24‐ and 26‐Homo‐1, 25‐dihydroxyvitamin D 3 Analogs: Potencies on in vitro bone resorption differ from those reported for cell differentiation

It has been proposed that the stimulatory effects of 1,25‐dihydroxyvitamin D on bone resorption may be mediated through actions on differentiation of marrow cells into monocytic osteoclast precursors. In human promyelocytic leukemia cells (HL‐60), 24‐ and 26‐homo‐1,25‐dihydroxyvitamin D 3 and their Δ 22 analogs and 24,24‐dihomo‐1,25‐dihydroxyvitamin D 3 are 10‐fold more potent than 1,25‐dihydroxyvitamin D 3 , and Δ 22 ‐24,24,24‐trihomo‐1,25‐dihydroxyvitamin D 3 is equipotent with 1,25‐dihydroxyvitamin D 3 in inducing differentiation into the monocytic phenotype. The effect of these 1,25‐dihydroxyvitamin D 3 analogs on resorption of fetal rat limb bones in vitro was determined in the present study. 1,25‐Dihydroxyvitamin D 3 was equipotent with 24‐homo‐1,25‐dihydroxyvitamin D 3 , Δ 22 ‐24‐homo‐1,25‐dihydroxyvitamin D 3 , 26‐homo‐1,25‐dihydroxyvitamin D 3 , and Δ 22 ‐26‐homo‐1,25‐dihydroxyvitamin D 3 for in vitro bone resorption, whereas 24,24‐dihomo‐1,25‐dihydroxyvitamin D 3 and Δ 22 ‐24,24,24‐trihomo‐1,25‐dihydroxyvitamin D 3 were inactive. The failure of these analogs to show a higher bone‐resorbing activity than 1,25‐dihydroxyvitamin D 3 provides evidence to suggest that the mechanism of 1,25‐dihydroxyvitamin D 3 ‐induced bone resorption may not involve stimulation of monocytic cell differentiation