新型抗癫痫药物对癫痫患儿骨代谢影响的前瞻性研究

Prospective study on effect of new antiepileptic drugs on bone metabolism in children with epilepsy

目的研究新型抗癫痫药物(AEDs)托吡酯(TPM)、奥卡西平(OXC)、拉莫三嗪(LTG)、左乙拉西坦(LEV)对4~12岁癫痫儿童骨代谢的影响。方法收集2016年7月至2017年6月在山西省儿童医院初次诊断癫痫患儿160例,根据患儿的发作类型,分别予口服TPM(40例)、OXC(40例)、LTG(40例)、LEV(40例)单药治疗,观察4组患儿治疗前及治疗3、6、12个月后骨密度(BMD)及骨代谢指标的变化,包括血钙(Ca)、血磷(P)、血碱性磷酸酶(ALP)、骨钙素(OC)、甲状旁腺素(PTH)、25羟维生素D[25-(OH)D]。结果1.各试验组用药前多种骨代谢指标及BMD比较,差异均无统计学意义(均P>0.05)。2.OXC组治疗6、12个月后血Ca较治疗前减低[2.38(0.08)mmol/L比2.47(0.17)mmol/L、2.44(0.10)mmol/L比2.47(0.17)mmol/L],PTH较治疗前升高[37.64(17.52)ng/L比34.23(20.53)ng/L、40.74(16.15)ng/L比34.23(20.53)ng/L];TPM组治疗6、12个月血Ca较治疗前降低[2.40(0.11)mmol/L比2.42(0.10)mmol/L、2.41(0.09)mmol/L比2.42(0.10)mmol/L],差异均有统计学意义(均P<0.05)。3.OXC组在治疗6、12个月血Ca低于LEV组[2.38(0.08)mmol/L比2.44(0.10)mmol/L、2.44(0.10)mmol/L比2.44(0.12)mmol/L]、LTG组[2.38(0.08)mmol/L比2.44(0.13)mmol/L、2.44(0.10)mmol/L比2.42(0.13)mmol/L],血PTH高于LEV组[37.64(17.52)ng/L比36.52(20.71)ng/L、40.74(16.15)ng/L比31.89(14.84)ng/L]、LTG组[37.64(17.52)ng/L比39.39(24.03)ng/L、40.74(16.15)ng/L比33.01(12.20)ng/L],TPM组在治疗12个月后血Ca低于LEV组[2.41(0.09)mmol/L比2.44(0.12)mmol/L]、LTG组[2.41(0.09)mmol/L比2.42(0.13)mmol/L],差异均有统计学意义(均P<0.05)。结论LEV、LTG对于癫痫患儿骨代谢影响较小,TPM可能会使癫痫患儿血Ca下降;OXC可能会使血Ca降低,血PTH升高,导致患儿的骨转换增加。

Objective To study the effects of new antiepileptic drugs(AEDs),including Topiramate(TPM),Oxcarbazepine(OXC),Lamotrigine(LTG),and Levetiracetam(LEV)monotherapy on bone metabolism in children with epilepsy aged 4-12.Method s One hundred and sixty children with epilepsy who were diagnosed for the first time at Shanxi Children′s Hospital from July 2016 to June 2017 were selected and given oral TPM(40 cases),OXC(40 cases),LTG(40 cases)and LEV(40 cases)respectively according to the type of seizure.The changes of bone mineral density(BMD)and bone metabolism indexes including serum calcium(Ca),phosphorus(P),alkaline phosphatase(ALP),osteocalcin(OC),parathyroid hormone(PTH),25 hydroxyvitamin D[25-(OH)D]before treatment and at 3,6 and 12 months after treatment were observed.Result s(1)Bone metabolism indicators and BMD had no significant difference among groups before treatment(all P>0.05).(2)After 6 and 12 months of treatment in OXC group,Ca was lower than before treatment[2.38(0.08)mmol/L vs.2.47(0.17)mmol/L,2.44(0.10)mmol/L vs.2.47(0.17)mmol/L],PTH was higher than before treatment[37.64(17.52)ng/L vs.34.23(20.53)ng/L,40.74(16.15)ng/L vs.34.23(20.53)ng/L];Ca in TPM group decreased after 6 and 12 months of treatment[2.40(0.11)mmol/L vs.2.42(0.10)mmol/L,2.41(0.09)mmol/L vs.2.42(0.10)mmol/L],and the differences were statistically significant(all P<0.05).(3)After 6 and 12 months of treatment,Ca in the OXC group was lower than that in the LEV group[2.38(0.08)mmol/L vs.2.44(0.10)mmol/L,2.44(0.10)mmol/L vs.2.44(0.12)mmol/L]and LTG group[2.38(0.08)mmol/L vs.2.44(0.13)mmol/L,2.44(0.10)mmol/L vs.2.42(0.13)mmol/L],and PTH in the OXC group was higher than that in the LEV group[37.64(17.52)ng/L vs.36.52(20.71)ng/L,40.74(16.15)ng/L vs.31.89(14.84)ng/L]and LTG group[37.64(17.52)ng/L vs.39.39(24.03)ng/L,40.74(16.15)ng/L vs.33.01(12.20)ng/L],Ca in TPM group after 12 months of treatment was lower than that in the LEV group[2.41(0.09)mmol/L vs.2.44(0.12)mmol/L]and LTG group[2.41(0.09)mmol/L vs.2.42(0.13)mmol/L],and the differences were statistically significant(all P<0.05).Conclusions In the new AEDs,LEV and OXC have no significant effect on bone metabolism.TPM may affect bone metabolism by reducing Ca in children with epilepsy,and OXC may cause the decrease of Ca and the increase of PTH,thereby leading to increased bone turnover in children with epilepsy.