Relation between bone mineralization, Ca absorption, and plasma Ca in phosphonate-treated rats.

Disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) is known to inhibit the crystallization of calcium phosphate salts in vitro. Large doses of EHDP administered in vivo inhibit skeletal mineralization, decrease intestinal calcium absorption, and produce hypercalcemia. In the present study, EHDP or one of 13 other phosphonates were given to rats at 10 mg P/kg-day sc for 7 days in order to better define the nature of the relationship between bone mineralization, intestinal absorption, and plasma calcium in the regulation of calcium homeostasis. Each of the phosphonates which inhibited skeletal mineralization in vivo also inhibited crystallization in vitro, but the converse was not true. A very close correlation was found between inhibition of skeletal mineralization, decreased intestinal calcium absorption, and slight hypercalcemia. A dose-response study with two compounds also revealed the same close correlation. It is argued that the impairment of intestinal calcium absorption in phosphonate-treated rats may represent a secondary homeostatic response to the primary effect of the drugs on bone mineralization. This response may be mediated by an elevation of a fraction of plasma calcium.