Interaction between 24R,25-dihydroxycholecalciferol and 1,25-dihydroxycholecalciferol on 45Ca release from bone in vitro

Interaction among vitamin D3 metabolites on bone receptor sites is not known. Therefore, interaction between the most potent vitamin D3 metabolite, 1,25(OH)2D3, and the most abundant dihydroxymetabolite, 24R,25(OH)2D3, was studied on isolated rat fetal bone by measuring 45Ca release from prelabeled bones. 24R,25(OH)2D3 at concentrations of 10-50 ng/ml caused marked inhibition of the bone-resorbing activity of 1,25(OH)2D3 at concentrations of 10-50 pg/ml. 24S,25(OH)2 (unnatural enantiometer), on the other hand, at a concentration of 100 ng/ml did not inhibit the bone-resorbing effect of 10 pg/ml 1,25(OH)2D3. 24R,25(OH)2D3 at a concentration of 20 ng/ml did not inhibit the 45Ca-releasing effect of a submaximal concentration of PTH (500 ng/ml). Therefore, the inhibitory effect of 24R,25(OH)2D3 on the bone response to 1,25(OH)2D3 appeared to be specific and probably due to a competitive inhibitory effect. In addition, the inhibitory effect of 24R,25(OH)2D3 was weak, since it could be partially overcome by increasing the concentration of 1,25(OH)2D3.