Knowledge of the biomechanical behavior and failure mechanisms of human bone is fundamental to understanding the etiology of bone fractures as well as the mechanisms by which aging, disease, and treatment can alter the mechanical competence of bone. In this context, the focus of this dissertation was to enhance the current understanding of the biomechanical mechanisms of bone strength, and more specifically, to elucidate the role of architecture and tissue material properties in overall bone strength and whole-bone failure behavior.

Using the latest advances in micro-computed tomography and high-resolution finite element modeling, we investigated the effect of typical population-variations in tissue-level ductility on human vertebral strength. We found that compared to the reference case, varying both cortical and trabecular tissue ultimate strains by ±1 SD from their mean values changed vertebral strength by at most ±8%, an effect that was relatively uniform across all the specimens. Overall strength changed similarly for similar (±1 SD) changes in trabecular versus cortical ductility. Further analysis revealed that only a tiny proportion of tissue failed (< 2%) when the whole bone reached its point of structure-level failure, and that the failure mode and location of this tiny amount were relatively insensitive to typical variations in tissue ductility. These findings suggest that it is the overall load transfer within the whole vertebral body —determined by bone volume fraction and microstructure— that dictates where failure occurs rather than typical variations in the ductility of the tissue. Together these findings suggest that typical variations in tissue ductility might have a relatively modest impact on vertebral strength compared to the multiple-fold variations in vertebral strength that are typically observed across any elderly population.

Combining micro-computed tomography, high-resolution finite element modeling and biomechanical testing, we sought to provide further insight into the tissue modulus of trabecular bone and better elucidate its relation with bone volume fraction and trabecular microarchitecture. Our results indicated that effective tissue modulus of vertebral trabecular bone varied greatly among the specimens and was negatively correlated with bone volume fraction of each vertebra (R² = 0.51, p < 0.05). These results suggest that there can be 3X variation in tissue modulus across the elderly human vertebrae, about 50% of which may be explained by variations in bone volume fraction. Together these findings suggest that as trabecular bone becomes older and thus more porous due to an imbalance between bone formation and resorption, the tissue may become stiffer to compensate for the bone loss.

The work presented in this dissertation has also provided substantial insight into the structure– function relations for trabecular bone from different anatomic sites. We investigated the main structure–function relation —characterized by bone volume fraction versus on-axis yield stress— for human calcaneal trabecular bone and compared this relation to that for trabecular bone from other anatomic sites. We found that the relation between yield stress and bone volume fraction of the calcaneus was most similar to that of the proximal tibia. Furthermore, our results demonstrated that while there was no universal yield stress–bone volume fraction relation for trabecular bone across different anatomic sites for on-axis loading, the general (normalized) yield stress–bone volume fraction relation was similar for all sites. This similarity in the normalized relation suggests that a given percentage deviation from the mean bone mass has the same mechanical consequence at the calcaneus as it does at the other anatomic sites.

In closure, this dissertation provides answers to some of the fundamental questions regarding the role of architecture and tissue material properties in explaining the variations in overall bone strength across individuals, and provides new insight into the etiology of age-related fractures. This work also outlines potential areas of future research to further advance our current understanding of overall bone strength and fracture etiology.