Inhibition by diphosphonates of bone resorption in mice and comparison with grey-lethal osteopetrosis.

Abstract

The effect of daily doses from birth of two diphosphonates, namely either ethane-1-hydroxy-1,1-diphosphonate (EHDP) or dichloromethylene diphosphonate (Cl2MDP), on the growth and the skeleton of mice has been studied. Diphosphonates slowed growth, the incisors did not erupt or erupted later, but the level of plasma calcium remained normal. The administration of Cl2MDP at a dose rate of 10 mg P/kg/day leads to skeletal changes that are similar to those observed in grey-lethal osteopetrotic mice, and the animals die after about four weeks of treatment. As compared with normal mice of similar age, treated mice had bones that were smaller, denser and more clubshaped, and the marrow cavities were filled with calcified bone or cartilage. The total amount of calcium in the carcass was not increased by diphosphonate treatment, as compared with the amount in normal mice of the same age. It is suggested that both in the grey-lethal and diphosphonate-treated mice many of the abnormalities are secondary to decreased bone resorption. The results are discussed with respect to the use of diphosphonates in pathological conditions of increased bone turnover and with respect to the role of bone resorption in the maintenance of plasma calcium levels.