The Influence of Two Diphosphonates on Calcium Metabolism in the Rat

Abstract

1. The effects of two diphosphonates, disodium ethane-I-hydroxy-l,1-diphosphonate (EHDP) and disodium dichloromethylene diphosphonate (C1,MDP) on several variables of calcium metabolism have been measured in the intact rat using the model of .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.-' day-'.3. C12MDP caused a decrease in the rates of bone formation (Vo+) and bone resorption (Vo-), 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-' day-' 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-' day-' caused a further fall in Vo-but also a great decrease in Vo + which was larger than the fall in Vo -. 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-' day-', C1,MDP 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.

Calcium absorption in diphosphonate‐treated rats: effect of parathyroid function, dietary calcium and phosphorus.

“…Thus the EHDP-induced inhibition of Ca absorption does not appear to be mediated by a reduced secretion of PTH. Such a mediation could have been suspected since the action of EHDP on the intestine is accompanied by an increase in plasma Ca (Gasser et al 1972;Bonjour et al 1973a). Furthermore, in the non-treated animals, thyroparathyroidectomy decreases Ca absorption (Fig.…”

Acute Kidney Injury and Bisphosphonate Use in Cancer: A Report From the Research on Adverse Drug Events and Reports (RADAR) Project

“…1 BPs are powerful inhibitors of bone resorption and lead to a positive calcium balance and increase in bone mineral content. 2 Preclinical evidence suggests that nitrogen-containing BPs, like zoledronic acid (ZOL), might have inherent antitumor and antiangiogenic properties. 1,3 Up to 75% of patients with breast and prostate cancer develop skeletal metastasis in stage IV disease.…”

The development of bisphosphonates for therapeutic uses, and bisphosphonate structure-activity consideration

“…[17][18][19][20][21] It is also used in the treatment of osteoporosis resulting from therapy with steroidal and other medications incorporated. [22][23][24][25][26] The effect on the osteoclast leads to a decrease in bone turnover, and is secondary to the inhibition of bone resorption. Several studies 22,24,[27][28][29][30] indicate that BPs can be classified into at least two groups, with different modes of action.…”