Evaluating the Performance of the WHO International Reference Standard for Osteoporosis Diagnosis in Postmenopausal Women of Varied Polygenic Score and Race

Background: Whether the bone mineral density (BMD) T-score performs differently in osteoporosis classification in women of different genetic profiling and race background remains unclear. Methods: The genomic data in the Women’s Health Initiative study was analyzed (n = 2417). The polygenic score (PGS) was calculated from 63 BMD-associated single nucleotide polymorphisms (SNPs) for each participant. The World Health Organization′s (WHO) definition of osteoporosis (BMD T-score ≤ −2.5) was used to estimate the cumulative incidence of fracture. Results: T-score classification significantly underestimated the risk of major osteoporotic fracture (MOF) in the WHI study. An enormous underestimation was observed in African American women (POR: 0.52, 95% CI: 0.30–0.83) and in women with low PGS (predicted/observed ratio [POR]: 0.43, 95% CI: 0.28–0.64). Compared to Caucasian women, African American, African Indian, and Hispanic women respectively had a 59%, 41%, and 55% lower hazard of MOF after the T-score was adjusted for. The results were similar when used for any fractures. Conclusions: Our study suggested the BMD T-score performance varies significantly by race in postmenopausal women.