Knowledge of the micromechanics of the human proximal femur is fundamental to improving clinical assessment of hip fracture risk and to understand the etiology of hip fractures. In this context, the focus of this dissertation was to enhance the current understanding of the role of bone microstructure and tissue-level ductility in the whole-bone failure behavior.

Combining the latest advances in micro-computed tomography and high-resolution finite element modeling, we investigated the fundamental issue of load-sharing between the cortical and trabecular bone in the proximal femur. Well-delineated, consistent regions of load-transfer in the proximal portion of the femoral neck and load-sharing in the distal portion were identified, both for a sideways fall and stance loading of the femur, and the mechanisms by which high stresses can develop in the cortical and trabecular bone tissue were demonstrated.

Using non-linear finite element analysis, microstructural failure mechanisms of the human proximal femur during a sideways fall loading were elucidated. The simulations revealed that structure-level failure of the weaker femurs was associated with a relatively lower proportion of tissue-level failure compared to the stronger femurs -- an indication of diminished structural redundancy in the weaker bones. The trabecular tissue failure always preceded and was more prominent than cortical tissue failure in all femurs, and dominated in the very weakest bones. A new morphological measure of hip fragility was identified:​ the proportion of trabecular bone compared with cortical bone in the femoral neck. This measure was a strong predictor of femoral strength even after adjusting for the effects of areal bone mineral density (aBMD), the current clinical gold-standard for fracture risk assessment.

The work presented in this dissertation has also provided new insight into the influence of tissue-level ductility on structure-level bone strength. It was revealed that the structure-level bone strength reduced substantially (by 40-60%) when the manner in which bone tissue deforms was altered from fully ductile to fully brittle. This effect was relatively uniform across all the specimens of an anatomic site subjected to similar kind of loading, but was greater for the femurs during a sideways fall compared to stance loading. This dissertation also evaluated the effect of typical population-variations in tissue-level ductility on the femoral strength. It was revealed that there was only a modest variation (~10-12%) in the femoral strength when both cortical and trabecular tissue ductility were simultaneously varied by one standard deviation about their mean.

In closure, this dissertation answers fundamental questions regarding the role of cortical and trabecular bone, and the underlying microstructural failure mechanisms, during age-related hip fractures, and provides new insight into the relationship between tissue-level ductility and structure-level bone strength. This work also outlines potential areas of future research to further advance our understanding of hip fracture etiology and describes a systematic approach to perform morphometric analysis on the bones so as to identify biomechanics-based structural determinants of femoral strength.