Objective:To evaluate the influence of epilepsy and antiepileptic drugs on bone mineral density(BMD) and bone metabolism in children with epilepsy. Methods:A retrospective analysis was carried out on 150 children with epilepsy. The children were divided into untreated group(n=50), VPA1 group(n=35), LEV1 group(n=33) and OXC1 group(n=32). Fifty normal children were selected as control group. The influence of epilepsy itself and antiepileptic drugs on BMD and bone metabolism was retrospectively analyzed. A prospective study was carried out on 100 pre-school age and 100 school age epileptic children, who were randomly divided into three groups,i.e., 33 in VPA2 and VPA3 group,34 in LEV2 and LEV3 group, 33 in OXC2 and OXC3 group. After 3, 6 and 12 months, BMD and bone metabolism were observed. Results:In the retrospective study, there were statistically differences in BMD and calcium, of which the untreated group and other three groups were lower than those of normal children(P<0.05), and VPA group was the lowest. In the prospective study, after treatment in pre-school age children for 3, 6 and 12 months, there were statistically differences in BMD and calcium, of which VPA2 group was lower than those of LEV2 group and OXC2 group(P<0.05).And bone alkaline phosphatase(BAP) of VPA2 group was higher than those of LEV2 group and OXC2 group(P<0.05).After treatment in school age children for 12 months, there were statistically differences in BMD and calcium, of which the VPA3 group was lower than those of LEV3 group and OXC3 group(P<0.05). And BAP was higher than those of LEV3 group and OXC3 group(P<0.05). Conclusion:Epilepsy itself affects BMD and bone metabolism in children. The influences of VPA on BMD and bone metabolism are increased with the course of treatment. However, LEV and OXC have no significant effect on BMD and bone metabolism, which is worth promoting in clinical practice. |
[1] 张守利,莫亚玲,赵德运,等.左乙拉西坦单药治疗癫痫患儿临床效果及其对骨代谢的影响[J].河北医科大学学报,2015,36(9):1076-1079.
[2] 潘晓雨,夏莉,闫福岭.表现为视幻觉的枕叶癫痫一例报道[J].东南大学学报(医学版),2014,33(4):500-503.
[3] PITETZIS D A,SPILIOTI M G,YOVOS J G,et al.The effect of VPA on bone:from clinical studies to cell cultures-the molecular mechanisms revisited[J].Seizure,2017,48:36-43.
[4] 赵群,司继刚,王冰洁.神经系统药物引起严重不良反应分析[J].河北医药,2015(4):615-617.
[5] YILDIZ E P,POYRAZOGLU S,BEKTAS G,et al.Potential risk factors for vitamin D levels in medium-and long-term use of antiepileptic drugs in childhood[J].Acta Neurol Belg,2017,117(2):447-453.
[6] 鞠俊.建立中国儿童骨代谢标志物正常值及探讨癫痫病和抗癫痫药物对患儿骨代谢的影响[D].北京:解放军总医院,2015.
[7] ENGEL J.Report of the ILAE classification core group[J].Epilepsia,2010,47(9):1558-1568.
[8] 张芳,李桂新.抗癫痫药对癫痫患儿骨代谢及生活质量的影响[J].陕西医学杂志,2016,45(1):28-30.
[9] FONG C Y,KONG A N,NOORDIN M,et al.Determinants of low bone mineral density in children with epilepsy[J].Eur J Paediatr Neurol,2018,22(1):155-163.
[10] DUSSAULT P M,LAZZARI A A.Epilepsy and osteoporosis risk[J].Curr Opin Endocrinol Diabetes Obes,2017,24(6):395-401.
[11] HAMED S A,MOUSSA E M,YOUSSEF A H,et al.Bone status in patients with epilepsy:relationship to markers of bone remodeling[J].Front Neurol,2014,5:142.
[12] MIRATASHI-YAZDI S A,ABBASI M,MIRATASHI-YAZDI S M.Epilepsy and vitamin D:a comprehensive review of current knowledge[J].Rev Neurosci,2017,28(2):185-201.
[13] 康静,白如玉,范百亚,等.丙戊酸钠联合拉莫三嗪对不同发作类型癫痫的临床疗效[J].河北医药,2017(24):3775-3777.
[14] 刘文晶,郝艳秋.抗癫痫药物对骨代谢的影响[J].儿科药学杂志,2017(5):58-62.
[15] 王盼.托吡酯和左乙拉西坦对学龄期癫痫患儿骨代谢的影响[D].石家庄:河北医科大学,2014.
[16] 金超,张双,庞保东.新型抗癫痫药物对癫痫患儿骨代谢影响的研究[J].中国妇幼保健,2014,29(5):718-720.
[17] NAKHAEE M M,TEIMOUR A,KHAJEH A,et al.Bone metabolism disorder in epileptic children[J].Iran J Child Neurol,2018,12(2):17-24.
[18] 王丽,陈苓,赵慧,等.左乙拉西坦对癫痫患儿骨代谢与认知功能的影响[J].贵州医药,2017,41(7):722-724.
[19] SINGLA S,KAUSHAL S,ARORA S,et al.Bone health in patients with epilepsy:a community-based pilot nested case-control study[J].Ann Indian Acad Neurol,2017,20(4):367-371.
[20] HUMPHREY E L,MORRIS G E,FULLER H R.Valproate reduces collagen and osteonectin in cultured bone cells[J].Epilepsy Res,2013,106(3):446-450.
[21] JENSEN E D,SCHROEDER T M,BAILEY J,et al.Histone deacetylase 7 associates with Runx2 and represses its activity during osteoblast maturation in a deacetylation-independent manner[J].Bone Miner Res,2008,23(3):361-372.
[22] PERUCCA E.Clinically relevant drug interactions with antiepileptic drugs[J].Br J Clin Pharmacol,2006,61(3):246-255.
[23] VRZAL R,DORICAKOVAA A,NOVATNA A,et al.Valproicacid augments vitamin D receptor-mediated induction of CYP24 by vitamin D3:a possible cause of valproic acid-induced osteomalacia?[J].Toxicol Lett,2011,200(3):146-153.
[24] VERROTTI A,LOIACONO G,LAUS M,et al.Hormonal and reproductive disturbances in epileptic male patients:emerging issues[J].Reprod Toxicol,2011,31(4):519-527. |