Abstracts

Osteoporosis and osteomalacia have been reported in patients with epilepsy, particularly those receiving enzyme inducing AEDs (EIAEDs) such as phenytoin (PHT) or carbamazepine (CBZ). Although the mechanism(s) responsible for these osteopathies remains uncertain, an interaction with vitamin D has been proposed, whereby increased degradation secondary to enzyme induction occurs, resulting in vitamin D deficiency. Vitamin D is metabolically activated and degraded through the actions of three CYP450 isozymes. Studies of AED mediated changes in vitamin D however, have had inconsistent results. One recent study reported increased bone turnover, but no significant effect upon vitamin D in patients treated with CBZ. Moreover, many studies are cross-sectional and do not address time course issues, nor potential differential AED effects on vitamin D. It may instead be useful to explore potential drug mediated effects by measuring vitamin D concentrations following deinduction, and conversion to a non-EIAED such as lamotrigine (LTG).
A pilot study of changes in vitamin D serum concentrations in patients being converted from either CBZ or PHT monotherapy to LTG monotherapy was conducted. Patients selected for the study were on stable doses of either CBZ or PHT and were also taking LTG. Reduction of the EIAED was carried out weekly. Serum concentrations 25-hydroxy vitamin D (25-OHD) were measured before, and 30 days following, complete withdrawal of the EIAED. No attempt was made to alter diet or sun exposure during this period. 25-OHD was measured by ELISA.
Four patients were evaluated (3 men/ 1 women). Two received CBZ (mean age [amp] dose were 60.5 yrs [amp] 450 mg/d) and two received PHT (mean age [amp] dose were 42.5 yrs [amp] 250 mg/d) at baseline.
For the patients receiving CBZ, mean 25-OHD at baseline and following withdrawal of the EIAED was 19.1 vs 17.1 ng/ml, respectively ( changes of +0.2 and -0.3 ng/ml for these 2 patients). For the PHT patients, mean baseline vs withdrawal 25 OHD values were 18.6 vs 22 ng/ml, respectively (changes of +3.9 and +2.9 ng/ml for these 2 patients). These changes represent an average 0.45 % decline for the CBZ patients, versus an average 18.45% increase for PHT patients.
These preliminary findings are consistent with previous observations that patients treated with EIAEDs tend to have low 25-OHD serum concentrations. In addition, our observations would also suggest that a differential effect of CBZ vs PHT may exist. In the case of CBZ, no appreciable change was noted in 25-OHD, while for PHT patients, withdrawal resulted in marked increase at 30 days. Further studies will be conducted to verify these apparent differences, as well as to more fully describe the time-course of change.