title: Risk of fractures and diabetes medications: a nationwide cohort study.
abstract: The effects of diabetes medications on risk of fracture were investigated using the South Korea nationwide claims database. We demonstrated that the use of dipeptidyl peptidase-4 inhibitor could be associated with decreased risk of fracture. Thiazolidinedione use was associated with about 60 % increased risk of fracture in real clinical practice.
  
  
  
  The effects of diabetes medication on fracture have important clinical health consequences, since most diabetes patients are at high risk of fracture. We aimed to investigate the effect of diabetes medication on fracture risk.
  
  
  
  The nationwide medical claim database in South Korea was investigated. Among 2,886,555 subjects with antidiabetes prescriptions, 207,558 subjects aged 50 years and older, who initiated diabetes medication from 2008 to 2011, were analyzed. The subjects were classified based on diabetes medication classes: non-user (insufficient exposure), metformin (MET), sulfonylurea (SU), alpha-glucosidase inhibitor (AGI), MET + SU, MET + thiazolidinedione (TZD), MET + dipeptidyl peptidase-4 inhibitor (DPP4-I), and SU + TZD.
  
  
  
  A total of 5996 fractures were observed. The fracture rate varied significantly across type of diabetes medications, with MET + DPP4-I combination group having the lowest rate and SU + TZD combination group having the highest rate. Compared to non-users, MET + DPP4-I inhibitor combination group had significantly reduced composite fracture risk (hazard ratio (HR) = 0.83, P = 0.025) and significantly reduced vertebral fracture risk (HR = 0.73, P = 0.013) in the unadjusted analysis. Compared to MET + SU users, MET + DPP4-I users showed a trend of lower non-vertebral fracture risk (HR = 0.82, P = 0.086) after adjusting for all confounding variables. Patients using TZD had significantly increased risk of fracture (HR = 1.59, P < 0.001) compared with patients not using TZDs adjusting for all confounding variables.
  
  
  
  The results of this nationwide study showed a trend that DPP4 inhibitor might have a protective effect on bone metabolism compared with SU, when added to MET. Clinicians should take these results into consideration when prescribing diabetes medication, especially in elderly patients or those at high risk or fracture.
authors.affiliation: Department of Anatomy, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: H J
authors.initials: HJ
authors.lastname: Choi
authors.affiliation: Division for Healthcare Technology Assessment Research, National Evidence-based Healthcare Collaborating Agency, Seoul, South Korea.
authors.forename: C
authors.initials: C
authors.lastname: Park
authors.affiliation: Department of Orthopaedic Surgery, Seoul National University Bundang Hospital, Seongnam, South Korea.
authors.forename: Y-K
authors.initials: YK
authors.lastname: Lee
authors.affiliation: Department of Orthopaedic Surgery, Chung-Ang University Hospital, Seoul, South Korea.
authors.forename: Y-C
authors.initials: YC
authors.lastname: Ha
authors.affiliation: College of Pharmacy Gachon University, Incheon, South Korea.
authors.forename: S
authors.initials: S
authors.lastname: Jang
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, 28 Yungun-Dong, Chongno-Gu, Seoul, 110-744, South Korea. csshin@snu.ac.kr.
authors.forename: C S
authors.initials: CS
authors.lastname: Shin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D005260:Female; D050723:Fractures, Bone / Q000453:epidemiology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D056910:Republic of Korea; D012189:Retrospective Studies; D012307:Risk Factors; D013453:Sulfonylurea Compounds
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds
keywords: Claim database; Diabetes; Fracture; Medication; Pharmacoepidemiology