丙戊酸钠对儿童癫患者骨密度和骨代谢的安全性评价  

Safety evaluation of valproate on bone mineral density and bone metabolism in children with epilepsy

作　　者：王海姣[1] 李倩[1] 谭戈[1] 朱丽娜[1] 储珊珊 刘凌[1] WANG Hai-jiao;LI Qian;TAN Ge;ZHU Li-na;CHU Shan-shan;LIU Ling(Department of Neurology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China)

机构地区：[1]四川大学华西医院神经内科,成都610041

出　　处：《中国现代神经疾病杂志》2018年第6期403-411,共9页Chinese Journal of Contemporary Neurology and Neurosurgery

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(Pub Med)、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Rev Man 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。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%Ch - 0.069-- 0.005, P = 0.020）. There was no significant change in serum calcium （SMD =- 0.284, 95%Ch -0.951-0.382; P = 0.400）, phosphorus （SMD =- 0.164, 95%Ch -0.457-0.129; P = 0.270）, alkaline phosphatase （ALP; SMD = 0.363, 95%Ch -0.294-1.020, P= 0.280）, parathyroid hormone （PTH; SMD = 0.102, 95%Ch -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.

关 键 词：丙戊酸 癫[疒间] 儿童 骨密度 骨和骨组织 代谢 Meta分析 

分 类 号：R742.1[医药卫生—神经病学与精神病学]