Elsevier

Seizure

Volume 73, December 2019, Pages 56-63
Seizure

Review
Effects of valproic acid on bone mineral density and bone metabolism: A meta-analysis

https://doi.org/10.1016/j.seizure.2019.10.017Get rights and content
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Highlights

  • Many patients with epilepsy need medication long time.

  • Risk of fracture was increased by long-term antiepileptic drugs.

  • Valproic acid may reduce bone mineral density and affect bone metabolism of patients.

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 and serum 25(OH)D3 level decreased in children with epilepsy treated with VPA. These parameters were unaltered in adults.

Keywords

Epilepsy
Valproic acid
Bone mineral density
Bone metabolism
Meta-analysis

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