24‐ and 26‐Homo‐1, 25‐dihydroxyvitamin D₃ 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 D₃ and their Δ²² analogs and 24,24‐dihomo‐1,25‐dihydroxyvitamin D₃ are 10‐fold more potent than 1,25‐dihydroxyvitamin D₃, and Δ²²‐24,24,24‐trihomo‐1,25‐dihydroxyvitamin D₃ is equipotent with 1,25‐dihydroxyvitamin D₃ in inducing differentiation into the monocytic phenotype. The effect of these 1,25‐dihydroxyvitamin D₃ analogs on resorption of fetal rat limb bones in vitro was determined in the present study. 1,25‐Dihydroxyvitamin D₃ was equipotent with 24‐homo‐1,25‐dihydroxyvitamin D₃, Δ²²‐24‐homo‐1,25‐dihydroxyvitamin D₃, 26‐homo‐1,25‐dihydroxyvitamin D₃, and Δ²²‐26‐homo‐1,25‐dihydroxyvitamin D₃ for in vitro bone resorption, whereas 24,24‐dihomo‐1,25‐dihydroxyvitamin D₃ and Δ²²‐24,24,24‐trihomo‐1,25‐dihydroxyvitamin D₃ were inactive. The failure of these analogs to show a higher bone‐resorbing activity than 1,25‐dihydroxyvitamin D₃ provides evidence to suggest that the mechanism of 1,25‐dihydroxyvitamin D₃‐induced bone resorption may not involve stimulation of monocytic cell differentiation