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

Bazelier, Marloes T., Gallagher, Arlene M., van Staa, Tjeerd-Pieter, Cooper, Cyrus, Leufkens, Hubert G. M., Vestergaard, Peter and de Vries, Frank (2012) Use of thiazolidinediones and risk of osteoporotic fracture: disease or drugs? Pharmacoepidemiology and Drug Safety, 21 (5), 507-514. (doi:10.1002/pds.3234). (PMID:22392882)

Abstract

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.

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Contributors

Author: Cyrus Cooper

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