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)2D3 in binding affinity for the vitamin D receptor but is at least 200 times more active than 1,25(OH)2D3 and equal to that of 2MD (2‐methylene‐19‐nor‐(20S)‐1α,25(OH)2D3, 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.
Keywords:
DXA; Analysis/Quantitation of Bone; Preclinical Studies; Animal Models; Osteoporosis; Diseases and Disorders of/Related to Bone, Vitamin D Analog