Effects of valproic acid on bone mineral density and bone metabolism: A meta-analysis
Abstract
PURPOSE: Numerous studies have shown that the risk of fracture is increased by long-term antiepileptic drugs (AEDs). Valproic acid (VPA) is one of the most commonly used AEDs. In this meta-analysis, we aimed to assess the effects of VPA on bone mineral density (BMD) and bone metabolism.
METHODS: PubMed, Embase, Cochrane and Web of Science databases were searched from inception to January 2019 for articles focusing on the effects of VPA on BMD and bone metabolism in adults or children. A meta-analysis was performed using RevMan 5. 3 software.
RESULTS: 18 studies were included in the meta-analysis. The BMD of lumber spine (MD= -0.06, 95%CI: -0.09 to -0.03, P < 0.0001) and femoral neck (MD= -0.05, 95% CI= -0.08 to -0.01, P = 0.02) was markedly decreased in the VPA group compared to healthy controls. Serum bone-specific alkaline phosphatase (BALP) level (SMD = 0.85, 95% CI: 0.30-1.40, P = 0.002) was notably increased in the VPA group compared to healthy groups. In the child group, the serum parathyroid hormone (PTH) level was higher than in healthy groups (SMD= -0.22, 95% CI: -0.40 to -0.04, P = 0.02); besides, the serum 25-hydroxy vitamin D3 (25(OH)D3) level was decreased (SMD= -0.22, 95% CI: -0.40 to -0.04, P = 0.02), while no significant alteration of these parameters was noted in the adult VPA group (P ≥ 0.05).
CONCLUSIONS: VPA may reduce the BMD of lumbar spine and femoral neck in patients with epilepsy while increasing the serum BALP level. Serum PTH level are increased…
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