Evaluation of Bone Mineral Metabolism in Children Receiving Carbamazepine and Valproic Acid

Abstract

Dual energy X-ray absorptiometry (DXA) was used to assess lumbar spine (L2-4) and femoral neck bone mineral density (BMD) in 36 children taking either carbamazepine or valproic acid for longer than one year, for generalized idiopathic epilepsy. Patients were matched with controls. Biochemical parameters of bone mineral metabolism were also measured. BMD values at both the femur neck and lumbar spine in both the carbamazepine and valproic acid groups were not significantly different from that of the control group. Serum levels of calcium were subnormal and alkaline phosphatase levels were high in the carbamazepine group. Urinary calcium levels were significantly lower in both groups than in the control group (p< or =0.05) and also significantly lower in the valproic acid group than in the carbamazepine group (p< or = 0.05). There were no other significant biochemical changes in either group. In conclusion, the results suggest that valproic acid and carbamazepine monotherapies have minimal effects on bone mineral metabolism, but routine monitoring of risk and consideration of prophylactic vitamin D supplementation is important.

Effects of antiepileptic drugs on bone mineral density and bone metabolism in children: A meta-analysis

“…The initial search yielded 1603 research reports, of which 228 were excluded due to identical title or authors; 1056 were excluded due to ineligible study design (including non-human studies, review articles, case reports, comment, letter, experimental study, and/or fractureonly outcome). After full-text screening, 22 studies were included (Chung and Ahn, 1994;Baer et al, 1997;Akin et al, 1998;Kafali et al, 1999;Erbayat Altay et al, 2000;Verrotti et al, 2002;Voudris et al, 2002;Ecevit et al, 2004;Oner et al, 2004;Babayigit et al, 2006;Kumandas et al, 2006;Nicolaidou et al, 2006;El-Hajj Fuleihan et al, 2008;Nettekoven et al, 2008;Gniatkowska-Nowakowska, 2010;Rauchenzauner et al, 2010;Babacan et al, 2012;Dimić et al, 2013;Razazizan et al, 2013;Turan et al, 2014). Table 1 summarizes the characteristics of the included studies published between 1994 and 2014.…”

“…A total of 11 studies comprising 23 datasets, which included 645 subjects and 579 controls, evaluated the effect of AEDs on lumbar spine BMD (Chung and Ahn, 1994;Akin et al, 1998;Kafali et al, 1999;Erbayat Altay et al, 2000;Oner et al, 2004;Babayigit et al, 2006;Kumandas et al, 2006;El-Hajj Fuleihan et al, 2008;Gniatkowska-Nowakowska, 2010;Babacan et al, 2012;Dimić et al, 2013) The changes in BMD of trochanter and femoral neck were assessed by three datasets from two studies (Oner et al, 2004;Ecevit et al, 2004) . Sensitivity analysis showed that no single study affected the summary estimates significantly.…”

Adverse effects of antiepileptic drugs on bone mineral density in children

“…Most of the available studies on AEDs and BMD have addressed the use of carbamazepine ( Table 1). None of the studies have shown a decrease in BMD or BMC in the total body, lumbar spine, hip or forearm [40][41][42][43][44][45]. Children were selected in good physical condition and did not have concomitant diseases (i.e., no influence from malnutrition or vitamin D deficiency could be expected) ( Table 1).…”

“…In contrast to carbamazepine, the results for valproate have been more diverse. Two studies, both from Turkey, in children aged 8 -12 years found no decrease in spine BMD [40,42] with the use of valproate. The first study had a duration of > 1 year [40], and the second ∼ 3 years [42].…”

Molecular mechanisms responsible for the impact of antiepileptic therapy on bone mineral density of epileptic patients

“…[35] у пациентов, при-нимающих ВК, показано значительное повышение уровня щелочной фосфатазы (ALP) по сравнению с контрольной группой, однако в работе E. Erbayat Altay и соавт. [48] про-демонстрирован уровень остеокальцина на верхней грани-це нормы. Несмотря на то что ВК может снижать МПК с изменением биохимических маркеров костной ткани, в работе J. Elliott и соавт.…”