Predictors of anticonvulsants-induced osteopathy in epileptic children

ABSTRACT

Anticonvulsants are known to have many side effects specially is growing epileptic children. Among these side effects are that bad effects on calcium metabolism and bone mineral density. This study was designed to find sensitive predictors of calcium homeostasis and bone mineral status with possible osteopathy in epileptic children. 60 epileptic children aged 4-14 years, admitted at neurology ward of pediatric department of Tanta university were enrolled in the study. They were subdivided into 4 subgroups according to monotherapy given 15 cases phenytion-treated, 15 cases phenobarbital-treated, 15 cases carbamazepine-treated and 15 cases valproate-treated. 15 healthy children matched for age and sex plotted as control. After establishment of diagnosis and control and after one year of initiation of anticonvalsant therapy they were subjected to full serological surgery of calcium metabolism serum calcium, serum phosphorus, serum alkaline phosphatase. As indicators of bone resorption, fasting urinary calcium and total urinary hydroxyproline were measured. Bone mineralization was estimated with plain X-ray films of spine and extremities and dual-energy X-ray absroptiometry for estimation of bone mineral density [BMD] at the trabecular and cortical bone of distal third of radius. We found normal calcium and phosphorous levels in the 4 patient groups denoting possibly the successful homeostasis by parathormone. But we found significant increase of urinary fasting excretion of calcium and hydroxyproline in patients receiving phenytion and phenobarbtione denoting bone resorption which is supported by the significant increase of alkaline phosphatase in these patient groups confirming osteoclastic activity found. Serum basal calcitonin was found to be significantly reduced in all patients groups except carbarnazepine treated group [mean 46.00 +/- 0.9 picogram/ml] denoting presented complete homeostasis of calcium in CBZ-treated children in contrast to the other three groups who are prone to osteopenia specially if the tendency to increased osteoclastic activity is aggravated by secondary' hyperparathyroidism. Bone mineral density [BMD] is decreased in the four patients groups, the worst was phenytoin - treated group [Mean 0.284 +/- 0.049 gm/cm[2]] as compared to controls [mean 0.436 +/- 0.047 gm/cm[2]]. The best BMD was in carbamazepine-treated group [mean 0.39 +/- 0.045 gm/cm[2]], denoting nearly no deleterious effect of the drug on both calcium homeostasis and bone mineral density. From this study, we recommend the full radiologic survey of epileptic children before and during anticonvulsant therapy specially if prolonged. We also recommend both high dietary calcium and vitamin D intake in patients treated with phenytion, phenobarbitone and valproate with special emphasis of 1,25 dihydroxy D3 supplement. Also we recommend radiological survey of these patients with attention to measurement of bone mineral density using sensitive non-invasive techniques as dual -energy x-ray absorptiometry