Epilepsy: fractures and the role of cumulative antiepileptic drug load

Abstract

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. 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. 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. 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.