121). This study demonstrated the profound effect of early T1DM on the organic compartment of the bone matrix in newly forming bone. Further studies in humans are required to ascertain whether T1DM also lead to similar effect on the quality of the bone matrix. Copyright © 2015 Elsevier Inc. All rights reserved.

Emulating Native Periosteum Cell Population and Subsequent Paracrine Factor Production To Promote Tissue Engineered Periosteum-Mediated Allograft Healing

PubMed Central

Hoffman, Michael D.

2015-01-01

Emulating autograft healing within the context of decellularized bone allografts has immediate clinical applications in the treatment of critical-sized bone defects. The periosteum, a thin, osteogenic tissue that surrounds bone, houses a heterogeneous population of stem cells and osteoprogenitors. There is evidence that periosteum-cell derived paracrine factors, specifically vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP2), orchestrate autograft healing through host cell recruitment and subsequent tissue elaboration. In previous work, we demonstrated that the use of poly(ethylene glycol) (PEG) hydrogels as a tissue engineered (T.E.) periosteum to localize mesenchymal stem cells (MSCs) to the surface of decellularized bone enhances allograft healing and integration. Herein, we utilize a mixed population of 50:50 MSCs and osteoprogenitor cells to better mimic native periosteum cell population and paracrine factor production to further promote allograft healing. This mixed cell population was localized to the surface of decellularized allografts within degradable hydrogels and shown to expedite allograft healing. Specifically, bone callus formation and biomechanical graft-host integration are increased as compared to unmodified allografts. These results demonstrate the dual importance of periosteum-mediated paracrine factors orchestrating host cell recruitment as well as new bone formation while developing clinically translatable strategies for allograft healing and integration. PMID:25818449

Skeletal unloading induces resistance to insulin-like growth factor I

NASA Technical Reports Server (NTRS)

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

1994-01-01

In previous studies with a hindlimb elevation model, we demonstrated that skeletal unloading transiently inhibits bone formation. This effect is limited to the unloaded bones (the normally loaded humerus does not cease growing), suggesting that local factors are of prime importance. IGF-I is one such factor; it is produced in bone and stimulates bone formation. To determine the impact of skeletal unloading on IGF-I production and function, we assessed the mRNA levels of IGF-I and its receptor (IGF-IR) in the proximal tibia and distal femur of growing rats during 2 weeks of hindlimb elevation. The mRNA levels for IGF-I and IGF-IR rose during hindlimb elevation, returning toward control values during recovery. This was accompanied by a 77% increase in IGF-I levels in the bone, peaking at day 10 of unloading. Changes in IGF binding protein levels were not observed. Infusion of IGF-I (200 micrograms/day) during 1 week of hindlimb elevation doubled the increase in bone mass of the control animals but failed to reverse the cessation of bone growth in the hindlimb-elevated animals. We conclude that skeletal unloading induces resistance to IGF-I, which may result secondarily in increased local production of IGF-I.

Orbital Osteoblastoma: Technical Innovations in Resection and Reconstruction Using Virtual Surgery Simulation.

PubMed

Novelli, Giorgio; Gramegna, Marco; Tonellini, Gabriele; Valente, Gabriella; Boni, Pietro; Bozzetti, Alberto; Sozzi, Davide

2016-09-01

Osteoblastoma is a benign tumor of bone, representing less than 1% of bone tumors. Craniomaxillofacial localizations account for up to 15% of the total and frequently involve the posterior mandible. Endo-orbital localization is very rare, with most occurring in young patients. Very few of these tumors become malignant. Orbital localization requires radical removal of the tumor followed by careful surgical reconstruction of the orbit to avoid subsequent aesthetic or functional problems. Here, we present a clinical case of this condition and describe a surgical protocol that uses and integrates state-of-the art technologies to achieve orbital reconstruction.

Disorders of Bone Remodeling

PubMed Central

Feng, Xu; McDonald, Jay M.

2013-01-01

The skeleton provides mechanical support for stature and locomotion, protects vital organs, and controls mineral homeostasis. A healthy skeleton must be maintained by constant bone modeling to carry out these crucial functions throughout life. Bone remodeling involves the removal of old or damaged bone by osteoclasts (bone resorption) and the subsequent replacement of new bone formed by osteoblasts (bone formation). Normal bone remodeling requires a tight coupling of bone resorption to bone formation to guarantee no alteration in bone mass or quality after each remodeling cycle. However, this important physiological process can be derailed by a variety of factors, including menopause-associated hormonal changes, age-related factors, changes in physical activity, drugs, and secondary diseases, which lead to the development of various bone disorders in both women and men. We review the major diseases of bone remodeling, emphasizing our current understanding of the underlying pathophysiological mechanisms. PMID:20936937

Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells

PubMed Central

Florencio-Silva, Rinaldo; Sasso-Cerri, Estela; Simões, Manuel Jesus; Cerri, Paulo Sérgio

2015-01-01

Bone tissue is continuously remodeled through the concerted actions of bone cells, which include bone resorption by osteoclasts and bone formation by osteoblasts, whereas osteocytes act as mechanosensors and orchestrators of the bone remodeling process. This process is under the control of local (e.g., growth factors and cytokines) and systemic (e.g., calcitonin and estrogens) factors that all together contribute for bone homeostasis. An imbalance between bone resorption and formation can result in bone diseases including osteoporosis. Recently, it has been recognized that, during bone remodeling, there are an intricate communication among bone cells. For instance, the coupling from bone resorption to bone formation is achieved by interaction between osteoclasts and osteoblasts. Moreover, osteocytes produce factors that influence osteoblast and osteoclast activities, whereas osteocyte apoptosis is followed by osteoclastic bone resorption. The increasing knowledge about the structure and functions of bone cells contributed to a better understanding of bone biology. It has been suggested that there is a complex communication between bone cells and other organs, indicating the dynamic nature of bone tissue. In this review, we discuss the current data about the structure and functions of bone cells and the factors that influence bone remodeling. PMID:26247020

Treatment with eldecalcitol positively affects mineralization, microdamage, and collagen crosslinks in primate bone.

PubMed

Saito, Mitsuru; Grynpas, Marc D; Burr, David B; Allen, Matthew R; Smith, Susan Y; Doyle, Nancy; Amizuka, Norio; Hasegawa, Tomoka; Kida, Yoshikuni; Marumo, Keishi; Saito, Hitoshi

2015-04-01

Eldecalcitol (ELD), an active form of vitamin D analog approved for the treatment of osteoporosis in Japan, increases lumbar spine bone mineral density (BMD), suppresses bone turnover markers, and reduces fracture risk in patients with osteoporosis. We have previously reported that treatment with ELD for 6 months improved the mechanical properties of the lumbar spine in ovariectomized (OVX) cynomolgus monkeys. ELD treatment increased lumbar BMD, suppressed bone turnover markers, and reduced histomorphometric parameters of both bone formation and resorption in vertebral trabecular bone. In this study, we elucidated the effects of ELD on bone quality (namely, mineralization, microarchitecture, microdamage, and bone collagen crosslinks) in OVX cynomolgus monkeys in comparison with OVX-vehicle control monkeys. Density fractionation of bone powder prepared from lumbar vertebrae revealed that ELD treatment shifted the distribution profile of bone mineralization to a higher density, and backscattered electron microscopic imaging showed improved trabecular bone connectivity in the ELD-treated groups. Higher doses of ELD more significantly reduced the amount of microdamage compared to OVX-vehicle controls. The fractionated bone powder samples were divided according to their density, and analyzed for collagen crosslinks. Enzymatic crosslinks were higher in both the high-density (≥2.0 mg/mL) and low-density (<2.0 mg/mL) fractions from the ELD-treated groups than in the corresponding fractions in the OVX-vehicle control groups. On the other hand, non-enzymatic crosslinks were lower in both the high- and low-density fractions. These observations indicated that ELD treatment stimulated the enzymatic reaction of collagen crosslinks and bone mineralization, but prevented non-enzymatic reaction of collagen crosslinks and accumulation of bone microdamage. Bone anti-resorptive agents such as bisphosphonates slow down bone remodeling so that bone mineralization, bone microdamage, and non-enzymatic collagen crosslinks all increase. Bone anabolic agents such as parathyroid hormone decrease bone mineralization and bone microdamage by stimulating bone remodeling. ELD did not fit into either category. Histological analysis indicated that the ELD treatment strongly suppressed bone resorption by reducing the number of osteoclasts, while also stimulating focal bone formation without prior bone resorption (bone minimodeling). These bidirectional activities of ELD may account for its unique effects on bone quality. Copyright © 2014. Published by Elsevier Inc.

A retrospective study on related factors affecting the survival rate of dental implants

PubMed Central

Kang, Jeong-Kyung; Lee, Ki; Lee, Yong-Sang; Park, Pil-Kyoo

2011-01-01

PURPOSE The aim of this retrospective study is to analyze the relationship between local factors and survival rate of dental implant which had been installed and restored in Seoul Veterans Hospital dental center for past 10 years. And when the relationship is found out, it could be helpful to predict the prognosis of dental implants. MATERIALS AND METHODS A retrospective study of patients receiving root-shaped screw-type dental implants placed from January 2000 to December 2009 was conducted. 6385 implants were placed in 3755 patients. The following data were collected from the dental records and radiographs: patient's age, gender, implant type and surface, length, diameter, location of implant placement, bone quality, prosthesis type. The correlations between these data and survival rate were analyzed. Statistical analysis was performed with the use of Kaplan-Meier analysis, Chi-square test and odds ratio. RESULTS In all, 6385 implants were placed in 3755 patients (3120 male, 635 female; mean age 65 ± 10.58 years). 108 implants failed and the cumulative survival rate was 96.33%. There were significant differences in age, implant type and surface, length, location and prosthesis type (P<.05). No significant differences were found in relation to the following factors: gender, diameter and bone quality (P>.05). CONCLUSION Related factors such as age, implant type, length, location and prosthesis type had a significant effect on the implant survival. PMID:22259704

Platelet-rich plasma for long bone healing

PubMed Central

Lenza, Mário; Ferraz, Silvia de Barros; Viola, Dan Carai Maia; dos Santos, Oscar Fernando Pavão; Cendoroglo, Miguel; Ferretti, Mario

2013-01-01

ABSTRACT Objective: To evaluate effectiveness of the use of platelet-rich plasma as coadjuvant for union of long bones. Methods: The search strategy included the Cochrane Library (via Central) and MEDLINE (via PubMed). There were no limits as to language or publication media. The latest search strategy was conducted in December 2011. It included randomized clinical trials that evaluated the use of platelet-rich plasma as coadjuvant medication to accelerate union of long bones (acute fractures, pseudoarthrosis and bone defects). The outcomes of interest for this review include bone regeneration, adverse events, costs, pain, and quality of life. The authors selected eligible studies, evaluated the methodological quality, and extracted the data. It was not possible to perform quantitative analysis of the grouped studies (meta-analyses). Results: Two randomized prospective clinical trials were included, with a total of 148 participants. One of them compared recombinant human morphogenic bone protein-7 versus platelet-rich plasma for the treatment of pseudoarthrosis; the other evaluated the effects of three coadjuvant treatments for union of valgising tibial osteotomies (platelet-rich plasma, platelet-rich plasma plus bone marrow stromal cells, and no coadjuvant treatment). Both had low statistical power and moderate to high risk of bias. Conclusion: There was no conclusive evidence that sustained the use of platelet-rich plasma as a coadjuvant to aid bone regeneration of fractures, pseudoarthrosis, or bone defects. PMID:23579757

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

PubMed

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

2016-08-01

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

The Consequences of GHRH-R Haplo-Insufficiency for Bone Quality and Insulin resistance

PubMed Central

Gois-Jr, Miburge B.; Salvatori, Roberto; Aguiar-Oliveira, Manuel H.; Pereira, Francisco A.; Oliveira, Carla R. P.; Oliveira-Neto, Luiz A.; Pereira, Rossana M. C.; Souza, Anita H.O.; Melo, Enaldo V.; de Paula, Francisco J. A.

2011-01-01

OBJECTIVE Growth hormone (GH)/insulin like growth factor (IGF) axis and insulin are key determinants of bone remodeling. Homozygous mutations in the GH releasing hormone receptor (GHRHR) gene (GHRHR) are a frequent cause of genetic isolated GHD (IGHD). Heterozygosity for GHRHR mutation causes changes in body composition and possibly an increase in insulin sensitivity, but its effects on bone quality are still unknown. The objective of this study was to assess the bone quality and metabolism and its correlation with insulin sensitivity in subjects heterozygous for a null mutation in the GHRHR. PATIENTS AND METHODS A cross-sectional study was performed on 76 normal subjects (68.4% females) (N/N) and 64 individuals (64.1% females) heterozygous for a mutation in the GHRHR (MUT/N). Anthropometric features, quantitative ultrasound (QUS) of the heel, bone markers (osteocalcin and CrossLaps), IGF-I, glucose, and insulin were measured and homeostasis model assessment of insulin resistance (HOMAIR) was calculated. RESULTS There were no differences in age or height between the two groups, but weight (p = 0.007) and BMI (p = 0.001) were lower in MUT/N. There were no differences in serum levels of IGF-I, glucose, T score, or absolute values of stiffness and osteocalcin, but insulin (p = 0.01), HOMAIR (p = 0.01) and CrossLaps (p = 0.01) were lower in MUT/N. There was no correlation between osteocalcin and glucose, osteocalcin and HOMAIR in the140 individuals as a whole or in the separate MUT/N or N/N groups. CONCLUSIONS The present study suggests that one allele mutation in the GHRHR gene has a greater impact on energy metabolism than on bone quality. PMID:21995288

Lifestyle in Multiple Myeloma - a longitudinal cohort study protocol.

PubMed

Heinrich, M; Fisher, A; Paton, B; McCourt, O; Beeken, R J; Hackshaw, A; Wardle, J; Yong, K

2016-07-04

Deterioration in bone health is one of the presenting symptoms of Multiple Myeloma (MM), a cancer of plasma cells. As a consequence of this condition, patients suffer bone pain and bone damage and report cancer-related fatigue, resulting in deterioration in their quality of life. Evidence in patients with solid tumours shows promise for the positive effects of physical activity on quality of life. However, in the case of patients with MM a better understanding of the association between physical fitness and quality of life factors is still required. Therefore, this cohort study aims to objectively and longitudinally assess activity and fitness levels in patients with MM in order to explore their role in bone health, fatigue and quality of life for this patient population. The study is a prospective cohort study of MM patients in remission to assess physical activity, fatigue and bone health. Clinical markers of health, self-reported measures of psychological and physical well-being, and lifestyle behaviours are assessed at baseline, 3, 6 and 12 months. At each time point, patients complete cardiopulmonary exercise testing (CPET) along with a series of objective tests to assess physical fitness (eg accelerometry) and a number of self-report measures. A complementary qualitative study will be carried out in order to explore patients' desire for lifestyle advice and when in their cancer journey they deem such advice to be useful. This study will be the first to prospectively and longitudinally explore associations between physical fitness and well-being, bone health, and fatigue (along with a number of other physical and clinical outcomes) in a cohort of patients with MM with the use of objective measures. The findings will also help to identify time points within the MM pathway at which physical activity interventions may be introduced for maximum benefit.

Reduced functional loads alter the physical characteristics of the bone-PDL-cementum complex

PubMed Central

Niver, Eric L.; Leong, Narita; Greene, Janelle; Curtis, Donald; Ryder, Mark I.; Ho, Sunita P.

2011-01-01

Background Adaptive properties of the bone-PDL-tooth complex have been identified by changing the magnitude of functional loads using small-scale animal models such as rodents. Reported adaptive responses as a result of lower loads due to softer diet include decreased muscle development, change in structure-function relationship of the cranium, narrowed PDL-space, changes in mineral level of the cortical bone and alveolar jaw bone, and glycosaminoglycans of the alveolar bone. However, the adaptive role of the dynamic bone-PDL-cementum complex due to prolonged reduced loads has not been fully explained to date, especially with regards to concurrent adaptations of bone, PDL and cementum. Hence, the temporal effect of reduced functional loads on physical characteristics such as morphology and mechanical properties, and mineral profiles of the bone-periodontal ligament (PDL)-cementum complex using a rat model was investigated. Materials and Methods Two groups of six-week-old male Sprague-Dawley rats were fed nutritionally identical food with a stiffness range of 127–158N/mm for hard pellet or 0.32–0.47N/mm for soft powder forms. Spatio-temporal adaptation of the bone-PDL-cementum complex was identified by mapping changes in: 1) PDL-collagen orientation and birefringence using polarized light microscopy, bone and cementum adaptation using histochemistry, and bone and cementum morphology using micro X-ray computed tomography, 2) mineral profiles of the PDL-cementum and PDL-bone interfaces by X-ray attenuation, and 3) microhardness of bone and cementum by microindentation of specimens at ages six, eight, twelve, and fifteen weeks. Results Reduced functional loads over prolonged time resulted in 1) altered PDL orientation and decreased PDL collagen birefringence indicating decreased PDL turnover rate and decreased apical cementum resorption; 2) a gradual increase in X-ray attenuation, owing to mineral differences, at the PDL-bone and PDL-cementum interfaces without significant differences in the gradients for either group; 3) significantly (p<0.05) lower microhardness of alveolar bone (0.93±0.16 GPa) and secondary cementum (0.803±0.13 GPa) compared to the higher load group (1.10±0.17 GPa and 0.940±0.15 GPa respectively) at fifteen weeks indicating a temporal effect of loads on local mineralization of bone and cementum. Conclusions Based on the results from this study, the effect of reduced functional loads for a prolonged time could differentially affect morphology and mechanical properties, and mineral variations and of the local load-bearing sites in a bone-PDL-cementum complex. These observed local changes in turn could help explain the overall biomechanical function and adaptations of the tooth-bone joint. From a clinical translation perspective, our study provides an insight into modulation of load on the complex for improved tooth function during periodontal disease, and/or orthodontic and prosthodontic treatments. PMID:21848615

k-space sampling optimization for ultrashort TE imaging of cortical bone: Applications in radiation therapy planning and MR-based PET attenuation correction

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

Hu, Lingzhi, E-mail: hlingzhi@gmail.com, E-mail: raymond.muzic@case.edu; Traughber, Melanie; Su, Kuan-Hao

Purpose: The ultrashort echo-time (UTE) sequence is a promising MR pulse sequence for imaging cortical bone which is otherwise difficult to image using conventional MR sequences and also poses strong attenuation for photons in radiation therapy and PET imaging. The authors report here a systematic characterization of cortical bone signal decay and a scanning time optimization strategy for the UTE sequence through k-space undersampling, which can result in up to a 75% reduction in acquisition time. Using the undersampled UTE imaging sequence, the authors also attempted to quantitatively investigate the MR properties of cortical bone in healthy volunteers, thus demonstratingmore » the feasibility of using such a technique for generating bone-enhanced images which can be used for radiation therapy planning and attenuation correction with PET/MR. Methods: An angularly undersampled, radially encoded UTE sequence was used for scanning the brains of healthy volunteers. Quantitative MR characterization of tissue properties, including water fraction and R2{sup ∗} = 1/T2{sup ∗}, was performed by analyzing the UTE images acquired at multiple echo times. The impact of different sampling rates was evaluated through systematic comparison of the MR image quality, bone-enhanced image quality, image noise, water fraction, and R2{sup ∗} of cortical bone. Results: A reduced angular sampling rate of the UTE trajectory achieves acquisition durations in proportion to the sampling rate and in as short as 25% of the time required for full sampling using a standard Cartesian acquisition, while preserving unique MR contrast within the skull at the cost of a minimal increase in noise level. The R2{sup ∗} of human skull was measured as 0.2–0.3 ms{sup −1} depending on the specific region, which is more than ten times greater than the R2{sup ∗} of soft tissue. The water fraction in human skull was measured to be 60%–80%, which is significantly less than the >90% water fraction in brain. High-quality, bone-enhanced images can be generated using a reduced sampled UTE sequence with no visible compromise in image quality and they preserved bone-to-air contrast with as low as a 25% sampling rate. Conclusions: This UTE strategy with angular undersampling preserves the image quality and contrast of cortical bone, while reducing the total scanning time by as much as 75%. The quantitative results of R2{sup ∗} and the water fraction of skull based on Dixon analysis of UTE images acquired at multiple echo times provide guidance for the clinical adoption and further parameter optimization of the UTE sequence when used for radiation therapy and MR-based PET attenuation correction.« less

Treatment of giant cell tumor of bone: Current concepts.

PubMed

Puri, Ajay; Agarwal, Manish

2007-04-01

Giant cell tumor (GCT) of bone though one of the commonest bone tumors encountered by an orthopedic surgeon continues to intrigue treating surgeons. Usually benign, they are locally aggressive and may occasionally undergo malignant transformation. The surgeon needs to strike a balance during treatment between reducing the incidence of local recurrence while preserving maximal function.Differing opinions pertaining to the use of adjuvants for extension of curettage, the relative role of bone graft or cement to pack the defect and the management of recurrent lesions are some of the issues that offer topics for eternal debate.Current literature suggests that intralesional curettage strikes the best balance between controlling disease and preserving optimum function in the majority of the cases though there may be occasions where the extent of the disease mandates resection to ensure adequate disease clearance.An accompanying treatment algorithm helps outline the management strategy in GCT.

Bone healing in 2016

PubMed Central

Buza, John A.; Einhorn, Thomas

2016-01-01

Summary Delayed fracture healing and nonunion occurs in up to 5–10% of all fractures, and can present a challenging clinical scenario for the treating physician. Methods for the enhancement of skeletal repair may benefit patients that are at risk of, or have experienced, delayed healing or nonunion. These methods can be categorized into either physical stimulation therapies or biological therapies. Physical stimulation therapies include electrical stimulation, low-intensity pulsed ultrasonography, or extracorporeal shock wave therapy. Biological therapies can be further classified into local or systemic therapy based on the method of delivery. Local methods include autologous bone marrow, autologous bone graft, fibroblast growth factor-2, platelet-rich plasma, platelet-derived growth factor, and bone morphogenetic proteins. Systemic therapies include parathyroid hormone and bisphosphonates. This article reviews the current applications and supporting evidence for the use of these therapies in the enhancement of fracture healing. PMID:27920804

Bone involvement in adult patients affected with Ehlers-Danlos syndrome.

PubMed

Eller-Vainicher, C; Bassotti, A; Imeraj, A; Cairoli, E; Ulivieri, F M; Cortini, F; Dubini, M; Marinelli, B; Spada, A; Chiodini, I

2016-08-01

The Ehlers-Danlos syndrome is characterized by abnormal connective tissue but bone involvement is debated. We found a reduced BMD and bone quality and increased prevalence of asymptomatic vertebral fractures in eugonadal patients with Ehlers-Danlos syndrome. These findings suggest the need of a bone health evaluation in these patients. The Ehlers-Danlos (EDS) syndrome is characterized by abnormalities of the connective tissue leading to ligamentous laxity and skin and tissue fragility. We evaluated the bone metabolism, bone mineral density (BMD) and bone quality (measured by trabecular bone score, TBS), and the prevalence of vertebral fractures (VFx) in a group of eugonadal adult EDS patients. Fifty consecutive Caucasian patients, aged 30-50 years (36 females, 14 males) with classical or hypermobility EDS and 50 age-, gender-, and body mass index (BMI)-matched control subjects were enrolled. In all subjects' calcium-phosphorous metabolism, bone turnover, BMD at the lumbar spine (LS) and femur (femoral neck, FN and total femur, FT) and TBS by dual-energy X-ray absorptiometry, and the VFx presence by spine radiograph were assessed. Patients showed reduced BMD (Z-scores LS -0.45 ± 1.00, FN -0.56 ± 1.01, FT -0.58 ± 0.92) and TBS (1.299 ± 0.111) and increased prevalence of morphometric VFx (32 %) than controls (Z-scores LS 0.09 ± 1.22, FN 0.01 ± 0.97, FT 0.08 ± 0.89; TBS 1.382 ± 0.176; VFx 8 %, p <0.05 for all comparisons), while vitamin D levels, calcium-phosphorous metabolism, and bone turnover were comparable. Fractured EDS patients showed lower TBS values than non-fractured ones (1.245 ± 0.138 vs 1.325 ± 0.086, p < 0.05), despite comparable BMD. In EDS patients, the VFx presence was significantly associated with TBS even after adjusting for sex, age, BMD, EDS type, and falls frequency. EDS patients have reduced BMD and bone quality (as measured by TBS) and increased prevalence of VFx.

Sex- and age-related differences in mid-thigh composition and muscle quality determined by computed tomography in middle-aged and elderly Japanese.

PubMed

Kasai, Takehiro; Ishiguro, Naoki; Matsui, Yasumoto; Harada, Atsushi; Takemura, Marie; Yuki, Atsumu; Kato, Yuki; Otsuka, Rei; Ando, Fujiko; Shimokata, Hiroshi

2015-06-01

Sex- and age-related differences in mid-thigh composition and muscle quality remain unclear. The present study aimed to clarify these differences using computed tomography in middle-aged and elderly Japanese. A total of 2310 participants (age 40-89 years), who were randomly selected from the local residents, underwent computed tomography examination of the right mid-thigh. Thigh circumference and cross-sectional areas of the thigh, muscle, quadriceps, non-quadriceps, fat, and bone were measured. Knee extension strength and muscle quality index (knee extension strength/quadriceps cross-sectional area) were also assessed. Sex- and age-related differences in these indices were analyzed. The thigh cross-sectional area in men and women decreased by 0.6% and 0.5%/year, respectively, because of a decrease in muscle cross-sectional area (men 75.2%, women 40.6%), fat cross-sectional area (men 24.4%, women 59.6%) and bone cross-sectional area (men 0.5%, women -0.2%). Muscle cross-sectional area in men and women decreased by 0.6% and 0.4%/year, respectively, because of a decrease in quadriceps cross-sectional area (men 65.6%, women 81.6%) and non-quadriceps cross-sectional area (men 34.4%, women 18.4%). Muscle quality in men and women decreased by 0.4% and 0.3%/year, respectively. Thigh cross-sectional area decreased with age mainly because of a decrease in muscle cross-sectional area in men and fat cross-sectional area in women. The rate of decrease in muscle cross-sectional area was 1.5-fold higher in men than in women. Muscle cross-sectional area decreased with age mainly because of a decrease in quadriceps cross-sectional area, especially in women. Decrease in muscle quality with age was similar in both sexes. © 2014 Japan Geriatrics Society.

2D FEA of evaluation of micromovements and stresses at bone-implant interface in immediately loaded tapered implants in the posterior maxilla

PubMed Central

Desai, Shrikar R.; Singh, Rika; Karthikeyan, I.

2013-01-01

Aim: The aim of the study is to evaluate the influence implant length on stress distribution at bone implant interface in single immediately loaded implants when placed in D4 bone quality. Materials and Methods: A 2-dimensional finite element models were developed to simulate two types of implant designs, standard 3.75 mm–diameter tapered body implants of 6 and 10 mm lengths. The implants were placed in D4 bone quality with a cortical bone thickness of 0.5 mm. The implant design incorporated microthreads at the crestal part and the rest of the implant body incorporated Acme threads. The Acme thread form has a 29° thread angle with a thread height half of the pitch; the apex and valley are flat. A 100 N of force was applied vertically and in the oblique direction (at an angle of 45°) to the long axis of the implants. The respective material properties were assigned. Micro-movements and stresses at the bone implant interface were evaluated. Results: The results of total deformation (micro-movement) and Von mises stress were found to be lower for tapered long implant (10 mm) than short implant (6 mm) while using both vertical as well as oblique loading. Conclusion: Short implants can be successfully placed in poor bone quality under immediate loading protocol. The novel approach of the combination of microthreads at the crestal portion and acme threads for body portion of implant fixture gave promising results. PMID:24174759

Assessment of imaging quality in magnified phase CT of human bone tissue at the nanoscale

NASA Astrophysics Data System (ADS)

Yu, Boliang; Langer, Max; Pacureanu, Alexandra; Gauthier, Remy; Follet, Helene; Mitton, David; Olivier, Cecile; Cloetens, Peter; Peyrin, Francoise

2017-10-01

Bone properties at all length scales have a major impact on the fracture risk in disease such as osteoporosis. However, quantitative 3D data on bone tissue at the cellular scale are still rare. Here we propose to use magnified X-ray phase nano-CT to quantify bone ultra-structure in human bone, on the new setup developed on the beamline ID16A at the ESRF, Grenoble. Obtaining 3D images requires the application of phase retrieval prior to tomographic reconstruction. Phase retrieval is an ill-posed problem for which various approaches have been developed. Since image quality has a strong impact on the further quantification of bone tissue, our aim here is to evaluate different phase retrieval methods for imaging bone samples at the cellular scale. Samples from femurs of female donors were scanned using magnified phase nano-CT at voxel sizes of 120 and 30 nm with an energy of 33 keV. Four CT scans at varying sample-to-detector distances were acquired for each sample. We evaluated three phase retrieval methods adapted to these conditions: Paganin's method at single distance, Paganin's method extended to multiple distances, and the contrast transfer function (CTF) approach for pure phase objects. These methods were used as initialization to an iterative refinement step. Our results based on visual and quantitative assessment show that the use of several distances (as opposed to single one) clearly improves image quality and the two multi-distance phase retrieval methods give similar results. First results on the segmentation of osteocyte lacunae and canaliculi from such images are presented.

Management strategy for unicameral bone cyst.

PubMed

Chuo, Chin-Yi; Fu, Yin-Chih; Chien, Song-Hsiung; Lin, Gau-Tyan; Wang, Gwo-Jaw

2003-06-01

The management of a unicameral bone cyst varies from percutaneous needle biopsy, aspiration, and local injection of steroid, autogenous bone marrow, or demineralized bone matrix to the more invasive surgical procedures of conventional curettage and grafting (with autogenous or allogenous bone) or subtotal resection with bone grafting. The best treatment for a unicameral bone cyst is yet to be identified. Better understanding of the pathology will change the concept of management. The aim of treatment is to prevent pathologic fracture, to promote cyst healing, and to avoid cyst recurrence and re-fracture. We retrospectively reviewed 17 cases of unicameral bone cysts (12 in the humerus, 3 in the femur, 2 in the fibula) managed by conservative observation, curettage and bone grafting with open reduction and internal fixation, or continuous decompression and drainage with a cannulated screw. We suggest percutaneous cannulated screw insertion to promote cyst healing and prevent pathologic fracture. We devised a protocol for the management of unicameral bone cysts.

A Direct Role of Collagen Glycation in Bone Fracture

PubMed Central

Poundarik, Atharva A.; Wu, Ping-Cheng; Evis, Zafer; Sroga, Grazyna E.; Ural, Ani; Rubin, Mishaela; Vashishth, Deepak

2015-01-01

Non-enzymatic glycation (NEG) is an age-related process accelerated by diseases like diabetes, and causes the accumulation of advanced glycation end-products (AGEs). NEG-mediated modification of bone’s organic matrix, principally collagen type-I, has been implicated in impairing skeletal physiology and mechanics. Here, we present evidence, from in vitro and in vivo models, and establish a causal relationship between collagen glycation and alterations in bone fracture at multiple length scales. Through atomic force spectroscopy, we established that NEG impairs collagen’s ability to dissipate energy. Mechanical testing of in vitro glycated human bone specimen revealed that AGE accumulation due to NEG dramatically reduces the capacity of organic and mineralized matrix to creep and caused bone to fracture under impact at low levels of strain (3000–5000 μstrain) typically associated with fall. Fracture mechanics tests of NEG modified human cortical bone of varying ages, and their age-matched controls revealed that NEG disrupted microcracking based toughening mechanisms and reduced bone propagation and initiation fracture toughness across all age groups. A comprehensive mechanistic model, based on experimental and modeling data, was developed to explain how NEG and AGEs are causal to, and predictive of bone fragility. Furthermore, fracture mechanics and indentation testing on diabetic mice bones revealed that diabetes mediated NEG severely disrupts bone matrix quality in vivo. Finally, we show that AGEs are predictive of bone quality in aging humans and have diagnostic applications in fracture risk. PMID:26530231

First High-Quality Draft Genome Sequence of Pasteurella multocida Sequence Type 128 Isolated from Infected Bone.

PubMed

Kavousi, Niloofar; Eng, Wilhelm Wei Han; Lee, Yin Peng; Tan, Lian Huat; Thuraisingham, Ravindran; Yule, Catherine M; Gan, Han Ming

2016-03-03

We report here the first high-quality draft genome sequence of Pasteurella multocida sequence type 128, which was isolated from the infected finger bone of an adult female who was bitten by a domestic dog. The draft genome will be a valuable addition to the scarce genomic resources available for P. multocida. Copyright © 2016 Kavousi et al.

Technical innovation changes standard radiographic protocols in veterinary medicine: is it necessary to obtain two dorsoproximal-palmarodistal oblique views of the equine foot when using computerised radiography systems?

PubMed

Whitlock, J; Dixon, J; Sherlock, C; Tucker, R; Bolt, D M; Weller, R

2016-05-21

Since the 1950s, veterinary practitioners have included two separate dorsoproximal-palmarodistal oblique (DPr-PaDiO) radiographs as part of a standard series of the equine foot. One image is obtained to visualise the distal phalanx and the other to visualise the navicular bone. However, rapid development of computed radiography and digital radiography and their post-processing capabilities could mean that this practice is no longer required. The aim of this study was to determine differences in perceived image quality between DPr-PaDiO radiographs that were acquired with a computerised radiography system with exposures, centring and collimation recommended for the navicular bone versus images acquired for the distal phalanx but were subsequently manipulated post-acquisition to highlight the navicular bone. Thirty images were presented to four clinicians for quality assessment and graded using a 1-3 scale (1=textbook quality, 2=diagnostic quality, 3=non-diagnostic image). No significant difference in diagnostic quality was found between the original navicular bone images and the manipulated distal phalanx images. This finding suggests that a single DPr-PaDiO image of the distal phalanx is sufficient for an equine foot radiographic series, with appropriate post-processing and manipulation. This change in protocol will result in reduced radiographic study time and decreased patient/personnel radiation exposure. British Veterinary Association.

Whole-Body and Microenvironmental Localization of Radium-223 in Naïve and Mouse Models of Prostate Cancer Metastasis

PubMed Central

Abou, Diane S.; Ulmert, David; Doucet, Michele; Hobbs, Robert F.; Riddle, Ryan C.

2016-01-01

Background: Bone-metastatic, castration-resistant prostate cancer (bmCRPC) represents a lethal stage of the most common noncutaneous cancer in men. The recent introduction of Radium-223 dichloride, a bone-seeking alpha particle (α)–emitting radiopharmaceutical, demonstrates statistically significant survival benefit and palliative effect for bmCRPC patients. Clinical results have established safety and efficacy, yet questions remain regarding pharmacodynamics and dosing for optimized patient benefit. Methods: We elucidated the biodistribution of 223Ra as well as interaction with the bone and tumor compartments in skeletally mature mice (C57Bl/6 and CD-1, n = 3–6) and metastasis models (LNCaP and PC3, n = 4). Differences in uptake were evaluated by µCT and histological investigation. Novel techniques were leveraged on whole-mount undecalcified cryosections to determine microdistribution of Radium-223. All statistical tests were two-sided. Results: 223Ra uptake in the bones (>30% injected activity per gram) at 24 hours was also accompanied by non-negligible remnant activity in the kidney (2.33% ± 0.36%), intestines (5.73% ± 2.04%), and spleen (10.5% ± 5.9%) Skeletal accumulation across strains did not correspond with bone volume or surface area but instead to local blood vessel density (P = .04). Microdistribution analysis by autoradiography and α camera revealed targeting of the ossifying surfaces adjacent to the epiphyseal growth plate. In models of PCa metastasis, radioactivity does not localize directly within tumors but instead at the apposite bone surface. Osteoblastic and lytic lesions display similar intensity, which is comparable with uptake at sites of normal bone remodeling. Conclusions: Profiling the macro- and microdistribution of 223Ra in healthy and diseased models has important implications to guide precision application of this emerging α-therapy approach for bmCRPC and other bone metastastic diseases. PMID:26683407

Bone marrow uptake of 99mTc-MIBI in patients with multiple myeloma.

PubMed

Fonti, R; Del Vecchio, S; Zannetti, A; De Renzo, A; Di Gennaro, F; Catalano, L; Califano, C; Pace, L; Rotoli, B; Salvatore, M

2001-02-01

In a previous study, we showed the ability of technetium-99m methoxyisobutylisonitrile (99mTc-MIBI) scan to identify active disease in patients with multiple myeloma (Eur J Nucl Med 1998; 25: 714-720). In particular, a semiquantitative score of the extension and intensity of bone marrow uptake was derived and correlated with both the clinical status of the disease and plasma cell bone marrow infiltration. In order to estimate quantitatively 99mTc-MIBI bone marrow uptake and to verify the intracellular localization of the tracer, bone marrow samples obtained from 24 multiple myeloma patients, three patients with monoclonal gammopathy of undetermined significance (MGUS) and two healthy donors were studied for in vitro uptake. After centrifugation over Ficoll-Hypaque gradient, cell suspensions were incubated with 99mTc-MIBI and the uptake was expressed as the percentage of radioactivity specifically retained within the cells. The cellular localization of the tracer was assessed by micro-autoradiography. Twenty-two out of 27 patients underwent 99mTc-MIBI scan within a week of bone marrow sampling. Whole-body images were obtained 10 min after intravenous injection of 555 MBq of the tracer; the extension and intensity of 99mTc-MIBI uptake were graded using the semiquantitative score. A statistically significant correlation was found between in vitro uptake of 99mTc-MIBI and both plasma cell infiltration (Pearson's coefficient of correlation r=0.69, P<0.0001) and in vivo score (Spearman rank correlation coefficient r=0.60, P<0.01). No specific tracer uptake was found in bone marrow samples obtained from the two healthy donors. Micro-autoradiography showed localization of 99mTc-MIBI inside the plasma cells infiltrating the bone marrow. Therefore, our findings show that the degree of tracer uptake both in vitro and in vivo is related to the percentage of infiltrating plasma cells which accumulate the tracer in their inner compartments.

Skeletal adaptation to external loads optimizes mechanical properties: fact or fiction

NASA Technical Reports Server (NTRS)

Turner, R. T.

2001-01-01

The skeleton adapts to a changing mechanical environment but the widely held concept that bone cells are programmed to respond to local mechanical loads to produce an optimal mechanical structure is not consistent with the high frequency of bone fractures. Instead, the author suggests that other important functions of bone compete with mechanical adaptation to determine structure. As a consequence of competing demands, bone architecture never achieves an optimal mechanical structure. c2001 Lippincott Williams & Wilkins, Inc.

Aneurysmal bone cyst of the scapula. A case report.

PubMed

Megas, Panagiotis; Papathanassiou, Zafiria G; Kasimatis, George; Papachristou, Dionysios J

2009-10-01

Aneurysmal bone cyst (ABC) is an uncommon, benign but locally destructive bone lesion of unknown origin. Differential diagnosis can be challenging as it shares common radiological and pathological features with other benign and malignant bone lesions. The degree of diagnostic difficulty grows even more when an unusual location has to be taken into account. We report a rare and challenging case of a large primary ABC located at the scapula of a young male, who was surgically treated with subtotal removal of the scapula.

Complications related to bone augmentation procedures of localized defects in the alveolar ridge. A retrospective clinical study.

PubMed

Jensen, Anders Torp; Jensen, Simon Storgård; Worsaae, Nils

2016-06-01

This retrospective clinical study aims to evaluate complications after augmentation of localized bone defects of the alveolar ridge. From standardized registrations, the following complications related to bone augmentation procedures were recorded: soft tissue dehiscence, infection, sensory disturbance, additional augmentation procedures needed, and early implant failure. A total of 223 patients (132 women, 91 men; mean age 23.5 years; range 17-65 years) with 331 bone defects had bone augmentation performed into which 350 implants were placed. Soft tissue dehiscence occurred in 1.7 % after GBR procedures, 25.9 % after staged horizontal ridge augmentation, and 18.2 % after staged vertical ridge augmentation. Infections were diagnosed in 2 % after GBR procedures, 12.5 % after sinus floor elevation (SFE) (transcrestal technique), 5 % after staged SFE, 11 % after staged horizontal ridge augmentation, and 9 % after staged vertical ridge augmentation. Additional augmentation procedures were needed in 2 % after GBR procedures, 37 % after staged horizontal ridge augmentation, and 9 % after staged vertical ridge augmentation. A total of six early implant failures occurred (1.7 %), four after GBR procedures (1.6 %), and two (12 %) after staged vertical ridge augmentation. Predictable methods exist to augment localized defects in the alveolar ridge, as documented by low complication rates and high early implant survival rates.

Congenital Bone Fractures in Spinal Muscular Atrophy: Functional Role for SMN Protein in Bone Remodeling

PubMed Central

Shanmugarajan, Srinivasan; Swoboda, Kathryn J.; Iannaccone, Susan T.; Ries, William L.; Maria, Bernard L.; Reddy, Sakamuri V.

2009-01-01

Spinal muscular atrophy is the second most common fatal childhood disorder. Core clinical features include muscle weakness caused by degenerating lower motor neurons and a high incidence of bone fractures and hypercalcemia. Fractures further compromise quality of life by progression of joint contractures or additional loss of motor function. Recent observations suggest that bone disease in spinal muscular atrophy may not be attributed entirely to lower motor neuron degeneration. The presence of the spinal muscular atrophy disease-determining survival motor neuron gene (SMN), SMN expression, and differential splicing in bone-resorbing osteoclasts was recently discovered. Its ubiquitous expression and the differential expression of splice variants suggest that SMN has specific roles in bone cell function. SMN protein also interacts with osteoclast stimulatory factor. Mouse models of human spinal muscular atrophy disease suggest a potential role of SMN protein in skeletal development. Dual energy x-ray absorptiometry analysis demonstrated a substantial decrease in total bone area and poorly developed caudal vertebra in the mouse model. These mice also had pelvic bone fractures. Studies delineating SMN signaling mechanisms and gene transcription in a cell-specific manner will provide important molecular insights into the pathogenesis of bone disease in children with spinal muscular atrophy. Moreover, understanding bone remodeling in spinal muscular atrophy may lead to novel therapeutic approaches to enhance skeletal health and quality of life. This article reviews the skeletal complications associated with spinal muscular atrophy and describes a functional role for SMN protein in osteoclast development and bone resorption activity. PMID:17761651

Negative Pressure Wound Therapy Reduces the Effectiveness of Traditional Local Antibiotic Depot in a Large Complex Musculoskeletal Wound Animal Model

DTIC Science & Technology

2012-09-01

in particular, local antibiotic delivery via polymethylmethacrylate (PMMA) bone cement and negative pressure wound therapy (NPWT). In cases with gross...release of gentamicin from polymethylmethacrylate beads. An experimental and pharmacoki- netic study. J Bone Joint Surg Br. 1978;60-B:270 275. 7...diffusion from antibiotic-impregnated polymethylmethacrylate beads. Clin Orthop Relat Res. 1992;278:244 252. Stinner et al J Orthop Trauma Volume

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

Gratama van Andel, H. A. F.; Venema, H. W.; Streekstra, G. J.

For clear visualization of vessels in CT angiography (CTA) images of the head and neck using maximum intensity projection (MIP) or volume rendering (VR) bone has to be removed. In the past we presented a fully automatic method to mask the bone [matched mask bone elimination (MMBE)] for this purpose. A drawback is that vessels adjacent to bone may be partly masked as well. We propose a modification, multiscale MMBE, which reduces this problem by using images at two scales: a higher resolution than usual for image processing and a lower resolution to which the processed images are transformed formore » use in the diagnostic process. A higher in-plane resolution is obtained by the use of a sharper reconstruction kernel. The out-of-plane resolution is improved by deconvolution or by scanning with narrower collimation. The quality of the mask that is used to remove bone is improved by using images at both scales. After masking, the desired resolution for the normal clinical use of the images is obtained by blurring with Gaussian kernels of appropriate widths. Both methods (multiscale and original) were compared in a phantom study and with clinical CTA data sets. With the multiscale approach the width of the strip of soft tissue adjacent to the bone that is masked can be reduced from 1.0 to 0.2 mm without reducing the quality of the bone removal. The clinical examples show that vessels adjacent to bone are less affected and therefore better visible. Images processed with multiscale MMBE have a slightly higher noise level or slightly reduced resolution compared with images processed by the original method and the reconstruction and processing time is also somewhat increased. Nevertheless, multiscale MMBE offers a way to remove bone automatically from CT angiography images without affecting the integrity of the blood vessels. The overall image quality of MIP or VR images is substantially improved relative to images processed with the original MMBE method.« less

Poly-cyclodextrin functionalized porous bioceramics for local chemotherapy and anticancer bone reconstruction.

PubMed

Chai, Feng; Abdelkarim, Mohamed; Laurent, Thomas; Tabary, Nicolas; Degoutin, Stephanie; Simon, Nicolas; Peters, Fabian; Blanchemain, Nicolas; Martel, Bernard; Hildebrand, Hartmut F

2014-08-01

The progress in bone cancer surgery and multimodal treatment concept achieve only modest improvement in the overall survival, due to failure in clearing out residual cancer cells at the surgical margin and extreme side-effects of adjuvant postoperative treatments. Our study aims to propose a new method based on cyclodextrin polymer (polyCD) functionalized hydroxyapatite (HA) for achieving a high local drug concentration with a sustained release profile and a better control of residual malignant cells via local drug delivery and promotion of the reconstruction of bone defects. PolyCD, a versatile carrier for therapeutic molecules, can be incorporated into HA (bone regeneration scaffold) through thermal treatment. The parameters of polyCD treatment on the macroporous HA (porosity 65%) were characterized via thermogravimetric analysis. Good cytocompatibility of polyCD functionalized bioceramics was demonstrated on osteoblast cells by cell vitality assay. An antibiotic (gentamicin) and an anticancer agent (cisplatin) were respectively loaded on polyCD functionalized bioceramics for drug release test. The results show that polyCD functionalization leads to significantly improved drug loading quantity (30% more concerning gentamicin and twice more for cisplatin) and drug release duration (7 days longer concerning gentamicin and 3 days longer for cisplatin). Conclusively, this study offers a safe and reliable drug delivery system for bioceramic matrices, which can load anticancer agents (or/and antibiotics) to reduce local recurrence (or/and infection). © 2014 Wiley Periodicals, Inc.

The promotion of mandibular defect healing by the targeting of S1P receptors and the recruitment of alternatively activated macrophages

PubMed Central

Das, Anusuya; Segar, Claire E; Hughley, Brian B; Bowers, Daniel T; Botchwey, Edward A

2013-01-01

Endogenous signals originating at the site of injury are involved in the paracrine recruitment, proliferation, and differentiation of circulating progenitor and diverse inflammatory cell types. Here, we investigate a strategy to exploit endogenous cell recruitment mechanisms to regenerate injured bone by local targeting and activation of sphingosine-1-phosphate (S1P) receptors. A mandibular defect model was selected for evaluating regeneration of bone following trauma or congenital disease. The particular challenges of mandibular reconstruction are inherent in the complex anatomy and function of the bone given that the area is highly vascularized and in close proximity to muscle. Nanofibers composed of poly(DL-lactide-co-glycolide) (PLAGA) and polycaprolactone (PCL) were used to delivery FTY720, a targeted agonist of S1P receptors 1 and 3. In vitro culture of bone progenitor cells on drug loaded constructs significantly enhanced SDF1α mediated chemotaxis of bone marrow mononuclear cells. In vivo results show that local delivery of FTY720 from composite nanofibers enhanced blood vessel ingrowth and increased recruitment of M2 alternatively activated macrophages, leading to significant osseous tissue ingrowth into critical sized defects after 12 weeks of treatment. These results demonstrate that local activation of S1P receptors is a regenerative cue resulting in recruitment of wound healing or anti-inflammatory macrophages and bone healing. Use of such small molecule therapy can provide an alternative to biological factors for the clinical treatment of critical size craniofacial defects. PMID:24064148

The promotion of mandibular defect healing by the targeting of S1P receptors and the recruitment of alternatively activated macrophages.

PubMed

Das, Anusuya; Segar, Claire E; Hughley, Brian B; Bowers, Daniel T; Botchwey, Edward A

2013-12-01

Endogenous signals originating at the site of injury are involved in the paracrine recruitment, proliferation, and differentiation of circulating progenitor and diverse inflammatory cell types. Here, we investigate a strategy to exploit endogenous cell recruitment mechanisms to regenerate injured bone by local targeting and activation of sphingosine-1-phosphate (S1P) receptors. A mandibular defect model was selected for evaluating regeneration of bone following trauma or congenital disease. The particular challenges of mandibular reconstruction are inherent in the complex anatomy and function of the bone given that the area is highly vascularized and in close proximity to muscle. Nanofibers composed of poly(DL-lactide-co-glycolide) (PLAGA) and polycaprolactone (PCL) were used to delivery FTY720, a targeted agonist of S1P receptors 1 and 3. In vitro culture of bone progenitor cells on drug-loaded constructs significantly enhanced SDF1α mediated chemotaxis of bone marrow mononuclear cells. In vivo results show that local delivery of FTY720 from composite nanofibers enhanced blood vessel ingrowth and increased recruitment of M2 alternatively activated macrophages, leading to significant osseous tissue ingrowth into critical sized defects after 12 weeks of treatment. These results demonstrate that local activation of S1P receptors is a regenerative cue resulting in recruitment of wound healing or anti-inflammatory macrophages and bone healing. Use of such small molecule therapy can provide an alternative to biological factors for the clinical treatment of critical size craniofacial defects. Copyright © 2013 Elsevier Ltd. All rights reserved.

Expression of nociceptive ligands in canine osteosarcoma.

PubMed

Shor, S; Fadl-Alla, B A; Pondenis, H C; Zhang, X; Wycislo, K L; Lezmi, S; Fan, T M

2015-01-01

Canine osteosarcoma (OS) is associated with localized pain as a result of tissue injury from tumor infiltration and peritumoral inflammation. Malignant bone pain is caused by stimulation of peripheral pain receptors, termed nociceptors, which reside in the localized tumor microenvironment, including the periosteal and intramedullary bone cavities. Several nociceptive ligands have been determined to participate directly or indirectly in generating bone pain associated with diverse skeletal abnormalities. Canine OS cells actively produce nociceptive ligands with the capacity to directly or indirectly activate peripheral pain receptors residing in the bone tumor microenvironment. Ten dogs with appendicular OS. Expression of nerve growth factor, endothelin-1, and microsomal prostaglandin E synthase-1 was characterized in OS cell lines and naturally occurring OS samples. In 10 dogs with OS, circulating concentrations of nociceptive ligands were quantified and correlated with subjective pain scores and tumor volume in patients treated with standardized palliative therapies. Canine OS cells express and secrete nerve growth factor, endothelin-1, and prostaglandin E2. Naturally occurring OS samples uniformly express nociceptive ligands. In a subset of OS-bearing dogs, circulating nociceptive ligand concentrations were detectable but failed to correlate with pain status. Localized foci of nerve terminal proliferation were identified in a minority of primary bone tumor samples. Canine OS cells express nociceptive ligands, potentially permitting active participation of OS cells in the generation of malignant bone pain. Specific inhibitors of nociceptive ligand signaling pathways might improve pain control in dogs with OS. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of American College of Veterinary Internal Medicine.

Investigating the Role of Global Histogram Equalization Technique for 99mTechnetium-Methylene diphosphonate Bone Scan Image Enhancement

PubMed Central

Pandey, Anil Kumar; Sharma, Param Dev; Dheer, Pankaj; Parida, Girish Kumar; Goyal, Harish; Patel, Chetan; Bal, Chandrashekhar; Kumar, Rakesh

2017-01-01

Purpose of the Study: 99mTechnetium-methylene diphosphonate (99mTc-MDP) bone scan images have limited number of counts per pixel, and hence, they have inferior image quality compared to X-rays. Theoretically, global histogram equalization (GHE) technique can improve the contrast of a given image though practical benefits of doing so have only limited acceptance. In this study, we have investigated the effect of GHE technique for 99mTc-MDP-bone scan images. Materials and Methods: A set of 89 low contrast 99mTc-MDP whole-body bone scan images were included in this study. These images were acquired with parallel hole collimation on Symbia E gamma camera. The images were then processed with histogram equalization technique. The image quality of input and processed images were reviewed by two nuclear medicine physicians on a 5-point scale where score of 1 is for very poor and 5 is for the best image quality. A statistical test was applied to find the significance of difference between the mean scores assigned to input and processed images. Results: This technique improves the contrast of the images; however, oversaturation was noticed in the processed images. Student's t-test was applied, and a statistically significant difference in the input and processed image quality was found at P < 0.001 (with α = 0.05). However, further improvement in image quality is needed as per requirements of nuclear medicine physicians. Conclusion: GHE techniques can be used on low contrast bone scan images. In some of the cases, a histogram equalization technique in combination with some other postprocessing technique is useful. PMID:29142344

Correlation of Bone Mineral Density on Quality of Life in Patients with Osteogenesis Imperfecta during Treatment with Denosumab.

PubMed

Hoyer-Kuhn, Heike; Stark, Christina; Franklin, Jeremy; Schoenau, Eckhard; Semler, Oliver

2017-11-01

Osteogenesis imperfecta (OI) is a rare hereditary skeletal disease leading to recurrent fractures, short stature and impaired mobility. The phenotype varies from mildly affected patients to perinatal lethal forms. In most cases an impaired collagen production due to mutations in COL1A1 or COL1A2 cause this hereditary bone fragility syndrome with an autosomal dominant inheritance. Currently an interdisciplinary therapeutic approach with antiresorptive drugs, physiotherapy and surgical procedures is the state of the art therapy. The effect of such a therapy is evaluated by measuring different surrogate parameters like areal bone mineral density or by using different mobility tests or questionnaires. Up till now the impact of these parameters on quality of life of the patients is not evaluated. Currently pharmacological strategies are based on antiresorptive treatment with bisphosphonates. In this trial we investigated the effect of an antiresorptive therapy with the monoclonal antibody denosumab decreasing the activity of osteoclasts. Denosumab was administered subcutaneously in a dose of 1mg/kg body weight in 10 children with OI (5-10 years of age) every 12 weeks for 48 weeks. Areal bone mineral density, mobility, pain scores and quality of life were measured. The results showed a good effect of the treatment on bone mineral density but this improvement showed no correlation to pain and quality of life. In conclusion further trials have to define parameters to assess interventions which influence activities of daily life of the patients. An interdisciplinary approach including physicians, basic researchers and patient organisation is needed to focus research on topics improving quality of life of patients with severe skeletal diseases. Copyright© of YS Medical Media ltd.

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.

Short-term muscle atrophy caused by botulinum toxin-A local injection impairs fracture healing in the rat femur.

PubMed

Hao, Yongqiang; Ma, Yongcheng; Wang, Xuepeng; Jin, Fangchun; Ge, Shengfang

2012-04-01

Damaged bone is sensitive to mechanical stimulation throughout the remodeling phase of bone healing. Muscle damage and muscular atrophy associated with open fractures and subsequent fixation are not beneficial to maintaining optimum conditions for mechanical stability. The aim of this study was to investigate whether local muscle atrophy and dysfunction affect fracture healing in a rat femur fracture model. We combined the rat model of a short period atrophy of the quadriceps with femur fracture. Forty-four-month-old male Wistar rats were adopted for this study. Two units of botulinum toxin-A (BXTA) were administered locally into the right side of the quadriceps of each rat, while the same dose of saline was injected into the contralateral quadriceps. After BXTA had been fully absorbed by the quadriceps, osteotomy was performed in both femurs with intramedullary fixation. Gross observation and weighing of muscle tissue, X-ray analysis, callus histology, and bone biomechanical testing were performed at different time points up to 8 weeks post-surgery. Local injection of BXTA led to a significant decrease in the volume and weight of the quadriceps compared to the control side. At the eighth week, the left side femurs of the saline-injected quadriceps almost reached bony union, and fibrous calluses were completely calcified into woven bone. However, a gap was still visible in the BXTA-treated side on X-ray images. As showed by bone histology, there were no mature osseous calluses or woven bone on the BXTA-treated side, but a resorption pattern was evident. Biomechanical testing indicated that the femurs of the BXTA-treated side exhibited inferior mechanical properties compared with the control side. The inferior outcome following BXTA injection, compared with saline injection, in terms of callus resistance may be the consequence of unexpected load and mechanical unsteadiness caused by muscle atrophy and dysfunction. Copyright © 2011 Orthopaedic Research Society.

Is it safe to preserve the deltoid when resecting the proximal humerus for a primary malignant bone tumour? A comparative study.

PubMed

Cladière-Nassif, V; Bourdet, C; Audard, V; Babinet, A; Anract, P; Biau, D

2017-09-01

Resection of the proximal humerus for the primary malignant bone tumour sometimes requires en bloc resection of the deltoid. However, there is no information in the literature which helps a surgeon decide whether to preserve the deltoid or not. The aim of this study was to determine whether retaining the deltoid at the time of resection would increase the rate of local recurrence. We also sought to identify the variables that persuade expert surgeons to choose a deltoid sparing rather than deltoid resecting procedure. We reviewed 45 patients who had undergone resection of a primary malignant tumour of the proximal humerus. There were 29 in the deltoid sparing group and 16 in the deltoid resecting group. Imaging studies were reviewed to assess tumour extension and soft-tissue involvement. The presence of a fat rim separating the tumour from the deltoid on MRI was particularly noted. The cumulative probability of local recurrence was calculated in a competing risk scenario. There was no significant difference (adjusted p = 0.89) in the cumulative probability of local recurrence between the deltoid sparing (7%, 95% confidence interval (CI) 1 to 20) and the deltoid resecting group (26%, 95% CI 8 to 50). Patients were more likely to be selected for a deltoid sparing procedure if they presented with a small tumour (p = 0.0064) with less bone involvement (p = 0.032) and a continuous fat rim on MRI (p = 0.002) and if the axillary nerve could be identified (p = 0.037). A deltoid sparing procedure can provide good local control after resection of the proximal humerus for a primary malignant bone tumour. A smaller tumour, the presence of a continuous fat rim and the identification of the axillary nerve on pre-operative MRI will persuade surgeons to opt for a deltoid resecting procedure. Cite this article: Bone Joint J 2017;99-B:1244-9. ©2017 The British Editorial Society of Bone & Joint Surgery.

[Local fixation of antibiotics by fibrin spray : In bone defects with soft tissue involvement].

PubMed

Janko, Maren; Nau, Christoph; Marzi, Ingo; Frank, Johannes

2017-02-01

In acute and chronic bone infections with concomitant soft tissue involvement the current gold standard is radical surgical debridement including explantation of the infected prosthetic devices. This is followed by initiation of systemic antibiotic therapy appropriate for the antibiogram. Several revision operations are often necessary to achieve complete healing. Additional treatment with local antibiotics or antibiotic-containing substances is routinely used in bone surgery. Apart from the typical procedures with commercially available products, we have conducted a study with 21 patients by application of local antibiotic treatment in combination with the fibrin glue spray technique and evaluated the results. Out of nine wounds of the lower extremities with bone involvement, total healing could be achieved in eight cases. We were also successful in two out of three very complex pelvic wounds; however, as expected the implant infections were complicated. Out of the seven desolate cases we were only able to achieve complete long-term healing in two cases. In the meantime we routinely use the described method in such special disastrous infection situations; however, this is carried out only in combination with established surgical procedures in sepsis surgery and anti-infection management.

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

Localization accuracy of sphere fiducials in computed tomography images

NASA Astrophysics Data System (ADS)

Kobler, Jan-Philipp; Díaz Díaz, Jesus; Fitzpatrick, J. Michael; Lexow, G. Jakob; Majdani, Omid; Ortmaier, Tobias

2014-03-01

In recent years, bone-attached robots and microstereotactic frames have attracted increasing interest due to the promising targeting accuracy they provide. Such devices attach to a patient's skull via bone anchors, which are used as landmarks during intervention planning as well. However, as simulation results reveal, the performance of such mechanisms is limited by errors occurring during the localization of their bone anchors in preoperatively acquired computed tomography images. Therefore, it is desirable to identify the most suitable fiducials as well as the most accurate method for fiducial localization. We present experimental results of a study focusing on the fiducial localization error (FLE) of spheres. Two phantoms equipped with fiducials made from ferromagnetic steel and titanium, respectively, are used to compare two clinically available imaging modalities (multi-slice CT (MSCT) and cone-beam CT (CBCT)), three localization algorithms as well as two methods for approximating the FLE. Furthermore, the impact of cubic interpolation applied to the images is investigated. Results reveal that, generally, the achievable localization accuracy in CBCT image data is significantly higher compared to MSCT imaging. The lowest FLEs (approx. 40 μm) are obtained using spheres made from titanium, CBCT imaging, template matching based on cross correlation for localization, and interpolating the images by a factor of sixteen. Nevertheless, the achievable localization accuracy of spheres made from steel is only slightly inferior. The outcomes of the presented study will be valuable considering the optimization of future microstereotactic frame prototypes as well as the operative workflow.

Grafton and local bone have comparable outcomes to iliac crest bone in instrumented single-level lumbar fusions.

PubMed

Kang, James; An, Howard; Hilibrand, Alan; Yoon, S Tim; Kavanagh, Eoin; Boden, Scott

2012-05-20

Prospective multicenter randomized clinical trail. The goal of our 2-year prospective study was to perform a randomized clinical trial comparing the outcomes of Grafton demineralized bone matrix (DBM) Matrix with local bone with that of iliac crest bone graft (ICBG) in a single-level instrumented posterior lumbar fusion. There has been extensive research and development in identifying a suitable substitute to replace autologous ICBG that is associated with known morbidities. DBMs are a class of commercially available grafting agents that are prepared from allograft bone. Many such products have been commercially available for clinical use; however, their efficacy for spine fusion has been mostly based on anecdotal evidence rather than randomized controlled clinical trials. Forty-six patients were randomly assigned (2:1) to receive Grafton DBM Matrix with local bone (30 patients) or autologous ICBG (16 patients). The mean age was 64 (females [F] = 21, males [M] = 9) in the DBM group and 65 (F = 9, M = 5) in the ICBG group. An independent radiologist evaluated plain radiographs and computed tomographic scans at 6-month, 1-year, and 2-year time points. Clinical outcomes were measured using Oswestry Disability Index (ODI) and Medical Outcomes Study 36-Item Short Form Health Survey. Forty-one patients (DBM = 28 and ICBG = 13) completed the 2-year follow-up. Final fusion rates were 86% (Grafton Matrix) versus 92% (ICBG) (P = 1.0 not significant). The Grafton group showed slightly better improvement in ODI score than the ICBG group at the final 2-year follow-up (Grafton [16.2] and ICBG [22.7]); however, the difference was not statistically significant (P = 0.2346 at 24 mo). Grafton showed consistently higher physical function scores at 24 months; however, differences were not statistically significant (P = 0.0823). Similar improvements in the physical component summary scores were seen in both the Grafton and ICBG groups. There was a statistically significant greater mean intraoperative blood loss in the ICBG group than in the Grafton group (P < 0.0031). At 2-year follow-up, subjects who were randomized to Grafton Matrix and local bone achieved an 86% overall fusion rate and improvements in clinical outcomes that were comparable with those in the ICBG group.

Specimen-specific modeling of hip fracture pattern and repair.

PubMed

Ali, Azhar A; Cristofolini, Luca; Schileo, Enrico; Hu, Haixiang; Taddei, Fulvia; Kim, Raymond H; Rullkoetter, Paul J; Laz, Peter J

2014-01-22

Hip fracture remains a major health problem for the elderly. Clinical studies have assessed fracture risk based on bone quality in the aging population and cadaveric testing has quantified bone strength and fracture loads. Prior modeling has primarily focused on quantifying the strain distribution in bone as an indicator of fracture risk. Recent advances in the extended finite element method (XFEM) enable prediction of the initiation and propagation of cracks without requiring a priori knowledge of the crack path. Accordingly, the objectives of this study were to predict femoral fracture in specimen-specific models using the XFEM approach, to perform one-to-one comparisons of predicted and in vitro fracture patterns, and to develop a framework to assess the mechanics and load transfer in the fractured femur when it is repaired with an osteosynthesis implant. Five specimen-specific femur models were developed from in vitro experiments under a simulated stance loading condition. Predicted fracture patterns closely matched the in vitro patterns; however, predictions of fracture load differed by approximately 50% due to sensitivity to local material properties. Specimen-specific intertrochanteric fractures were induced by subjecting the femur models to a sideways fall and repaired with a contemporary implant. Under a post-surgical stance loading, model-predicted load sharing between the implant and bone across the fracture surface varied from 59%:41% to 89%:11%, underscoring the importance of considering anatomic and fracture variability in the evaluation of implants. XFEM modeling shows potential as a macro-level analysis enabling fracture investigations of clinical cohorts, including at-risk groups, and the design of robust implants. © 2013 Published by Elsevier Ltd.

Ghosts of Yellowstone: Multi-Decadal Histories of Wildlife Populations Captured by Bones on a Modern Landscape

PubMed Central

Miller, Joshua H.

2011-01-01

Natural accumulations of skeletal material (death assemblages) have the potential to provide historical data on species diversity and population structure for regions lacking decades of wildlife monitoring, thereby contributing valuable baseline data for conservation and management strategies. Previous studies of the ecological and temporal resolutions of death assemblages from terrestrial large-mammal communities, however, have largely focused on broad patterns of community composition in tropical settings. Here, I expand the environmental sampling of large-mammal death assemblages into a temperate biome and explore more demanding assessments of ecological fidelity by testing their capacity to record past population fluctuations of individual species in the well-studied ungulate community of Yellowstone National Park (Yellowstone). Despite dramatic ecological changes following the 1988 wildfires and 1995 wolf re-introduction, the Yellowstone death assemblage is highly faithful to the living community in species richness and community structure. These results agree with studies of tropical death assemblages and establish the broad capability of vertebrate remains to provide high-quality ecological data from disparate ecosystems and biomes. Importantly, the Yellowstone death assemblage also correctly identifies species that changed significantly in abundance over the last 20 to ∼80 years and the directions of those shifts (including local invasions and extinctions). The relative frequency of fresh versus weathered bones for individual species is also consistent with documented trends in living population sizes. Radiocarbon dating verifies the historical source of bones from Equus caballus (horse): a functionally extinct species. Bone surveys are a broadly valuable tool for obtaining population trends and baseline shifts over decadal-to-centennial timescales. PMID:21464921

Inflammatory Pseudotumor of the Temporal Bone: A Case Series.

PubMed

Ortlip, Timothy E; Drake, Virginia E; Raghavan, Prashant; Papadimitriou, John C; Porter, Neil C; Eisenman, David J; Hertzano, Ronna

2017-08-01

Inflammatory pseudotumor of the temporal bone is a benign, idiopathic inflammatory process that is locally invasive and a cause of significant morbidity. This study reviews our experience with seven patients and is currently the largest series to date. Retrospective review from January 1, 2014 to January 1, 2016. Single tertiary medical center. There were five male and two female (n = 7) subjects with a diagnosis of temporal bone inflammatory pseudotumor. The mean age at presentation was 41 years old. The most common presenting symptoms were hearing loss (7/7) and headache (4/7). Four patients demonstrated an inflammatory aural polyp. Two patients experienced facial nerve paralysis. Seven patients underwent computed tomography and six underwent magnetic resonance imaging. Corticosteroids and antibiotics were the initial treatment of choice. Five patients also underwent surgery. As adjuvant therapy, two patients received Rituximab, one patient received radiation, and one received mycophenolate mofetil. Clinical courses were followed with focus on symptoms, disease recurrence, duration, and treatment. Mean follow-up was 17.8 months. The primary lesions demonstrated T2 hypo-intensity and enhancement as well as diffuse dural thickening on magnetic resonance imaging in five of six patients. Histopathology demonstrated chronic inflammation in the setting of hyalinized fibrosis (7/7). All the patients are currently symptomatically stable. Inflammatory pseudotumor of the temporal bone can cause devastating effects on neurological function and quality of life. Recognition of characteristic imaging and histopathology can expedite appropriate treatment. Patients may require chronic steroid therapy. Adjunctive therapy with radiation and immuno-modulation are currently being explored.

Skeletal robustness and bone strength as measured by anthropometry and ultrasonography as a function of physical activity in young adults.

PubMed

Scheffler, Christiane; Gniosdorz, Birgit; Staub, Kaspar; Rühli, Frank

2014-01-01

During the last 10 years, skeletal robustness in children has generally decreased. The reasons for this phenomenon, as well as its outcomes, are undetermined so far. The present study explores the association between anthropometric skeletal measurements, bone quality measurements, and physical activity in young adults. 118 German young men (N = 68; 19-25 years old) and women (N = 50; 19-24 years old) were investigated by anthropometric methods (i.e., height, weight, shoulder, elbow breadth, and pelvic breadth) and quantitative ultrasound measurement (QUS). Strength and stability of Os calcis have been determined by speed of sound (in m/s) and broadband ultrasound attenuation (in dB/Mhz); individual physical activity was analyzed by a pedometer and by questionnaire. The results show a correlation between sports hours per week and bone quality index in males. But no correlation exists between anthropometric data and QUSs for either sexes, as well as no correlation between total steps per day and internal bone quality or external bone dimensions. These results are discussed in the context of generally decreasing physical activity, the outcomes of prevention programs as well as evolutionary adaptation of human phenotypic plasticity in a changing environment. Copyright © 2014 Wiley Periodicals, Inc.

Effects on the torsional vibration behavior in the investigation of dental implant osseointegration using resonance frequency analysis: a numerical approach.

PubMed

Zhai, Min; Li, Bing; Li, Dehua

2017-09-01

Resonance frequency analysis (RFA) methods are widely used to assess implant stability, particularly the Osstell ® device. The potential effects associated with this method have been discussed in the literature. Torsional RFA (T-RFA), mentioned in our previous study, could represent a new measurement method. The purpose of this study was to simulate T-shaped and Osstell ® transducer-implant-bone system models; compare their vibration modes and corresponding resonance frequencies; and investigate the effects of their parameters, such as the effective implant length (EIL), bone quality, and osseointegration level, on the torsional resonance frequency (TRF) and bending resonance frequency (BRF) using three-dimensional finite element analysis. Following the finite element model validation, the TRFs and BRFs for three different EILs and four types of bone quality were obtained, and the change rates during 25 degrees of osseointegration were observed. The analysis showed that an increase in the EIL and a decrease in bone quality have less effect on the declination rate of TRFs than on that of BRFs. TRFs are highly sensitive to the stiffness of the implant-bone interface during the healing period. It was concluded that T-RFA has better sensitivity and specificity.

Effect of type 2 diabetes-related non-enzymatic glycation on bone biomechanical properties

PubMed Central

Karim, Lamya; Bouxsein, Mary L.

2015-01-01

There is clear evidence that patients with type 2 diabetes mellitus (T2D) have increased fracture risk, despite having high bone mineral density (BMD) and body mass index (BMI). Thus, poor bone quality has been implicated as a mechanism contributing to diabetic skeletal fragility. Poor bone quality in T2D may result from the accumulation of advanced glycation end-products (AGEs), which are post-translational modifications of collagen resulting from a spontaneous reaction between extracellular sugars and amino acid residues on collagen fibers. This review discusses what is known and what is not known regarding AGE accumulation and diabetic skeletal fragility, examining evidence from in vitro experiments to simulate a diabetic state, ex vivo studies in normal and diabetic human bone, and diabetic animal models. Key findings in the literature are that AGEs increase with age, affect bone cell behavior, and are altered with changes in bone turnover. Further, they affect bone mechanical properties and microdamage accumulation, and can be inhibited in vitro by various inhibitors and breakers (e.g. aminoguanidine, N-Phenacylthiazolium Bromide, vitamin B6). While a few studies report higher AGEs in diabetic animal models, there is little evidence of AGE accumulation in bone from diabetic patients. There are several limitations and inconsistencies in the literature that should be noted and studied in greater depth including understanding the discrepancies between glycation levels across reported studies, clarifying differences in AGEs in cortical versus cancellous bone, and improving the very limited data available regarding glycation content in diabetic animal and human bone, and its corresponding effect on bone material properties in T2D. PMID:26211993

Qualitative evaluation of titanium implant integration into bone by diffraction enhanced imaging.

PubMed

Wagner, A; Sachse, A; Keller, M; Aurich, M; Wetzel, W-D; Hortschansky, P; Schmuck, K; Lohmann, M; Reime, B; Metge, J; Arfelli, F; Menk, R; Rigon, L; Muehleman, C; Bravin, A; Coan, P; Mollenhauer, J

2006-03-07

Diffraction enhanced imaging (DEI) uses refraction of x-rays at edges, which allows pronounced visualization of material borders and rejects scattering which often obscures edges and blurs images. Here, the first evidence is presented that, using DEI, a destruction-free evaluation of the quality of integration of metal implants into bone is possible. Experiments were performed in rabbits and sheep with model implants to investigate the option for DEI as a tool in implant research. The results obtained from DEI were compared to conventional histology obtained from the specimens. DE images allow the identification of the quality of ingrowth of bone into the hydroxyapatite layer of the implant. Incomplete integration of the implant with a remaining gap of less than 0.3 mm caused the presence of a highly refractive edge at the implant/bone border. In contrast, implants with bone fully grown onto the surface did not display a refractive signal. Therefore, the refractive signal could be utilized to diagnose implant healing and/or loosening.

Qualitative evaluation of titanium implant integration into bone by diffraction enhanced imaging

NASA Astrophysics Data System (ADS)

Wagner, A.; Sachse, A.; Keller, M.; Aurich, M.; Wetzel, W.-D.; Hortschansky, P.; Schmuck, K.; Lohmann, M.; Reime, B.; Metge, J.; Arfelli, F.; Menk, R.; Rigon, L.; Muehleman, C.; Bravin, A.; Coan, P.; Mollenhauer, J.

2006-03-01

Diffraction enhanced imaging (DEI) uses refraction of x-rays at edges, which allows pronounced visualization of material borders and rejects scattering which often obscures edges and blurs images. Here, the first evidence is presented that, using DEI, a destruction-free evaluation of the quality of integration of metal implants into bone is possible. Experiments were performed in rabbits and sheep with model implants to investigate the option for DEI as a tool in implant research. The results obtained from DEI were compared to conventional histology obtained from the specimens. DE images allow the identification of the quality of ingrowth of bone into the hydroxyapatite layer of the implant. Incomplete integration of the implant with a remaining gap of less than 0.3 mm caused the presence of a highly refractive edge at the implant/bone border. In contrast, implants with bone fully grown onto the surface did not display a refractive signal. Therefore, the refractive signal could be utilized to diagnose implant healing and/or loosening.

Mechanical Unloading of Mouse Bone in Microgravity Significantly Alters Cell Cycle Gene Set Expression

NASA Astrophysics Data System (ADS)

Blaber, Elizabeth; Dvorochkin, Natalya; Almeida, Eduardo; Kaplan, Warren; Burns, Brnedan

2012-07-01

Spaceflight factors, including microgravity and space radiation, have many detrimental short-term effects on human physiology, including muscle and bone degradation, and immune system dysfunction. The long-term progression of these physiological effects is still poorly understood, and a serious concern for long duration spaceflight missions. We hypothesized that some of the degenerative effects of spaceflight may be caused in part by an inability of stem cells to proliferate and differentiate normally resulting in an impairment of tissue regenerative processes. Furthermore, we hypothesized that long-term bone tissue degeneration in space may be mediated by activation of the p53 signaling network resulting in cell cycle arrest and/or apoptosis in osteoprogenitors. In our analyses we found that spaceflight caused significant bone loss in the weight-bearing bones of mice with a 6.3% reduction in bone volume and 11.9% decrease in bone thickness associated with increased osteoclastic activity. Along with this rapid bone loss we also observed alterations in the cell cycle characterized by an increase in the Cdkn1a/p21 cell cycle arrest molecule independent of Trp53. Overexpression of Cdkn1a/p21 was localized to osteoblasts lining the periosteal surface of the femur and chondrocytes in the head of the femur, suggesting an inhibition of proliferation in two key regenerative cell types of the femur in response to spaceflight. Additionally we found overexpression of several matrix degradation molecules including MMP-1a, 3 and 10, of which MMP-10 was localized to osteocytes within the shaft of the femur. This, in conjunction with 40 nm resolution synchrotron nano-Computed Tomography (nano-CT) observations of an increase in osteocyte lacunae cross-sectional area, perimeter and a decrease in circularity indicates a potential role for osteocytic osteolysis in the observed bone degeneration in spaceflight. To further investigate the genetic response of bone to mechanical unloading in spaceflight, we conducted genome wide microarray analysis of total RNA isolated from the mouse pelvis. Specifically, 16 week old mice were subjected to 15 days spaceflight onboard NASA's STS-131 space shuttle mission. The pelvis of the mice was dissected, the bone marrow was flushed and the bones were briefly stored in RNAlater. The pelvii were then homogenized, and RNA was isolated using TRIzol. RNA concentration and quality was measured using a Nanodrop spectrometer, and 0.8% agarose gel electrophoresis. Samples of cDNA were analyzed using an Affymetrix GeneChip\\S Gene 1.0 ST (Sense Target) Array System for Mouse and GenePattern Software. We normalized the ST gene arrays using Robust Multichip Average (RMA) normalization, which summarizes perfectly matched spots on the array through the median polish algorithm, rather than normalizing according to mismatched spots. We also used Limma for statistical analysis, using the BioConductor Limma Library by Gordon Smyth, and differential expression analysis to identify genes with significant changes in expression between the two experimental conditions. Finally we used GSEApreRanked for Gene Set Enrichment Analysis (GSEA), with Kolmogorov-Smirnov style statistics to identify groups of genes that are regulated together using the t-statistics derived from Limma. Preliminary results show that 6,603 genes expressed in pelvic bone had statistically significant alterations in spaceflight compared to ground controls. These prominently included cell cycle arrest molecules p21, and p18, cell survival molecule Crbp1, and cell cycle molecules cyclin D1, and Cdk1. Additionally, GSEA results indicated alterations in molecular targets of cyclin D1 and Cdk4, senescence pathways resulting from abnormal laminin maturation, cell-cell contacts via E-cadherin, and several pathways relating to protein translation and metabolism. In total 111 gene sets out of 2,488, about 4%, showed statistically significant set alterations. These alterations indicate significant impairment of normal cellular function in the mechanically unloaded environment of space and could provide important genetic insight into the observed uncoupling of bone formation and resorption in space.

The effect of implant design and bone quality on insertion torque, resonance frequency analysis, and insertion energy during implant placement in low or low- to medium-density bone.

PubMed

Wang, Tong-Mei; Lee, Ming-Shu; Wang, Juo-Song; Lin, Li-Deh

2015-01-01

This study investigated the effect of implant design and bone quality on insertion torque (IT), implant stability quotient (ISQ), and insertion energy (IE) by monitoring the continuous change in IT and ISQ while implants were inserted in artificial bone blocks that simulate bone of poor or poor-to-medium quality. Polyurethane foam blocks (Sawbones) of 0.16 g/cm³ and 0.32 g/cm³ were respectively used to simulate low density and low- to medium-density cancellous bone. In addition, some test blocks were laminated with a 1-mm 0.80 g/cm³ polyurethane layer to simulate cancellous bone with a thin cortical layer. Four different implants (Nobel Biocare Mk III-3.75, Mk III-4.0, Mk IV-4.0, and NobelActive-4.3) were placed into the different test blocks in accordance with the manufacturer's instructions. The IT and ISQ were recorded at every 0.5-mm of inserted length during implant insertion, and IE was calculated from the torque curve. The peak IT (PIT), final IT (FIT), IE, and final ISQ values were statistically analyzed. All implants showed increasing ISQ values when the implant was inserted more deeply. In contrast to the ISQ, implants with different designs showed dissimilar IT curve patterns during the insertion. All implants showed a significant increase in the PIT, FIT, IE, and ISQ when the test-block density increased or when the 1-mm laminated layer was present. Tapered implants showed FIT or PIT values of more than 40 Ncm for all of the laminated test blocks and for the nonlaminated test blocks of low to medium density. Parallel-wall implants did not exhibit PIT or FIT values of more than 40 Ncm for all of the test blocks. NobelActive-4.3 showed a significantly higher FIT, but a significantly lower IE, than Mk IV-4.0. While the existence of cortical bone or implant designs significantly affects the dynamic IT profiles during implant insertion, it does not affect the ISQ to a similar extent. Certain implant designs are more suitable than others if high IT is required in bone of poor quality. The manner in which IT, IE, and ISQ represent the implant primary stability requires further study.