Interaction between 24R,25-dihydroxycholecalciferol and 1,25-dihydroxycholecalciferol on45Ca release from bone in vitro

Summary 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 measuring⁴⁵Ca 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 the⁴⁵Ca-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.