[卡马西平和丙戊酸对癫痫患儿骨代谢的影响]

Song Xiao-qing, Wang Zhi-ping, Bao Ke-rong, Zhang Jian-ming, Wu Jie, Yan Chong-huai, Shen Xiao-ming

Department of Pediatrics, Xinhua Hospital of Shanghai Second Medical University, Shanghai 200433, China.

Zhonghua Er Ke Za Zhi. 2005 Oct;43(10):728-32.

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.

目的

通过定量超声（QUS）评估接受卡马西平（CBZ）或丙戊酸盐（VPA）治疗的癫痫儿童的骨骼健康状况，并测定骨代谢的生化指标，为改善癫痫儿童的生活质量提供建议。

方法

对92例接受CBZ或VPA治疗超过两年的癫痫儿童进行胫骨中段和桡骨远端三分之一处的骨密度（BMD）评估。还评估了包括尿脱氧吡啶啉（DPD）和血清骨钙素（OC）在内的骨代谢生化指标以及每日钙摄入量。35名年龄匹配的健康儿童作为对照。BMD降低定义为胫骨中段和（或）桡骨远端三分之一处的声速（SOS）Z评分小于-0.7。

结果

与对照组相比，癫痫儿童的BMD显著降低（P<0.05）。此外，抗癫痫药物（AEDs）使用时间与BMD之间存在负相关（r(s)=-0.21--0.31，P<0.05），治疗时间最长的儿童BMD最低。癫痫儿童的血清OC值相对于对照组显著降低（P<0.01），服用VPA的儿童OC值最低。然而，癫痫儿童与健康儿童的尿DPD值无显著差异（P>0.05）；服用CBZ的儿童DPD值最高。32例癫痫儿童（35%）和5例（14%）年龄和性别匹配的健康儿童BMD降低，两者之间存在显著差异（P<0.05）。此外，BMD降低的癫痫儿童似乎体重指数（BMI）较高（P<0.05），每日钙摄入量较少（P<0.01），AEDs使用时间较长（P<0.01）。癫痫儿童BMD降低的两个危险因素是接受AEDs治疗超过五年和BMI较高，而保护因素是每日钙摄入量。

结论

长期使用CBZ或VPA与骨代谢异常有关，包括BMD降低和骨转换减少（主要是骨形成减少）。长期抗癫痫治疗是癫痫儿童骨骼健康受损的重要因素，而低钙摄入量和高BMI可能是两个加重因素。QUS是评估长期接受抗癫痫治疗的癫痫儿童BMD以及识别骨骼健康状况的有用方法，有助于通过补充钙和维生素D促进癫痫儿童的骨骼健康并改善其生活质量。