二膦酸盐长期服用可造成去势大鼠成骨矿化障碍  

Disturbance of bone mineralization induced by continuous administration of etidronate disodium in ovariectomized rats

作　　者：于顺禄[1] 叶伟胜[1] 徐瑾[1] 李健兵[1] 孔德诚[1] 

机构地区：[1]天津医院骨科研究所,300211

出　　处：《中华风湿病学杂志》2001年第6期354-357,T001,共5页Chinese Journal of Rheumatology

基　　金：国家中医药管理局九五攻关基金资助项目 ( 96F0 0 2 )

摘　　要：目的　观察羟乙膦酸钠 (二膦酸盐 )长期服药与间歇服药对去卵巢大鼠实验模型股骨骺板及骺板下骨小梁结构的骨组织形态计量学变化 ,为指导二膦酸盐药物的用药方式 ,探讨膦酸盐类对骨质疏松的疗效机制提供依据。方法　 5 0只SD雌性大鼠分 5组 ,假手术A组、去卵巢B组、去卵巢服用雌激素C组 (尼尔雌醇 0 1mg·kg-1·d-1)与去卵巢间歇服用羟乙膦酸钠D组(10mg·kg-1·d-1,用药 2周 ,停药 5周 ,重复 1次 )和连续服用羟乙膦酸钠E组 (10mg·kg-1·d-1,连续用药 10 0d)。各组均在服药 10 0d后处死 ,进行全股骨骨密度测量及股骨下端不脱钙切片的骨计量学观察。结果　大鼠模型的离体全股骨骨密度测定发现 ,间歇给药组能明显增加股骨的BMC和BMD矿物含量且去势对照组差异显著。间歇组BMD值为 (4 1 8± 8 4)mg/cm2 ,去势组 (31 6± 7 0 )mg/cm2 ,假手术对照组 (4 7 6± 2 7)mg/cm2 ,而连续给药组仅为 (2 9 4± 9 4)mg/cm2 ,与间歇组比较差异具有显著性 (P <0 0 1)。骨组织形态计量学研究发现 ,间歇用药组骨体积值 (5 0 2± 2 5 ) % ,连续用药组仅为(38 2± 3 4) %与去势对照组相似 (34 0± 2 9) % ,连续组与间歇组两者之间差异具有显著性 (P <0 0 0 1)。两组间最大差别在于类骨质量的多少与四环素标记率所体现?Objective To compare the different effects of continuous and intermittent administration of etidronate disodium in bone formation for osteoporosis.Methods Fifty 3 month old virgin female rats weighing (200±10) g were divided equally into 5 groups:pseudo ovariectomized group (group A), ovariectomized group (group B),estrogen replacement group (group C),intermittent etidronate disodium administered group (group D) and continuous etidronate disodium administered group (group E).Postoperative 30 days,group C was given nylostricl 0 1 mg·kg -1 ·d -1 for 100 d;group D was intermittently given etrdonate disodium 10 mg·kg -1 ·d -1 for 14 d and after 35 d interval the drugs were given once more;group E was continuously given etrdonate disodium 10 mg·kg -1 ·d -1 for 100 d.All rats were given drugs orally and were killed at day 100.The bone density,bone mineral content and bone histomorphometrical study were made.Results The average of BMD values of group A,B,C,D,E were [(47 6±2 7),(31 6±7 0),(38 2±4 9),(41 8±8 4),and (29 4±9 4) ( [AKx-]±s ),mg/cm 2] respectively.The value of group E was significant lower than that of group A and group D ( P <0 01).In bone histomorphmetric study,the average of BV values of group A to E was 63 2%,34 0%,43 9%,50 2%,and 38 2% respectively.Among which the value of the group E and group D appeared to be great significant differences ( P <0 001) as well as the values of OS (group D=15 6%,group E=94 2%, P <0 001) and O.Wi (group D= 5 8 μm, group E=65 0 μm, P <0 001) also showed great significant differences ( P <0 001).The measurement of DTS,STS/DTS,Mlt,MAR and iMAR appears to be zero,in group E. respectively.The value of group E was significant lower than that of group A and group D ( P <0 01).In bone histomorphmetric study,the average of BV values of group A to E was 63 2%,34 0%,43 9%,50 2%,and 38 2% respectively.Among which the value of the group E and group D appeared to be great significant dif

关 键 词：二膦酸盐类 卵巢切除术 大鼠 骨组织形态计量学 骨质疏松 

分 类 号：R68[医药卫生—骨科学]