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Background  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.    Methods  Studies 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).    Results  Fourteen 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.    Conclusion  Long-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.

Effects of valproic acid on skeletal metabolism in children with epilepsy: a systematic evaluation and meta-analysis based on 14 studies