常用抗癫药物对癫患儿骨代谢的影响

Effect of Antiepileptic Drugs on Bone Metabolism in Children with Epilepsy

目的了解卡马西平(CBZ)、丙戊酸钠(VPA)、托吡酯(TPM)对患儿癫骨代谢的影响,探讨其发生机制,为临床制订防治措施提供理论依据。方法收集73例无肝、肾损害及其他特殊疾病、近期未应用糖皮质激素和治疗剂量VitD的癫患儿的血清和尿液,其中服药前的癫患儿13例作为对照组,CBZ组15例,VPA组15例,TPM组30例。测定其血清ALP和尿脱氧吡啶啉/尿肌酐(DPD/Cr),同时检测服用TPM的患儿血Ca2+、HCO3-水平。结果与对照组比较,CBZ组和TPM组血清ALP均显著增高(Pa<0.01),VPA组血清ALP与对照组比较无统计学差异(P>0.05);TPM组尿DPD/Cr与对照组比较差异有统计学意义(P<0.05),CBZ组和VPA组尿DPD/Cr与对照组比较无统计学差异(Pa>0.05)。TPM组、CBZ组、VPA组和对照组血清ALP与尿DPD/Cr之间均无相关性(r=-0.083、-0.036、-0.304、-0.396,Pa>0.05)。TPM组血Ca2+、HCO3-水平分别为(1.10±0.08)mmol.L-1、(16.28±1.09)mmol.L-1,均低于正常值。TPM组血Ca2+水平与ALP和DPD/Cr水平无相关性(r=-0.183、-0.288,Pa>0.05),血HCO3-水平与ALP和DPD/Cr水平亦无相关性(r=0.321、0.285,Pa>0.05),血Ca2+与HCO3-之间无相关性(r=-0.064,P>0.05)。结论 CBZ对骨代谢的影响主要体现在骨形成方面,服用CBZ的癫患儿应注意补充钙剂和VitD;VPA在短期内对骨代谢可能无影响;TPM对儿童骨代谢的影响包括骨形成和骨吸收2个方面,服用TPM的癫患儿不仅需要补充钙剂和VitD,而且还应定期检测血HCO3-水平。

Objective To investigate the effects of carbamazepine（CBZ）,valproate（VPA）,topiratmate（TPM） on bone metabolism in children,and discuss the influencing mechanism,in order to provide a theoretical basis on drawing prophylactic and therapeutic measures.Methods The entrance standard was epileptic children who hadn′t received glucocorticosteroid,therapeutic dose of vitamin D（VitD）,and with no liver,renal or the other special disorders,and 73 children with epilepsy were enrolled in this study.Thirteen children without treatment as control group,15 children were treated with CBZ（CBZ group）,15 children were treated with VAP（VAP group）,30 children were treated with TPM（TPM group）.The markers of serum alkaline phosphatase（ALP） and urine deoxypyridinoline/ urine creatinine（DPD/Cr） were measured.At the same time,plasma calcium（Ca^2＋） and bicarbonate（HCO3-）levels were measured routinely in children treated with TPM in laboratory.Results Compared with control group,the ALP level in TPM group and CBZ group were significantly increased（Pa〈0.01）.There was no significant difference of ALP level between VPA group and control group（P〉0.05）.There was significant difference of DPD/Cr level between TPM group and control group（P〈0.05）.Compared with control group,there was no significant difference of DPD/Cr level in CBZ group and VPA group（Pa〉0.05）.There was no significant correlation between ALP level and DPD/Cr level in every group（r=-0.083,-0.036,-0.304,-0.396,Pa〉0.05）.The level of plasma Ca2＋ and HCO3-in TPM group was（1.10±0.08） mmol·L^-1,（16.28±1.09） mmol·L^-1,respectively,and both were lower than the range of normal level.There was no significant correlation between plasma Ca2＋ and ALP or DPD/Cr in TPM group（r=-0.183,-0.288,Pa〉0.05）.There was no significant correlation between plasma HCO3-and ALP or DPD/Cr in TPM group（r=0.321,0.285,Pa〉0.05）.There was no significant correlation between plasma Ca2＋ and plasma HCO3-（r=-0.064,P〉0.05）.Conclusions CBZ affect bone metabolism mainly be reflect on bone formation,and the patient treated with CBZ should be supplement calcium and VitD.VPA has no obvious effect on bone metabolism in short term.TPM may be affected bone metabolism,including bone formation and bone absorption,and the patient treated with TPM need not only supplementation of calcium and VitD,but also periodic measurements of plasma HCO3^-.