卡马西平和丙戊酸钠对癫癎患儿骨代谢的影响

目的探讨长期服用卡马西平（CBZ）或丙戊酸钠（VPA）对癫痫患儿骨代谢的影响。方法对92名单独服用CBZ或VPA2年以上的癫痫患儿及35名年龄匹配的健康儿童的骨密度进行测量,测定骨代谢特异性生化指标,血清骨钙素（OC,骨形成指标）和尿脱氧吡啶酚（DPD,骨吸收指标）,并调查每日钙摄入量。结果癫痫患儿骨密度明显低于对照组（P〈0．05）,服用抗癫痫药物（AEDs）的时间与骨密度呈负相关（rs=-0．21～-0．31,P〈0．05）。癫痫患儿中低骨密度患儿32人,占35％,明显高于对照组14％（P〈0．05）。低骨密度的癫痫患儿多体重指数较高（P〈0．05）,每日钙摄入量较少（P〈0．01）,服用AEDs的时间相对较长（P〈0．01）。癫痫患儿血清OC浓度明显低于对照组（P〈0．01）;而尿DPD浓度与对照组基本一致（P〉0．05）。结论长期服用CBZ或VPA会导致骨代谢异常,骨密度下降、骨转换降低（以骨形成减少为主）;而钙摄入量不足及体重指数偏高是加剧骨骼异常的诱发因素。

Effect of carbamazepine and valproate on bone metabolism in children with epilepsy

OBJECTIVE: To assess bone health in epileptic children who have been treated with carbamazepine (CBZ) or valproate (VPA) by using quantitative ultrasound (QUS) and determining the biochemical indices of bone metabolism, and to provide a proposal to improve quality of life of epileptic children. METHODS: Ninety-two epileptic children who had been treated with CBZ or VPA for more than two years were evaluated for bone mineral density (BMD) at the mid-shaft tibia and the distal third of the radius. Biochemical indices of bone metabolism including urine deoxypyridinoline (DPD) and serum osteocalcin (OC), and daily calcium intake were also evaluated. Thirty-five age-matched healthy children were used as controls. Reduced BMD was defined as speed of sound (SOS) Z scores of the mid-shaft tibia and (or) the distal third of the radius less than -0.7. RESULTS: BMD was reduced in epileptic children significantly when compared to the controls (P < 0.05). In addition, a negative correlation was found between the duration of anti-epileptic drugs (AEDs) use and BMD (r(s) = -0.21 - -0.31, P < 0.05), the lowest BMD was observed in those who had been treated for the longest time. The serum values of OC in epileptic children were significantly reduced relative to the controls (P < 0.01), children who took VPA had the lowest value of OC. However, the urine values of DPD showed no significant difference between epileptic and healthy children (P > 0.05); children who took CBZ had the highest value of DPD. Thirty-two epileptic children (35%) and five (14%) sex- and age-matched healthy children had reduced BMD, significant difference was found between them (P < 0.05). Moreover, epileptic children with reduced BMD seemed to have higher body mass index (BMI) (P < 0.05), take less daily calcium intake (P < 0.01), and had longer duration of AEDs (P < 0.01). The two risk factors of having reduced BMD in epileptic children were those who had been treated with AEDs for more than five years and higher BMI, while the protective factor was daily calcium intake. CONCLUSIONS: Long-term use of CBZ or VPA is associated with bone metabolism abnormalities, which include reduced BMD and decreased bone turnover (mainly decreased bone formation). Long-term anti-epileptic therapy is an important factor for impaired bone health in epileptic children, and that low calcium intake and high BMI could be two aggravating factors. QUS is a useful method to evaluate BMD of epileptic children who are on long-term anti-epileptic therapy, and to recognize the status of bone health, in helping to promote bone health and improve quality of life in epileptic children by the use of calcium and vitamin D supplementation.