24- and 26-Homo-1, 25-dihydroxyvitamin D3 Analogs: Potencies on in vitro bone resorption differ from those reported for cell differentiation

Abstract

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