NEW YORK CITY—Bone loss proceeds eight times faster in young women who take phenytoin to control epilepsy than in young women not taking antiepileptic drugs (AEDs). Women taking carbamazepine, lamotrigine, or valproate did not show similar bone loss. Alison M. Pack, MD, of Columbia University in New York City and colleagues reported the longitudinal study in Neurology.1

“The 2.6% loss we observed in the women receiving phenytoin is more than 8 times greater than that observed in this cohort of [normal] young women.”—Alison M. Pack, MD.
“To put this in context, in 614 premenopausal women aged 24 to 44 years, femoral neck BMD (bone mineral density) declined by 0.3%. The 2.6% loss we observed in the women receiving phenytoin is more than eight times greater than that observed in this cohort of young women. If such rates of bone loss were to be sustained over time, premenopausal women receiving long-term phenytoin therapy might enter their menopausal years with lower than normal bone mass, and their vulnerability to postmenopausal fractures might be considerably increased,” Dr. Pack said.

The research group had previously observed biochemical evidence of increased bone turnover in a premenopausal women taking phenytoin compared with those taking other AEDs. They then examined bone metabolism and BMD of the proximal femur and lumbar spin at baseline and at 1 year in 93 premenopausal women with epilepsy taking a single AED: 41 were on carbamazepine, 23 on lamotrigine, 15 on phenytoin, and 14 on valproate. All women had calcium intake >1000 mg/day, were physically active, and were aged 18-40 years; all had normal menses.

“After 1 year of AED treatment, significant [BMD] loss was seen only in the group that received phenytoin (-0.023 ± 0.030 g/cm2 or 2.6%) and only at the femoral neck,” Dr. Pack reported. The underlying mechanism appears to be secondary hyperparathyroidism with increased bone turnover. The investigators found that in women taking phenytoin lower 25-OHD concentrations were significantly associated with higher serum parathyroid hormone, bone-specific alkaline phosphatase, and urine NTx (cross-linked N-telopeptide of type I bone collagen).

Reference
1. Pack AM, Morrell MJ, Randall A, et al. Bone health in young women with epilepsy after one year of antiepileptic drug monotherapy. Neurology. 2008;70:1586-1593.