Exposure to antiepileptic drugs and the risk of hip fracture: A case-control study


Address correspondence to Ioannis Tsiropoulos, Department of Neurology, Odense University Hospital, Sdr Boulevard 29, 5000 Odense C, Denmark. E-mail: iotsi@dadlnet.dk


Purpose: To investigate whether the use of antiepileptic drugs (AEDs) increases the risk of hip fracture.

Methods: We performed a case-control study using data from the Funen County (population 2004: 475,000) hip fracture register. Cases (n = 7,557) were all patients admitted to county hospitals with a hip fracture during the period 1996–2004. Controls (n = 27,575) were frequency matched by age and gender. Information on use of AEDs, other drugs, and hospital contacts was available from local registers. Odds ratios (ORs) with 95% confidence intervals (CI) for hip fracture were estimated by unconditional logistic regression.

Results: Fracture risk was increased with ever use of any AED (OR: 1.31; 95% CI: 1.16–1.48). The risk was also increased with use of only enzyme inducing (OR: 1.31; 95% CI: 1.14–1.51), but not with use of only noninducing AEDs (OR: 1.03; 95% CI: 0.77–1.37). Current (OR: 1.92; 95% CI: 1.58–2.33) and recent use, as well as high daily (OR: 1.50; 95% CI: 1.24–1.82) and cumulative dose increased fracture risk, but long treatment duration or previous use did not. The risk was modified by the presence of an epilepsy diagnosis.

Conclusion: Use of AEDs modestly increases the risk of hip fracture. The risk increase is probably associated to a higher degree with a dose dependent effect on CNS with current and recent use, than with an effect on bone tissue.