The roles of architecture and estrogen depletion in microdamage risk in trabecular bone.

Bone quantity, or density, has insufficient power to discriminate fracture risk in individuals. Additional measures of bone quality, such as microarchitectural characteristics and bone tissue properties, including the presence of damage, may improve the diagnosis of fracture risk. Microdamage and microarchitecture are two aspects of trabecular bone quality that are interdependent, with several microarchitectural changes strongly correlated to damage risk after compensating for bone density. This study aimed to delineate the effects of microarchitecture and estrogen depletion on microdamage susceptibility in trabecular bone using an ovariectomized sheep model to mimic post-menopausal osteoporosis. The propensity for microdamage formation in trabecular bone of the distal femur was studied using a sequence of compressive and torsional overloads. Ovariectomy had only minor effects on the microarchitecture at this anatomic site. Microdamage was correlated to bone volume fraction and structure model index (SMI), and ovariectomy increased the sensitivity to these parameters. The latter may be due to either increased resorption cavities acting as stress concentrations or to altered bone tissue properties. Pre-existing damage was also correlated to new damage formation. However, sequential loading primarily generated new cracks as opposed to propagating existing cracks, suggesting that pre-existing microdamage contributes to further damage of bone by shifting load bearing to previously undamaged trabeculae, which are subsequently damaged. The transition from plate-like to rod-like trabeculae, indicated by SMI, dictates this shift, and may be a hallmark of bone that is already predisposed to accruing greater levels of damage through compromised microarchitecture.

Alterations in trabecular bone microarchitecture in the ovine spine and distal femur following ovariectomy.

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, microarchitectural 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.

Shear strength and toughness of trabecular bone are more sensitive to density than damage.

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.

Density and architecture have greater effects on the toughness of trabecular bone than damage.

Bone damage has been cited as an important aspect of bone quality. As such, understanding the effects of damage on the toughness of trabecular bone should provide insight into trabecular bone behavior during energy-limiting cases, such as falls. The effects of damage on the toughness of 35 bovine trabecular bone specimens were studied. Damage was induced by compressing the on-axis specimens to either 1.5% or 2.5% strain, followed by compression to 7.5% strain. The overloads resulted in significant decreases in both modulus and elastic toughness, with significantly greater decreases for the high-damage group than the low-damage group. Following damage, the elastic toughness of the high-damage group was also lower than the undamaged elastic toughness of the control group. In contrast, there was no detectable effect of damage level on toughness measured to 7.5% strain. Toughness increased linearly with BMD (R(2)=0.50) and by a power law relationship with volume fraction (BV/TV) (R(2)=0.65). Microarchitectural parameters also predicted the toughness in the absence of BV/TV or BMD. Toughness decreased with increasing slenderness ratio (Tb.Sp/Tb.Th) and structure model index (SMI) (R(2)=0.68, multiple regression), again independent of damage level, suggesting that failure is influenced by trabecular buckling. Taken together, the results show that normal variations in toughness due to density and architecture dominate the changes due to damage at the levels induced in this study. Moreover, measuring toughness is sensitive to the final strain, as differences found in the elastic and initial plastic regions were undetectable at higher strains. The self-limiting nature of microcracks in trabecular bone, or the trabecular architecture itself, may inhibit microcracks from propagating to macroscopic trabecular fractures, thereby limiting the effect of damage on toughness and making it difficult to detect in comparison to normal population variability.