Abstracts

Evidence suggests that certain antiepileptic drugs (AED), particularly cytochrome P450 inducers, may decrease serum 25-hydroxy-vitamin D (25-OH-D) and increase bone turnover. We sought to determine whether 25-OH-D levels and bone turnover are affected by treatment with carbamazepine (CBZ) or the similar newer AED oxcarbazepine (OXC). We measured 25-OH-D serum levels, serum parathormone (PTH) levels, and several biochemical markers of bone turnover, including serum osteocalcin (OSCL), serum bone alkaline phosphatase (BAP), and urinary crosslinked N-telopeptides of type I collagen (NTX) in normal adult controls (n=24) and adult epilepsy patients taking either CBZ (n=22) or OXC (n=24) in monotherapy for over 8 weeks. CBZ patients were then switched overnight in a 2:3 ratio to OXC monotherapy, and after 6 weeks the same tests were repeated. 25-OH-D levels were lower in each drug-treated group (OXC 19.4 [plusmn] 2.3pg/ml, CBZ 20.4 [plusmn] 2.4) than in the controls (27.5 [plusmn] 2.8) (ANOVA, p=0.052). Post-tests showed significance for the comparison of OXC to controls (p[lt]0.05). PTH values in the OXC (55.6 [plusmn] 6.5pg/ml) and CBZ groups (55.6 [plusmn] 6.2) were higher than in controls (45.7 [plusmn] 4.7), though not significantly (p[gt]0.1). BAP levels were somewhat higher, and NTX levels lower, in the OXC and CBZ groups compared to controls, but without significance (p[gt]0.05). OSCL levels were somewhat elevated in the OXC group (2.79 [plusmn] 0.47ng/ml) and more clearly elevated in the CBZ group (3.63 [plusmn] 0.36) compared to controls (2.38 [plusmn] 0.41), with the overall comparison being significant (p[lt]0.05) and the post-tests showing some significance in the comparison between CBZ and control groups (p=0.053). Because all of the data (except OSCL) were so similar between OXC and CBZ groups, they were combined to increase statistical power. The combined drug treatment group had significantly higher BAP (p=0.02) and significantly lower 25-OH-D (p=0.015) than controls. The latter effect was signficant even after accounting for the confounding effects of age on 25-OH-D levels (p[lt]0.05). No differences were found in the CBZ patients before and after switch to OXC. Epilepsy patients taking OXC or CBZ have significantly lower 25-OH-D and significantly higher bone turnover (as measured by BAP) than do normal controls. These patients are likely to be at risk for long term bone loss. Our data cannot exclude the possibilty that this is a function of the disease rather than the treatment, though data from other studies suggests this is unlikely. Pending further investigations, it may be prudent for patients on CBZ or OXC to be co-administered high-dose 25-OH-D replacement. (Supported by Novartis Pharmaceutical Corporation.)