Use of thiazolidinediones and risk of osteoporotic fracture: disease or drugs?

Marloes T Bazelier, Arlene M Gallagher, Tjeerd-Pieter van Staa, Cyrus Cooper, Hubert G M Leufkens, Peter Vestergaard, Frank de Vries*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


PURPOSE: Clinical and observational studies suggest that use of thiazolidinediones (TZDs) is associated with an increased fracture risk. In addition, type 2 diabetes mellitus (T2DM) is a risk factor for osteoporotic fracture. Our aim was to estimate fracture risks in TZD users and users of other antidiabetic drugs, classified according to proxies of disease severity.

METHODS: We conducted a population-based cohort study utilizing the Dutch PHARMO database (1998-2008). PHARMO links pharmacy-dispensing data to the National Hospital Registry. Oral antidiabetic users (n = 123,452) were matched 1:4 by year of birth and sex to non-users. Cox proportional hazards models were used to estimate hazard ratios (HRs) of fracture in TZD users. We created a proxy indicator for disease severity. The first stage was defined as current use of either a biguanide or a sulfonylureum, the second stage as current use of a biguanide and a sulfonylureum at the same time, the third stage was assigned to patients using TZDs and the fourth stage to patients using insulin.

RESULTS: The risk of osteoporotic fracture was increased 1.5-fold (HR 1.49, 95%CI 1.28-1.73) in patients who currently used TZDs (stage 3), and for patients using insulin (stage 4), the risk was increased 1.2-fold (HR 1.24, 1.14-1.36), as compared with controls. In the first and second stages, risks were lower: HR 1.11 (1.06-1.17) for stage 1 and HR 1.03 (0.96-1.11) for stage 2.

CONCLUSIONS: When observational studies assess risk of fracture in patients with TZDs, the severity of T2DM should be taken into account.

Original languageEnglish
Pages (from-to)507-14
Number of pages8
JournalPharmacoepidemiology and Drug Safety
Issue number5
Publication statusPublished - May 2012
Externally publishedYes


  • Administration, Oral
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Cohort Studies
  • Databases, Factual
  • Diabetes Mellitus, Type 2/drug therapy
  • Female
  • Follow-Up Studies
  • Humans
  • Hypoglycemic Agents/administration & dosage
  • Male
  • Middle Aged
  • Netherlands
  • Osteoporotic Fractures/epidemiology
  • Proportional Hazards Models
  • Registries
  • Risk Factors
  • Severity of Illness Index
  • Thiazolidinediones/administration & dosage
  • Young Adult

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