Reference values and clinical predictors of bone strength for HR-pQCT-based distal radius and tibia strength assessments in women and men.

Reference values for radius and tibia strength using multiple-stack high-resolution peripheral quantitative computed tomography (HR-pQCT) with homogenized finite element analysis are presented in order to derive critical values improving risk prediction models of osteoporosis. Gender and femoral neck areal bone mineral density (aBMD) were independent predictors of bone strength. INTRODUCTION: The purpose was to obtain reference values for radius and tibia bone strength computed by using the homogenized finite element analysis (hFE) using multiple stacks with a HR-pQCT. METHODS: Male and female healthy participants aged 20-39 years were recruited at the University Hospital of Bern. They underwent interview and clinical examination including hand grip, gait speed and DXA of the hip. The nondominant forearm and tibia were scanned with a double and a triple-stack protocol, respectively, using HR-pQCT (XCT II, SCANCO Medical AG). Bone strength was estimated by using the hFE analysis, and reference values were calculated using quantile regression. Multivariable analyses were performed to identify clinical predictors of bone strength. RESULTS: Overall, 46 women and 41 men were recruited with mean ages of 25.1 (sd 5.0) and 26.2 (sd 5.2) years. Sex-specific reference values for bone strength were established. Men had significantly higher strength for radius (mean (sd) 6640 (1800) N vs. 4110 (1200) N; p < 0.001) and tibia (18,200 (4220) N vs. 11,970 (3150) N; p < 0.001) than women. In the two multivariable regression models with and without total hip aBMD, the addition of neck hip aBMD significantly improved the model (p < 0.001). No clinical predictors of bone strength other than gender and aBMD were identified. CONCLUSION: Reference values for radius and tibia strength using multiple HR-pQCT stacks with hFE analysis are presented and provide the basis to help refining accurate risk prediction models. Femoral neck aBMD and gender were significant predictors of bone strength.

Perspectives on the non-invasive evaluation of femoral strength in the assessment of hip fracture risk.

We reviewed the experimental and clinical evidence that hip bone strength estimated by BMD and/or finite element analysis (FEA) reflects the actual strength of the proximal femur and is associated with hip fracture risk and its changes upon treatment. INTRODUCTION: The risk of hip fractures increases exponentially with age due to a progressive loss of bone mass, deterioration of bone structure, and increased incidence of falls. Areal bone mineral density (aBMD), measured by dual-energy X-ray absorptiometry (DXA), is the most used surrogate marker of bone strength. However, age-related declines in bone strength exceed those of aBMD, and the majority of fractures occur in those who are not identified as osteoporotic by BMD testing. With hip fracture incidence increasing worldwide, the development of accurate methods to estimate bone strength in vivo would be very useful to predict the risk of hip fracture and to monitor the effects of osteoporosis therapies. METHODS: We reviewed experimental and clinical evidence regarding the association between aBMD and/orCT-finite element analysis (FEA) estimated femoral strength and hip fracture risk as well as their changes with treatment. RESULTS: Femoral aBMD and bone strength estimates by CT-FEA explain a large proportion of femoral strength ex vivo and predict hip fracture risk in vivo. Changes in femoral aBMD are strongly associated with anti-fracture efficacy of osteoporosis treatments, though comparable data for FEA are currently not available. CONCLUSIONS: Hip aBMD and estimated femoral strength are good predictors of fracture risk and could potentially be used as surrogate endpoints for fracture in clinical trials. Further improvements of FEA may be achieved by incorporating trabecular orientations, enhanced cortical modeling, effects of aging on bone tissue ductility, and multiple sideway fall loading conditions.

Validation of distal radius failure load predictions by homogenized- and micro-finite element analyses based on second-generation high-resolution peripheral quantitative CT images.

This study developed a well-standardized and reproducible approach for micro-finite element (mFE) and homogenized-FE (hFE) analyses that can accurately predict the distal radius failure load using either mFE or hFE models when using the approaches and parameters developed in this study. INTRODUCTION: Micro-FE analyses based on high-resolution peripheral quantitative CT (HR-pQCT) images are frequently used to predict distal radius failure load. With the introduction of a second-generation HR-pQCT device, however, the default modelling approach no longer provides accurate results. The aim of this study was to develop a well-standardized and reproducible approach for mFE and hFE analyses that can provide precise and accurate results for distal radius failure load predictions based on second-generation HR-pQCT images. METHODS: Second-generation HR-pQCT was used to scan the distal 20-mm section of 22 cadaver radii. The sections were excised and mechanically tested afterwards. For these sections, mFE and hFE models were made that were used to identify required material parameters by comparing predicted and measured results. Using these parameters, the models were cropped to represent the 10-mm region recommended for clinical studies to test their performance for failure load prediction. RESULTS: After identification of material parameters, the measured failure load of the 20-mm segments was in good agreement with the results of mFE models (R2 = 0.969, slope = 1.035) and hFE models (R2 = 0.966, slope = 0.890). When the models were restricted to the clinical region, mFE still accurately predicted the measured failure load (R2 = 0.955, slope = 1.021), while hFE predictions were precise but tended to overpredict the failure load (R2 = 0.952, slope = 0.780). CONCLUSIONS: It was concluded that it is possible to accurately predict the distal radius failure load using either mFE or hFE models when using the approaches and parameters developed in this study.

The thermal conductivity of cortical and cancellous bone.

Surgical interventions close to vulnerable structures, such as nerves, require precise handling of surgical instruments and tools. These tools not only pose the risk of mechanical damage to soft tissues, but they also generate heat, which can lead to thermal necrosis of bone or soft tissues. Researchers and engineers are trying to improve those tools through experimentation and simulations. To simulate temperature distributions in anatomical structures, reliable material constants are needed. Therefore, this study aimed at investigating the thermal conductivity of cortical and cancellous bone. Accordingly, a custom-made steady-state experimental setup was designed and validated. 6 bovine and 3 human cortical bone samples, as well as 32 bovine cancellous bone samples, with variable bone volume fraction were tested. The cancellous bone samples were scanned by micro-computed tomography (µCT) and micro-finite element (µFE) voxel models were created to calculate iteratively the thermal conductivity of the bone marrow. The experimental results provided 0.64 ± 0.04 W/mK for bovine cortical bone and 0.68 ± 0.01 W/mK for human cortical bone. A linear dependency of thermal conductivity on bone volume fraction was found for cancellous bone [R-square (R2) = 0.8096, standard error of the estimates (SEE) = 0.0355 W/mK]. The thermal conductivity of the bone marrow was estimated to be 0.42 ± 0.05 W/mK. These results will help to improve thermal finite element simulations of the human skeleton and aid the development of new surgical tools or procedures.

Rebound-associated vertebral fractures after discontinuation of denosumab-from clinic and biomechanics.

UNLABELLED: Rebound-associated vertebral fractures may follow treatment discontinuation of highly potent reversible bone antiresorptives, resulting from the synergy of rapid bone resorption and accelerated microdamage accumulation in trabecular bone. INTRODUCTION: The purposes of this study are to characterize rebound-associated vertebral fractures following the discontinuation of a highly potent reversible antiresorptive therapy based on clinical observation and propose a pathophysiological rationale. METHODS: This study is a case report of multiple vertebral fractures early after discontinuation of denosumab therapy in a patient with hormone receptor-positive non-metastatic breast cancer treated with an aromatase inhibitor. RESULTS: Discontinuation of highly potent reversible bone antiresorptives such as denosumab may expose patients to an increased fracture risk due to the joined effects of absent microdamage repair during therapy followed by synchronous excess activation of multiple bone remodelling units at the time of loss-of-effect. We suggest the term rebound-associated vertebral fractures (RVF) for this phenomenon characterized by the presence of multiple new clinical vertebral fractures, associated with either no or low trauma, in a context consistent with the presence of high bone turnover and rapid loss of lumbar spine bone mineral density (BMD) occurring within 3 to 12 months after discontinuation (loss-of-effect) of a reversible antiresorptive therapy in the absence of secondary causes of bone loss or fractures. Unlike atypical femoral fractures that emerge from failure of microdamage repair in cortical bone with long-term antiresorptive treatment, RVF originate from the synergy of rapid bone resorption and accelerated microdamage accumulation in trabecular bone triggered by the discontinuation of highly potent reversible antiresorptives. CONCLUSIONS: Studies are urgently needed to i) prove the underlying pathophysiological processes suggested above, ii) establish the predictive criteria exposing patients to an increased risk of RVF, and iii) determine appropriate treatment regimens to be applied in such patients.

Characterizing microcrack orientation distribution functions in osteonal bone samples.

Prefailure microdamage in bone tissue is considered to be the most detrimental factor in defining its strength and toughness with respect to age and disease. To understand the influence of microcracks on bone mechanics it is necessary to assess their morphology and three-dimensional distribution. This requirement reaches beyond classic histology and stereology, and methods to obtain such information are currently missing. Therefore, the aim of the study was to develop a methodology that allows to characterize three-dimensional microcrack distributions in bulk bone samples. Four dumbbell-shaped specimens of human cortical bone of a 77-year-old female donor were loaded beyond yield in either tension, compression or torsion (one control). Subsequently, synchrotron radiation micro-computed tomography (SRµCT) was used to obtain phase-contrast images of the damaged samples. A microcrack segmentation algorithm was developed and used to segment microcrack families for which microcrack orientation distribution functions were determined. Distinct microcrack families were observed for each load case that resulted in distinct orientation distribution functions. Microcracks had median areas of approximately 4.7 µm2 , 33.3 µm2 and 64.0 µm2 for tension, compression and torsion. Verifying the segmentation algorithm against a manually segmented ground truth showed good results when comparing the microcrack orientation distribution functions. A size dependence was noted when investigating the orientation distribution functions with respect to the size of the volume of interest used for their determination. Furthermore, a scale separation between tensile, compressive and torsional microcracks was noticeable. Visual comparison to classic histology indicated that microcrack families were successfully distinguished. We propose a methodology to analyse three-dimensional microcrack distributions in overloaded cortical bone. Such information could improve our understanding of bone microdamage and its impact on bone failure in relation to tissue age and disease.

Early changes in biochemical markers of bone formation during teriparatide therapy correlate with improvements in vertebral strength in men with glucocorticoid-induced osteoporosis.

UNLABELLED: Changes of the bone formation marker PINP correlated positively with improvements in vertebral strength in men with glucocorticoid-induced osteoporosis (GIO) who received 18-month treatment with teriparatide, but not with risedronate. These results support the use of PINP as a surrogate marker of bone strength in GIO patients treated with teriparatide. INTRODUCTION: To investigate the correlations between biochemical markers of bone turnover and vertebral strength estimated by finite element analysis (FEA) in men with GIO. METHODS: A total of 92 men with GIO were included in an 18-month, randomized, open-label trial of teriparatide (20 µg/day, n = 45) and risedronate (35 mg/week, n = 47). High-resolution quantitative computed tomography images of the 12th thoracic vertebra obtained at baseline, 6 and 18 months were converted into digital nonlinear FE models and subjected to anterior bending, axial compression and torsion. Stiffness and strength were computed for each model and loading mode. Serum biochemical markers of bone formation (amino-terminal-propeptide of type I collagen [PINP]) and bone resorption (type I collagen cross-linked C-telopeptide degradation fragments [CTx]) were measured at baseline, 3 months, 6 months and 18 months. A mixed-model of repeated measures analysed changes from baseline and between-group differences. Spearman correlations assessed the relationship between changes from baseline of bone markers with FEA variables. RESULTS: PINP and CTx levels increased in the teriparatide group and decreased in the risedronate group. FEA-derived parameters increased in both groups, but were significantly higher at 18 months in the teriparatide group. Significant positive correlations were found between changes from baseline of PINP at 3, 6 and 18 months with changes in FE strength in the teriparatide-treated group, but not in the risedronate group. CONCLUSIONS: Positive correlations between changes in a biochemical marker of bone formation and improvement of biomechanical properties support the use of PINP as a surrogate marker of bone strength in teriparatide-treated GIO patients.

Advanced CT based in vivo methods for the assessment of bone density, structure, and strength.

Based on spiral 3D tomography a large variety of applications have been developed during the last decade to asses bone mineral density, bone macro and micro structure, and bone strength. Quantitative computed tomography (QCT) using clinical whole body scanners provides separate assessment of trabecular, cortical, and subcortical bone mineral density (BMD) and content (BMC) principally in the spine and hip, although the distal forearm can also be assessed. Further bone macrostructure, for example bone geometry or cortical thickness can be quantified. Special high resolution peripheral CT (hr-pQCT) devices have been introduced to measure bone microstructure for example the trabecular architecture or cortical porosity at the distal forearm or tibia. 3D CT is also the basis for finite element analysis (FEA) to determine bone strength. QCT, hr-pQCT, and FEM are increasingly used in research as well as in clinical trials to complement areal BMD measurements obtained by the standard densitometric technique of dual x-ray absorptiometry (DXA). This review explains technical developments and demonstrates how QCT based techniques advanced our understanding of bone biology.

QCT-based finite element models predict human vertebral strength in vitro significantly better than simulated DEXA.

SUMMARY: While dual energy X-ray absorptiometry (DXA) is considered the gold standard to evaluate fracture risk in vivo, in the present study, the quantitative computed tomography (QCT)-based finite element modeling has been found to provide a quantitative and significantly improved prediction of vertebral strength in vitro. This technique might be used in vivo considering however the much larger doses of radiation needed for QCT. INTRODUCTION: Vertebral fracture is a common medical problem in osteoporotic individuals. Bone mineral density (BMD) is the gold standard measure to evaluate fracture risk in vivo. QCT-based finite element (FE) modeling is an engineering method to predict vertebral strength. The aim of this study was to compare the ability of FE and clinical diagnostic tools to predict vertebral strength in vitro using an improved testing protocol. METHODS: Thirty-seven vertebral sections were scanned with QCT and high resolution peripheral QCT (HR-pQCT). Bone mineral content (BMC), total BMD (tBMD), areal BMD from lateral (aBMD-lat), and anterior-posterior (aBMD-ap) projections were evaluated for both resolutions. Wedge-shaped fractures were then induced in each specimen with a novel testing setup. Nonlinear homogenized FE models (hFE) and linear micro-FE (µFE) were generated from QCT and HR-pQCT images, respectively. For experiments and models, both structural properties (stiffness, ultimate load) and material properties (apparent modulus and strength) were computed and compared. RESULTS: Both hFE and µFE models predicted material properties better than structural ones and predicted strength significantly better than aBMD computed from QCT and HR-pQCT (hFE: R² = 0.79, µFE: R² = 0.88, aBMD-ap: R² = 0.48-0.47, aBMD-lat: R² = 0.41-0.43). Moreover, the hFE provided reasonable quantitative estimations of the experimental mechanical properties without fitting the model parameters. CONCLUSIONS: The QCT-based hFE method provides a quantitative and significantly improved prediction of vertebral strength in vitro when compared to simulated DXA. This superior predictive power needs to be verified for loading conditions that simulate even more the in vivo case for human vertebrae.

Bone and cellular immune system of multiparous sows are insensitive to ovariectomy and nutritive calcium shortage.

Research in osteoporosis, which is a complex systemic disease, demands suitable large animal models. In pigs, most research has been done in growing minipigs, which probably are not ideal models for postmenopausal osteoporosis. Therefore, our aim was to analyze the effects of ovariectomy (OVX) and nutritive calcium shortage on multiparous Large White sows. 32 animals were randomly assigned to 4 groups in a cross design with OVX vs. sham and physiological calcium supplementation (0.75% calcium) vs. dietary calcium shortage (0.3% calcium). The observation period was 10 months with blood sampling every 2 months for hematological, immunological, and biochemical bone marker measurements. At the termination of the experiment, animals were sacrificed. Samples of trabecular bone of distal radius, proximal tibia, and sixth lumbar vertebra were subjected to micro-computed tomography imaging and ashed afterwards. Dual X-ray absorptiometry scans of the proximal femora were performed with prepared bones being placed in a water bath for mimicking soft tissue. Analyses of bone marker and cytokine profile kinetics, distribution of leukocyte subpopulations, and morphometrical and densitometrical analyses showed no evidence of any impact of OVX or calcium shortage. In conclusion, the skeleton of adult sows of a conventional breed is seemingly protected from effects of OVX and calcium shortage.

OPG-Fc treatment in growing pigs leads to rapid reductions in bone resorption markers, serum calcium, and bone formation markers.

Inhibition of the receptor activator of NF-κB ligand (RANKL) is a novel therapeutic option in the treatment of osteoporosis and related diseases. The aim of this study was to evaluate bone metabolism and structure in pigs after RANKL inhibition. 12 growing pigs were assigned to 2 groups with 6 animals each. The OPG group received recombinant human OPG-Fc (5 mg/kg IV) at day 0, the control group was given 0.9% NaCl solution. Serum levels of OPG-Fc, calcium (Ca), phosphorus (P), and bone turnover markers were evaluated every 5 days, and pigs were euthanized on day 20. Serum OPG-Fc concentration peaked at day 5 and coincided with significantly decreased Ca, P, and bone turnover markers. By day 15, measureable OPG-Fc serum levels could only be detected in 2/6 animals. With OPG-Fc clearance starting at day 10, serum Ca and P concentrations were not different between the 2 groups. TRACP5b, P1CP, and BAP levels significantly decreased by 40-70% relative to vehicle controls in the OPG-Fc group between days 5 and 10, indicating that pharmacologic concentration of OPG-Fc led to systemic concomitant inhibition of bone formation and resorption in young growing pigs. Dual X-ray absorptiometry data derived from the proximal femur did not differ between the 2 groups. µCT analysis of selected bone sites demonstrated an OPG-Fc-induced improvement of specific bone architectural indices and bone mineralization.

A calibration methodology of QCT BMD for human vertebral body with registered micro-CT images.

PURPOSE: The accuracy of QCT-based homogenized finite element (FE) models is strongly related to the accuracy of the prediction of bone volume fraction (BV/TV) from bone mineral density (BMD). The goal of this study was to establish a calibration methodology to relate the BMD computed with QCT with the BV/TV computed with micro-CT (microCT) over a wide range of bone mineral densities and to investigate the effect of region size in which BMD and BV/TV are computed. METHODS: Six human vertebral bodies were dissected from the spine of six donors and scanned submerged in water with QCT (voxel size: 0.391 x 0.391 x 0.450 mm3) and microCT (isotropic voxel size: 0.018(3) mm3). The microCT images were segmented with a single level threshold. Afterward, QCT-grayscale, microCT-grayscale, and microCT-segmented images were registered. Two isotropic grids of 1.230 mm (small) and 4.920 mm (large) were superimposed on every image, and QCT(BMD) was compared both with microCT(BMD) and microCT(BV/TV) for each grid cell. RESULTS: The ranges of QCT(BMD) for large and small regions were 9-559 mg/cm3 and -90 to 1006 mg/cm3, respectively. QCT(BMD) was found to overestimate microCT(BMD). No significant differences were found between the QCT(BMD)-microCT(BV/TV) regression parameters of the two grid sizes. However, the R2 was higher, and the standard error of the estimate (SEE) was lower for large regions when compared to small regions. For the pooled data, an extrapolated QCTBMD value equal to 1062 mg/ cm3 was found to correspond to 100% microCT(BV/TV). CONCLUSIONS: A calibration method was defined to evaluate BV/TV from QCTBMD values for cortical and trabecular bone in vitro. The QCT(BMD-microCT(BV/TV) calibration was found to be dependent on the scanned vertebral section but not on the size of the regions. However, the higher SEE computed for small regions suggests that the deleterious effect of QCT image noise on FE modelling increases with decreasing voxel size.

Mapping anisotropy improves QCT-based finite element estimation of hip strength in pooled stance and side-fall load configurations.

Hip fractures are one of the most severe consequences of osteoporosis. Compared to the clinical standard of DXA-based aBMD at the femoral neck, QCT-based FEA delivers a better surrogate of femoral strength and gains acceptance for the calculation of hip fracture risk when a CT reconstruction is available. Isotropic, homogenised voxel-based, finite element (hvFE) models are widely used to estimate femoral strength in cross-sectional and longitudinal clinical studies. However, fabric anisotropy is a classical feature of the architecture of the proximal femur and the second determinant of the homogenised mechanical properties of trabecular bone. Due to the limited resolution, fabric anisotropy cannot be derived from clinical CT reconstructions. Alternatively, fabric anisotropy can be extracted from HR-pQCT images of cadaveric femora. In this study, fabric anisotropy from HR-pQCT images was mapped onto QCT-based hvFE models of 71 human proximal femora for which both HR-pQCT and QCT images were available. Stiffness and ultimate load computed from anisotropic hvFE models were compared with previous biomechanical tests in both stance and side-fall configurations. The influence of using the femur-specific versus a mean fabric distribution on the hvFE predictions was assessed. Femur-specific and mean fabric enhance the prediction of experimental ultimate force for the pooled, i.e. stance and side-fall, (isotropic: r2=0.81, femur-specific fabric: r2=0.88, mean fabric: r2=0.86,p<0.001) but not for the individual configurations. Fabric anisotropy significantly improves bone strength prediction for the pooled configurations, and mapped fabric provides a comparable prediction to true fabric. The mapping of fabric anisotropy is therefore expected to help generate more accurate QCT-based hvFE models of the proximal femur for personalised or multiple load configurations.

Effect of boundary conditions on yield properties of human femoral trabecular bone.

Trabecular bone plays an important mechanical role in bone fractures and implant stability. Homogenized nonlinear finite element (FE) analysis of whole bones can deliver improved fracture risk and implant loosening assessment. Such simulations require the knowledge of mechanical properties such as an appropriate yield behavior and criterion for trabecular bone. Identification of a complete yield surface is extremely difficult experimentally but can be achieved in silico by using micro-FE analysis on cubical trabecular volume elements. Nevertheless, the influence of the boundary conditions (BCs), which are applied to such volume elements, on the obtained yield properties remains unknown. Therefore, this study compared homogenized yield properties along 17 load cases of 126 human femoral trabecular cubic specimens computed with classical kinematic uniform BCs (KUBCs) and a new set of mixed uniform BCs, namely periodicity-compatible mixed uniform BCs (PMUBCs). In stress space, PMUBCs lead to 7-72 % lower yield stresses compared to KUBCs. The yield surfaces obtained with both KUBCs and PMUBCs demonstrate a pressure-sensitive ellipsoidal shape. A volume fraction and fabric-based quadric yield function successfully fitted the yield surfaces of both BCs with a correlation coefficient [Formula: see text]. As expected, yield strains show only a weak dependency on bone volume fraction and fabric. The role of the two BCs in homogenized FE analysis of whole bones will need to be investigated and validated with experimental results at the whole bone level in future studies.

Experimental validation of a nonlinear µFE model based on cohesive-frictional plasticity for trabecular bone.

Trabecular bone is a porous mineralized tissue playing a major load bearing role in the human body. Prediction of age-related and disease-related fractures and the behavior of bone implant systems needs a thorough understanding of its structure-mechanical property relationships, which can be obtained using microcomputed tomography-based finite element modeling. In this study, a nonlinear model for trabecular bone as a cohesive-frictional material was implemented in a large-scale computational framework and validated by comparison of µFE simulations with experimental tests in uniaxial tension and compression. A good correspondence of stiffness and yield points between simulations and experiments was found for a wide range of bone volume fraction and degree of anisotropy in both tension and compression using a non-calibrated, average set of material parameters. These results demonstrate the ability of the model to capture the effects leading to failure of bone for three anatomical sites and several donors, which may be used to determine the apparent behavior of trabecular bone and its evolution with age, disease, and treatment in the future.

Quantitative analysis of imprint shape and its relation to mechanical properties measured by microindentation in bone.

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.

Heterogeneity of bone lamellar-level elastic moduli.

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.

Mechanical characterization of brushite and hydroxyapatite cements.

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.

A combined atomic force microscopy and nanoindentation technique to investigate the elastic properties of bone structural units.

To our knowledge, this study applied for the first time a recently developed combination of atomic force microscopy (AFM) and nanoindentation on trabecular and compact bone tissue. The major aim was to check the advantage of the available AFM-mode over the conventionally used optical microscope. First, we investigated if removal of the water content helped to prevent enzymatic degradation of the bone tissue and preserve its mechanical properties during a week. After the positive issue of this test, we quantified the intrinsic mechanical properties of single bone structural units (BSU). Bone specimens were obtained from the femoral neck of an 86 year old female. Four BSU were randomly selected and tested each with 24 indents of 5 mN maximum force. The available AFM mode proved to be a very useful tool for surface characterization and precise selection of the indentation area. The elastic modulus ranged from 18 -/+ 1.7 GPa for a BSU of compact bone to 22.5 -/+ 3.1 GPa for a BSU of trabecular bone. Hardness showed values between 0.6 -/+ 0.11 GPa for compact bone and 1.1 -/+ 0.17 GPa for trabecular bone. The results suggest that the micromechanics of bone tissue may also be described as an assembly of distinct structural units with rather homogeneous material properties.