癫痫及长期应用抗癫痫药物对儿童骨代谢影响的研究进展

Advances in Research on the Effects of Epilepsy and Long-term Use of Antiepileptic Drugs on Bone Metabolism in Children

我国癫痫(Epilepsy)患者约有600万,其中60%于儿童时期起病。童年及青春期是骨骼矿化的关键时期。患儿在儿童和青少年时期没有达到合格的骨量,其患骨质疏松的概率更高。绝大多数的癫痫患儿需长期口服抗癫痫药物(Antiepileptic drugs-AEDs)治疗。长期使用AEDs的儿童容易出现低骨矿物质密度,同时骨折风险也会增大。目前,越来越多的证据显示,癫痫患者骨折的风险与健康人群相比增加了两倍,尤其未得到控制的个体。骨代谢异常中,近2/3归因于抗癫痫药物的累积效应。临床试验表明长期服用传统肝酶诱导性AEDs(如苯妥英钠等)会严重影响患儿骨代谢平衡,进而影响生长发育。肝酶抑制剂[如丙戊酸钠(Valproate,VPA)及些新型药物左乙拉西坦(Levetiracetam,LEV)、托吡酯(Topiramate,TPM)、拉莫三嗪(Lamotrigine,LTG)等]相关性骨病被广泛研究,但结果相互矛盾。AEDs导致骨代谢异常的潜在的机制很大程度上仍然未知。因此本文对癫痫及长期应用抗癫痫药物(单药与多药)对患骨代谢指标的影响等方面进行综述。

There are about 6 million patients with epilepsy(Epilepsy)in our country,and 60%of them started in childhood.Childhood and adolescence are critical periods of bone mineralization.Children who do not reach the qualified bone mass in childhood and adolescence are more likely to suffer from osteoporosis.The vast majority of children with epilepsy require long-term oral antiepileptic drugs(AEDs)treatment.Children who use AEDs for a long time are prone to low bone mineral density,and the risk of fractures is also increased.At present,more and more evidences show that the risk of fracture in patients with epilepsy has tripled compared with healthy people,especially in uncontrolled individuals.Among abnormal bone metabolism,nearly two-thirds are attributed to the cumulative effect of anti-epileptic drugs.Clinical trials have shown that long-term use of traditional liver enzyme induced AEDs(such as phenytoin sodium)will seriously affect the bone metabolism balance of children,and then affect the growth and development.Liver enzyme inhibitors such as valproate(VPA)and some new drugs(levetiracetam,topiramate,LTG,et al)related bone diseases have been widely studied,but the results are contradictory.The underlying mechanism of bone metabolism abnormalities caused by AEDs remains largely unknown.Therefore,this article reviews the effects of epilepsy and long-term use of anti-epileptic drugs(single and multiple drugs)on bone metabolism indicators.