To investigate the effect of topiramate on bone mass and metabolism in premenopausal women with epilepsy.Thirty-six women on long-term (at least 1 year) topiramate monotherapy were compared with 36 women taking carbamazepine, 32 women taking valproate, and 36 age- and sex-matched controls. Subjects completed bone mineral density (BMD) studies. Serum was analyzed for indices of bone metabolism.BMD Z-scores, and serum 25-hydroxyvitamin D and 1alpha,25-dihydroxyvitamin D(3) concentrations did not differ among the groups. Serum calcium concentrations were significantly lower in patients receiving topiramate than in those receiving valproate, and in patients receiving carbamazepine than in those receiving valproate and controls. Patients taking topiramate had lower levels of parathyroid hormone compared with controls and those taking carbamazepine or valproate. Patients receiving topiramate had higher levels of bone-specific alkaline phosphatase and osteocalcin when compared with controls and higher levels of C-terminal telopeptide of type 1 collagen when compared with those taking carbamazepine or valproate. Patients receiving carbamazepine had higher levels of bone-specific alkaline phosphatase compared with controls and those receiving valproate. Serum bicarbonate concentrations were significantly lower in patients receiving topiramate than in the other groups.Our results demonstrate that use of topiramate is associated with lower parathyroid hormone and bicarbonate concentrations along with mild hypocalcemia and increased bone turnover, which suggests that topiramate may have long-term effects on bone.