The association between thiazolidinediones and hospitalisation for fracture in type 2 diabetic patients: a Taiwanese population-based nested case-control study.
OBJECTIVE
Evidence from the USA has emerged that thiazolidinediones may have a negative effect on the skeleton and increase the risk of fracture, but the association between thiazolidinediones use and fractures has not been evaluated in an Asian population. Using the 2000-2005 Taiwan National Health Insurance claims database, this Taiwanese population-based nested case-control study explored the association between thiazolidinediones use and hospitalisation for bone fracture in type 2 diabetic patients.


METHODS
In the study cohort of type 2 diabetic patients, we identified 18,003 patients with fracture and 90,015 matched controls. Multivariable conditional logistic regressions were used to estimate the association between exposure to thiazolidinediones and fractures. Duration of thiazolidinediones use was defined on the basis of cumulative days of exposure to thiazolidinediones during the year prior to the index date, i.e. <30 days, 30 to 180 days and >180 days.


RESULTS
More type 2 diabetic patients with fractures than controls used thiazolidinediones (fractures 5.99% vs control 4.06%). Thiazolidinediones use was associated with hospitalisation for fracture and the association was stronger with longer term exposure to thiazolidinediones (<30 days OR 1.32 [95% CI 1.09-1.54], p = 0.005; 30-180 days 1.42 [1.24-1.62], p < 0.0001; and >180 days 1.54 [1.37-1.74], p < 0.0001). This dose-response relationship was significantly evident in women (<30 days, 1.20 [0.93-1.55], p = 0.17; 30-180 days, 1.57 [1.32-1.86], p < 0.0001; and >180 days, 1.76 [1.52-2.04], p < 0.0001), but not in men.


CONCLUSIONS
Long-term exposure of type 2 diabetic patients to thiazolidinediones was associated with higher odds of fractures among women without a significant increase in odds of fractures among men.
Hsiao
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FY
Pharmaceutical Health Services Research Department, University of Maryland School of Pharmacy, 220 Arch Street, 12th Floor, Baltimore, MD 21201, USA. shsiao@rx.umaryland.edu
Mullins
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CD
D000368:Aged; D016022:Case-Control Studies; D015331:Cohort Studies; D048909:Diabetes Complications / Q000473:pathology*; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D050723:Fractures, Bone / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D013624:Taiwan; D045162:Thiazolidinediones / Q000009:adverse effects*
D045162:Thiazolidinediones