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

ABSTRACT

A new 1α,25-dihydroxy vitamin D3 analog (2-methylene-22(E)-(24R)-22-dehydro-1α,24,25-trihydroxy-19-norvitamin D3 or WT-51) has been tested as a possible therapeutic for osteoporosis. It is 1/10th as active as 1,25(OH)2 D3 in binding affinity for the vitamin D receptor but is at least 200 times more active than 1,25(OH)2 D3 and equal to that of 2MD (2-methylene-19-nor-(20S)-1α,25(OH)2 D3 , 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.