Background/Purpose:

Accelerated rate of bone loss leading to osteopenia and osteoporosis is a well recognized adverse effect of long term anticonvulsant use, particularly phenytoin, phenobarbital, sodium valproate or carbamazepine. Futher, compared to the general population, epileptics experience a two-fold increase in the incidence of vertebral and non-vertebral fractures.

In this trial, we sought to evaluate whether a bisphosphonate in addition to calcium and vitamin D supplementation can prevent bone loss and fractures in an epileptic population chronically treated with phenytoin, phenobarbital, sodium valproate or carbamazepine.
Methods:

This was a phase IV randomized, two year  double blinded, placebo-controlled trial of an epileptic male population of veterans. This study involved 80 patients with various types of seizures who were being treated with phenytoin, phenobarbital, sodium valproate or carbamazepine for a minimum of two years. At initial visit, patients underwent DXA scan on 5^th generation GE IDXA. Subjects who had a T-score > -2.5 at AP spine or hip were randomized into two one of two groups. Group R received calcium and vitamin D supplementation along with risedronate 35mg weekly, while Group P received calcium and vitamin D supplementation along with a matching placebo tablet weekly. We excluded those subjects who had were found to be osteoporotic according to WHO criteria (BMD T-score < -2.5 at spine or hip) or were found to be vitamin D deficient.

BMD of bilateral proximal femur, LVA, A-P lumbar spine, total body and forearm were evaluated utilizing a GE Lunar Bone Densitometer or an iDXA instrument and had measurements of 25-OH Vit D, NTX, serum calcium and blood chemistries.
 Results:

80 patients were randomly enrolled in either the B or P groups.

 Baseline characteristics of both groups were similar. Average age was 60+/-13 years. Average bilateral total proximal femur mean BMD was 0.991+/-0.122 for the B group and 0.992+/- 0.213 g/cm2 for the P group. Lumbar spine baseline BMD was 1.284+/-0.190 for the B group and 1.237+/-0.249 g/cm2 for the P group. Total body BMD was  1.229 +/- 0.107 for the P group and 1.185 +/- 0.110 for the B group. A total of 56 patients competed the study. At the end of the study 12 out 28 patients from group B and 10 out 28 patients from group P had a significant increase of BMD as determined at the total proximal femur which was above the LSC for our site; further, 18 out 28 of group B and 22 out of 28 on group P demonstrated a significant increase of BMD at the L-Spine . Improvement of BMD at different sites was observed in more than 78% of patients who completed the study taking calcium and vit D both in the P or B groups. Five new vertebral fractures were observed only on the P group.

Conclusion:
In this cohort, supplementation with calcium and vitamin D or use of calcium, vitamin D and bisphosphonates decrease rate of bone loss and at the same time increased bone mass associated with chronic treatment with phenytoin, phenobarbital, sodium valproate or carbamazepine. Prevention of new vertebral fractures was not observed in the group receiving only calcium and vitamin D.