Selective androgen receptor modulator (SARM) treatment prevents bone loss and reduces body fat in ovariectomized rats

Jeffrey D. Kearbey, Wenqing Gao, Ramesh Narayanan, Scott J. Fisher, Di Wu, Duane Miller, James T. Dalton

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Purpose. 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.

Original languageEnglish (US)
Pages (from-to)328-335
Number of pages8
JournalPharmaceutical Research
Volume24
Issue number2
DOIs
StatePublished - Feb 1 2007

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Androgen Receptors
Modulators
Adipose Tissue
Rats
Bone
Fats
Bone Density
Bone and Bones
Ovariectomy
Body Composition
Minerals
Fracture Fixation
Lumbar Vertebrae
Incidence
Muscle Strength
Therapeutics
Muscle
Femur
Sprague Dawley Rats
Composition effects

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

Cite this

Selective androgen receptor modulator (SARM) treatment prevents bone loss and reduces body fat in ovariectomized rats. / Kearbey, Jeffrey D.; Gao, Wenqing; Narayanan, Ramesh; Fisher, Scott J.; Wu, Di; Miller, Duane; Dalton, James T.

In: Pharmaceutical Research, Vol. 24, No. 2, 01.02.2007, p. 328-335.

Research output: Contribution to journalArticle

Kearbey, Jeffrey D. ; Gao, Wenqing ; Narayanan, Ramesh ; Fisher, Scott J. ; Wu, Di ; Miller, Duane ; Dalton, James T. / Selective androgen receptor modulator (SARM) treatment prevents bone loss and reduces body fat in ovariectomized rats. In: Pharmaceutical Research. 2007 ; Vol. 24, No. 2. pp. 328-335.
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