It has been known since the late 1960s that certain antiepileptic drugs are associated with disorders of bone metabolism in both adults and children. The most severe manifestations of these disorders are osteopenia, osteomalacia, and fractures. Radiological or histologic evidence of bone disease as well as biochemical abnormalities, including hypocalcemia, hypophosphatemia, elevated serum alkaline phosphatase, elevated parathyroid hormone [PTH] and reduced levels of active vitamin D have been detected in patients taking AEDs. At present, the clinical significance of these biochemical abnormalities has not been conclusively characterized. The severity of bone and chemical abnormalities has been thought to correlate with the duration of AED exposure and the number of antiepileptic agents used. In monotherapy, the AEDs most commonly associated with altered bone metabolism are phenytoin, primidone, and phenobarbital. Associations between other AEDs and bone disease have also been noted. Although a previous study found conflicting results relative to carbamazepine, a recent study found an association between carbamazepine monotherapy and """"""""anticonvulsant osteomalacia"""""""" also identified and associated between valproate monotherapy and reduced bone density in children. Additional studies are needed to elucidate these findings. Several theories have been proposed to explain the link between certain AEDs and bone disease. Agents which induced hepatic cytochrome P450 enzymes may induce the metabolism of vitamin D to inactive metabolites. Decrease availability of active vitamin D would result in decreased intestinal calcium absorption and eventually increase the mobilization of bone calcium stores. Secondly AEDs may interfere directly with intestinal absorption of calcium leading to hypocalcemia and feedback hypersecretion of PTH. Thirdly, there is some suggestion that AEDs may directly affect bone cell function, possibly through inhibition of the cellular response to the cellular responses to PTH. Methodology This is a prospective study of bone turnover and bone mass in adult women on AED monotherapy. Three classes of AED will be investigated: 1] AED which does not effect the cytochrome P450 hepatic-mixed function system; lamotrigine 2] AED, which induce the cytochrome P450 hepatic-mixed function system: carbamazepine, phenytoin 3] AED, which inhibits the cytochrome P450 hepatic-mixed function system: divalproex sodium.
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