Abstracts

We previously reported significant bone loss at the femoral neck of the hip in women with epilepsy receiving phenytoin (PHT) when followed for 1 year longitudinally. It has been postulated that adverse effects on bone secondary to PHT treatment are a result of enzyme inducing increased metabolism of vitamin D. We hypothesized that concentrations of vitamin D metabolites after 1 year of treatment would be significantly lower in women treated with PHT than other AEDs including carbamazepine (CBZ), valproate (VPA), and lamotrigine (LTG). Women with epilepsy aged 18-40 receiving AED monotherapy were recruited. AEDs studied were PHT, CBZ, VPA and LTG. Subjects had baseline bone mineral density (BMD) studies as assessed by DXA and serologic measurements of calcium and vitamin D metabolites (25, hydroxyvitamin D and 1,25 dihydroxyvitamin D). Subjects were followed for 1 year and repeat studies were obtained. Correlation between change in BMD and calcium and vitamin D metabolites after 1 year of treatment was evaluated. Data was obtained from 66 women. There were 7 women receiving PHT, 27 receiving CBZ, 13 receiving VPA, and 19 receiving LTG. Serum calcium levels did not change significantly after 1 year of treatment in all AED treated groups. As we previously reported, baseline calcium levels were significantly lower in women treated with PHT, CBZ, and VPA compared to those treated with LTG. Serum 25, hydroxyvitamin D concentrations also did not change significantly in any of the AED treated groups. As we previously reported, there was no significant difference among baseline levels of 25, hydroxyvitamin D among the AED treated groups. Serum 1,25 dihydroxyvitamin D concentrations were significantly higher after 1 year of treatment in LTG treated women (32.80 [ndash] 39.55 pg/ml; p=0.0067). Although not significant, there was a reduction in 1,25 dihydroxyvitamin D concentrations in women treated with PHT (31.10 [ndash] 24.70 pg/ml). BMD loss at the femoral neck of the hip did not correlate with changes in calcium or vitamin D metabolite concentrations. Calcium and 25, hydroxyvitamin D concentrations did not change significantly in women treated with PHT, CBZ, VPA, and LTG and followed longitudinally for 1 year. Serum 25, hydroxyvitamin D is the most commonly used index of vitamin D status. Although not significant, there was a reduction in 1,25 dihydroxyvitamin D concentrations in women treated with PHT for 1 year. BMD loss did not correlate with changes in either calcium or vitamin D metabolites. The lack of significance of these findings may in part be explained by the small sample size of the PHT treated group. However, they do suggest that previously reported bone loss in PHT treated women may not be secondary to effects on vitamin D metabolism. (Supported by GlaxoSmithKline.)