Comparison of 26, 27-Hexafluoro-1α, 25-dihydroxyvitamin D₃ and 1α, 25-Dihydroxyvitamin D₃ on the Resorption of Bone Explants Ex Vivo

Abstract

26, 27-Hexafluoro-1α, 25-dihydroxyvitamin D₃ [F₆-1, 25-(OH)₂D₃] is more potent than 1α, 25-dihydroxyvitamin D₃ [l, 25(OH)₂D₃] in stimulating bone resorption in vitro and in vivo. The reason why F₆-1, 25(OH)2D₃ is more active remains unclear. To clarify the relationship between the bone-resorbing activity of each vitamin D₃ analogue and the metabolism of each analogue, in the present study, we used an ex vivo method that was established by Reynolds et al (Calcif Tissue Res, 1974, 15, 333-339). The effect of F₆-1, 25(OH)₂D₃ or 1, 25(OH)₂D₃ on ⁴⁵Ca release from parietal bones, prepared at 3, 14 and 24 h after injection of 1.9, 3.8, 7.6 or 15.2 pmol vitamin D analog /g body weight, was examined. F6-1, 25(OH)₂D₃ was more potent than 1, 25(OH)₂D₃ during each in vivo time period. 1, 25(OH)₂D₃ at 3h after the injection was more active compared to the control (no injection of 1, 25(OH)₂D₃), but not at 14 and 24h. The radioactivity of the bones after the injection of [₃H]-F₆-, 25(OH)₂D₃ was retained even at 24h. In the case of [₃H]-1, 25(OH)₂D₃, the radioactivity of bones decreased with an increase in the in vivo period. In a HPLC analysis of the lipid extract of bone homogenate, [³H]-F₆-1, 25(OH)₂D₃ alone was detected at 3 h after the injection and both [₃H]-F₆-1, 25(OH)₂D₃ and [³H]-26, 27-hexafluoro-1α, 23S, 25-trihydroxy-vitamin D₃ [F₆-1, 23, 25(OH)₃D₃] were detected at 14 and 24h after the injection. [³H]-1, 25(OH)₂D₃ was highly detected at 3 h after the injection, but it decreased with an increase in the in vivo period. In the ex vivo test, the activity of F₆-1, 23, 25(OH)₃D₃ was less than that of F₆-1, 25(OH)₂D₃ but similar to that of 1, 25(OH)₂D₃. The present study indicates that F₆-1, 25(OH)₂D₃ is more active and more long-lasting than 1, 25(OH)₂D₃ in the ex vivo method. A higher potency of F₆-1, 25(OH)₂D₃ is explained, at least partly, by the results that the amounts of both F₆-1, 25(OH)₂D₃ and its active metabolite, F₆-1, 23, 25(OH)₃D₃, in the bones are higher than that of 1, 25(OH)₂D₃, and that F₆-1, 25(OH)₂D₃ and its metabolite are retained in bones longer than 1, 25(OH)₂D₃.