Prognostic Association of Handgrip-Defined Probable or Possible Sarcopenia Status and Polygenic Risk with 10-Year Fracture Incidence among Black, Hispanic, and White Women: A Women's Health Initiative Study

Purpose: The Fracture Risk Assessment Tool (FRAX) excludes objective skeletal muscle health and genetic variables. We evaluated the prognostic associations of handgrip-defined probable/possible sarcopenia and genome-wide polygenic scores (GPS) with 10-year fracture risk, and their incremental predictive value beyond FRAX across racial/ethnic groups and GPS strata. Methods: We analyzed 2,051 postmenopausal women from the Women's Health Initiative. Race-specific analyses focused on Black, Hispanic, and White participants (n=2,009), excluding American Indian/Alaska Native and Asian/Pacific Islander individuals due to sparse fracture events. Sarcopenia status was operationalized by low handgrip strength alone via EWGSOP2 (<16.0 kg) and AWGS 2025 (<18.0-20.0 kg) criteria. Fine-Gray models estimated subdistribution hazard ratios (sHR), treating death as a competing risk. Predictive performance at 10 years was assessed using time-dependent AUC, Brier scores, and decision curve analysis (DCA). Results: Handgrip-defined probable or possible sarcopenia prevalence was 4.4% (EWGSOP2) and 6.4% (AWGS 2025). Black women demonstrated lower risk for major osteoporotic fractures (MOF) (adjusted sHR=0.19, 95% CI: 0.08-0.48) and hip fractures (adjusted sHR=0.07, 95% CI: 0.01-0.52) compared to White women. Neither sarcopenia status nor high GPS showed statistically significant independent associations with fractures after FRAX adjustment. Adding sarcopenia status to baseline FRAX (AUC: 0.71 for MOF; 0.69 for hip) yielded near-identical AUCs, Brier scores, and within-sample net benefit. Conclusion: Handgrip-defined probable/possible sarcopenia and current GPS do not provide independent or incremental predictive value beyond the clinical FRAX framework within this genomic sub-sample of older women.