Effect of Antiepileptic Drugs on Bone Mineral Density in Children Between Ages 6 and 2 Years

Abstract

We assessed the effects of sodium valproate and carbamazepine monotherapy on bone mineral density (BMD) in children. BMD at the lumbar vertebrae (L1-L4) and radius-ulna was measured by the dual-energy x-ray absorptiometry (DEXA) method in 19 children (9 girls, 10 boys) with uncomplicated epilepsy and in 57 healthy children (28 girls, 29 boys), between the ages of 6 and 12 years. The study patients had been receiving either sodium valproate (n = 13) or carbamazepine (n = 6) monotherapy for more than 6 months. There were no significant differences between the control and study patients in age, height, weight, physical activity, or of serum concentrations of calcium, phosphate, and transaminases (aspartate aminotransferase, alanine aminotransferase). However, the serum alkaline phosphatase concentration was greater in the patient group as compared with the control group. BMD values were lower in girl patients (L1-L4; 0.497 +/- 0.08 vs 0.566 +/- 0.07 g/cm2, p < 0.05), but not in boys (0.534 +/- 0.06 vs 0.530 +/- 0.08 g/cm2). While BMD reduction was 8% in valproate therapy (midregion of radius-ulna; 0.287 +/- 0.03 vs 0.312 +/- 0.04 g/cm2, p < 0.04), it was reduced only 4.5% in the carbamazepine-treated group (0.298 +/- 0.01 vs 0.312 +/- 0.04 g/cm2, statistically not significant), although the mean durations of monotherapy with valproate (1.8 +/- 0.7 years) and carbamazepine (1.7 +/- 0.8 years) were similar. Thus decreased bone mineralization was observed in children with epilepsy, treated with sodium valproate even though treatment was for a rather short time.

Bone mineral density and serum levels of 25 OH vitamin D in chronic users of antiepileptic drugs

“…Studies indicate that 20 to 60% of AED users can develop rickets or osteomalacia, especially among older and institutionalized patients. However, in outpatient populations, some studies have not demonstrated a deleterious effect of AED on bone metabolism [7][8][9] . Drugs such as CBZ, PB, PRM and DPH are known to induce hepatic mixed function oxidase activity throughout the microsomal enzymes (P450) in the liver.…”

Antiepileptic drug use and rates of hip bone loss in older men

“…2 Evidence linking phenytoin (EIAED) [3][4][5][6][7] and phenobarbital (EIAED) 4,5 to lower bone mineral density (BMD) is generally consistent with this theory. However, carbamazepine (EIAED) [6][7][8][9][10] has not been associated with lower BMD, while valproic acid (nonenzyme-inducing AED [NEIAED]) 3,7-9 has been associated with lower BMD. Thus, multiple mechanisms underlying AEDrelated bone loss appear to exist, and all types of AED are potentially implicated.…”

Analysis of the Musculoskeletal System in Children and Adolescents Receiving Anticonvulsant Monotherapy With Valproic Acid or Carbamazepine

“…6 However, other authors reported that areal BMD was normal in such patients 7 or that areal BMD was decreased in girls but not in boys. 8 These studies were limited to the analysis of areal BMD (g/cm 2 ), a measure integrating both bone size and 3-dimensional ("volumetric") BMD (vBMD). 9 The size dependence of areal BMD often makes results difficult to interpret in the pediatric setting, because short children will have a lower areal BMD than their peers, even if their (smaller) bones are absolutely normal.…”