2MD, a new anabolic agent for osteoporosis treatment.
BACKGROUND
2-Methylene-19-nor-(20S)-1alpha,25-dihydroxyvitamin D3 (2MD) is a new analog of 1alpha,25-dihydroxyvitamin D3 (1,25-(OH)2D3) that has unique properties (distinct from 1alpha,25-dihydroxyvitamin D3) in stimulating osteoblasts to form bone in culture. This analog has now been extensively tested in aged ovariectomized female rats maintained on a diet adequate in calcium and phosphorus.


METHODS
Retired female rats obtained from Sprague-Dawley were ovariectomized, and were either dosed with vehicle or 2MD at 5-7 ng/kg body weight each day.


RESULTS
A marked increase in total bone mass resulted during the 28-week study. This increase in bone mass resulted from an increase in both cortical and trabecular bone, with increases to the order of 25% in the cancellous bone. Histomorphometry revealed that 2MD increased bone mass primarily by increasing bone formation. It also revealed little or no effect on bone resorption. The resulting bone is of high quality revealed by histology and biomechanical testing.


CONCLUSIONS
Throughout the study, serum calcium remained within the normal range and thus 2MD shows great promise for the treatment of bone diseases characterized by bone loss, including osteoporosis.
Plum
L A
LA
Department of Biochemistry, College of Agricultural and Life Sciences, University of Wisconsin-Madison, 433 Babcock Drive, Madison, WI, 53706-1544, USA, deluca@biochem.wisc.edu.
Fitzpatrick
L A
LA
Ma
X
X
Binkley
N C
NC
Zella
J B
JB
Clagett-Dame
M
M
DeLuca
H F
HF
D045930:Anabolic Agents / Q000627:therapeutic use; D000704:Analysis of Variance; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001862:Bone Resorption / Q000188:drug therapy*; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002118:Calcium / Q000097:blood; D005260:Female; D010012:Osteogenesis / Q000187:drug effects*; D010024:Osteoporosis / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley
C468519:2-methylene-1,25-dihydroxy-19-norvitamin D3; D045930:Anabolic Agents; D050071:Bone Density Conservation Agents; D002117:Calcitriol; D002118:Calcium