Chronic Antiepileptic Monotherapy, Bone Metabolism, and Body Composition in Non-Institutionalized Children

Dev Med Child Neurol. 2010 Mar;52(3):283-8. doi: 10.1111/j.1469-8749.2009.03402.x. Epub 2009 Aug 26.


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 12 y 5 mo, SD 3 y 4 mo) were treated with valproate and 40 children (28 males, 12 females; mean age 11 y 10 mo, SD 3 y) were treated with other AEDs (lamotrigine, sulthiame, or oxcarbazepine), comprising the non-valproate group. Forty-one healthy children (29 males 12 females; mean age 12 y 1 mo, SD 3 y 5 mo) served as a comparison group. Height, weight, body impedance analysis, 25-hydroxyvitamin D, calcium, phosphate, two bone resorption markers (receptor activator of nuclear factor kappaB 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 25 nmol/l (<10 ng/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.

MeSH terms

  • Anthropometry / methods
  • Anticonvulsants / administration & dosage
  • Anticonvulsants / therapeutic use*
  • Body Composition
  • Body Height
  • Body Mass Index
  • Body Weight
  • Carbamazepine / analogs & derivatives
  • Carbamazepine / therapeutic use
  • Child
  • Drug Administration Schedule
  • Drug Therapy / statistics & numerical data*
  • Epilepsy / drug therapy*
  • Epilepsy / epidemiology
  • Female
  • Fractures, Bone / epidemiology
  • Humans
  • Lamotrigine
  • Male
  • Oxcarbazepine
  • Prevalence
  • Thiazines / therapeutic use
  • Triazines / therapeutic use
  • Valproic Acid / therapeutic use


  • Anticonvulsants
  • Thiazines
  • Triazines
  • Carbamazepine
  • Valproic Acid
  • sulthiame
  • Lamotrigine
  • Oxcarbazepine