title: Thiazolidinediones and fractures in men and women.
abstract: BACKGROUND
  Clinical trials and meta-analyses have found that rosiglitazone maleate, a thiazolidinedione that is prescribed for type 2 diabetes mellitus, increases the risk of fractures in women. The association between the use of thiazolidinediones and fractures in men and women is not adequately understood.
  
  
  METHODS
  We conducted a prospective cohort study. The primary outcome was peripheral fractures in men and women who were exposed to thiazolidinediones compared with sulfonylureas. We studied 84 339 patients from British Columbia, Canada, who began treatment with a thiazolidinedione or a sulfonylurea. The association between the use of thiazolidinediones and fractures was examined using multivariate-adjusted Cox models.
  
  
  RESULTS
  The mean age of the patients in the study was 59 years, and 43% were women. In this cohort, treatment with a thiazolidinedione was associated with a 28% increased risk of peripheral fractures compared with treatment with a sulfonylurea (hazard ratio [HR], 1.28; 95% confidence interval [CI], 1.10-1.48). The use of pioglitazone hydrochloride was associated with an increased risk of peripheral fracture of 77% in women (HR, 1.76; 95% CI 1.32-2.38). Compared with exposure to sulfonylureas, exposure to pioglitazone was associated with more peripheral fractures in men (HR, 1.61; 95% CI 1.18-2.20), but we did not observe a similar association with exposure to rosiglitazone (HR, 1.00; 95% CI, 0.75-1.34).
  
  
  CONCLUSIONS
  Both men and women who take thiazolidinediones could be at increased risk of fractures. Pioglitazone may be more strongly associated with fractures than rosiglitazone. Larger observational studies are needed, and fracture data from clinical trials need to be fully published so that fracture risks can be known with greater certainty.
authors: Department of Anesthesiology, Pharmacology, and Therapeutics, University of British Columbia, Victoria, BC V8W 1Y2, Canada. colin.dormuth@ti.ubc.ca
authors: Colin R
authors: CR
authors: Dormuth
authors: Greg
authors: G
authors: Carney
authors: Bruce
authors: B
authors: Carleton
authors: Ken
authors: K
authors: Bassett
authors: James M
authors: JM
authors: Wright
mesh_terms: D000328:Adult; D000368:Aged; D001955:British Columbia; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005260:Female; D005598:Fractures, Spontaneous / Q000139:chemically induced*; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D000077205:Pioglitazone; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012306:Risk; D000077154:Rosiglitazone; D012737:Sex Factors; D013453:Sulfonylurea Compounds / Q000008:administration & dosage / Q000009:adverse effects; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000009:adverse effects*; D053778:Thiazolidines / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; D045162:Thiazolidinediones; D053778:Thiazolidines; D000077154:Rosiglitazone; D000077205:Pioglitazone