A New 1,25 Dihydroxy Vitamin D Analog with Strong Bone Anabolic Activity in OVX Rats with Little or no Bone Resorptive Activity

摘要

ABSTRACT A new 1α,25‐dihydroxy vitamin D 3 analog (2‐methylene‐22(E)‐(24R)‐22‐dehydro‐1α,24,25‐trihydroxy‐19‐norvitamin D 3 or WT‐51) has been tested as a possible therapeutic for osteoporosis. It is 1/10th as active as 1,25(OH) 2 D 3 in binding affinity for the vitamin D receptor but is at least 200 times more active than 1,25(OH) 2 D 3 and equal to that of 2MD (2‐methylene‐19‐nor‐(20S)‐1α,25(OH) 2 D 3 , an analog previously tested in postmenopausal women), in supporting bone formation by isolated osteoblasts in culture. However, in contrast to 2MD, it is virtually inactive on bone resorption in vivo. WT‐51 markedly increased bone mass (lumbar and femur) in ovariectomized (OVX) female rats. Further, bone strength tested by the three‐point bending system is significantly increased by WT‐51. Thus, WT‐51 is an attractive candidate for the treatment of postmenopausal osteoporosis. ? 2019 American Society for Bone and Mineral Research.