The calcium antagonist diltiazem inhibits calcification enhanced by calcitonin in growth cartilage of rats in ethane-1-hydroxy-1,1-diphosphonate (EHDP)-induced rickets

Abstract

Abstract. In an animal model of human rickets developed by giving a short-term administration of large doses of EHDP to young rats, concomitant administration of [Asu1,7]eel calcitonin (CT) with EHDP resulted in the promotion of calcification in growth cartilage. In an attempt to clarify the mechanisms related to the accelerated calcification due to CT, the effects of diltiazem, a calcium antagonist, were studied. Diltiazem suppressed, in a dose-dependent manner, the accelerated calcification due to CT in the growth cartilage, as determined by findings on the soft X-ray photos, contact microradiograph and light microscopic histology of the proximal region of the tibia. This suppression was only evident when diltiazem and CT were given concomitantly. If it is assumed that diltiazem inhibits the entry of calcium ion into the cells of growth cartilage, in the same manner as seen in case of smooth muscle and myocardial cells, then our results indicate that intracellular concentrations of calcium might play an important role in the occurrence of accelerated calcification due to CT.