The effects of vitamin D analogues on bone resorption.

A series of analogues of vitamin D have been tested for their ability to stimulate bone resorption in two test systems used previously to investigate the metabolites of vitamine D. These analogues were tested (a) by directly comparing their action on bone explants of mouse half-calvaria in vitro, and (b) by injecting them into young mice and measuring the degree of resorption in vitro when explants were prepared 18 hours after the injection. It is concluded that the key functional groups concerned with enhancing the activity of vitamin D are the 1α- and the 25-hydroxyl, both together; the cis ring structure for ring A appears necessary. 1α-Hydroxycholecalciferol (1α-OHD) is about as active as 25-OHD in the direct test, but its potency is much nearer to that of 1,25-(OH)D when tested by the second (indirect) method; it seems likely that 1α-OHD is converted into 1,25-(OH)D in vivo. The results are discussed in relation to the designing of analogues for clinical and experimental use. [ABSTRACT FROM AUTHOR]