Comparison of the time-dependent discriminatory accuracy of femoral strength and bone mineral density for predicting future hip and major osteoporotic fractures: a 16-year follow-up of the AGES-Reykjavik cohort

Abstract

The discriminative accuracy of femoral strength was significantly higher than that of aBMD over 16 years of follow-up for classifying hip fractures and major osteoporotic fractures. The use of accurate thresholds, whether for aBMD or other imaging-based biomarkers, is crucial to improve sensitivity and identify high-risk older adults.

Background: Areal bone mineral density (aBMD) is a surrogate for bone strength but has limited prognostic value. Finite element (FE)-derived femoral strength offers a biomechanical alternative to aBMD for fracture risk assessment, but its long-term predictive value remains unclear. This study compared the discriminatory accuracy of aBMD and femoral strength for hip (HFs) and major osteoporotic fractures (MOFs) over 16 years, accounting for mortality risk.

Methods: In the prospective Age Gene/Environment Susceptibility-Reykjavik (AGES-Reykjavik) Study, elderly participants underwent CT scans at entry and automated algorithms were used to compute aBMD and femoral strength. Time-dependent area under the receiver operating characteristic curves (AUC) was used to compare the predictive abilities of aBMD and femoral strength. Optimal cutoffs at the Youden's index were compared with the World Health Organization (WHO)-defined aBMD cutoffs at various time points.

Results: The cohort comprised 4621 older adults (mean age 76 ± 5 years). Femoral strength had a significantly higher AUC than aBMD in identifying HFs (p < 0.05) from the 6th year in males and females, while their AUCs in predicting MOFs were similar. WHO-defined aBMD showed low sensitivity (17-52%) but high specificity (78-94%) for both HFs and MOFs. The sensitivity of optimal femoral strength was significantly higher than that of aBMD at comparable specificity by 5-19% for HFs and 2-10% for MOFs (p < 0.05).

Conclusions: Both image-based markers predict long-term fracture risk and enable opportunistic screening with existing CT scans. However, femoral strength demonstrates better discriminatory accuracy than aBMD. The low sensitivity of the WHO-defined aBMD demonstrates the necessity to revise current risk assessment criteria.

Keywords: Bone mineral density; Competing risk; Diagnostic accuracy; Finite-element modelling; Osteoporotic fractures; Prediction; Time-dependent AUC.