title: Risk of fractures in subjects with antihypertensive medications: A nationwide claim study.
abstract: BACKGROUND
  The effect of antihypertensives on fracture has important clinical implications, since antihypertensives are frequently prescribed with lifelong exposure. This study aimed to compare risk of fracture between antihypertensive medication classes and non-users among adults.
  
  
  METHODS
  Nationwide claim data from January 1, 2007 to December 31, 2011 were analyzed. Among 8,315,709 subjects with antihypertensive prescriptions in nationwide medical claim database in South Korea, 528,522 subjects, who initiated single-drug antihypertensives or non-users, were analyzed. Subjects were classified as non-user, alpha-blocker (AB), angiotensin-converting-enzyme-inhibitor (ACEI), angiotensin-receptor-blocker (ARB), beta-blocker (BB), calcium-channel-blocker (CCB), and diuretic users. Subjects with combination antihypertensive medications were excluded.
  
  
  RESULTS
  A total of 16,805 fracture outcomes were observed during mean follow-up duration of 1.9 years. Fracture rate per 10,000 person-years varied significantly across type of antihypertensives, with ARB having the lowest rate (152.7, 95% confidence interval (CI) 145.4-160.4), and AB having the highest rate (323.7, 95% CI 237.4-441.4). Non-users had fracture rates (152.2, 95% CI 148.7-155.7) similar to ARB users. In models adjusting for age, gender, comorbidity score, diagnosis of diabetes, diagnosis of osteoporosis, osteoporosis treatment, and osteoporosis related diseases, AB users (adjusted hazard ratio (aHR)=2.26), ACEI users (aHR=1.68), diuretic users (aHR=1.45), CCB users (aHR=1.23), and BB users (aHR=1.15) showed significantly increased risk of fractures compared with non-users (P<0.05). Only the fracture risk of ARB users (aHR=1.00, 95% CI 0.95-1.05) was not significantly different from the non-users.
  
  
  CONCLUSIONS
  The use of antihypertensives except for ARB is associated with increased risk of fracture, with ACEI and AB having higher risk among hypertensive adults.
authors.affiliation: Department of Internal Medicine, Chungbuk National University Hospital, Cheongju, Republic of Korea.
authors.forename: Hyung Jin
authors.initials: HJ
authors.lastname: Choi
authors.affiliation: Division for Healthcare Technology Assessment Research, National Evidence-based Healthcare Collaborating Agency, Seoul, Republic of Korea.
authors.forename: Chanmi
authors.initials: C
authors.lastname: Park
authors.affiliation: Department of Orthopaedic Surgery, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
authors.forename: Young-Kyun
authors.initials: YK
authors.lastname: Lee
authors.affiliation: Department of Orthopaedic Surgery, Chung-Ang University Hospital, Seoul, Republic of Korea.
authors.forename: Yong-Chan
authors.initials: YC
authors.lastname: Ha
authors.affiliation: College of Pharmacy Gachon University, Incheon, Republic of Korea.
authors.forename: Sunmee
authors.initials: S
authors.lastname: Jang
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address: csshin@snu.ac.kr.
authors.forename: Chan Soo
authors.initials: CS
authors.lastname: Shin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000959:Antihypertensive Agents / Q000009:adverse effects*; D015331:Cohort Studies; D016208:Databases, Factual / Q000639:trends; D005260:Female; D005500:Follow-Up Studies; D050723:Fractures, Bone / Q000139:chemically induced / Q000175:diagnosis / Q000453:epidemiology; D006801:Humans; D007345:Insurance Claim Review / Q000639:trends*; D008297:Male; D008875:Middle Aged; D058866:Osteoporotic Fractures / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology*; D056910:Republic of Korea / Q000453:epidemiology; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D000959:Antihypertensive Agents
keywords: Antihypertensives; Fracture; Pharmacoepidemiology