Bone Reports · Nov 2026
A heel-ultrasound-derived polygenic score and 5-year fracture risk beyond bone density in midlife Taiwanese women: A TPMI cohort study
By Hsu YS, Tseng SC, Deng YL et al.
Purpose Fracture risk tools discriminate poorly in midlife women, and the value of polygenic scores beyond bone mineral density (BMD) is unquantified in East Asians. We assessed whether published bone-related scores refine 5-year fracture risk beyond age and BMD in Taiwanese women. Methods We followed 1866 women aged 45–64 years from the Taiwan Precision Medicine Initiative biobank linked to a dual-energy X-ray absorptiometry registry, censoring at death, 5 years, or end of data. The outcome was incident major osteoporotic fracture at the four standard sites. Sixty-six Polygenic Score Catalog scores were evaluated in Cox models adjusted for age and minimum T-score, with incremental discrimination estimated by repeated cross-validation in which the score was selected inside each training fold. Results Ninety-nine women had fractures (5-year cumulative incidence 6.5%). Heel-ultrasound-derived scores carried the signal, with the three leading scores similar. For PGS001955, the hazard ratio per standard deviation was 1.73 (95% CI 1.42–2.10), and 1.71 (1.26–2.32) after adjustment for FRAX in 1175 women with a reported value. With selection inside the resampling, the 5-year area under the curve rose from 0.613 to 0.676 (difference + 0.063, 95% CI +0.016 to +0.108). Five-year risk was 12.3% in the top and 2.2% in the bottom quartile. The association did not differ by osteoporosis status (interaction P = 0.78). Conclusion Heel-ultrasound-derived polygenic scores developed in Europeans were associated with 5-year major osteoporotic fracture beyond age and measured BMD in midlife Taiwanese women. These hypothesis-generating findings require validation in an independent East Asian cohort with genotype-level data.