Search

Current clinical methods of bone health assessment depend to a great extent on bone mineral density (BMD) measurements. However, these methods only act as a proxy for bone strength and are often only carried out after the fracture occurs. Besides BMD, composition and tissue-level mechanical properties are expected to affect the whole bone's strength and toughness. While the elastic properties of the bone extracellular matrix (ECM) have been extensively investigated over the past two decades, there is still limited knowledge of the yield properties and their relationship to composition and architecture. In the present study, morphological, compositional and micropillar compression bone data was collected from patients who underwent hip arthroplasty. Femoral neck samples from 42 patients were collected together with anonymous clinical information about age, sex and primary diagnosis (coxarthrosis or hip fracture). The femoral neck cortex from the inferomedial region was analyzed in a site-matched manner using a combination of micromechanical testing (nanoindentation, micropillar compression) together with micro-CT and quantitative polarized Raman spectroscopy for both morphological and compositional characterization. Mechanical properties, as well as the sample-level mineral density, were constant over age. Only compositional properties demonstrate weak dependence on patient age: decreasing mineral to matrix ratio (p = 0.02, R 2  = 0.13, 2.6 % per decade) and increasing amide I sub-peak ratio I ∼ 1660 (p = 0.04, R ∼  = 0.11, 1.5 % per decade). The patient's sex and diagnosis did not seem to influence investigated bone properties. A clear zonal dependence between interstitial and osteonal cortical zones was observed for compositional and elastic bone properties (p < 0.0001). Site-matched microscale analysis confirmed that all investigated mechanical properties except yield strain demonstrate a positive correlation with the mineral fraction of bone. The output database is the first to integrate the experimentally assessed microscale yield properties, local tissue composition and morphology with the available patient clinical information. The final dataset was used for bone fracture risk prediction in-silico through the principal component analysis and the Naïve Bayes classification algorithm. The analysis showed that the mineral to matrix ratio, indentation hardness and micropillar yield stress are the most relevant parameters for bone fracture risk prediction at 70 % model accuracy (0.71 AUC). Due to the low number of samples, further studies to build a universal fracture prediction algorithm are anticipated with the higher number of patients (N > 200). The proposed classification algorithm together with the output dataset of bone tissue properties can be used for the future comparison of existing methods to evaluate bone quality as well as to form a better understanding of the mechanisms through which bone tissue is affected by aging or disease.1683 (p = 0.04, R 2  = 0.11, 1.5 % per decade). The patient's sex and diagnosis did not seem to influence investigated bone properties. A clear zonal dependence between interstitial and osteonal cortical zones was observed for compositional and elastic bone properties (p < 0.0001). Site-matched microscale analysis confirmed that all investigated mechanical properties except yield strain demonstrate a positive correlation with the mineral fraction of bone. The output database is the first to integrate the experimentally assessed microscale yield properties, local tissue composition and morphology with the available patient clinical information. The final dataset was used for bone fracture risk prediction in-silico through the principal component analysis and the Naïve Bayes classification algorithm. The analysis showed that the mineral to matrix ratio, indentation hardness and micropillar yield stress are the most relevant parameters for bone fracture risk prediction at 70 % model accuracy (0.71 AUC). Due to the low number of samples, further studies to build a universal fracture prediction algorithm are anticipated with the higher number of patients (N > 200). The proposed classification algorithm together with the output dataset of bone tissue properties can be used for the future comparison of existing methods to evaluate bone quality as well as to form a better understanding of the mechanisms through which bone tissue is affected by aging or disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Recent applications of high-resolution peripheral quantitative computed tomography (HR-pQCT) have demonstrated that changes in local bone remodelling can be quantified in vivo using longitudinal three-dimensional image registration. However, certain emerging applications, such as fracture healing and joint analysis, require larger multi-stack scan regions that can result in stack shift image artifacts. These artifacts can be detrimental to the accurate alignment of the bone structure across multiple timepoints. The purpose of this study was to establish a multi-stack registration protocol for evaluating longitudinal HR-pQCT images and to assess the accuracy and precision error in comparison with measures obtained using previously established three-dimensional longitudinal registration., Methods: Three same day multi-stack HR-pQCT scans of the radius (2 stacks in length) and tibia (3 stacks in length) were obtained from 39 healthy individuals who participated in a previous reproducibility study. A fully automated multi-stack registration algorithm was developed to re-align stacks within a scan by leveraging slight offsets between longitudinal scans. Stack shift severity before and after registration was quantified using a newly proposed stack-shift severity score. The false discovery rate for bone remodelling events and precision error of bone morphology and micro-finite element analysis parameters were compared between longitudinally registered scans with and without the addition of multi-stack registration., Results: Most scans (82 %) improved in stack alignment or maintained the lowest stack shift severity score when multi-stack registration was implemented. The false discovery rate of bone remodelling events significantly decreased after multi-stack registration, resulting in median false detection of bone formation and resorption fractions between 3.2 to 7.5 % at the radius and 3.4 to 5.3 % at the tibia. Further, precision error was significantly reduced or remained unchanged in all standard bone morphology and micro-finite element analysis parameters, except for total and trabecular cross-sectional areas., Conclusion: Multi-stack registration is an effective strategy for accurately aligning multi-stack HR-pQCT scans without modification of the image acquisition protocol. The algorithm presented here is a viable approach for performing accurate morphological analysis on multi-stack HR-pQCT scans, particularly for advanced application investigating local bone remodelling in vivo., Competing Interests: Declaration of competing interest The authors declare they have no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Local mechanical stimuli in the bone microenvironment are essential for the homeostasis and adaptation of the skeleton, with evidence suggesting that disruption of the mechanically-driven bone remodelling process may lead to bone loss. Longitudinal clinical studies have shown the combined use of high-resolution peripheral quantitative computed tomography (HR-pQCT) and micro-finite element analysis can be used to measure load-driven bone remodelling in vivo; however, quantitative markers of bone mechanoregulation and the precision of these analyses methods have not been validated in human subjects. Therefore, this study utilised participants from two cohorts. A same-day cohort (n = 33) was used to develop a filtering strategy to minimise false detections of bone remodelling sites caused by noise and motion artefacts present in HR-pQCT scans. A longitudinal cohort (n = 19) was used to develop bone imaging markers of trabecular bone mechanoregulation and characterise the precision for detecting longitudinal changes in subjects. Specifically, we described local load-driven formation and resorption sites independently using patient-specific odds ratios (OR) and 99 % confidence intervals. Conditional probability curves were computed to link the mechanical environment to the remodelling events detected on the bone surface. To quantify overall mechanoregulation, we calculated a correct classification rate measuring the fraction of remodelling events correctly identified by the mechanical signal. Precision was calculated as root-mean-squared averages of the coefficient of variation (RMS-SD) of repeated measurements using scan-rescan pairs at baseline combined with a one-year follow-up scan. We found no significant mean difference (p < 0.01) between scan-rescan conditional probabilities. RMS-SD was 10.5 % for resorption odds, 6.3 % for formation odds, and 1.3 % for correct classification rates. Bone was most likely to be formed in high-strain and resorbed in low-strain regions for all participants, indicating a consistent, regulated response to mechanical stimuli. For each percent increase in strain, the likelihood of bone resorption decreased by 2.0 ± 0.2 %, and the likelihood of bone formation increased by 1.9 ± 0.2 %, totalling 38.3 ± 1.1 % of strain-driven remodelling events across the entire trabecular compartment. This work provides novel robust bone mechanoregulation markers and their precision for designing future clinical studies., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Osteogenesis Imperfecta (OI) is an inherited form of bone fragility characterised by impaired synthesis of type I collagen, altered trabecular bone architecture and reduced bone mass. High resolution peripheral computed tomography (HR-pQCT) is a powerful method to investigate bone morphology at peripheral sites including the weight-bearing distal tibia. The resulting 3D reconstructions can be used as a basis of micro-finite element (FE) or homogenized finite element (hFE) models for bone strength estimation. The hFE scheme uses homogenized local bone volume fraction (BV/TV) and anisotropy information (fabric) to compute healthy bone strength within a reasonable computation time using fabric-elasticity relationships. However, it is unclear if these relationships quantified previously for healthy controls are valid for trabecular bone from OI patients. Thus, the aim of this study is to investigate fabric-elasticity relationships in OI trabecular bone compared to healthy controls. In the present study, the morphology of distal tibiae from 50 adults with OI were compared to 120 healthy controls using second generation HR-pQCT. Six cubic regions of interest (ROIs) were selected per individual in a common anatomical region. A first matching between OI and healthy control group was performed by selecting similar individuals to obtain identical mean and median age and sex distribution. It allowed us to perform a first morphometric analysis and compare the outcome with literature. Then, stiffness tensors of the ROIs were computed using μFE and multiple linear regressions were performed with the Zysset-Curnier orthotropic fabric-elasticity model. An initial fit was performed on both the OI group and the healthy control group using all extracted ROIs. Then, data was filtered according to a fixed threshold for a defined coefficient of variation (CV) assessing ROI heterogeneity and additional linear regressions were performed on these filtered data sets. These full and filtered data were in turn compared with previous results from μCT reconstructions obtained in other anatomical locations. Finally, the ROIs of both groups were matched according to their BV/TV and degree of anisotropy (DA). Linear regressions were performed using these matched data to detect statistical differences between the two groups. Compared to healthy controls, we found the OI samples to have significantly lower BV/TV and trabecular number (Tb.N.), significantly higher CV, trabecular separation (Tb.Sp.) and trabecular separation standard deviation (Tb.Sp.SD), but no differences in trabecular thickness (Tb.Th.). These results are in agreement with previous studies. The stiffnesses of highly heterogeneous ROIs were randomly lower with respect to the fabric-elasticity relationships, which reflects the limit of validity of the computational homogenisation methodology. This limitation does not challenge the fabric-elasticity relationship, which extrapolation to heterogeneous ROIs is probably reasonable but can simply not be evaluated with the employed homogenisation methodology. Moreover, due to their low BV/TV, the potential (unknown) errors on these heterogeneous ROIs would have negligible influence on whole bone stiffness in comparison to homogeneous ROIs which are orders of magnitude stiffer. The filtering of highly heterogeneous ROIs removed these low stiffness ROIs and led to similar correlation coefficients for both OI and healthy groups. Finally, the BV/TV and DA matched data revealed no significant differences in fabric-elasticity parameters between OI and healthy individuals. Moreover, the filtering step did not exclude a particular OI type. Compared to previous studies, the stiffness constants from the 61 μm resolution HR-pQCT ROIs were lower than for the 36 μm resolution μCT ROIs. In conclusion, OI trabecular bone of the distal tibia was shown to be significantly more heterogeneous and have a lower BV/TV than healthy controls. Despite the reduced linear regression parameters found for HR-pQCT images, the fabric-elasticity relationships between OI and healthy individuals are similar when the trabecular bone ROIs are sufficiently homogeneous to perform the computational stiffness analysis. Accordingly, the elastic properties used for FEA of healthy bones are also valid for OI bones., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Micro finite element analysis (μFE) is a widely applied tool in biomedical research for assessing in vivo mechanical properties of bone at measurement sites, including the ultra-distal radius and tibia. A finite element approach (hFE) based on homogenized constitutive models for trabecular bone offers an attractive alternative for clinical use, as it is computationally less expensive than traditional μFE. The respective patient-specific models for in vivo bone strength estimation are usually based on standard clinical high-resolution peripheral quantitative CT (HR-pQCT) measurements. They include a scan region of roughly 10 mm in height and are referred to as single-sections. It has been shown, that these small peripheral bone sections don't reliably cover the fracture line in Colles' fractures and therefore the weakest region at the radius. Recently introduced multiple section (multiple adjacent single-sections) measurements might improve the evaluation of bone strength, but little is known about the repeatability of hFE estimations in general, and especially for multiple section measurement protocols. Accordingly, the aim of the present work is to quantify repeatability of clinical in vivo bone strength measurement by hFE on multiple section HR-pQCT reconstructions at the distal radius and tibia., Methods: Nineteen healthy Swiss women (43.6y ± 17.8y) and twenty men (48.2y ± 19.4y) were examined with HR-pQCT at 61 μm isotropic voxel resolution. Each subject was first scanned three times using a double-section (336 slices) at the distal radius and then three times using a triple-section (504 slices) at the distal tibia. The multiple section HR-pQCT reconstructions were graded for motion artefacts and non-linear hFE models (radius and tibia) and linear μFE models (only radius) were generated for estimation of stiffness and ultimate load. Then in vivo repeatability errors were computed in terms of root mean square coefficients of variation (CV)., Results: In vivo repeatability errors of non-linear hFE stiffness (S) and ultimate load (F) were significantly higher at the radius (S: 2.71% and F: 2.97%) compared to the tibia (S: 1.21%, F: 1.45%). Multiple section linear μFE at the radius resulted in substantially higher repeatability errors (S: 5.38% and F: 10.80%) compared to hFE., Discussion/conclusion: Repeatability errors of hFE outcomes based on multiple section measurements at the distal radius and tibia were generally lower compared to respective reported single-section μFE repeatability errors. Therefore, hFE is an attractive alternative to today's gold standard of μFE models and should especially be encouraged when analyzing multiple section measurements., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Including structural information of trabecular bone improves the prediction of bone strength and fracture risk. However, this information is available in clinical CT scans, only for peripheral bones. We hypothesized that a correlation exists between the shape of the bone, its volume fraction (BV/TV) and fabric, which could be characterized using statistical modeling. High-resolution peripheral computed tomography (HR-pQCT) images of 73 proximal femurs were used to build a combined statistical model of shape, BV/TV and fabric. The model was based on correspondence established by image registration and by morphing of a finite element mesh describing the spatial distribution of the bone properties. Results showed no correlation between the distribution of bone shape, BV/TV and fabric. Only the first mode of variation associated with density and orientation showed a strong relationship (R 2 >0.8). In addition, the model showed that the anisotropic information of the proximal femur does not vary significantly in a population of healthy, osteoporotic and osteopenic samples. In our dataset, the average anisotropy of the population was able to provide a close approximation of the patient-specific anisotropy. These results were confirmed by homogenized finite element (hFE) analyses, which showed that the biomechanical behavior of the proximal femur was not significantly different when the average anisotropic information of the population was used instead of patient-specific fabric extracted from HR-pQCT. Based on these findings, it can be assumed that the fabric information of the proximal femur follows a similar structure in an elderly population of healthy, osteopenic and osteoporotic proximal femurs., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Current homogenized finite element (hFE) models of the patella lack a validated material law and mostly overlook trabecular anisotropy. The objective of this study was to identify the elastic constants of patellar trabecular bone. Using μCT scans of 20 fresh-frozen cadaveric patellae, we virtually extracted 200 trabecular cubes (5.3mm side length). Bone volume fraction and fabric tensor were measured. The elastic constants were identified from six independent load cases using micro finite element (μFE) analyses. Both anisotropic and isotropic material laws were considered. The elastic constants were validated by comparing stiffness, strain and stress between hFE and μFE predictions of 18 patellar sections and six load cases. The hFE section models were built from μCT (anisotropic law) and CT (isotropic law) scans. The homogenized anisotropic model induced less error (13±5%) in the global stiffness prediction than the isotropic one (18±6%), and less error in the prediction of local apparent strain, stress, and strain energy, compared to the isotropic one. This validated hFE model could be used for future applications, either with the anisotropic constants, or with the isotropic ones when the trabecular fabric is unavailable., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Trans-olecranon chevron osteotomies (COs) remain the gold standard surgical approach to type C fractures of the distal humerus. This technique is associated with a high complication rate and development of an extra-articular olecranon osteotomy may be advantageous. The aim of this study was to compare the load to failure of COs with extra-articular oblique osteotomies (OOs) as well as modified, extra-articular step osteotomies (SOs)., Methods: These three osteotomies and their subsequent fixation utilizing a standardized tension band wiring technique were tested in 42 composite analog ulnae models at 20° and 70° of flexion. Triceps loading was simulated with a servo hydraulic testing machine. All specimens were isometrically loaded until failure. Kinematic and force data, as well as interfragmentary motion were recorded., Results: At 70°, CO failed at a mean load of 963 N (SD 104 N), the OO at 1512 N (SD 208 N) and the SO at 1484 N (SD 153 N), (P<0.001). At 20°, CO failed at a mean load of 707 N (SD 104 N) and OO at 1009 N (SD 85 N) (P=0.006). The highest load to failure was observed for the SO, which was 1277 N (SD 172 N). The load to failure of the SO was significantly higher than the CO as well as the OO., Conclusion: Extra-articular osteotomies showed a significantly higher load to failure in comparison to traditional CO. At near full extension (20° of flexion), this biomechanical advantage was further enhanced by a step-cut modification of the extra-articular oblique osteotomy., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Denosumab reduced the incidence of new fractures in postmenopausal women with osteoporosis by 68% at the spine and 40% at the hip over 36 months compared with placebo in the FREEDOM study. This efficacy was supported by improvements from baseline in vertebral (18.2%) strength in axial compression and femoral (8.6%) strength in sideways fall configuration at 36 months, estimated in Newtons by an established voxel-based finite element (FE) methodology. Since FE analyses rely on the choice of meshes, material properties, and boundary conditions, the aim of this study was to independently confirm and compare the effects of denosumab on vertebral and femoral strength during the FREEDOM trial using an alternative smooth FE methodology. Unlike the previous FE study, effects on femoral strength in physiological stance configuration were also examined. QCT data for the proximal femur and two lumbar vertebrae were analyzed by smooth FE methodology at baseline, 12, 24, and 36 months for 51 treated (denosumab) and 47 control (placebo) subjects. QCT images were segmented and converted into smooth FE models to compute bone strength. L1 and L2 vertebral bodies were virtually loaded in axial compression and the proximal femora in both fall and stance configurations. Denosumab increased vertebral body strength by 10.8%, 14.0%, and 17.4% from baseline at 12, 24, and 36 months, respectively (p<0.0001). Denosumab also increased femoral strength in the fall configuration by 4.3%, 5.1%, and 7.2% from baseline at 12, 24, and 36 months, respectively (p<0.0001). Similar improvements were observed in the stance configuration with increases of 4.2%, 5.2%, and 5.2% from baseline (p≤0.0007). Differences between the increasing strengths with denosumab and the decreasing strengths with placebo were significant starting at 12 months (vertebral and femoral fall) or 24 months (femoral stance). Using an alternative smooth FE methodology, we confirmed the significant improvements in vertebral body and proximal femur strength previously observed with denosumab. Estimated increases in strength with denosumab and decreases with placebo were highly consistent between both FE techniques., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Microindentation in bone is a micromechanical testing technique routinely used to extract material properties related to bone quality. As the analysis of microindentation data is based on assumptions about the contact between sample and surface, the aim of this study was to quantify the topological variability of indentations in bone and examine its relationship with mechanical properties. Indentations were performed in dry human and ovine bone in axial and transverse directions and their topology was measured by atomic force microscopy. Statistical shape modeling of the residual imprint allowed to define a mean shape and to describe the variability in terms of 21 principal components related to imprint depth, surface curvature and roughness. The indentation profile of bone was found to be highly consistent and free of any pile up while differing mostly by depth between species and direction. A few of the topological parameters, in particular depth, showed significant but rather weak and inconsistent correlations to variations in mechanical properties. The mechanical response of bone as well as the residual imprint shape was highly consistent within each category. We could thus verify that bone is rather homogeneous in its micromechanical properties and that indentation results are not strongly influenced by small deviations from an ideally flat surface., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Quantitative computer tomography (QCT)-based finite element (FE) models of vertebral body provide better prediction of vertebral strength than dual energy X-ray absorptiometry. However, most models were validated against compression of vertebral bodies with endplates embedded in polymethylmethalcrylate (PMMA). Yet, loading being as important as bone density, the absence of intervertebral disc (IVD) affects the strength. Accordingly, the aim was to assess the strength predictions of the classic FE models (vertebral body embedded) against the in vitro and in silico strengths of vertebral bodies loaded via IVDs. High resolution peripheral QCT (HR-pQCT) were performed on 13 segments (T11/T12/L1). T11 and L1 were augmented with PMMA and the samples were tested under a 4° wedge compression until failure of T12. Specimen-specific model was generated for each T12 from the HR-pQCT data. Two FE sets were created: FE-PMMA refers to the classical vertebral body embedded model under axial compression; FE-IVD to their loading via hyperelastic IVD model under the wedge compression as conducted experimentally. Results showed that FE-PMMA models overestimated the experimental strength and their strength prediction was satisfactory considering the different experimental set-up. On the other hand, the FE-IVD models did not prove significantly better (Exp/FE-PMMA: R²=0.68; Exp/FE-IVD: R²=0.71, p=0.84). In conclusion, FE-PMMA correlates well with in vitro strength of human vertebral bodies loaded via real IVDs and FE-IVD with hyperelastic IVDs do not significantly improve this correlation. Therefore, it seems not worth adding the IVDs to vertebral body models until fully validated patient-specific IVD models become available., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Cathepsin S is a cysteine protease that controls adipocyte differentiation and has been implicated in vascular and metabolic complications of obesity. Considering the inverse relation of osteoblasts and adipocytes and their mutual precursor cell, we hypothesized that cathepsin S may also affect osteoblast differentiation and bone remodeling. Thus, the fat and bone phenotypes of young (3 months old) and aged (12 or 18 months old) cathepsin S knock-out (KO) and wild-type (WT) mice were determined. Cathepsin S KO mice had a normal body weight at both ages investigated, even though the amount of subscapular and gonadal fat pads was reduced by 20%. Further, cathepsin S deficiency impaired adipocyte formation (-38%, p<0.001), which was accompanied by a lower expression of adipocyte-related genes and a reduction in serum leptin, IL-6 and CCL2 (p<0.001). Micro-CT analysis revealed an unchanged trabecular bone volume fraction and density, while tissue mineral density was significantly lower in cathepsin S KO mice at both ages. Aged KO mice further had a lower cortical bone mass (-2.3%, p<0.05). At the microarchitectural level, cathepsin S KO mice had thinner trabeculae (-8.3%), but a better connected trabecular network (+24%). Serum levels of the bone formation marker type 1 procollagen amino-terminal-propeptide and osteocalcin were both 2-3-fold higher in cathepsin S KO mice as was the mineralized surface. Consistently, osteogenic differentiation was increased 2-fold along with an increased expression of osteoblast-specific genes. Interestingly, serum levels of C-terminal telopeptide of type I collagen were also higher (+43%) in cathepsin S KO mice as were histological osteoclast parameters and ex vivo osteoclast differentiation. Thus, cathepsin S deficiency alters the balance between adipocyte and osteoblast differentiation, increases bone turnover, and changes bone microarchitecture. Therefore, bone and fat metabolisms should be monitored when using cathepsin S inhibitors clinically., (Copyright © 2014 Elsevier Inc. All rights reserved.)

High-resolution quantitative computed tomography (HRQCT)-based analysis of spinal bone density and microstructure, finite element analysis (FEA), and DXA were used to investigate the vertebral bone status of men with glucocorticoid-induced osteoporosis (GIO). DXA of L1-L3 and total hip, QCT of L1-L3, and HRQCT of T12 were available for 73 men (54.6±14.0years) with GIO. Prevalent vertebral fracture status was evaluated on radiographs using a semi-quantitative (SQ) score (normal=0 to severe fracture=3), and the spinal deformity index (SDI) score (sum of SQ scores of T4 to L4 vertebrae). Thirty-one (42.4%) subjects had prevalent vertebral fractures. Cortical BMD (Ct.BMD) and thickness (Ct.Th), trabecular BMD (Tb.BMD), apparent trabecular bone volume fraction (app.BV/TV), and apparent trabecular separation (app.Tb.Sp) were analyzed by HRQCT. Stiffness and strength of T12 were computed by HRQCT-based nonlinear FEA for axial compression, anterior bending and axial torsion. In logistic regressions adjusted for age, glucocorticoid dose and osteoporosis treatment, Tb.BMD was most closely associated with vertebral fracture status (standardized odds ratio [sOR]: Tb.BMD T12: 4.05 [95% CI: 1.8-9.0], Tb.BMD L1-L3: 3.95 [1.8-8.9]). Strength divided by cross-sectional area for axial compression showed the most significant association with spine fracture status among FEA variables (2.56 [1.29-5.07]). SDI was best predicted by a microstructural model using Ct.Th and app.Tb.Sp (r(2)=0.57, p<0.001). Spinal or hip DXA measurements did not show significant associations with fracture status or severity. In this cross-sectional study of males with GIO, QCT, HRQCT-based measurements and FEA variables were superior to DXA in discriminating between patients of differing prevalent vertebral fracture status. A microstructural model combining aspects of cortical and trabecular bone reflected fracture severity most accurately., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: Femoral fracture is a common medical problem in osteoporotic individuals. Bone mineral density (BMD) is the gold standard measure to evaluate fracture risk in vivo. Quantitative computed tomography (QCT)-based homogenized voxel finite element (hvFE) models have been proved to be more accurate predictors of femoral strength than BMD by adding geometrical and material properties. The aim of this study was to evaluate the ability of hvFE models in predicting femoral stiffness, strength and failure location for a large number of pairs of human femora tested in two different loading scenarios., Methods: Thirty-six pairs of femora were scanned with QCT and total proximal BMD and BMC were evaluated. For each pair, one femur was positioned in one-legged stance configuration (STANCE) and the other in a sideways configuration (SIDE). Nonlinear hvFE models were generated from QCT images by reproducing the same loading configurations imposed in the experiments. For experiments and models, the structural properties (stiffness and ultimate load), the failure location and the motion of the femoral head were computed and compared., Results: In both configurations, hvFE models predicted both stiffness (R(2)=0.82 for STANCE and R(2)=0.74 for SIDE) and femoral ultimate load (R(2)=0.80 for STANCE and R(2)=0.85 for SIDE) better than BMD and BMC. Moreover, the models predicted qualitatively well the failure location (66% of cases) and the motion of the femoral head., Conclusions: The subject specific QCT-based nonlinear hvFE model cannot only predict femoral apparent mechanical properties better than densitometric measures, but can additionally provide useful qualitative information about failure location., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Recently published compression tests on PMMA/bone specimens extracted after vertebral bone augmentation indicated that PMMA/bone composites were not reinforced by the trabecular bone at all. In this study, the reasons for this unexpected behavior should be investigated by using non-linear micro-FE models. Six human vertebral bodies were augmented with either standard or low-modulus PMMA cement and scanned with a HR-pQCT system before and after augmentation. Six cylindrical PMMA/bone specimens were extracted from the augmented region, scanned with a micro-CT system and tested in compression. Four different micro-FE models were generated from these images which showed different bone tissue material behavior (with/without damage), interface behavior (perfect bonding, frictionless contact) and PMMA shrinkage due to polymerization. The non-linear stress-strain curves were compared between the different micro-FE models as well as to the compression tests of the PMMA/bone specimens. Micro-FE models with contact between bone and cement were 20% more compliant compared to those with perfect bonding. PMMA shrinkage damaged the trabecular bone already before mechanical loading, which further reduced the initial stiffness by 24%. Progressing bone damage during compression dominated the non-linear part of the stress-strain curves. The micro-FE models including bone damage and PMMA shrinkage were in good agreement with the compression tests. The results were similar with both cements. In conclusion, the PMMA/bone interface properties as well as the initial bone damage due to PMMA polymerization shrinkage clearly affected the stress-strain behavior of the composite and explained why trabecular bone did not contribute to the stiffness and strength of augmented bone., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Bone mineral density and microarchitecture was found to predict 70-95% of bone strength. Microdamage, as factor of bone quality, might help to explain the remaining uncertainties. The goal of this study was to investigate whether microindentation can discriminate between intact and severely damaged human vertebral bone tissue in vitro. One portion from each human vertebral slice (N=35) tested in compression in a previous study was embedded, polished and tested in wet conditions by means of microindentation. The indentation moduli and hardness (HV) of trabecular, osteonal and interstitial bone structural units were computed along the cranio-caudal direction. Each indented region was defined as damaged or intact as seen under a light microscope. A total of 1190 indentations were performed. While both hardness and indentation modulus were independent from gender, both mechanical properties were affected by damage and microstructure. The damaged regions showed 50% lower stiffness and hardness compared to undamaged ones. Interstitial bone was stiffer and harder (13.2±4.4 GPa and 44.7±20.3 HV) than osteonal bone (10.9±3.8 GPa and 37.8±17.3 HV), which was stiffer and harder than trabecular bone (8.1±3.0 GPa and 28.8±11.2 HV) indented in the transverse direction. Moreover, along the axial direction intact trabecular bone (11.4±4.3 GPa) was 16% less stiff than the intact interstitial bone and as stiff as intact osteonal bone. In conclusion microindentation was found to discriminate between highly damaged and intact tissue in both trabecular and cortical bone tested in vitro. It remains to be investigated whether this technique would be able to detect also the damage, which is induced by physiological load in vivo., (Copyright © 2012 Elsevier Inc. All rights reserved.)

In the present study a rat animal model of lathyrism was employed to decipher whether anatomically confined alterations in collagen cross-links are sufficient to influence the mechanical properties of whole bone. Animal experiments were performed under an ethics committee approved protocol. Sixty-four female (47 day old) rats of equivalent weights were divided into four groups (16 per group): Controls were fed a semi-synthetic diet containing 0.6% calcium and 0.6% phosphorus for 2 or 4 weeks and β-APN treated animals were fed additionally with β-aminopropionitrile (0.1% dry weight). At the end of this period the rats in the four groups were sacrificed, and L2-L6 vertebra were collected. Collagen cross-links were determined by both biochemical and spectroscopic (Fourier transform infrared imaging (FTIRI)) analyses. Mineral content and distribution (BMDD) were determined by quantitative backscattered electron imaging (qBEI), and mineral maturity/crystallinity by FTIRI techniques. Micro-CT was used to describe the architectural properties. Mechanical performance of whole bone as well as of bone matrix material was tested by vertebral compression tests and by nano-indentation, respectively. The data of the present study indicate that β-APN treatment changed whole vertebra properties compared to non-treated rats, including collagen cross-links pattern, trabecular bone volume to tissue ratio and trabecular thickness, which were all decreased (p<0.05). Further, compression tests revealed a significant negative impact of β-APN treatment on maximal force to failure and energy to failure, while stiffness was not influenced. Bone mineral density distribution (BMDD) was not altered either. At the material level, β-APN treated rats exhibited increased Pyd/Divalent cross-link ratios in areas confined to a newly formed bone. Moreover, nano-indentation experiments showed that the E-modulus and hardness were reduced only in newly formed bone areas under the influence of β-APN, despite a similar mineral content. In conclusion the results emphasize the pivotal role of collagen cross-links in the determination of bone quality and mechanical integrity. However, in this rat animal model of lathyrism, the coupled alterations of tissue structural properties make it difficult to weigh the contribution of the anatomically confined material changes to the overall mechanical performance of whole bone. Interestingly, the collagen cross-link ratio in bone forming areas had the same profile as seen in actively bone forming trabecular surfaces in human iliac crest biopsies of osteoporotic patients., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Vertebroplasty forms a porous PMMA/bone composite which was shown to be weaker and less stiff than pure PMMA. It is not known what determines the mechanical properties of such composites in detail. This study investigated the effects of bone volume fraction (BV/TV), cement porosity (PV/(TV-BV), PV…pore volume) and cement stiffness. Nine human vertebral bodies were augmented with either standard or low-modulus PMMA cement and scanned with a HR-pQCT system before and after augmentation. Fourteen cylindrical PMMA/bone biopsies were extracted from the augmented region, scanned with a micro-CT system and tested in compression until failure. Micro-finite element (FE) models of the complete biopsies, of the trabecular bone alone as well as of the porous cement alone were generated from CT images to gain more insight into the role of bone and pores. PV/(TV-BV) and experimental moduli of standard/low-modulus cement (R(2)=0.91/0.98) as well as PV/(TV-BV) and yield stresses (R(2)=0.92/0.83) were highly correlated. No correlation between BV/TV (ranging from 0.057 to 0.138) and elastic moduli was observed (R(2)< 0.05). Interestingly, the micro-FE models of the porous cement alone reproduced the experimental elastic moduli of the standard/low-modulus cement biopsies (R(2)=0.75/0.76) more accurately than the models with bone (R(2)=0.58/0.31). In conclusion, the mechanical properties of the biopsies were mainly determined by the cement porosity and the cement material properties. The study showed that bone tissue inside the biopsies was mechanically "switched off" such that load was carried essentially by the porous PMMA., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Tissue grafts are implanted in orthopedic surgery every day. In order to minimize infection risk, bone allografts are often delipidated with supercritical CO₂ and sterilized prior to implantation. This treatment may, however, impair the mechanical behavior of the bone graft tissue. The goal of this study was to determine clinically relevant mechanical properties of treated/sterilized human trabecular bone grafts, e.g. the apparent modulus, strength, and the ability to absorb energy during compaction. They were compared with results of identical experiments performed previously on untreated/fresh frozen human trabecular bone from the same anatomical site (Charlebois, 2008). We tested the hypothesis that the morphology-mechanical property relationships of treated cancellous allografts are similar to those of fresh untreated bone. The morphology of the allografts was determined by μCT. Subsequently, cylindrical samples were tested in unconfined and confined compression. To account for various morphologies, the experimental data was fitted to phenomenological mechanical models for elasticity, strength, and dissipated energy density based on bone volume fraction (BV/TV) and the fabric tensor determined by MIL. The treatment/sterilization process does not appear to influence bone graft stiffness. However, strength and energy dissipation of the bone grafts were found to be significantly reduced by 36% to 47% and 66% to 81%, respectively, for a broad range of volume fraction (0.14

In the 1920s and 1930s, Terzaghi and coworkers realized that the failure of various porous geomaterials under internal pore pressure is given through evaluating the failure function for the same materials at zero pressure, with 'total stress plus pore pressure' instead of 'total stress alone' as argument. As to check, probably for the first time, the relevance of this ('Terzaghi's') failure criterion for trabecular bone, a series of poromechanical and ultrasonic tests was conducted on bovine and human trabecular bone samples. Evaluation of respective experimental results within the theoretical framework of microporomechanics showed that (i) Terzaghi's effective stress indeed governs trabecular bone failure, (ii) deviatoric stress states at the level of the solid bone matrix (also called tissue level) are primary candidates for initiating bone failure, and (iii) the high heterogeneity of these deviatoric tissue stresses, which increases with increasing intertrabecular porosity, governs the overall failure of trabecular bone. Result (i) lets us use the widely documented experimental results for strength values of bone samples without pore pressure, as to predict failure of the same bone samples under internal pore pressure. Result (ii) suggests a favorable mode for strength modeling of solid bone matrix. Finally, result (iii) underlines the suitability of microfinite element simulations for trabecular bone microstructures., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Vertebral compression fracture is a common medical problem in osteoporotic individuals. The quantitative computed tomography (QCT)-based finite element (FE) method may be used to predict vertebral strength in vivo, but needs to be validated with experimental tests. The aim of this study was to validate a nonlinear anatomy specific QCT-based FE model by using a novel testing setup. Thirty-seven human thoracolumbar vertebral bone slices were prepared by removing cortical endplates and posterior elements. The slices were scanned with QCT and the volumetric bone mineral density (vBMD) was computed with the standard clinical approach. A novel experimental setup was designed to induce a realistic failure in the vertebral slices in vitro. Rotation of the loading plate was allowed by means of a ball joint. To minimize device compliance, the specimen deformation was measured directly on the loading plate with three sensors. A nonlinear FE model was generated from the calibrated QCT images and computed vertebral stiffness and strength were compared to those measured during the experiments. In agreement with clinical observations, most of the vertebrae underwent an anterior wedge-shape fracture. As expected, the FE method predicted both stiffness and strength better than vBMD (R(2) improved from 0.27 to 0.49 and from 0.34 to 0.79, respectively). Despite the lack of fitting parameters, the linear regression of the FE prediction for strength was close to the 1:1 relation (slope and intercept close to one (0.86 kN) and to zero (0.72 kN), respectively). In conclusion, a nonlinear FE model was successfully validated through a novel experimental technique for generating wedge-shape fractures in human thoracolumbar vertebrae., (2010 Elsevier Ltd. All rights reserved.)

Previous antiresorptive treatment may influence the anabolic response to teriparatide. The OPTAMISE (Open-label Study to Determine How Prior Therapy with Alendronate or Risedronate in Postmenopausal Women with Osteoporosis Influences the Clinical Effectiveness of Teriparatide) study reported greater increases in biochemical markers of bone turnover and volumetric bone mineral density (BMD) when 12 months of teriparatide treatment was preceded by 2 years or more of risedronate versus alendronate treatment. The objective of this study was to use quantitative computed tomography (CT)-based nonlinear finite element modeling to evaluate how prior therapy with alendronate or risedronate in postmenopausal women with osteoporosis influences the biomechanical effectiveness of teriparatide. Finite element models of the L1 vertebra were created from quantitative CT scans, acquired before and after 12 months of therapy with teriparatide, from 171 patients from the OPTAMISE study. These models were subjected to uniaxial compression. Total BMD-derived bone volume fraction (BV/TV(d), i.e., bone volume [BV]/total volume [TV]), estimated from quantitative CT-based volumetric BMD, vertebral stiffness, and failure load (strength) were calculated for each time measurement point. The results of this study demonstrated that 12 months of treatment with teriparatide following prior treatment with either risedronate or alendronate increased BMD-derived BV/TV(d), the predicted vertebral stiffness, and failure load. However, the effects of teriparatide were more pronounced in patients treated previously with risedronate, which is consistent with the findings of the OPTAMISE study. The mean (+/-standard error) increase in stiffness was greater in the prior risedronate group than the prior alendronate group (24.6+/-3.2% versus 14.4+/-2.8%, respectively; p=0.0073). Similarly, vertebral failure load increased by 27.2+/-3.5% in the prior risedronate group versus 15.3+/-3.1% in the prior alendronate group (p=0.0042). The mechanical variables increased in greater proportion than BV/TV(d), which increased by 6.9+/-0.9% versus 4.6+/-0.8% in the prior-risedronate and prior-alendronate groups, respectively (p=0.0290). Our finding indicated that while teriparatide can be used with success on patients who have previously undergone treatment with risedronate and alendronate, it demonstrated greater anabolic effect on biomechanical properties in prior-risedronate patients in the first year of teriparatide treatment., (Copyright (c) 2009 Elsevier Inc. All rights reserved.)

The aim of this study was to investigate the capabilities of the state of the art HR-pQCT technique to predict mineral content, volume fraction and fabric of trabecular bone structure compared to the gold standard microCT. Four cadaveric human forearms were scanned with HR-pQCT and the dissected radius epiphyses with microCT. After registering the images, bone mineral density (BMD), volume fraction (BV/TV) and fabric were computed on corresponding cubical regions of interest for both image sources. In particular, the effect of the segmentation procedure on BV/TV was analyzed. Assessment of fabric was performed with three different methods comparing their efficiency and robustness against resolution change. The results showed that in order to achieve optimal results at the lower image resolution, different filtering and thresholding approaches needed to be selected for different tasks. Therefore, to preserve BV/TV, the BMD-based volume fraction provided best match with the reference values of microCT, while in case of Mean Intercept Length (MIL) fabric a Gaussian filter and a histogram-based threshold were optimal. Using the latter, MIL was found to be more robust against resolution change than the other approaches. Additionally, we proposed a linear model for describing the mathematical transformation that the second order fabric tensor undergoes when the resolution of the input images changes. As a conclusion, we found that the investigated properties of trabecular bone structure can be adequately predicted from the lower resolution technique that is available in vivo for peripheral bones, when proper image processing and corrections are applied.

The physical principles underlying quantitative ultrasound (QUS) measurements in trabecular bone are not fully understood. The translation of QUS results into bone strength remains elusive. However, ultrasound being mechanical waves, it is likely to assess apparent bone elasticity. The aim of this study is to derive the sensitivity of QUS parameters to variations of apparent bone elasticity, a surrogate for strength. The geometry of 34 human trabecular bone samples cut in the great trochanter was reconstructed using 3-D synchrotron micro-computed tomography. Finite-difference time-domain simulations coupled to 3-D micro-structural models were performed in the three perpendicular directions for each sample and each direction. A voxel-based micro-finite element linear analysis was employed to compute the apparent Young's modulus (E) of each sample for each direction. For the antero-posterior direction, the predictive power of speed of sound and normalized broadband ultrasonic attenuation to assess E was equal to 0.9 and 0.87, respectively, which is better than what is obtained using bone density alone or coupled with micro-architectural parameters and of the same order of what can be achieved with the fabric tensor approach. When the direction of testing is parallel to the main trabecular orientation, the predictive power of QUS parameters decreases and the fabric tensor approach always gives the best results. This decrease can be explained by the presence of two longitudinal wave modes. Our results, which were obtained using two distinct simulation tools applied on the same set of samples, highlight the potential of QUS techniques to assess bone strength.

Osteoporotic fractures are harmful injuries and their number is on the rise. Distal radius fractures are precursors of other osteoporotic fractures. The wrist's bony geometry and trabecular architecture can be assessed in vivo using the recently introduced HR-pQCT. The goal of this study was the validation of a newly developed HR-pQCT based anatomy specific FE technique including separation of cortical and trabecular bone regions using an experimental model for producing Colles' fractures. Mechanical compression tests of 21 embalmed human radii were conducted. Continuum level FE models were built using HR-pQCT images of the bones and nonlinear analyses were performed using boundary conditions highly similar to the mechanical tests. Density and fabric based material properties were taken from previous tests on biopsies and no adjustments were made. Numerical results provided good prediction of the experimental stiffness (R(2)=0.793) and even better for strength (R(2)=0.874). High damage zones of the FE models coincided with the actual failure patterns of the specimens. These encouraging results allow to conclude that the developed method represents an attractive and efficient tool for simulation of Colles' fracture.

Assessment of the mechanical properties of trabecular bone is of major biological and clinical importance for the investigation of bone diseases, fractures and their treatments. Finite element (FE) methods are getting increasingly popular for quantifying the elastic and failure properties of trabecular bone. In particular, voxel-based FE methods have been previously used to calculate the effective elastic properties of trabecular microstructures. However, in most studies, bone tissue moduli were assumed or back-calculated to match the apparent elastic moduli from experiments, which often lead to surprisingly low values when compared to nanoindentation results. In this study, voxel-based FE analysis of trabecular bone is combined with physical measures of volume fraction, micro-CT (microCT) reconstructions, uniaxial mechanical tests and specimen-specific nanoindentation tests for proper validation of the method. Cylindrical specimens of cancellous bone were extracted from human femurs and their volume fraction determined with Archimede's method. Uniaxial apparent modulus of the specimens was measured with an improved tension-compression testing protocol that minimizes boundary artefacts. Their microCT reconstructions were segmented to match the measured bone volume fraction and used to create full-size voxel models with 30-45 microm element size. For each specimen, linear isotropic elastic material properties were defined based on specific nanoindentation measurements of its embedded bone tissue. Linear FE analyses were finally performed to simulate the uniaxial mechanical tests. Additional parametric analyses were performed to evaluate the potential errors on the predicted apparent modulus arising from variations in segmentation threshold, tissue modulus, and the use of 125-mm(3) cubic sub-regions. The results demonstrate an excellent correspondence between experimental measures and FE predictions of uniaxial apparent modulus. In conclusion, the adopted voxel-based FE approach is found to be a robust method to predict the linear elastic properties of human cancellous bone, provided segmentation of the microCT reconstructions is carefully calibrated, tissue modulus is known a priori and the entire region of interest is included in the analysis.

Bone strength depends on bone mass, geometry, microarchitecture, and intrinsic tissue quality. Whether intrinsic bone tissue properties could be influenced by changes in dietary protein is not known. To address this issue, nanoindentation tests were performed on the lateral, anterior, and posterior site of L5 vertebral bodies in adult female rats fed a normal protein containing diet and in ovariectomized (OVX) rats receiving an isocaloric low protein diet with or without isocaloric essential amino acids supplements. The tissue properties varied significantly between the different sites (anterior, posterior, lateral), suggesting possible effects of heterogeneous stress distribution on the vertebrae in vivo. Isocaloric low protein intake associated with ovariectomy led to significant decreases of indentation modulus, hardness, and dissipated energy on the posterior vertex. Axial compression tests of adjacent vertebral bodies were correlated with the indentation results. Correlations between macroscopic mechanical data obtained by axial compression of vertebral body, and intrinsic tissue properties measured by nanoindentation test suggest that postelastic behavior strongly varied with material fragility detected on the tissue level. Macroscopic stiffness however may be dominated by bone geometry changes and less by variations of intrinsic bone tissue properties. Combining parameters of tissue properties and bone mineral density was highly predictive of vertebral body ultimate strength. Besides geometry and microarchitecture, intrinsic bone tissue properties are important determinants of the mechanical competence of rat vertebrae. Changes in intrinsic tissue properties could thus contribute to the increased bone fragility found in protein undernutrition.

The mechanical response of the bovine periodontal ligament (PDL) subjected to uniaxial tension and compression is reported. Several sections normal to the longitudinal axis of bovine incisors and molars were extracted from different depths. Specimens with dimensions 10 x 5 x 2 mm including dentine, PDL and alveolar bone were obtained from these sections. Scanning electron microscopy suggested a strong similarity between the bovine PDL and the human PDL microstructure described in the literature. The prepared specimens were tested in a custom made uniaxial testing machine. They were clamped on their bone and dentine extremities and immersed in a saline solution at 37 degrees C. Stress-strain curves indicated that the PDL is characterized by a non-linear and time-dependent mechanical behaviour with the typical features of collagenous soft tissues. The curves exhibited hysteresis and preconditioning effects. The mechanical parameters evaluated in tension were maximum tangent modulus, strength, maximizer strain and strain energy density. For the molars, all these parameters increased with depth except for the apical region. For the incisors, all parameters increased with depth except ultimate strain which decreased. It was assumed that collagen fibre density and orientation were responsible for these findings.

This work consists of the validation of a novel approach to estimate the local anisotropic elastic constants of the bone extracellular matrix using nanoindentation. For this purpose, nanoindentation on two planes of material symmetry were analyzed and the resulting longitudinal elastic moduli compared to the moduli measured with a macroscopic tensile test. A combined lathe and tensile system was designed that allows machining and testing of cylindrical microspecimens of approximately 4mm in length and 300 microm in diameter. Three bovine specimens were tested in tension and their outer geometry and porosity assessed by synchrotron radiation microtomography. Based on the results of the traction test and the precise outer geometry, an apparent longitudinal Young's modulus was calculated. Results between 20.3 and 27.6 GPa were found that match with previously reported values for bovine compact bone. The same specimens were then characterized by nanoindentation on a transverse and longitudinal plane. A longitudinal Young's modulus for the bone matrix was then derived using the numerical scheme proposed by Swadener and Pharr and the fabric-elasticity relationship by Zysset and Curnier. Based on the matrix modulus and a power law effective volume fraction, an apparent longitudinal Young's modulus was predicted for each microspecimen. This alternative approach provided values between 19.9 and 30.0 GPa, demonstrating differences between 2% and 13% to the values provided by the initial tensile test. This study therefore raises confidence in our nanoindentation protocol of the bone extracellular matrix and supports the underlying hypotheses used to extract the anisotropic elastic constants.

Precipitated hydroxyapatite cement scaffolds with macroporosity of controlled size and shape were successfully built using a solid freeform fabrication process. The negative macroporosity was designed using CAD software and built with an inkjet machine. A slip casting process using a plaster mold was used to precipitate the cement and manufacture samples for mechanical testing. The negative macroporosity was then extracted from the samples using a thermal process. Compression, tension and torsion tests were completed successfully on the precipitated hydroxyapatite cement samples in moist condition. Elastic and strength properties were measured for these three loading cases and compared to the plain hydroxyapatite cement properties reported in a previous study. Homogenization theory was applied to estimate the elastic properties of the manufactured scaffolds. A good correlation was obtained between the experimental data and the theory.

Mechanical properties of single lamellae of human compact and trabecular bone tissue were measured with a combined atomic force microscopy (AFM) and nanoindentation technique. This combination allows for both characterization of bone surface topography and indentation of the bone extracellular matrix (ECM) with depths of between 100 and 600 nm. Four bone structural units (BSUs) were tested with 400 indents under dry conditions, and four BSUs with 160 indents were tested in a liquid cell under physiological conditions. A correspondence was established between the optical appearance of bone lamellae and the topography of the polished bone surface. The indentation modulus and hardness of bone ECM were investigated as a function of lamella type and indentation depth under wet and dry conditions. For low depth indents, thick lamellae showed a higher indentation modulus than thin lamellae. With increasing indentation depth, thick lamellae exhibited a significant decrease in indentation modulus and hardness, whereas, for thin lamellae, the effect of indentation depth was much less significant. These trends were similar for dry and physiological conditions and support compositional and/or ultrastructural differences between thick and thin lamellae.

Compression, tension and torsion tests were designed and completed successfully on a brushite and a precipitated hydroxyapatite cement in moist condition. Elastic and strength properties were measured for these three loading cases. For each cement, the full set of strength data was fitted to an isotropic Tsai-Wu criterion and the associated coefficients identified. Since the compressive Young's moduli were about 10% larger than the tensile moduli, the full set of elastic data of each cement was fitted to a conewise linear elastic model. Hysteresis of the stress-strain curves was also observed, indicating dissipation mechanisms within these cement microstructures. A comparison of the measured mechanical properties with human cancellous bone confirmed the indication of brushite as a bone filling material and the potential of the hydroxyapatite cement as a structural biomaterial.

Advances in our ability to assess fracture risk, predict implant success, and evaluate new therapies for bone metabolic and remodeling disorders depend on our understanding of anatomically specific measures of local tissue mechanical properties near and surrounding bone cells. Using nanoindentation, we have quantified elastic modulus and hardness of human lamellar bone tissue as a function of tissue microstructures and anatomic location. Cortical and trabecular bone specimens were obtained from the femoral neck and diaphysis, distal radius, and fifth lumbar vertebra of ten male subjects (aged 40-85 years). Tissue was tested under moist conditions at room temperature to a maximum depth of 500 nm with a loading rate of 10 nm/sec. Diaphyseal tissue was found to have greater elastic modulus and hardness than metaphyseal tissues for all microstructures, whereas interstitial elastic modulus and hardness did not differ significantly between metaphyses. Trabecular bone varied across locations, with the femoral neck having greater lamellar-level elastic modulus and hardness than the distal radius, which had greater properties than the fifth lumbar vertebra. Osteonal, interstitial, and primary lamellar tissues of compact bone had greater elastic moduli and hardnesses than trabecular bone when comparing within an anatomic location. Only femoral neck interstitial tissue had a greater elastic modulus than its osteonal counterpart, which suggests that microstructural distinctions can vary with anatomical location and may reflect differences in the average tissue age of cortical bone or mineral and collagen organization.

The mechanical properties of bone tissue are determined by composition as well as structural, microstructural and nanostructural organization. The aim of this study was to quantify the elastic properties of bone at the lamellar level and compare these properties among osteonal, interstitial and trabecular microstructures from the diaphysis and the neck of the human femur. A nanoindentation technique with a custom irrigation system was used for simultaneously measuring force and displacement of a diamond tip pressed 500 nm into the moist bone tissue. An isotropic elastic modulus was calculated from the unloading curve with an assumed Poisson ratio of 0.3, while hardness was defined as the maximal force divided by the corresponding contact area. The elastic moduli ranged from 6.9 +/- 4.3 GPa in trabecular tissue from the femoral neck of a 74 yr old female up to 25.0 +/- 4.3 GPa in interstitial tissue from the diaphyseal cortex of a 69 yr old female. The mean elastic modulus was found to be significantly influenced by the type of lamella (p < 10(-6)) and by donor (p < 10(-6)). The interaction between the type of lamella and the donor was also highly significant (p < 10(-6)). Hardness followed a similar distribution as elastic modulus among types of lamellae and donor, but with lower statistical contrast. It is concluded that the nanostructure of bone tissue must differ substantially among lamellar types, anatomical sites and individuals and suggests that tissue heterogeneity is of potential importance in bone fragility and adaptation.

Motivated by the role of damage in normal and pathological conditions of trabecular bone, a novel 3D constitutive law was developed that describes anisotropic elasticity and the rate-independent degradation in mechanical properties resulting from the growth of cracks or voids in the trabecular tissue. The theoretical model was formulated within the framework of continuum damage mechanics and based on two fabric tensors characterizing the local trabecular morphology. Experimental validation of the model was achieved by uniaxial and torsional testing of waisted bovine trabecular bone specimens. Strong correlations were found between cumulated permanent strain, reduction in elastic moduli and nonlinear postyield stress, which support the hypothesis that these variables reflect the same underlying damage process.

A numerical model of a femoral total hip component based on the finite element method is developed to evaluate the relative micromotions at the bone-implant interface and the stress distribution in the femoral bone. The interface is modelled as unilateral contact involving Coulomb's dry friction between the bone and the implant. In addition, the model includes inhomogeneity, anisotropy as well as plasticity of both cortical and spongious bones. An automatic data processor coupled to a three-dimensional mesh generator is designed to extract cortical bone geometry and inhomogeneous distribution of trabecular bone density from data obtained with quantitative computed tomography (QCT). A preliminary application is conducted to evaluate the mechanical behaviour of an existing bone-prosthesis structure for two typical loadings: a load simulating the single leg stance and a load simulating the stair climbing stance. The obtained results are subdivided in two parts. Firstly, the characterization of stress transfer and micromotions at the bone-stem interface. The peak value of the shear micromotions reaches 600 microns in the proximal medial region with a friction coefficient equal to 0.6. An analysis of the influence of the friction coefficient reveals that the shear and distractive micromotions as well as the shear and normal stresses depend strongly on this coefficient. Secondly, the representation of stresses in the femoral bone. Determination of complementary invariants such as the hydrostatic pressure, the deviatoric stress and anisotropic stresses brings additional insights in the evaluation of the stress field in the femoral bone.