Abstracts

Antiepileptic drugs (AEDs), particularly those that induce the hepatic cytochrome P450 system, have been associated with abnormal vitamin D metabolism and osteoporosis. Recent studies have reported that low bone mineral density (BMD) in adults on AEDs is common and associated with multidrug regimens, generalized seizures, longer disease duration, and increased bone turnover markers. We therefore examined the effects of individual AEDs on healthy premenopausal women with epilepsy (WWE), hypothesizing that those receiving enzyme inducing AEDs, particularly phenytoin (PHT) and carbamazepine (CBZ), would have more bone loss than those receiving valproate (VPA), an enzyme inhibitor, or lamotrigine (LTG) which has no effect on the cytochrome P450 system. Community-dwelling WWE aged 18-40 receiving AED monotherapy for at least 6 months were recruited. BMD was measured at the lumbar spine (LS), total hip (TH) and femoral neck (FN) of the hip by dual energy X-ray densitometry at baseline and one year, if they remained on the originally prescribed AED. Serum calcium, 25-(OH) vitamin D (25-OHD), parathyroid hormone (PTH), bone specific alkaline phosphatase (BAP, marker of bone formation) and urine N-telopeptide of type I collagen (NTX, marker of bone resorption) were measured at baseline and examined with respect to percent change in BMD. Of 71 women, 11 were on PHT, 26 on CBZ, 14 on VPA and 18 on LTG. Average age was 32 +/- 5.9 years and BMI was 26.5 +/- 6.3 kg/m² with no significant between-groups differences. Baseline Z scores were normal at all sites and did not differ among AED groups (range: -0.42 [ndash] 0.34). BMD was stable at the LS and TH in all groups after 1 year of treatment. In women on PHT, FN BMD declined by -2.75% +/- 2.76, p=0.05, compared to the other groups (CBZ, +0.49% +/- 4.03; VPA, +1.09% +/- 3.73; LTG, -0.005% +/- 0.02). In the group overall, bone loss correlated with serum calcium levels, but not other markers of bone function. In general, BMD is stable in premenopausal WWE on AED monotherapy. We observed significant bone loss at the FN in those taking PHT. The bone loss was associated with lower serum calcium levels but not with serum 25-OHD or PTH levels, nor with markers of bone turnover. Although the mechanism of the bone loss is uncertain, our results suggest that premenopausal women receiving PHT are at significant risk for considerable bone loss and warrant BMD monitoring. (Supported by Research grant from GlaxoSmithKline)