Antiepileptic drug-induced bone disease

Abstract

Antiepileptic drug-induced bone disease, such as osteomalacia and osteoporosis, can occur with chronic treatment with antiepileptic drugs (AEDs). Chronic therapy with AEDs can cause vitamin, mineral, and bone metabolism disorders causing defects that can lead to symptomatic bone disease. The mechanism of development of these bone disorders is AED inhibition of intestinal calcium absorption and acceleration of conversion of vitamin D to nonbiologically active more polar metabolites by induced hepatic enzymes. These effects lead to decreased serum calcium, decreased circulating and tissue active vitamin D metabolite levels, decreased serum phosphate, increased PTH, and alterations in bone remodeling. Because patients are frequently treated for many years with AEDs, the risk for bone complications is often enhanced. AEDs that induce hepatic microsomal cytochrome P450 enzymes, such as phenytoin, phenobarbital, and carbamazepine, lower serum calcium, vitamin D, and 25-OHD levels in the body, which can lead to AED-induced bone disease. Other AEDs that do not induce hepatic microsomal cytochrome P450 enzymes, such as valproate and its derivatives, ethosuxamide, gabapentin, vigabatrin, and lamotrigine, do not affect serum calcium, vitamin D, and 25-OHD levels in the body, and do not cause AED-induced bone disease.