Bone mineral status in ambulatory pediatric patients on long-term anti-epileptic drug therapy


Hirokazu Tsukahara MD, PhD, Department of Pediatrics, Fukui Medical University, Fukui 910-1193, Japan. Email:


Background: For ambulatory pediatric outpatients, reports of abnormalities of bone metabolism associated with anti-epileptic drugs are inconsistent and may be difficult to interpret.

Methods: The effects of long-term anti-epileptic therapy (mainly valproic acid and/or carbamazepine) on bone mineral status were evaluated in ambulatory epileptic patients (seven males and 11 females) aged 5.5−15.9 years. Bone mineral density (BMD) at the lumbar spine was measured by dual-energy X-ray absorptiometry and markers of bone and mineral metabolism were determined.

Results: The mean BMD was decreased by 9% in our patients relative to the control, and five patients (all males) showed osteopenia, defined as BMD SD scores less than − 1.5. Serum levels of minerals, intact parathyroid hormone and 1α,25 (OH)2 vitamin D were within the normal ranges. In most patients, serum levels of intact osteocalcin, carboxyterminal propeptide of type I procollagen and pyridinoline cross-linked telopeptide of type I collagen were reduced relative to the corresponding mean control values. The BB genotype by BsmI restriction fragment length polymorphism, associated with low BMD, was not found in our patients. The dietary calcium intake in the osteopenic patients was significantly lower than that of the non-osteopenic patients.

Conclusions: Our results indicate that long-term anti-epileptic treatment induces a state of decreased bone turnover in children, resulting in osteopenia preferentially in males. The alterations may be due, at least in part, to direct effects of the drugs on bone cells; and that low calcium intake could be an aggravating factor for anti-epileptic-associated osteopenia.