Chronic antiepileptic monotherapy, bone metabolism, and body composition in non-institutionalized children

AIM The aim of this study was to determine the influence of chronic monotherapy with antiepileptic drugs (AEDs) on vitamin D levels, bone metabolism, and body composition. METHOD Eighty-five children (38 males, 47 females; mean age 12y 5mo, SD 3y 4mo) were treated with valproate and 40 children (28 males, 12 females; mean age 11y 10mo, SD 3y) were treated with other AEDs (lamotrigine, sulthiame, or oxcarbazepine), comprising the non-valproate group. Forty-one healthy children (29 males 12 females; mean age 12y 1mo, SD 3y 5mo) served as a comparison group. Height, weight, body impedance analysis, 25-hydroxyvitamin D, calcium, phosphate, two bone resorption markers (receptor activator of nuclear factor kappa B ligand [RANKL] and tartrate-resistant acid phosphatase 5b [TRAP5b]), osteoprotegerin, and leptin were measured. RESULTS No child was vitamin D deficient as defined by a 25-hydroxyvitamin D (25OHD) level of less than 25nmol/l (<10ng/ml). Leptin, body fat, weight standard deviation score (SDS), and body mass index (BMI) SDS were all significantly higher (each p < 0.001) in valproate-treated children than in the non-valproate group, as were calcium (p = 0.027) and RANKL (p = 0.007) concentrations. Similarly, leptin was significantly higher in the valproate group than in control participants (p< 0.001), as were body fat (p = 0.023), weight SDS (p = 0.046), BMI SDS (p = 0.047), calcium (p< 0.001), and RANKL (p< 0.001), whereas TRAP5b concentrations were significantly lower in the valproate-treated group (p = 0.002). Furthermore, calcium and RANKL levels were significantly higher in the non-valproate group than in comparison participants (p< 0.001 and p = 0.016 respectively). INTERPRETATION Non-enzyme-inducing or minimal enzyme-inducing AED monotherapy does not cause vitamin D deficiency in otherwise healthy children with epilepsy. Valproate therapy is associated with increases in weight, body fat, and leptin concentration, as well as with a bone metabolic profile that resembles slightly increased parathyroid hormone action.