Performance of FRAX in Predicting Fractures in US Postmenopausal Women with Varied Race and Genetic Profiles

Background: Whether the Fracture Risk Assessment Tool (FRAX) performed differently in estimating the 10-year fracture probability in women of different genetic profiling and race remained unclear. Methods: The genomic data in the Women’s Health Initiative (WHI) study was analyzed (n = 23,981). The genetic risk score (GRS) was calculated from 14 fracture-associated single nucleotide polymorphisms (SNPs) for each participant. FRAX without bone mineral density (BMD) was used to estimate fracture probability. Results: FRAX significantly overestimated the risk of major osteoporotic fracture (MOF) in the WHI study. The most significant overestimation was observed in women with low GRS (predicted/observed ratio (POR): 1.61, 95% CI: 1.45–1.79) specifically Asian women (POR: 3.5, 95% CI 2.48–4.81) and in African American women (POR: 2.59, 95% CI: 2.33–2.87). Compared to the low GRS group, the 10-year probability of MOF adjusted for the FRAX score was 21% and 30% higher in the median GRS group and high GRS group, respectively. Asian, African American, and Hispanic women respectively had a 78%, 76%, and 56% lower hazard than Caucasian women after the FRAX score was adjusted. The results were similar for hip fractures. Conclusions: Our study suggested the FRAX performance varies significantly by both genetic profile and race in postmenopausal women.