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Use of thiazolidinediones and risk of osteoporotic fracture: disease or drugs?
Author(s) -
Bazelier Marloes T.,
Gallagher Arlene M.,
Staa TjeerdPieter,
Cooper Cyrus,
Leufkens Hubert G. M.,
Vestergaard Peter,
Vries Frank
Publication year - 2012
Publication title -
pharmacoepidemiology and drug safety
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.023
H-Index - 96
eISSN - 1099-1557
pISSN - 1053-8569
DOI - 10.1002/pds.3234
Subject(s) - medicine , hazard ratio , proportional hazards model , pharmacoepidemiology , population , cohort study , cohort , hip fracture , type 2 diabetes , disease , diabetes mellitus , osteoporosis , endocrinology , pharmacology , confidence interval , medical prescription , environmental health
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. Copyright © 2012 John Wiley & Sons, Ltd.