Abstracts

Rationale: Previous studies have shown that use of antiepileptic drug (AED) therapy is a risk factor for osteoporosis and fractures in postmenopausal women. Recent data in males is still scarce. One of the leading theories for this is the enhanced metabolism of Vit D by AEDs. Several AEDs induce the metabolic capacity of the CYP450 system, specifically the isozyme 3A4, which is involved in the degradation of active Vit D. It is thought that chronically decreasing the level of active Vit D induces a secondary hyperparathyroidism with elevated parathyroid hormone levels and low calcium levels. The 3A4 EIAEDs include PHT, PB, CBZ, OXC, and FBM.Methods: 25-OH-D3, iPTH, and iCA levels was examined in 567 male veterans attending an outpatient seizure clinic (age range: 25-90; mean: 59). Patients had a median duration of 14 yrs for AED txmt. Patients were divided into two groups: 1)on at least one EIAED (n=296) and 2)on only NEIAEDs (n=247). Both groups had to be on the AED for at least 6 months. Patients taking VPA were analyzed separately (n=24).Results: Out of 567 male patients, 296 were on EI and 247 were on NEI. The average age of patients on EI was 59 while that for NEI was 57. On both groups patients were mostly Hispanic and White Caucasians. On average patients had been on AEDs for 17 yrs on EI and 10 yrs NEI. In general patients on EI had higher levels of iPTH and lower levels of iCa and Vit D.Conclusions: Patients taking enzyme-inducing AEDs for seizure disorder have a significantly lower level of Vitamin D3 and calcium, and a significantly elevated level of PTH compared with patients taking non enzyme-inducing AEDs. These levels are consistent with a secondary hyperparathyroidism suggesting that the enzyme-inducing AEDs negatively affect Vitamin D levels and possibly their metabolism. This fact suggests that these male patients may need supplementation with vitamin D to avoid osteoporosis.