Effects of selective androgen receptor modulator (SARM) treatment in osteopenic female rats

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

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Purpose: Although androgens are known to protect bone, side effects and poor oral bioavailability have limited their use. We previously reported that S-3-(4-acetylamino-phenoxy)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethyl- phenyl)-propionamide (S-4) is a potent and tissue-selective androgen receptor modulator (SARM). This study was designed to evaluate the skeletal effects of S-4 in an osteopenic model. Methods: Aged female rats were gonadectomized or sham operated on day 1 and assigned to treatment groups. Dosing was initiated on day 90 and continued daily until day 210. Whole animal bone mineral density (BMD), body weight, and fat mass were determined by dual energy x-ray absorptiometry (DEXA). Regional analysis of excised bones was performed using DEXA or computed tomography. Femur strength was evaluated by 3-point bending. Results: S-4 restored whole body and lumbar vertebrae (L5-L6) BMD to the level of intact controls. Significant increases in cortical bone quality were observed at the femoral midshaft, resulting in increased load bearing capacity. Conclusions: S-4 demonstrated partial/complete recovery of bone parameters to age-matched intact levels. Increased efficacy observed in cortical bone sites is consistent with reported androgen action in bone. The ability of S-4 to promote bone anabolism, prevent bone resorption, and increase skeletal muscle mass/strength positions these drugs as promising new alternatives for the treatment of osteoporosis.

Original languageEnglish (US)
Pages (from-to)2471-2477
Number of pages7
JournalPharmaceutical Research
Volume26
Issue number11
DOIs
StatePublished - Nov 1 2009

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Androgen Receptors
Modulators
Rats
Bone
Bone and Bones
Bone Density
Androgens
X-Rays
Lumbar Vertebrae
Weight-Bearing
Muscle Strength
Bone Resorption
Thigh
Femur
Biological Availability
Osteoporosis
Minerals
Adipose Tissue
Skeletal Muscle
Tomography

All Science Journal Classification (ASJC) codes

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

Cite this

Effects of selective androgen receptor modulator (SARM) treatment in osteopenic female rats. / Kearbey, Jeffrey D.; Gao, Wenqing; Fisher, Scott J.; Wu, Di; Miller, Duane; Dalton, James T.

In: Pharmaceutical Research, Vol. 26, No. 11, 01.11.2009, p. 2471-2477.

Research output: Contribution to journalArticle

Kearbey, Jeffrey D. ; Gao, Wenqing ; Fisher, Scott J. ; Wu, Di ; Miller, Duane ; Dalton, James T. / Effects of selective androgen receptor modulator (SARM) treatment in osteopenic female rats. In: Pharmaceutical Research. 2009 ; Vol. 26, No. 11. pp. 2471-2477.
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