O'Hara J P, Jowsey J, Williams G A
J Lab Clin Med. 1975 Nov;86(5):793-802.
This study compared bone remodeling, bone mineralization, and parathyroid hormone secretion in rats treated with ethane-1-hydroxy-1,1-diphosphonate (EHDP) or dichloromethylene diphosphonate (Cl2MDP). The results were compared with findings in rachitic and control rats. In addition, calcification was induced in the skin by administration of lead acetate intravenously and polymyxin B subcutaneously; the efficacies of EHDP and Cl2MDP in preventing the calcific plaque were compared. Both the serum biochemical values and the morphologic findings indicate that Cl2MDP and EHDP influence bone and mineral metabolism differently. Even with the relatively large doses used in this study, Cl2MDP had a minor or no effect while EHDP had a marked effect that, in general, is undersirable. EHDP caused increase in circulating immunoreactive parathyroid hormone to levels greater than those in rachitic rats. Both diphosphonates appear to have a similar effect on the ectopic mineralization produced by calciphylaxis, suggesting that Cl2MDP may be the agent of choice in this problem because the undersirable side-effects would be avoided.
本研究比较了用乙烷-1-羟基-1,1-二膦酸盐(EHDP)或二氯亚甲基二膦酸盐(Cl2MDP)处理的大鼠的骨重塑、骨矿化及甲状旁腺激素分泌情况。并将结果与佝偻病大鼠和对照大鼠的研究结果进行比较。此外,通过静脉注射醋酸铅和皮下注射多粘菌素B诱导皮肤钙化;比较了EHDP和Cl2MDP预防钙化斑块的效果。血清生化值和形态学结果均表明,Cl2MDP和EHDP对骨和矿物质代谢的影响不同。即使在本研究中使用了相对大的剂量,Cl2MDP的作用较小或无作用,而EHDP则有明显作用,总体而言这种作用并不理想。EHDP使循环中免疫反应性甲状旁腺激素水平升高,高于佝偻病大鼠。两种二膦酸盐对钙化防御引起的异位矿化似乎有相似作用,这表明Cl2MDP可能是解决此问题的首选药物,因为可以避免不良副作用。