Bound and pore water contributions to fracture in lateral femoral cortex: MRI-based extended finite element and fuzzy approximation modeling.

Atypical femoral fracture (AFF) is a rare fracture associated with long-term bisphosphonate treatment that occurs in the subtrochanteric and midshaft femur. AFF is not fully explained by bone mineral density motivating identification of biomarkers of AFF risk that reflect bone quality. Cortical bone water has been linked to mechanical properties of bone. Ultra-short echo time magnetic resonance imaging (UTE MRI) can quantify water compartments in bone, including matrix-associated bound water (BW) and porosity-related pore water (PW). Here, we investigated the influence of BW and PW on fracture formation in the AFF region using MRI-based extended finite element modeling and applied fuzzy approximation to capture nonlinear effects between BW and PW on mechanical outcomes. Simulation results showed that individually, mean BW and PW were not correlated with FE-predicted whole femur fracture load or stiffness. Mean porosity index, which is the ratio of PW to total water, was negatively associated with strain at the crack site (R = -0.54, p = 0.026). Stiffness values from BW and PW-based FE simulations were significantly correlated (R = 0.92, p < 0.01), whereas no correlation was observed for fracture load. Fuzzy sensitivity analysis showed that PW and BW are interrelated variables, and their relative influence on stiffness and strain at crack location depends on their levels within the AFF region. These results provide new insights into mechanisms of AFF using MRI including the compartment-specific roles of bone water.