The Influence of Two Diphosphonates on Calcium Metabolism in the Rat

Abstract

1. The effects of two diphosphonates, disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) and disodium dichloromethylene diphosphonate (Cl2MDP) on several variables of calcium metabolism have been measured in the intact rat using the model of Aubert & Milhaud (1960). 2. The animals were bred from weaning on a diet containing 1·3% calcium. At the age of 54 days they were switched to a diet with 0·5% calcium. Some of the animals were also given daily injections of one of the diphosphonates from the day the intake was decreased. The doses of the compounds were 0·01–10 mg of P kg body wt.−1 day−1. 3. Cl2MDP caused a decrease in the rates of bone formation (V0+) and bone resorption (V0–), and these effects were proportional to the logarithm of the dose of the compound. There was a small increase in the retention of calcium due to a decrease in the endogenous faecal calcium. 4. EHDP in doses of up to 1 mg of P kg−1 day−1 decreased bone resorption but had little effect on bone formation. The retention of calcium increased due to an increased absorption of dietary calcium and a decreased endogenous faecal calcium. EHDP at a dose of 10 mg of P kg−1 day−1 caused a further fall in V0_ but also a great decrease in V0+ which was larger than the fall in V0_. The net absorption of calcium was diminished, the urinary excretion of calcium was increased, the retention of calcium was greatly diminished and there was a greatly diminished ash content in the femur. Thus, for equal doses of up to 1 mg of P kg−1 day−1, Cl2MDP was more potent in decreasing bone turnover than EHDP, but the two compounds caused a similar increase in the retention of calcium. At high doses EHDP inhibited the mineralization of epiphyseal cartilage. 5. These results are discussed in relation to the possible clinical applications of the diphosphonates.