EFFECTS OF 2 DIPHOSPHONATES ON BONE METABOLISM IN THE RAT

The effects of low doses of the diphosphonates, ethane-1-hydroxy-1,1-diphosphonate (EHDP) and dichloromethylene diphosphonate (CI3MDP), were studied in weanling rats for 14 and 60 day periods. Cl2MDP was given in a dose of 0.1, 0.5 and 2.5 mg P/kg per day, and EHDP 1.0 mg P/kg per day for the 14-day experiments; the dose of each was 0.5 mg P/kg per day in the 60-day experiment. Parameters measured included serum calcium, phosphorus, immunoreactive parathyroid hormone (iPTH); bone formation, mineralization, resorption, and the number of osteoclast cell units in the diaphyseal sampling site; and selected enzymes in homogenates of metaphyseal bone. With increasing doses of/or prolonged treatment with diphosphonates, changes were found in serum calcium, phosphorus and (in one group) iPTH. The most important finding in this study was, however, a decrease in the linear rate of bone resorption as a function of the log dose of CI2MDP. The decrease in the linear rate was accompanied by two additional changes, both of which may have been compensatory: an increase in the number of osteoclast cell units and a decrease in endosteal bone formation. © 1979.