Abstract
BackgroundPrevious studies have reported that long-term use of valproic acid can cause changes in bone metabolism in children. We conducted this meta-analysis to determine the effects of valproic acid on bone metabolism and bone mineral density (BMD) in children with epilepsy.MethodsStudies were searched from the databases of PubMed, Embase, Ovid, Cochrance Library, Springer Link and Web of Science. The effects of valproic acid on bone metabolism indicators and BMD were assessed through calculating the standardized mean difference (SMD) with 95% confidence interval (CI).ResultsFourteen studies with 987 individuals were included in this analysis. The long-term use of valproic acid did not affect the levels of serum calcium (p = 0.99), phosphorus (p = 0.28), ALP (p = 0.76), PTH (p = 0.36) and osteocalcin (p = 0.72), but it led to a decrease in 25-OH-VitD (p = 0.01) and BMD (p = 0.002 for the vertebra; p = 0.004 for the femur) in treating children with epilepsy.ConclusionLong-term use of valproic acid in treating children with epilepsy can lead to a reduction in 25-OH-VitD and BMD. Measurements of 25-OH-VitD and BMD should be performed regularly in children taking the drug to detect early osteopenia caused by the drug.
Highlights
Previous studies have reported that long-term use of valproic acid can cause changes in bone metabolism in children
Cytochrome P450 (CYP450) isozyme can be induced by antiepileptic drugs (AEDs) such as carbamazepine, phenytoin sodium, phenobarbital and valproic acid, which may lead to vitamin D deficiency, hypocalcemia, increased fracture risk [6]
Inclusion criteria The inclusion criteria used were: (1) The diagnosis of children with epilepsy which met diagnostic criteria of the International Anti-Epilepsy Alliance; (2) Children were under 18 years old and could participate in outdoor activities; (3) The design type must be cohort study or case-control study; (4) The valproic acid group must be treated with valproic acid monotherapy for more than 6 months; (5) The control group must be composed of healthy children not receiving any medications; and (6)
Summary
Previous studies have reported that long-term use of valproic acid can cause changes in bone metabolism in children. We conducted this meta-analysis to determine the effects of valproic acid on bone metabolism and bone mineral density (BMD) in children with epilepsy. As early as 2004, it was reported that several factors affect bone metabolism in children with epilepsy, suggesting that long-term use of AEDs may cause damage to the skeletal system [5]. Opinions suggest that long-term use of this drug may have an impact on bone metabolism in children [1,2,3, 7]. We performed a meta-analysis to determine the effects of valproic acid on bone metabolism and bone mineral density (BMD) in epileptic children
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