The etiology of hip fractures remains unclear but might be elucidated by an improved understanding of the microstructural failure mechanisms of the human proximal femur during a sideways fall impact. In this context, we biomechanically tested 12 cadaver proximal femurs (aged 76 ± 10 years; 8 female, 4 male) to directly measure strength for a sideways fall and also performed micro-computed tomography (CT)-based, nonlinear finite element analysis of the same bones (82-micron-sized elements, ∼120 million elements per model) to estimate the amount and location of internal tissue-level failure (by ductile yielding) at initial structural failure of the femur. We found that the correlation between the directly measured yield strength of the femur and the finite element prediction was high (R(2) = 0.94, p < 0.0001), supporting the validity of the finite element simulations of failure. In these simulations, the failure of just a tiny proportion of the bone tissue (1.5% to 6.4% across all bones) led to initial structural failure of the femur. The proportion of failed tissue, estimated by the finite element models, decreased with decreasing measured femoral strength (R(2) = 0.88, p < 0.0001) and was more highly correlated with measured strength than any measure of bone volume, mass, or density. Volume-wise, trabecular failure occurred earlier and was more prominent than cortical failure in all femurs and dominated in the very weakest femurs. Femurs with low measured strength relative to their areal bone mineral density (BMD) (by dual-energy X-ray absorptiometry [DXA]) had a low proportion of trabecular bone compared with cortical bone in the femoral neck (p < 0.001), less failed tissue (p < 0.05), and low structural redundancy (p < 0.005). We conclude that initial failure of the femur during a sideways fall is associated with failure of just a tiny proportion of the bone tissue, failure of the trabecular tissue dominating in the very weakest femurs owing in part to a lack of structural redundancy.

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