Epilepsy: fractures and the role of cumulative antiepileptic drug load

Background - An association between antiepileptic drugs (AEDs), low bone mineral density (BMD), fractures, and abnormalities in bone metabolism has been suggested for a longer period, although conclusive evidence has not been reported. We aimed at studying patient characteristics in a high-risk population. Methods - All adult patients from a residential unit of a tertiary epilepsy center who were diagnosed with osteoporosis and consequently treated with a bisphosphonate at that moment were included. Correlations between reported fractures and patient characteristics were explored. Results Of the total population of 261 adult patients, 54 patients were included resulting in a high prevalence rate of 21% osteoporosis in this population. The number of fractures correlated significantly with ambulatory status (r = -0.269, P = 0.05), drug load (r = 0.286, P = 0.04), and current number of AEDs (r = 0.283, P = 0.04). Correlations could not be provided for individual drugs in our population as only a minority was on monotherapy and even less patients had always been on monotherapy of the same antiepileptic drug. Linear regression analysis showed that cumulative drug load (defined by a surrogate parameter: the total duration of epilepsy multiplied by the number of AEDs) was the dominant factor explaining the occurrence of fractures. Conclusion - In this high-risk population, we obtained a positive and strong correlation between the occurrence of fractures in a diagnosed population with osteoporosis and the cumulative drug load of AEDs. This effect seems general, independent of the type of AEDs that were used.