Fracture prediction using 3D-DXA-finite element based femoral strength: a prospective study in postmenopausal women

Although areal bone mineral density (aBMD) measured by DXA is a good predictor of fractures, nearly half of low-trauma fractures occur in individuals without osteoporosis (T-score > -2.5 SD). This study investigated whether femoral strength estimated from 3D DXA-based finite element (FE) analysis enhances the prediction of incident fractures compared with conventional 2D DXA-derived aBMD. Baseline hip DXA scans from 740 postmenopausal women in the Geneva Retirees Cohort were analyzed. 3D reconstructions of the proximal femur were generated to estimate femoral strength using FE analysis and to derive structural bone parameters. Over a mean follow-up of 5.7 ± 1.5 years, 100 low-trauma fractures were recorded, including 44 major osteoporotic fractures (MOF), 89% at non-hip sites. Femoral strength, total and trabecular vBMD, some cortical parameters, and conventional areal BMD were all significantly associated with incident low-trauma fractures (risk increase of 23-38% per SD decrease) and major osteoporotic fractures (36-59%), with femoral strength showing hazard ratios (95% confidence interval) of 1.32 (1.08-1.60) and 1.50 (1.12-2.01), respectively. A strength threshold of 2600 N improved fracture risk classification beyond conventional aBMD thresholds and outperformed the previously proposed fragile strength 3000 N threshold. Notably, 25% of women with low-trauma fractures and 27% with MOF were non-osteoporotic by aBMD but exhibited fragile femoral strength (≤3000 N), with 14% and 16% respectively below the very fragile threshold (≤2600 N). In conclusion, 3D DXA-derived femoral strength provides complementary value to aBMD in identifying women at elevated fracture risk, particularly those not classified as osteoporotic by conventional criteria.