Role of 1,25-dihydroxyvitamin D3 in maintaining serum phosphorus and curing rickets

Abstract

The intravenous injection of a single dose of 650 pmoles of 1,25-dihydroxyvitamin D(3) to rats fed a vitamin D-deficient, low-phosphorus diet caused an elevation of serum phosphorus within 5 hours which reached a maximum in about 10-12 hours. This elevated serum phosphorus returned to deficiency levels 2-3 days later. On the other hand, a single injection of 650 pmoles of 25-hydroxyvitamin D(3) produced a significant rise at 12 hours, reached a maximum in 24-36 hours, and was maintained for at least 7 days. The single dose of 1,25-dihydroxyvitamin D(3) supported little calcification of bone, whereas the 25-hydroxyvitamin D(3) produced marked calcification. Six-hundred and fifty pmoles of 24,25-dihydroxyvitamin D(3) increased serum phosphorus only slightly and induced no calcification. When 1,25-dihydroxyvitamin D(3) was given each day, a sustained increase in serum phosphorus and marked bone calcification resulted. In contrast to the serum phosphorus responses, intestinal calcium transport remained high 5 days after administration of a single dose of 1,25-dihydroxyvitamin D(3). Serum calcium was not changed appreciably by any of the metabolites. Thyroparathyroidectomized rats or rats fed a diet extremely deficient in phosphate still exhibited a marked elevation of serum phosphorus in response to 1,25-dihydroxyvitamin D(3). The effect of 1,25-dihydroxyvitamin D(3) on serum phosphorus was greatly reduced in nephrectomized rats, suggesting that the serum phosphorus response to 1,25-dihydroxyvitamin D(3) may arise from an enhancement of phosphate reabsorption in the renal tubules. It is suggested that 1,25-dihydroxyvitamin D(3) cures rickets in rats by increasing the concentration of serum phosphorus rather than by increasing serum calcium concentration and calcium absorption.