title: Prediction of Future Osteoporotic Fracture Occurrence by Genetic Profiling: A 6-Year Follow-Up Observational Study.
abstract: BACKGROUND
  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.
  
  
  METHODS
  A retrospective observational cohort study.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
authors.affiliation: Division 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.
authors.forename: Seung Hun
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Division 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.
authors.forename: Eun-Hee
authors.initials: EH
authors.lastname: Cho
authors.affiliation: Division 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.
authors.forename: Seong Hee
authors.initials: SH
authors.lastname: Ahn
authors.affiliation: Division 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.
authors.forename: Hyeon-Mok
authors.initials: HM
authors.lastname: Kim
authors.affiliation: Division 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.
authors.forename: Kyeong-Hye
authors.initials: KH
authors.lastname: Lim
authors.affiliation: Division 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.
authors.forename: Beom-Jun
authors.initials: BJ
authors.lastname: Kim
authors.affiliation: Division 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.
authors.forename: Sang-Wook
authors.initials: SW
authors.lastname: Kim
authors.affiliation: Division 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.
authors.forename: Tae-Ho
authors.initials: TH
authors.lastname: Kim
authors.affiliation: Division 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.
authors.forename: Shin-Yoon
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Division 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.
authors.forename: Ghi Su
authors.initials: GS
authors.lastname: Kim
authors.affiliation: Division 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.
authors.forename: Moo Il
authors.initials: MI
authors.lastname: Kang
authors.affiliation: Division 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.
authors.forename: Jung-Min
authors.initials: JM
authors.lastname: Koh
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D050071:Bone Density Conservation Agents / Q000627:therapeutic use; D004164:Diphosphonates / Q000627:therapeutic use; D015914:Estrogen Replacement Therapy; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000175:diagnosis* / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics*; D058866:Osteoporotic Fractures / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics* / Q000517:prevention & control; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates