Rachitogenic Activity of Dietary Strontium: I. INHIBITION OF INTESTINAL CALCIUM ABSORPTION AND 1,25-DIHYDROXYCHOLECALCIFEROL SYNTHESIS

Abstract

Abstract Inhibition of calcium absorption by dietary strontium is the result of a block in the renal synthesis of 1,25-dihydroxycholecalciferol (1,25-(OH)2CC) from 25-hydroxycholecalciferol (25-OHCC). The administration of 1,25-(OH)2CC but not 25-OHCC restores to normal calcium absorption in strontium-fed chicks. Kidney mitochondria from strontium-fed chicks do not metabolize 25-OHCC to 1,25-(OH)2CC, but rather to a metabolite designated Peak Va. The function of Peak Va is unknown while it is believed that 1,25-(OH)2CC is the metabolically active form of vitamin D in the stimulation of calcium absorption from intestine and mobilization from bone. The changes in the kidney metabolism of 25-OHCC in response to dietary strontium occur over a period of several days and correlate closely with changes in intestinal calcium absorption. Feeding a normal calcium diet can correct the strontium-induced inhibition of intestinal calcium absorption. This restoration of calcium absorption correlates with an increased rate of in vitro 1,25-(OH)2CC synthesis. The exact mechanism whereby strontium alters the renal metabolism of 25-OHCC is unknown. However, indirect evidence suggests that it may operate through humoral agents such as parathyroid hormone, or calcitonin, or both, which are responsible for maintenance of plasma calcium concentration.