External validation of a novel HR-pQCT fracture risk assessment tool (FRAC) in a female cohort: Sahlgrenska university hospital prospective evaluation of risk of bone fractures (SUPERB) study

Introduction The Microarchitecture Fracture Risk Assessment Calculator (μFRAC) was developed to predict osteoporotic fracture risk using direct measures of bone microarchitecture. However, its performance has not yet been externally validated in women. This study aims to evaluate the performance of the μFRAC model in predicting osteoporotic fracture risk in a cohort of older women. Methods The performance of μFRAC was assessed in a population of 2307 postmenopausal women aged 75–80 years in Gothenburg, Sweden. All participants underwent high resolution peripheral quantitative computed tomography (HR-pQCT) scanning of the distal radius and distal tibia (82 μm). Incident fracture information was collected from regional X-ray archives up until March 2023. The μFRAC 5-year and 10-year risk of major osteoporotic fracture (MOF) and any fracture (AOF) were calculated for all participants. The model discrimination was assessed using receiver operator characteristic curves (ROCs) and area under the curve (AUCs). FRAX and FN aBMD were used as reference models for comparison. Results During the follow-up period (mean 6.82 ± 2.48 years), 584 participants (25.3 %) sustained a MOF. The AUCs for MOF models for 5- and 10-year predictions were similar for μFRAC (AUC = 0.601 – 0.634) compared to reference models of FRAX (AUC = 0.615 - 0.618) and FN aBMD (AUC = 0.596). Overall, μFRAC showed good generalizability (regression slope 0.82 – 1.00) to the external cohort. Conclusion Fracture risk prediction by μFRAC was demonstrated to perform consistently with FRAX and FN aBMD in this external cohort of elderly females, suggesting it is a viable alternative fracture risk prediction tool. A benefit of μFRAC is that it is based on bone microarchitecture rather than binary clinical risk factors, so it has potential to be sensitive to changes in bone fragility as a function of age-related deterioration or anti-osteoporosis treatment.