Effects of antiepileptic drugs on bone mineral density and bone metabolism in children: A meta-analysis
The aim of our meta-analysis was to assess the effects of antiepileptic drugs on bone mineral density and bone metabolism in epileptic children. Searches of PubMed and Web of Science were undertaken to identify studies evaluating the association between antiepileptic drugs and bone mineral density and bone metabolism. A total of 22 studies with 1492 subjects were included in our research. We identified: (1) a reduction in bone mineral density at lumbar spine (standardized mean difference (SMD)=−0.30, 95% confidence interval (CI) [−0.61, −0.05]), trochanter (mean difference (MD)=−0.07, 95% CI [−0.10, −0.05]), femoral neck (MD=−0.05, 95% CI [−0.09, −0.02]), and total body bone mineral density (MD=−0.33, 95% CI [−0.51, −0.15]); (2) a reduction in 25-hydroxyvitamin D (MD=−3.37, 95% CI [−5.94, −0.80]) and an increase in serum alkaline phosphatase (SMD=0.71, 95% CI [0.38, 1.05]); (3) no significant changes in serum parathyroid hormone, calcium, or phosphorus. Our meta-analysis suggests that treatment with antiepileptic drugs may be associated with decreased bone mineral density in epileptic children. 癫痫是神经系统常见病,半数以上患者儿童时期便发病,癫痫病患者常需终身服用抗癫痫药。研究表明,长期服用抗癫痫药物会影响骨代谢,加速骨矿物质的丢失,导致骨质疏松。但是,每种抗癫痫药物的具体作用还不清楚。作为典型的肝酶诱导剂的抗癫痫药物,卡马西平已经公认有降低骨密度的作用,但是作为非肝酶诱导剂的丙戊酸钠,还没有定论。在新型抗癫痫药物中,奥卡西平、托吡酯和拉莫三嗪等对骨密度似乎没有影响,但目前相关的研究很少,各研究所得结果也不一致。本研究拟通过荟萃分析评估抗癫痫药对癫痫病儿童骨密度和骨代谢的影响。 目前已有荟萃分析评估抗癫痫药对成人骨密度的影响,但尚无研究分析抗癫痫药对儿童的影响。 检索PubMed 和Web of Science 数据库中评估抗癫痫药与儿童骨密度及骨代谢关系的临床试验。入选标准为:(1)至少包括一项骨代谢的标志物;(2)骨密度用双能×线吸收计量法计算;(3)研究结果包括平均的骨密度和骨密度的标准差;(4)年龄小于18 岁;(5)患者采用单药或多药治疗;(6)具有健康对照组;(7)必须是观察性研究或随机对照研究。采用固定效应模型和随机效应模型对22 篇文献的1492 例患者中的骨密度及骨代谢资料进行荟萃分析,结果用加权均数差(WMD)或标准均数差(SMD)进行评估。 共22 篇文献符合纳入标准,共计1492 例患者。荟萃分析的结果显示,抗癫痫药物的使用可以引起儿童:(1)腰椎、转子、股骨颈的骨密度和全身骨密度的下降;(2)维生素D 下降和血清碱性磷酸酶的上升;(3)甲状旁腺激素、钙和磷没有显著改变。荟萃分析的结果表明,抗癫痫药的使用可能和癫痫病患儿骨密度降低相关。