Premium
A New 1,25 Dihydroxy Vitamin D Analog with Strong Bone Anabolic Activity in OVX Rats with Little or no Bone Resorptive Activity
Author(s) -
Plum Lori A,
Zella Julia,
ClagettDame Margaret,
DeLuca Hector F
Publication year - 2020
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.3838
Subject(s) - ovariectomized rat , endocrinology , medicine , osteoporosis , anabolism , bone resorption , vitamin d and neurology , chemistry , bone remodeling , in vivo , bone mineral , vitamin , hormone , biology , microbiology and biotechnology
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.