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The amount of microdamage in bone tissue impairs mechanical performance and may act as a stimulus for bone remodeling. Here we determine how loading mode (tension vs. compression) and microstructure (trabecular microarchitecture, local trabecular thickness, and presence of resorption cavities) influence the number and volume of microdamage sites generated in cancellous bone following a single overload. Twenty paired cylindrical specimens of human vertebral cancellous bone from 10 donors (47–78 years) were mechanically loaded to apparent yield in either compression or tension, and imaged in three dimensions for microarchitecture and microdamage (voxel size 0.7×0.7×5.0 μm3). We found that the overall proportion of damaged tissue was greater (p=0.01) for apparent tension loading (3.9±2.4%, mean±SD) than for apparent compression loading (1.9±1.3%). Individual microdamage sites generated in tension were larger in volume (p

Type 1 Gaucher disease (GD) is an autosomal recessive lysosomal storage disease, affecting bone metabolism, structure and strength. Current bone assessment methods are not ideal. Semi-quantitative MRI scoring is unreliable, not standardized, and only evaluates bone marrow. DXA BMD is also used but is a limited predictor of bone fragility/fracture risk. Our purpose was to measure trabecular bone microarchitecture, as a biomarker of bone disease severity, in type 1 GD individuals with different GD genotypes and to apply machine learning based analytics to discriminate between GD patients and healthy individuals. Micro-MR imaging of the distal radius was performed on 20 type 1 GD patients and 10 healthy controls (HC). Fifteen stereological and textural measures (STM) were calculated from the MR images. General linear models demonstrated significant differences between GD and HC, and GD genotypes. Stereological measures, main contributors to the first two principal components (PCs), explained ~50% of data variation and were significantly different between males and females. Subsequent PCs textural measures were significantly different between GD patients and HC individuals. Textural measures also significantly differed between GD genotypes, and distinguished between GD patients with normal and pathologic DXA scores. PCA and SVM predictive analyses discriminated between GD and HC with maximum accuracy of 73% and area under ROC curve of 0.79. Trabecular STM differences can be quantified between GD patients and HC, and GD sub-types using micro-MRI and machine learning based analytics. Work is underway to expand this approach to evaluate GD disease burden and treatment efficacy. [ABSTRACT FROM AUTHOR]

Osteoporosis is a bone disease resulting in increased fracture risk as a result of alterations in both quantity and quality of bone. Bone quality is a combination of metabolic and microarchitectural properties of bone that can help to explain the increased susceptibility to fracture. Translational animal models are essential to understanding the pathology and for evaluating potential treatments of this disease. Large animals, such as the ovariectomized sheep, have been used as models for post-menopausal osteoporosis. However, long-term studies have not been carried out to observe the effects of ovariectomy after more than one year. This study employed micro-computed tomography to quantify changes in microarchitectural and mechanical parameters in femoral condyles and vertebral bodies of sheep that were sacrificed one or two years following ovariectomy. In the vertebral body, microarch-itectural characteristics were significantly degraded following one year of ovariectomy in comparison to controls. The mechanical anisotropy, determined from micro-scale finite element models, was also greater in the ovariectomized groups, although the fabric tensor anisotropy was similar. There was no greater architectural degradation following two years of ovariectomy compared to one. Ovariectomy had minimal effects on the trabecular architecture of the distal femur even after two years. These results indicate that the vertebral body is the preferred anatomic site for studying bone from the ovariectomized sheep model, and that architectural changes stabilize after the first year. [ABSTRACT FROM AUTHOR]

During insertion of a cancellous bone screw, the torque level reaches a plateau, at the engagement of all the screw threads prior to the screw head contact. This plateau torque (TPlateau) was found to be a good predictor of the insertion failure torque (stripping) and also exhibited strong positive correlations with areal bone mineral density (aBMD) in ovine bone. However, correlations between TPlateau and aBMD, as well as correlations between TPlateau and bone microarchitecture, have never been explored in human bone. The aim of this study was to determine whether TPlateau, a predictor of insertion failure torque, depends on aBMD and/or bone microarchitecture in human femoral heads. Fifty-two excised human femoral heads were obtained. The aBMD and microarchitecture of each specimen were evaluated using dual X-ray Absorptiometry and micro-computed tomography. A cancellous screw was inserted into specimens using an automated micro-mechanical test device, and Tplateau was calculated from the insertion profile. Tplateau exhibited the strongest correlation with the structure model index (SMI, R =-0.82, p < 0.001), followed by bone volume fraction (BV/TV, R=0.80, p < 0.01) and aBMD (R = 0.76, p < 0.01). Stepwise forward regression analysis showed an increase for the prediction of TPlateau when aBMD was combined with microarchitectural parameters, i.e., aBMD combined with SMI (R² increased from 0.58 to 0.72) and aBMD combined with BV/TV and BS/TV (R² increased from 0.58 to 0.74). In conclusion, TPlateau, a strong predictor for insertion failure torque, is significantly dependent on bone microarchitecture (particularly SMI and BV/TV) and aBMD. [ABSTRACT FROM AUTHOR]

The role of tissue-level post-yield behavior on the apparent-level strength of trabecular bone is a potentially important aspect of bone quality. To gain insight into this issue, we compared the apparent-level strength of trabecular bone for the hypothetical cases of fully brittle versus fully ductile failure behavior of the trabecular tissue. Twenty human cadaver trabecular bone specimens (5 mm cube; BV/TV=6-36%) were scanned with micro-CT to create 3D finite element models (22-micron element size). For each model, apparent-level strength was computed assuming either fully brittle (fracture with no tissue ductility) or fully ductile (yield with no tissue fracture) tissue-level behaviors. We found that the apparent-level ultimate strength for the brittle behavior was only about half the value of the apparent-level 0.2%-offset yield strength for the ductile behavior, and the ratio of these brittle to ductile strengths was almost constant (mean ± SD=0.5670.02; n=20; R²=0.99 between the two measures). As a result of this small variation, although the ratio of brittle to ductile strengths was positively correlated with the bone volume fraction (R²=0.44, p=0.01) and structure model index (SMI, R²=0.58, po0.01), these effects were small. Mechanistically, the fully ductile behavior resulted in a much higher apparent-level strength because in this case about 16-fold more tissue was required to fail than for the fully brittle behavior; also, there was more tensile- than compressive-mode of failure at the tissue level for the fully brittle behavior. We conclude that, in theory, the apparent-level strength behavior of human trabecular bone can vary appreciably depending on whether the tissue fails in a fully ductile versus fully brittle manner, and this effect is largely constant despite appreciable variations in bone volume fraction and microarchitecture. [ABSTRACT FROM AUTHOR]

Abstract: The shear strength of human trabecular bone may influence overall bone strength under fall loading conditions and failure at bone-implant interfaces. Here, we sought to compare shear and compressive yield strengths of human trabecular bone and elucidate the underlying failure mechanisms. We analyzed 54 specimens (5-mm cubes), all aligned with the main trabecular orientation and spanning four anatomic sites, 44 different cadavers, and a wide range of bone volume fraction (0.06–0.38). Micro-CT-based non-linear finite element analysis was used to assess the compressive and shear strengths and the spatial distribution of yielded tissue; the tissue-level constitutive model allowed for kinematic non-linearity and yielding with strength asymmetry. We found that the computed values of both the shear and compressive strengths depended on bone volume fraction via power law relations having an exponent of 1.7 (R 2=0.95 shear; R 2=0.97 compression). The ratio of shear to compressive strengths (mean±SD, 0.44±0.16) did not depend on bone volume fraction (p=0.24) but did depend on microarchitecture, most notably the intra-trabecular standard deviation in trabecular spacing (R 2=0.23, p<0.005). For shear, the main tissue-level failure mode was tensile yield of the obliquely oriented trabeculae. By contrast, for compression, specimens having low bone volume fraction failed primarily by large-deformation-related tensile yield of horizontal trabeculae and those having high bone volume failed primarily by compressive yield of vertical trabeculae. We conclude that human trabecular bone is generally much weaker in shear than compression at the apparent level, reflecting different failure mechanisms at the tissue level. [Copyright &y& Elsevier]

Abstract: Microdamage occurs in trabecular bone under normal loading, which impairs the mechanical properties. Architectural degradation associated with osteoporosis increases damage susceptibility, resulting in a cumulative negative effect on the mechanical properties. Treatments for osteoporosis could be targeted toward increased bone mineral density, improved architecture, or repair and prevention of microdamage. Delineating the relative roles of damage and architectural degradation on trabecular bone strength will provide insight into the most beneficial targets. In this study, damage was induced in bovine trabecular bone samples by axial compression, and the effects on the mechanical properties in shear were assessed. The damaged shear modulus, shear yield stress, ultimate shear stress, and energy to failure all depended on induced damage and decreased as the architecture became more rod-like. The changes in ultimate shear strength and toughness were proportional to the decrease in shear modulus, consistent with an effective decrease in the cross-section of trabeculae based on cellular solid analysis. For typical ranges of bone volume fraction in human bone, the strength and toughness were much more sensitive to decreased volume fraction than to induced mechanical damage. While ultimately repairing or avoiding damage to the bone structure and increasing bone density both improve mechanical properties, increasing bone density is the more important contributor to bone strength. [Copyright &y& Elsevier]

Abstract: The relative biomechanical effects of antiresorptive treatment on cortical thickness vs. trabecular bone microarchitecture in the spine are not well understood. To address this, T-10 vertebral bodies were analyzed from skeletally mature female beagle dogs that had been treated with oral saline (n=8 control) or a high dose of oral risedronate (0.5mg/kg/day, n=9 RIS-suppressed) for 1 year. Two linearly elastic finite element models (36-μm voxel size) were generated for each vertebral body—a whole-vertebra model and a trabecular-compartment model—and subjected to uniform compressive loading. Tissue-level material properties were kept constant to isolate the effects of changes in microstructure alone. Suppression of bone turnover resulted in increased stiffness of the whole vertebra (20.9%, p=0.02) and the trabecular compartment (26.0%, p=0.01), while the computed stiffness of the cortical shell (difference between whole-vertebra and trabecular-compartment stiffnesses, 11.7%, p=0.15) was statistically unaltered. Regression analyses indicated subtle but significant changes in the relative structural roles of the cortical shell and the trabecular compartment. Despite higher average cortical shell thickness in RIS-suppressed vertebrae (23.1%, p=0.002), the maximum load taken by the shell for a given value of shell mass fraction was lower (p=0.005) for the RIS-suppressed group. Taken together, our results suggest that—in this canine model—the overall changes in the compressive stiffness of the vertebral body due to suppression of bone turnover were attributable more to the changes in the trabecular compartment than in the cortical shell. Such biomechanical studies provide an unique insight into higher-scale effects such as the biomechanical responses of the whole vertebra. [Copyright &y& Elsevier]

Abstract: This study addressed the effects of changes in trabecular microarchitecture induced by suppressed bone turnover—including changes to the remodeling space—on the trabecular bone strength–volume fraction characteristics independent of changes in tissue material properties. Twenty female beagle dogs, aged 1–2 years, were treated daily with either oral saline (n=10 control) or high doses of oral risedronate (0.5mg/kg/day, n=10 suppressed) for a period of 1 year, the latter designed (and confirmed) to substantially suppress bone turnover. High-resolution micro-CT-based finite element models (18-μm voxel size) of canine trabecular bone cores (n=2 per vertebral body) extracted from the T-10 vertebrae were analyzed in both compressive and torsional loading cases. The same tissue-level material properties were used in all models, thus providing measures of tissue-normalized strength due only to changes in the microarchitecture. Suppressed bone turnover resulted in more plate-like architecture with a thicker and more dense trabecular structure, but the relationship between the microarchitectural parameters and volume fraction was unaltered (p>0.05). Though the suppressed group had a greater tissue-normalized strength as compared to the control group (p<0.001) for both compressive and torsional loading, the relationship between tissue-normalized strength and volume fraction was not significantly altered for compression (p>0.13) or torsion (p>0.09). In this high-density, non-osteoporotic animal model, the increases in tissue-normalized strength seen with suppression of bone turnover were entirely commensurate with increases in bone volume fraction and thus, no evidence of microarchitecture-related or “stress-riser” effects which may disproportionately affect strength were found. [Copyright &y& Elsevier]

Abstract: Finite element (FE) modelling based on data from three-dimensional high-resolution computed tomography (CT) imaging systems provides a non-invasive method to assess structural mechanics. Automated mesh generation from these voxel based image data can be achieved by direct conversion to hexahedron elements, however these model representations have jagged edges. This paper proposes an automated method to generate smoothed FE meshes from voxel-based image data. Mesh fairing processes are utilized that allow constraints that control the smoothing process, and are computationally efficient. Surfaces of the mesh on the exterior, as well as interfaces between two tissues, can be smoothed by varying fairing parameters and constraint criteria. The method was tested on a variety of real and simulated three-dimensional data sets, resulting in both hexahedron and tetrahedron meshes. It was shown that the fairing process is linearly related to the number of smoothing iterations, and that peak stresses are reduced in FE simulations of the smoothed models. Although developed for micro-CT data sets, this fast and reliable mesh smoothing method could be applied to any three-dimensional image data where node and element connectivity have been defined. [Copyright &y& Elsevier]