Selective Androgen Receptor Modulator (SARM) treatment prevents bone loss and reduces body fat in ovariectomized rats.
OBJECTIVE
This study was conducted to examine the bone and body composition effects of S-4, an aryl-propionamide derived Selective Androgen Receptor Modulator (SARM) in an ovariectomy induced model of accelerated bone loss.


METHODS
One hundred twenty female Sprague-Dawley rats aged to twenty-three weeks were randomly assigned to twelve treatment groups. Drug treatment was initiated immediately following ovariectomy and continued for one hundred twenty days. Whole body bone mineral density (BMD), body composition, and lumbar vertebrae BMD were measured by dual energy x-ray absorptiometry. More stringent regional pQCT and biomechanical strength testing was performed on excised femurs.


RESULTS
We found that S-4 treatment maintained whole body and trabecular BMD, cortical content, and increased bone strength while decreasing body fat in these animals.


CONCLUSIONS
The data presented herein show the protective skeletal effects of S-4. Our previous reports have shown the tissue selectivity and muscle anabolic activity of S-4. Together these data suggest that S-4 could reduce the incidence of fracture via two different mechanisms (i.e., via direct effects in bone and reducing the incidence of falls through increased muscle strength). This approach to fracture reduction would be advantageous over current therapies in these patients which are primarily antiresorptive in nature.
Kearbey
Jeffrey D
JD
College of Pharmacy, Division of Pharmaceutics, The Ohio State University, Columbus, Ohio 43210, USA.
Gao
Wenqing
W
Narayanan
Ramesh
R
Fisher
Scott J
SJ
Wu
Di
D
Miller
Duane D
DD
Dalton
James T
JT
D015502:Absorptiometry, Photon; D000081:Acetamides / Q000627:therapeutic use; D050154:Adiposity / Q000187:drug effects*; D000627:Aminophenols / Q000627:therapeutic use; D000818:Animals; D001696:Biomechanical Phenomena; D001823:Body Composition / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D002454:Cell Differentiation / Q000187:drug effects; D013196:Dihydrotestosterone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D010006:Osteoblasts / Q000187:drug effects; D010010:Osteoclasts / Q000187:drug effects; D015663:Osteoporosis, Postmenopausal / Q000517:prevention & control*; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D011944:Receptors, Androgen / Q000187:drug effects*
D000081:Acetamides; D000627:Aminophenols; D050071:Bone Density Conservation Agents; D011944:Receptors, Androgen; D013196:Dihydrotestosterone; C492992:andarine