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Prediction of Future Osteoporotic Fracture Occurrence by Genetic Profiling: A 6-Year Follow-Up Observational Study
Seung Hun Lee1, Eun-Hee Cho1, Seong Hee Ahn1
1Division of Endocrinology and Metabolism (S.H.L., H.-M.K., K.-H.L., B.-J.K., G.S.K., J.-M.K.), Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea; Department of Internal Medicine (E.-H.C., S.-W.K.), Kangwon National University College of Medicine, Chuncheon 24289, Korea; Department of Endocrinology (S.H.A.), Inha University School of Medicine, Incheon 22332, Republic of Korea; Skeletal Diseases Genome Research Center and Department of Orthopedic Surgery (T.-H.K., S.-Y.K.), Kyungpook National University School of Medicine, Daegu 41944, Korea; and Department of Endocrinology and Metabolism (M.I.K.), The Catholic University of Korea, College of Medicine, Seoul 137-701, Korea.
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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