BONE-RESORBING ACTIVITIES OF 24-EPI-1-ALPHA-HYDROXYVITAMIN D-2 AND 24-EPI-1-ALPHA-25-DIHYDROXYVITAMIN D-2

Bone-resorbing activities of 24-epi-1 alpha-hydroxyvitamin D-2 [24-epi -1 alpha(OH)D-2], 24-epi-1 alpha,25-dihydroxyvitamin D-2 [24-epi-1,25( OH)(2)D-2], and 1 alpha,24S,25-trihydroxyvitamin D-2 [1,24S,25(OH)(3)D -2], which might be a metabolite of 24-epi-1,25(OH)(2)D-2, were invest igated. In an in vitro bone resorption test, the activity of 24-epi-1 alpha(OH)D-2 was similar to that of 1 alpha-hydroxyvitamin D-3 [1 alph a(OH)D-3] at 10(-9) M-10(-6) M. The activity of 24-epi-1,25(OH)(2)D-2 was weaker than that of 1 alpha,25-dihydroxyvitamin D-3 [1,25(OH)(2)D- 3] at 10(-11) M-10(-8) M. On the other hand, the activity of 1,24S,25( OH)(3)D-2 was similar to that of 24-epi-1,25(OH)(2)D-2 at 10(-11) M-10 (-9) M. In the formation assay of osteoclast-like cells, the activity of 24-epi-1 alpha(OH)D-2 was weaker than that of 1 alpha(OH)D-3 at 10( -7) M. The activity of 24-epi-1,25(OH)(2)D-2 was almost similar to tha t of 1,25(OH)(2)D-3 at 10(-11) M-10(-7) M. The activity of 1,24S,25(OH )(2)D-2 was significantly weaker than that of 24-epi-1,25(OH)(3)D-2 at 10(-11) M-10(-9) M. In the two experiments, the potencies of 24-epi-1 ,25(OH)(2)D-2 were about 100 times higher than those of 24-epi-1 alpha (OH)D-2. In an in vivo/in vitro bone resorption test, the activity of 24-epi-1 alpha(OH)D-2 was almost similar to those of 1 alpha(OH)D-2 an d 1,25(OH)(2)D-3 and higher than those of 24-epi-1,25(OH)(2)D-2 and 1, 24S,25(OH)(3)D-2. 24-epi-1 alpha-(OH)D-2 and 1 alpha(OH)D-3 were longe r lasting than 24-epi-1,25(OH)(2)D-2 and 1,25(OH)(2)D-3 in this experi ment. These results suggested that 24-epi-1 alpha(OH)D-2 as well as 1 alpha(OH)D-3 was converted into dihydroxy form in vivo.