Bone metabolism alteration on antiepileptic drug therapy

To investigate whether serum total alkaline phosphatase (ALP), bone-specific ALP (bone ALP), calcium, phosphorus, 25-hydroxyvitamin D (25-OHvit D) concentrations are altered early in the course of treatment with carbamazepine or valproic acid monotherapy in ambulatory children with adequate sun exposure; and to determine the effectiveness of simultaneous supplementation with calcium and 25-OHvit D at recommended dietary allowance doses on these biochemical parameters.

For each drug, children were divided into two groups (Group A: without supplementation; and Group B: with supplementation) and serum biochemical parameters estimated at 0, 30, 60, and 90 days of starting treatment.

Serial changes in serum biochemical parameters (mean +/- SD) were compared within each of the four groups using student's paired t test. Also for each drug, serum biochemical parameters were compared between Groups A and B at 0, 30, 60, and 90 days of starting treatment using student's unpaired t test.

For both drugs, in Group A, serum total ALP levels were significantly increased above the normal range (P<0.0001) by 90 days of starting treatment; however, serum bone ALP level was significantly increased (P=0.002) only in children on valproic acid. For both drugs when serum biochemical parameters were compared between Groups A and B, supplementation resulted in a significant decrease in serum total ALP (P<0.0001) and bone ALP levels (P<0.001), and a significant increase in serum calcium (P<0.0001) and 25-OHvit D levels (P<0.0001) by 90 days of starting treatment.

Serum biochemical changes which indicate predisposition to development of rickets or osteomalacia appear within 90 days of starting carbamazepine or valproic acid monotherapy. However simultaneous supplementation with oral calcium and 25-OHvit D is effective in preventing the development of these adverse biochemical changes.