Fracture risk with use of liver enzyme inducing antiepileptic drugs in people with active epilepsy: Cohort study using the General Practice Research Database

PURPOSE Liver enzyme inducing antiepileptic drugs (LEI AEDs) have adverse effects on bone metabolism but it is unclear whether this translates into increased fracture risk. This population based cohort study aimed to evaluate whether treatment with LEI AEDs is associated with increased risk of fracture in people with active epilepsy. METHODS The cohort included patients diagnosed with epilepsy and prescribed AEDs while registered at a GPRD general practice during 1993-2008. The hazard ratio with current use of LEI AEDs for fracture at any site and hip fracture was estimated using Cox proportional hazards models. RESULTS There were 7356 fractures (788 hip fractures) in 63259 participants. In women, the adjusted hazard ratio with use of LEI AEDs was 1.22 for fracture (95% CI 1.12-1.34; p<0.001) and 1.49 for hip fracture (1.15-1.94; p=0.002). In men, the hazard ratio for fracture was 1.09 (0.98-1.20; p=0.123) and for hip fracture 1.53 (1.10-2.12; p=0.011). For every 10000 women treated with LEI AEDs for one year, there could be 48 additional fractures, including 10 additional hip fractures. For every 10000 men treated with LEI AEDs for one year, there could be 4 additional hip fractures. CONCLUSIONS LEI AEDs may increase the risk of fracture in people with epilepsy. In patients at high risk of osteoporotic fracture alternative AED therapy may be appropriate. Further information is urgently needed on the safety of valproate and newer AEDs and on strategies to maintain bone health in people who need to be treated with LEI.