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.
Original language | English |
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Pages (from-to) | 507-14 |
Number of pages | 8 |
Journal | Pharmacoepidemiology and Drug Safety |
Volume | 21 |
Issue number | 5 |
DOIs | |
Publication status | Published - May 2012 |
Externally published | Yes |
Keywords
- 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