Bone health in young women with epilepsy after one year of antiepileptic drug monotherapy

Abstract

Objective-Antiepileptic drugs (AEDs) may have adverse effects on bone mineral density (BMD) and metabolism. We previously reported biochemical evidence of increased bone turnover in pre-menopausal women with epilepsy on phenytoin monotherapy compared with those on carbamazepine, lamotrigine, and valproate. We therefore hypothesized that rates of bone loss would be higher in young women treated with phenytoin.Methods-Ninety-three premenopausal women with epilepsy receiving a single AED (carbamazepine, lamotrigine, phenytoin, or valproate) participated. Subjects completed nutritional and physical activity questionnaires. Biochemical indices of bone and mineral metabolism and BMD of the proximal femur and lumbar spine were measured at baseline and 1 year.Results-Participants reported high calcium intake (>1,000 mg/day) and were physically active. Significant loss (2.6%) was seen at the femoral neck in the phenytoin group. BMD remained stable in the other AED groups. Bone turnover markers and calciotropic hormones were unchanged after 1 year in all groups except for a significant decline in urine N-telopeptide in the phenytoin group. In women receiving phenytoin, lower serum 25-hydroxyvitamin D concentrations were associated with higher parathyroid hormone, bone alkaline phosphatase, and urine N-telopeptide levels, a biochemical pattern consistent with secondary hyperparathyroidism and increased remodeling.Conclusion-In this study, young women treated with phenytoin had significant femoral neck bone loss over 1 year. In contrast, those treated with carbamazepine, lamotrigine, and valproate did not have detectable adverse effects on bone turnover or bone mineral density. These results raise concerns about the long-term effects of phenytoin monotherapy on bone in young women with epilepsy.Antiepileptic drug (AED) treatment has adverse effects on bone and mineral metabolism that may ultimately increase the risk of fracture. 1 Most studies of AED effects on bone and mineral metabolism are cross-sectional. Of the few longitudinal studies, some revealed bone loss in children and adults as well as changes in indices of bone and mineral metabolism. [2][3][4][5] None have evaluated the effects of individual AEDs.We previously reported results of a cross-sectional study of bone mineral density (BMD) and indices of bone and mineral metabolism in premenopausal women with epilepsy taking Herein, we report our findings in women treated with one of four AEDs in monotherapy followed up for 1 year. Given the biochemical evidence of increased turnover at baseline in women receiving phenytoin, we hypothesized that there would be more bone loss in this group. METHODS SubjectsPremenopausal women with epilepsy (n = 147) aged between 18 and 40 years and with normal menstrual cycles participated in the study. Subjects were enrolled at Stanford University (n = 83) or Columbia University (n = 64) between September 1997 and January 2004. Baseline data on the first 93 subjects enrolled were published previously. 6 Of the 147 subjects, ...

Effects of the Antiepileptic Drugs Phenytoin, Gabapentin, and Levetiracetam on Bone Strength, Bone Mass, and Bone Turnover in Rats

“…26) In support of this hypothesis, several clinical studies have reported the elevation of serum PTH levels 27) and the reduction of serum 25(OH) D levels in patients treated with enzyme-inducing AEDs. 28) In contrast to this finding, several studies have observed no significant differences in these parameters. 29,30) In this study, we investigated the effect of AEDs on vitamin D metabolism, and found no significant difference in serum calcium, 25(OH) D, and PTH levels between the control group and the AED-treated groups.…”

Women with epilepsy: clinically relevant issues

“…Cytochrome-inducing AEDs are known to affect bone mineral density and are associated with bone disorders such as osteoporosis and fractures during and after menopause. Phenytoin has been found to be associated with decreased levels of bone-specific alkaline phosphatase, as well as increased bone turnover, which can predispose to fractures, especially to the neck of femur (Pack et al, 2008). Finally, topiramate use is associated with low parathyroid hormone levels and increased bone turnover in premenopausal women (Heo et al, 2011).…”

Metabolic consequences of antiepileptic drugs

“…Pack and colleagues (11) followed women on AED monotherapy with PHT, CBZ, LTG or VPA for a year. They found significant loss of bone at the femoral neck in PHT-treated patients; they also found that reductions in 25-OHD were associated with increases in bone turnover markers, all of which is consistent with the aforementioned prevailing hypothesis.…”