title: Rosiglitazone-associated fractures in type 2 diabetes: an Analysis from A Diabetes Outcome Progression Trial (ADOPT).
abstract: OBJECTIVE
  The purpose of this study was to examine possible factors associated with the increased risk of fractures observed with rosiglitazone in A Diabetes Outcome Progression Trial (ADOPT).
  
  
  METHODS
  Data from the 1,840 women and 2,511 men randomly assigned in ADOPT to rosiglitazone, metformin, or glyburide for a median of 4.0 years were examined with respect to time to first fracture, rates of occurrence, and sites of fractures.
  
  
  RESULTS
  In men, fracture rates did not differ between treatment groups. In women, at least one fracture was reported with rosiglitazone in 60 patients (9.3% of patients, 2.74 per 100 patient-years), metformin in 30 patients (5.1%, 1.54 per 100 patient-years), and glyburide in 21 patients (3.5%, 1.29 per 100 patient-years). The cumulative incidence (95% CI) of fractures in women at 5 years was 15.1% (11.2-19.1) with rosiglitazone, 7.3% (4.4-10.1) with metformin, and 7.7% (3.7-11.7) with glyburide, representing hazard ratios (95% CI) of 1.81 (1.17-2.80) and 2.13 (1.30-3.51) for rosiglitazone compared with metformin and glyburide, respectively. The increase in fractures with rosiglitazone occurred in pre- and postmenopausal women, and fractures were seen predominantly in the lower and upper limbs. No particular risk factor underlying the increased fractures in female patients who received rosiglitazone therapy was identified.
  
  
  CONCLUSIONS
  Further investigation into the risk factors and underlying pathophysiology for the increased fracture rate in women taking rosiglitazone is required to relate them to preclinical data and better understand the clinical implications of and possible interventions for these findings.
authors.affiliation: Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, VA Puget Sound Health Care System and University of Washington, Seattle, Washington 98108, USA. skahn@u.washington.edu
authors.forename: Steven E
authors.initials: SE
authors.lastname: Kahn
authors.forename: Bernard
authors.initials: B
authors.lastname: Zinman
authors.forename: John M
authors.initials: JM
authors.lastname: Lachin
authors.forename: Steven M
authors.initials: SM
authors.lastname: Haffner
authors.forename: William H
authors.initials: WH
authors.lastname: Herman
authors.forename: Rury R
authors.initials: RR
authors.lastname: Holman
authors.forename: Barbara G
authors.initials: BG
authors.lastname: Kravitz
authors.forename: Dahong
authors.initials: D
authors.lastname: Yu
authors.forename: Mark A
authors.initials: MA
authors.lastname: Heise
authors.forename: R Paul
authors.initials: RP
authors.lastname: Aftring
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Viberti
mesh_terms: D017668:Age of Onset; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D018450:Disease Progression; D005260:Female; D050723:Fractures, Bone / Q000453:epidemiology*; D005905:Glyburide / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000009:adverse effects*; D016896:Treatment Outcome
chemical_list: D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D008687:Metformin; D005905:Glyburide