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 sub-lethal 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 mg 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.