Abstract:

Objective  To evaluate the safety of valproate (VPA) on bone mineral density and bone metabolism in children with epilepsy.  Methods  Retrieve relevant research from online databases (January 1, 1980-March 1, 2018) as PubMed, EBMASE/SCOPUS and Cochrane Library with key words: epilepsy, bone, child. Selection of studies was performed according to pre?designed inclusion and exclusion criteria. Quality of studies was evaluated by using Newcastle?Ottawa Scale (NOS). All data were pooled by RevMan 5.2 software for Meta?analysis.  Results  The research enrolled 1455 articles, from which 13 studies with NOS score ≥ 6 were chosen after excluding duplicates and those not meeting the inclusion criteria. A total of 683 children with epilepsy using VPA and 436 children in control group were included. Meta?analysis showed that comparing with control group, bone mineral density of lumbar (BMDL) in children treated with VPA has no significant difference (MD = -0.019, 95% CI: ? 0.044-0.006; P = 0.140), but there was a significant decrease in bone mineral density of femur (BMDF; MD = -0.037, 95%CI: -0.069--0.005, P = 0.020). There was no significant change in serum calcium (SMD = -0.284, 95% CI: -0.951-0.382; P = 0.400), phosphorus (SMD = -0.164, 95%CI: -0.457-0.129; P = 0.270), alkaline phosphatase (ALP; SMD = 0.363, 95%CI: - 0.294-1.020, P = 0.280), parathyroid hormone (PTH; SMD = 0.102, 95%CI: -0.291-0.495, P = 0.610) and 25-hydroxy vitamin D [25(OH)D; SMD = -0.104, 95%CI：-0.620-0.413, P = 0.690] in bone metabolic markers. Sensitivity analysis showed Meta-anlaysis of BMDF, serum phosphorus and 25(OH)D was unstable, therefore, it should be cautious when explaining the results.  Conclusions  VPA has less effect on bone mineral density and bone metabolism, but for children with epilepsy using VPA, their BMDF should be monitored.

Key words: Valproic acid, Epilepsy, Child, Bone density, Bone and bones, Metabolism, Meta-analysis

摘要：

目的 系统评价丙戊酸钠对儿童癫患者骨密度和骨代谢的安全性。 方法 以epilepsy、bone、child 等英文词汇计算机检索1980 年1 月1 日-2018 年3 月1 日美国国立医学图书馆生物医学信息检索系统（PubMed）、荷兰医学文摘（EMBASE/SCOPUS）、Cochrane 图书馆等数据库收录的关于丙戊酸钠对儿童癫患者骨密度和骨代谢影响的队列研究，采用Newcastle-Ottawa 量表（NOS）和RevMan 5.2 统计软件进行文献质量评价和Meta 分析。 结果 共获得1455 篇文献，经剔除重复和不符合纳入标准者，最终纳入13 项高质量（NOS 评分≥ 6 分）临床研究共计683 例丙戊酸钠组患儿和436 例对照组受试者。Meta 分析显示，丙戊酸钠组患儿仅股骨骨密度低于对照组（MD = -0.037，95%CI：-0.069 ~ ? 0.005；P =0.020），而腰椎骨密度（MD = -0.019，95%CI：-0.044 ~ 0.006；P = 0.140）以及血清钙离子（SMD = -0.284，95%CI：-0.951 ~ 0.382；P = 0.400）、磷离子（SMD = -0.164，95%CI：-0.457 ~ 0.129；P = 0.270）、碱性磷酸酶（SMD =0.363，95%CI：-0.294 ~ 1.020；P = 0.280）、甲状旁腺激素（SMD = 0.102，95%CI：-0.291 ~ 0.495；P =0.610）、25?羟基维生素D（SMD = -0.104，95%CI：-0.620 ~ 0.413；P = 0.690）组间差异均无统计学意义。敏感性分析显示，股骨骨密度、血清磷离子和25?羟基维生素D 的Meta 分析结果不稳定，解释结果时需谨慎。 结论 丙戊酸钠对儿童和青少年癫患者骨密度和骨代谢的影响较小，但应注意监测股骨骨密度。

关键词: 丙戊酸, 癫痫, 儿童, 骨密度, 骨和骨组织, 代谢, Meta分析