Fracture Risk Indices From DXA-Based Finite Element Analysis Predict Incident Fractures Independently From FRAX: The Manitoba BMD Registry

Objective: Finite element analysis (FEA) is a computational method to predict the behavior of materials under applied loading. We developed a software tool that automatically performs FEA on dual-energy X-ray absorptiometry hip scans to generate site-specific fracture risk indices (FRIs) that reflect the likelihood of hip fracture from a sideways fall. This longitudinal study examined associations between FRIs and incident fractures. Methods: Using the Manitoba Bone Mineral Density (BMD) Registry, femoral neck (FN), intertrochanter (IT), and subtrochanter (ST) FRIs were automatically derived from 13,978 anonymized dual-energy X-ray absorptiometry scans (Prodigy, GE Healthcare) in women and men aged 50 yr or older (mean age 65 yr). Baseline covariates and incident fractures were assessed from population-based data. We compared c-statistics for FRIs vs FN BMD alone and fracture risk assessment (FRAX) probability computed with BMD. Cox regression was used to estimate hazard ratios and 95% confidence intervals (95% CIs) for incident hip, major osteoporotic fracture (MOF) and non-hip MOF adjusted for relevant covariates including age, sex, FN BMD, FRAX probability, FRAX risk factors, and hip axis length (HAL). Results: During mean follow-up of 6 yr, there were 268 subjects with incident hip fractures, 1003 with incident MOF, and 787 with incident non-hip MOF. All FRIs gave significant stratification for hip fracture (c-statistics FN-FRI: 0.76, 95% CI 0.73–0.79, IT-FRI 0.74, 0.71–0.77; ST-FRI 0.72, 0.69–0.75). FRIs continued to predict hip fracture risk even after adjustment for age and sex (hazard ratio per standard deviation FN-FRI 1.89, 95% CI 1.66–2.16); age, sex, and BMD (1.26, 1.07–1.48); FRAX probability (1.30, 1.11–1.52); FRAX probability with HAL (1.26, 1.05–1.51); and individual FRAX risk factors (1.32, 1.09–1.59). FRIs also predicted MOF and non-hip MOF, but the prediction was not as strong as for hip fracture. Summary: Automatically-derived FN, IT, and ST FRIs are associated with incident hip fracture independent of multiple covariates, including FN BMD, FRAX probability and risk factors, and HAL.