斑马线还是生长障碍线:静脉双膦酸盐对儿童骨骼的特殊影响  

Zebra line or growth arrest line:specific effects of intravenous bisphosphonates on children's bone

作　　者：郑文彬 李大伟 李路娇 赵笛辰 王鸥 姜艳 夏维波 邢小平 余卫[3] 李梅 ZHENG Wen-bin;LI Da-wei;LI Lu-jiao;ZHAO Di-chen;WANG Ou;JIANG Yan;XIA Wei-bo;XING Xiao-ping;YU Wei;LI Mei(Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences &Peking Union Medical College, Key Laboratory of Endocrinology of National Health Commission ofthe People's Republic China, Beijing 100730, China;Department of Endocrinology, the First Affiliated Hospital ofHainan Medical University, Haikou 570100, China;Department of Radiology, Peking Union Medical College Hospital,Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China)

机构地区：[1]中国医学科学院,北京协和医学院,北京协和医院内分泌科,国家卫生健康委员会内分泌重点实验室,北京100730 [2]海南医学院第一附属医院内分泌科,海口570100 [3]中国医学科学院,北京协和医学院,北京协和医院放射科,北京100730

出　　处：《中华骨质疏松和骨矿盐疾病杂志》2020年第3期191-197,共7页Chinese Journal Of Osteoporosis And Bone Mineral Research

基　　金：国家自然科学基金面上项目(81570802,81873668);中国医学科学院医学与健康科技创新工程项目(2016-I2M-3-003);国家重点研发计划(2016YFC0901501)。

摘　　要：目的本研究旨在了解双膦酸盐类(bisphosphonates,BPs)药物治疗成骨不全症(osteogenesis imperfecta,OI)患儿,X线检查见长骨两端出现致密条带的性质。方法选取2012-2017年在北京协和医院诊断的OI患儿60例,按照2∶1随机分配,分别予静脉输注唑来膦酸(zoledronic acid,ZOL)5 mg/年或口服阿仑膦酸钠(alendronate,ALN)70 mg/周治疗。测量治疗期间生长速度的变化,检测骨转换生化指标,采用双能X线吸收检测仪测量腰椎及髋部骨密度(bone mineral density,BMD),分析X线片所见长骨两端致密条带的特点及其相关因素。结果两组患者基线年龄、身高、骨密度比较,差异无统计学意义(P>0.05)。ZOL组患者治疗12、24个月后长骨两端分别出现一条和两条致密线,口服ALN组治疗期间患者骨骼未出现致密线。治疗24个月后,ZOL和ALN组腰椎骨密度分别增加66.8%±39.5%和67.8%±34.4%,股骨颈骨密度增加51.8%±36.6%和53.0%±33.6%(与基线相比,均P<0.01)。ZOL和ALN组血清碱性磷酸酶(alkaline phosphatase,ALP)分别下降28.0%±28.2%和24.2%±24.8%,血清β交联Ⅰ型胶原羧基末端肽(βcross-linked carboxy-terminal telopeptide of type I collagen,β-CTX)水平则下降37.5%±24.6%和31.8%±30.0%(与基线比较,均P<0.05)。两组身高较基线明显增加,生长速度与正常儿童相似,提示ZOL不影响患儿生长速度,长骨两端致密线为静脉BPs引起骨骼矿化短期增加而致的特殊斑马线,并非生长障碍线。结论本研究首次在中国OI儿童患者中发现静脉唑来膦酸治疗导致长骨两端出现特异性斑马线,条带数目与静脉双膦酸盐治疗次数相同,患者生长速度正常,其并非生长障碍线。Objective Metaphyseal dense bands were found at the ends of long bones in osteogenesis imperfecta(OI)children treated by intravenous bisphosphonates(BPs).We aimed to study the characteristics of the specific dense bands.Methods A total of 60 children with OI were included from 2012 to 2017,and they were randomly administrated at ratio of 2∶1 to receive intravenous infusion of zoledronic acid(ZOL)5 mg annually or alendronate(ALN)70 mg weekly.The growth rate was assessed.Bone turnover biomakers were detected and BMD at lumbar spine and proximal hip were measured by dual-energy X-ray absorptiometry.Radiography of long bones was detected to analyze the characteristics of dense bands and related factors.Results After 12-month and 24-month of treatment,films indicated one and two dense lines parallel to the growth plate in long bones in ZOL group,while no line was found in ALN group.BMD at spine in two groups increased by 66.8%±39.5%and 67.8%±34.4%,and BMD at femoral neck increased by 51.8%±36.6%and 53.0%±33.6%in ZOL group and ALN group(all P<0.01 vs baseline),respectively.Serum ALP levels decreased by 28.0%±28.2%and 24.2%±24.8%,andβ-CTX levels decreased by 37.5%±24.6%and 31.8%±30.0%in two groups(all P<0.05 vs baseline).Height significantly increased,and the growth speed of OI children treated with ZOL was similar to normal children,suggesting that ZOL did not retard the growth of the children.The dense metaphyseal lines were zebra lines,which were caused by the short-term increase of bone mineralization,rather than growth arrest lines.Conclusions We firstly found that intravenous zoledronic acid treatment resulted in zebra lines in long bones in Chinese OI children,and zebra lines number was same with the number of BPs infusion.ZOL did not affect the growth rate of OI children,which indicated that zebra lines were not growth arrest lines.

关 键 词：成骨不全症 儿童 唑来膦酸 斑马线 生长障碍线 

分 类 号：R681[医药卫生—骨科学]