Guo C Y, Ronen G M, Atkinson S A
Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.
Epilepsia. 2001 Sep;42(9):1141-7. doi: 10.1046/j.1528-1157.2001.416800.x.
To determine whether long-term treatment with valproate (VPA) and/or lamotrigine (LTG) in children with epilepsy is associated with altered growth and/or bone metabolism.
Twenty-seven boys and 26 girls, aged 3 to 17 years (9.2 +/- 3.9, mean +/- SD), with epilepsy treated with VPA and/or LTG for > or =2 years were evaluated for growth, nutrient intakes, physical activity, bone mineral density (BMD), and blood biochemical indices of mineral and bone metabolism.
Twenty-three (43.4%) of the children had a body height below the 10th percentile. Z-scores for BMD below -1.5 occurred in 24.4% of the children. When patients were divided into two groups according to daily activity score, a significantly lower Z-score for total body BMD (p = 0.007), percentile for body height (p = 0.05), and plasma parathyroid hormone (PTH; p = 0.04), osteocalcin (p = 0.04) and 25-hydroxyvitamin D (25OHD) (p = 0.01) were found in the inactive compared with the active group. Z-score for total body BMD was correlated with daily activity score (r = 0.43, p = 0.008). Plasma intact osteocalcin and intact PTH values correlated significantly (r = 0.36, p = 0.02). Plasma 1,25-dihydroxyvitamin D was within normal range for all subjects. When patients were divided into LTG-alone, VPA-alone, and LTG-plus-VPA treatment groups, significantly lower (p < 0.05) plasma osteocalcin and percentile for body height were found in the VPA-plus-LTG treatment group.
Long-term VPA and LTG therapy, particularly when combined, is associated with short stature, low BMD, and reduced bone formation. These alterations may be mediated primarily through reduced physical activity rather than through a direct link to the VPA and/or LTG therapy.
确定丙戊酸盐（VPA）和/或拉莫三嗪（LTG）长期治疗癫痫患儿是否与生长发育改变和/或骨代谢异常有关。
对27名男孩和26名女孩进行评估，年龄3至17岁（平均9.2±3.9岁，均值±标准差），这些癫痫患儿接受VPA和/或LTG治疗≥2年，评估其生长发育、营养摄入、身体活动、骨密度（BMD）以及矿物质和骨代谢的血液生化指标。
23名（43.4%）儿童身高低于第10百分位数。24.4%的儿童骨密度Z值低于-1.5。根据日常活动评分将患者分为两组时，与活跃组相比，不活跃组全身骨密度Z值显著更低（p = 0.007）、身高百分位数（p = 0.05）、血浆甲状旁腺激素（PTH；p = 0.04）、骨钙素（p = 0.04）和25-羟基维生素D（25OHD）（p = 0.01）。全身骨密度Z值与日常活动评分相关（r = 0.43，p = 0.008）。血浆完整骨钙素和完整PTH值显著相关（r = 0.36，p = 0.02）。所有受试者血浆1,25-二羟基维生素D均在正常范围内。当患者分为单用LTG、单用VPA以及LTG加VPA治疗组时，VPA加LTG治疗组血浆骨钙素和身高百分位数显著更低（p < 0.05）。
长期VPA和LTG治疗，尤其是联合使用时，与身材矮小、低骨密度和骨形成减少有关。这些改变可能主要通过身体活动减少介导，而非直接与VPA和/或LTG治疗相关。
