Comparison of 26,27-hexafluoro-1 alpha,25-dihydroxyvitamin D-3 and 1 alpha,25-dihydroxyvitamin D-3 on the resorption of bone explants ex vivo

26,27-Hexaffuoro-1 alpha,25-dihydroxyvitamin D-3 [F-6-1,25(OH)(2)D-3] is mo re potent than 1 alpha,25-dihydroxyvitamin D-3 [1,25(OH)(2)D-3] in stimulat ing bone resorption in vitro and in vivo. The reason why F-6-1,25(OH)(2)D-3 is more active remains unclear. To clarify the relationship between the bo ne-resorbing activity df each vitamin D-3 analogue and the metabolism of ea ch analogue, in the present study, we used an ex vivo method that was estab lished by Reynolds et al (Calcif Tissue Res, 1974, 15, 333-339). The effect of F-6-1,25(OH)(2)D-3 or 1,25(OH)(2)D-3 on Ca-45 release from parietal bon es, prepared at 3, 14 and 24 h after injection of 1.9, 3.8, 7.6 or 15.2 pmo l vitamin D analog/g body weight, was examined. F-6-1,25(OH)(2)D-3 was more potent than 1,25(OH)(2)D-3 during each in vive time period. 1,25(OH)(2)D-3 at 3 h after the injection was more active compared to the control (no inj ection of 1,25(OH)(2)D-3), but not at 14 and 24 h. The radioactivity of the bones after the injection of [H-3]-F-6-1,25(OH)(2)D-3 was retained even at 24 h. In the case of [H-3]-1,25(OH)(2)D-3, the radioactivity of bones decr eased with an increase in the in vive period. In a HPLC analysis of the lip id extract of bone homogenate, [H-3]-F-6-1,25(OH)(2)D-3 alone was detected at 3 h after the injection and both [H-3]-F-6-1,25(OH)(2)D-3 and [H-3]-26,2 7-hexafluoro-1 alpha,23S,25-trihydroxyvitamin D-3 [F-6-1,23,25(OH)(3)D-3] w ere detected at 14 and 24 h after the injection. [H-3]-1,25(OH)(2)D-3 was h ighly detected at 3 h after the injection, but it decreased with an increas e in the in vive period. In the ex vivo test, the activity of F-6-1,23,25(O H)(3)D-3 was less than that of F-6-1,25(OH)(2)D-3 but similar to that of 1, 25(OH)(2)D-3. The present study indicates that F-6-1,25(OH)(2)D-3 is more a ctive and more long-lasting than 1,25(OH)(2)D-3 in the ex vivo method. A hi gher potency of F-6-1,25(OH)(2)D-3 is explained, at least partly, by the re sults that the amounts of both F-6-1,25(OH)(2)D-3 and its active metabolite , F-6-1,23,25(OH)(3)D-3, in the bones are higher than that of 1,25(OH)(2)D- 3, and that F-6-1,25(OH)(2)D-3 and its metabolite are retained in bones lon ger than 1,25(OH)(2)D-3.