Effects of dichloromethylene diphosphonate, ethane-1-hydroxy-1,1-diphosphonate, and rickets in rats

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.