Adverse effects of antiepileptic drugs on bone structure - Epidemiology, mechanisms and therapeutic implications

Antiepileptic drugs (AEDs) were first associated with disorders of bone in both adults and children in the late 1960s. The most severe manifestations of these disorders are osteopenia/osteoporosis, osteomalacia and fractures. Bone disease has been described in several groups of patients receiving AE Ds. Groups identified as being more vulnerable to AED-associated bone disea se include institutionalised patients, postmenopausal women, older men and children. Radiological and histological evidence of bone disease is found in patients taking AEDs. Numerous biochemical abnormalities of bone metabolism have al so been described. The severity of bone and biochemical abnormalities is th ought to correlate with the duration of AED exposure and the number of AEDs used. In monotherapy, the AEDs most commonly associated with altered bone metabolism are phenytoin, primidone and phenobarbital (phenobarbitone). To date there have been no reports of altered bone metabolism in individuals r eceiving the newer anticonvulsants (specifically lamotrigine, topiramate, v igabatrin and gabapentin). The mechanisms of AED-associated bone disease are not clearly elucidated; h owever, several theories have been proposed to explain the link. No definit ive guidelines for evaluation or treatment have yet been determined.