Prediction of Future Osteoporotic Fracture Occurrence by Genetic Profiling: A 6-Year Follow-Up Observational Study

Context: Heredity is an important risk factor for osteoporotic fracture, but it remains unclear whether genetic factors improve the predictability of future fracture occurrence. Objective: To compare an integration model of genetic profiling with the current model for predicting future fracture occurrence. Design and Setting: A retrospective observational cohort study. Participants: Postmenopausal women aged 45–93 years who were untreated (n = 117), hormone-treated (n = 491), or bisphosphonate (BP)-treated (n = 415), with a mean 6.1-year follow-up. Main Outcomes Measures: The main outcome was incident fractures. Ninety-five single nucleotide polymorphisms were genotyped. We calculated the Korean-specific genetic risk score 35 (GRS35) from 35 single nucleotide polymorphisms associated with osteoporosis-related traits at the baseline visit. Results: Osteoporotic fracture occurred more frequently in the highest GRS35 tertile group than in the lower two tertile groups after adjustments for confounders (hazard...