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


METHODS
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).


CONCLUSIONS
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.
Rauchenzauner
Markus
M
Department of Paediatrics IV, Division of Neuropaediatrics, Medical University Innsbruck, Innsbruck, Austria. markus.rauchenzauner@uki.at
Griesmacher
Andrea
A
Tatarczyk
Tobias
T
Haberlandt
Edda
E
Strasak
Alexander
A
Zimmerhackl
Lothar-Bernd
LB
Falkensammer
Gerda
G
Luef
Gerhard
G
Högler
Wolfgang
W
D000886:Anthropometry / Q000379:methods; D000927:Anticonvulsants / Q000008:administration & dosage / Q000627:therapeutic use*; D001823:Body Composition; D001827:Body Height; D015992:Body Mass Index; D001835:Body Weight; D002220:Carbamazepine / Q000031:analogs & derivatives / Q000627:therapeutic use; D002648:Child; D004334:Drug Administration Schedule; D004358:Drug Therapy / Q000706:statistics & numerical data*; D004827:Epilepsy / Q000188:drug therapy* / Q000453:epidemiology; D005260:Female; D050723:Fractures, Bone / Q000453:epidemiology; D006801:Humans; D000077213:Lamotrigine; D008297:Male; D000078330:Oxcarbazepine; D015995:Prevalence; D013843:Thiazines / Q000627:therapeutic use; D014227:Triazines / Q000627:therapeutic use; D014635:Valproic Acid / Q000627:therapeutic use; D000096926:Benzenesulfonamides
D000927:Anticonvulsants; D002220:Carbamazepine; D000077213:Lamotrigine; D000078330:Oxcarbazepine; D013843:Thiazines; D014227:Triazines; D014635:Valproic Acid; C084593:sulthiame; D000096926:Benzenesulfonamides