title: Thiazolidinedione use and the longitudinal risk of fractures in patients with type 2 diabetes mellitus.
abstract: BACKGROUND
  Thiazolidinedione (TZD) use has recently been associated with an increased risk of fractures.
  
  
  OBJECTIVE
  The aim of this study was to determine the time-dependent relationship between TZD use and fracture risk.
  
  
  METHODS
  We conducted a retrospective cohort study in a large health system in southeast Michigan.
  
  
  METHODS
  PATIENTS who received care from the health system were included if they were at least 18 yr of age, had a diagnosis of diabetes, and had at least one prescription for an oral diabetes medication. These criteria identified 19,070 individuals (9,620 women and 9,450 men).
  
  
  METHODS
  This study compared patients treated with TZDs to patients without TZD treatment. Cox proportional hazard models were used to assess the relationship between exposure and outcomes.
  
  
  METHODS
  The primary outcome was the time to fracture. Secondary analyses examined the risk of fractures in subgroups defined by sex and age.
  
  
  RESULTS
  TZD use was associated with an increased risk of fracture in the cohort overall [adjusted hazard ratio (aHR), 1.35; 95% confidence interval (CI), 1.05-1.71] and in women (aHR, 1.57; 95% CI, 1.16-2.14), but not in men (aHR, 1.05; 95% CI, 0.70-1.58). Women more than 65 yr of age appeared to be at greatest risk for fracture (aHR, 1.72; 95% CI, 1.17-2.52). Among women, the increased fracture risk was not apparent until after 1 yr of TZD treatment.
  
  
  CONCLUSIONS
  TZD use was associated with an increased risk for fractures in women, particularly at ages above 65 yr. Clinicians should be aware of this association when considering TZD therapy so as to appropriately manage and counsel their patients.
authors.affiliation: Center for Health Services Research, Henry Ford Health System, 1 Ford Place, 3A Center for Health Services Research, Detroit, Michigan 48202, USA.
authors.forename: Zeina A
authors.initials: ZA
authors.lastname: Habib
authors.forename: Suzanne L
authors.initials: SL
authors.lastname: Havstad
authors.forename: Karen
authors.initials: K
authors.lastname: Wells
authors.forename: George
authors.initials: G
authors.lastname: Divine
authors.forename: Manel
authors.initials: M
authors.lastname: Pladevall
authors.forename: L Keoki
authors.initials: LK
authors.lastname: Williams
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005260:Female; D050723:Fractures, Bone / Q000139:chemically induced*; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D047495:PPAR gamma / Q000819:agonists / Q000502:physiology; D012189:Retrospective Studies; D012306:Risk; D045162:Thiazolidinediones / Q000009:adverse effects*
chemical_list: D007004:Hypoglycemic Agents; D047495:PPAR gamma; D045162:Thiazolidinediones