The amino bisphosphonate ibandronate prevents calciphylaxis in the rat at doses that inhibit bone resorption

The present experiments were carried out to test the hypothesis that there is a common underlying biochemical mechanism that accounts for the different kinds of soft tissue calcification observed in animals that are treated with toxic doses of vitamin D. In previous studies we showed that lethal doses of vitamin D cause extensive calcification of arteries, lungs, kidneys, and cartilage, and that doses of the amino bisphosphonate ibandronate that inhibit bone resorption completely inhibit each of these soft tissue calcifications and prevent death. In the present experiments we have examined the effect of ibandronate on an entirely different type of calcification, the calciphylaxis induced by administration of a challenger to rats previously treated with sublethal doses of vitamin D. These studies show that ibandronate doses that inhibit bone resorption completely inhibit artery calcification as well as, in the same rat, the calciphylactic responses to either subcutaneous injection of 300 mug FeCl3 or intrascapular epilation. Since the vitamin D-treated animals had dramatically increased levels of bone resorption, and concurrent treatment with ibandronate normalized resorption, these results support the hypothesis that soft tissue calcifications in the vitamin D-treated rat may be linked to bone resorption. The ability of ibandronate to inhibit all vitamin D-associated calcifications in the rat cannot be explained by an effect of ibandronate on serum calcium, since serum calcium remained 30% above control levels in the vitamin D-treated animals that also received ibandronate.