Evaluation of radius microstructure and areal bone mineral density improves fracture prediction in postmenopausal women

A majority of low-trauma fractures occur in subjects with only moderate decrease of areal bone mineral density (aBMD), ie, osteopenia, assessed by dual-energy X-ray absorptiometry (DXA) or low fracture probability assessed by FRAX. We investigated whether peripheral bone microstructure and estimated strength improve the prediction of incident fractures beyond central DXA and FRAX. In this population-based study of 740 postmenopausal women (aged 65.0 ± 1.4 years) from the Geneva Retirees Cohort (ISRCTN registry 11865958), we assessed at baseline cortical (Ct) and trabecular (Tb) volumetric bone mineral density (vBMD) and microstructure by peripheral quantitative computed tomography (HR-pQCT); bone strength by micro-finite element analysis; aBMD and trabecular bone score (TBS) by DXA; and FRAX fracture probability. Eighty-five low-trauma fractures occurred in 68 women over a follow-up of 5.0 ± 1.8 years. Tb and Ct vBMD and microstructure predicted incident fractures, independently of each other and of femoral neck (FN) aBMD and FRAX (with BMD ± TBS). However, the associations were markedly attenuated after adjustment for ultra-distal radius aBMD (same bone site). The best discrimination between women with and without fracture was obtained at the radius with total vBMD, the combination of a Tb with a Ct parameter, or with failure load, which improved the area under the curve (AUC) for major osteoporotic fracture when added to FN aBMD (0.760 versus 0.695, p = 0.022) or to FRAX-BMD (0.759 versus 0.714, p = 0.015). The replacement of failure load by ultra-distal aBMD did not significantly decrease the AUC (0.753, p = 0.747 and 0.750, p = 0.509, respectively). In conclusion, peripheral bone microstructure and strength improve the prediction of fractures beyond central DXA and FRAX but are partially captured in aBMD measured by DXA at the radius. Because HR-pQCT is not widely available for clinical purposes, assessment of ultra-distal radius aBMD by DXA may meanwhile improve fracture risk estimation.