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

초록

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 ratio [HR], 1.73; 95% confidence interval [CI], 1.17-2.55). The associations of the GRS35 with incident fracture were only significant in the BP group (HR, 2.25; 95% CI, 1.28-3.95) and not in the untreated (HR, 1.26; 95% CI, 0.34-4.66) and hormone-treated (HR, 1.21; 95% CI, 0.62-2.36) groups. Integration of the GRS35 into the current model further improved its predictability for incident fracture occurrence by 6.3% (P = .010). Conclusions: Genetic profiling can more accurately predict future fracture risk, especially in individuals taking BPs.

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