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Evaluation of ostarine as a selective androgen receptor modulator in a rat model of postmenopausal osteoporosis

  • D. B. Hoffmann
  • M. Komrakova
  • S. Pflug
  • M. von Oertzen
  • D. Saul
  • L. Weiser
  • T. A. Walde
  • M. Wassmann
  • A. F. Schilling
  • W. Lehmann
  • S. Sehmisch
Original Article

Abstract

Selective androgen receptor modulators (SARMs) have shown beneficial effects on muscle wasting, general physical function and bone properties in male mammals. However, data on the effects of SARMs in postmenopausal osteoporotic bone are scarce. We evaluated the effects of the SARM drug ostarine on postmenopausal osteoporotic bone in a rat osteoporosis model. Ovariectomy was performed on 46 of 56 3-month-old female Sprague–Dawley rats. Eight weeks after ovariectomy, ostarine was orally administered daily for 5 weeks in dosages of 0.04 (low, OVX + Ost. 0.04), 0.4 (intermediate, OVX + Ost. 0.4), and 4 mg/kg (high, OVX + Ost. 4) body weight. Another ovariectomized group received no ostarine. Lumbar vertebrae and femora were removed for biomechanical, gene expression, ashing, and computer tomography analyses. Low dose showed no effects. The effects of intermediate and high doses were comparable overall. Improvements were mainly seen in structural properties such as bone mineral density and bone volume density. However, the effects in femora were superior to effects in vertebrae. Ostarine treatment for 5 weeks did not improve significantly biomechanical properties. mRNA expression of the receptor activator of NF-κB ligand decreased after treatment, and uterine weight increased. Serum levels of phosphorus increased following ostarine treatment in intermediate and high-dose groups. Short-term treatment of osteoporotic bone with ostarine leads to improvement of several microstructural bone indices. While we did not observe changes in biomechanics, it is conceivable that longer treatment may also improve biomechanical properties. Further studies are needed to characterize longer time effects and side effects of ostarine in osteoporosis.

Keywords

Osteoporosis SARM Ostarine Rat model of osteoporosis 

Abbreviations

ALP

Alkaline phosphatase

BMD

Bone mineral density

BV/TV

Bone volume density

BW

Body weight

DHT

Dihydrotestosterone

ERα

Estrogen receptor alpha

Fmax

Maximal load

N.Nd.

Trabecular nodes

OC

Osteocalcin

OPG

Osteoprotegerin

OVX

Ovariectomy

RANKL

Receptor activator of NF-κB ligand

S-4

S-3-(4-acetylamino-phenoxy)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethyl-phenyl)-propionamide

SARM

Selective androgen receptor modulator

SERM

Selective estrogen receptor modulator

TRAP

Tartrate-resistant acid phosphatase

Tb.Sp

Trabecular spacing

Tb.th

Trabecular thickness

Tb.Wi

Trabecular thickness (2-Dscan)

Notes

Acknowledgements

The present study was funded by the German Research Foundation (DFG SE 1966/6-1, KO 4646/3-1). The authors are grateful to R. Castro-Machguth and A. Witt for technical support.

Compliance with ethical standards

Conflict of interest

All authors have no conflicts of interest.

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Copyright information

© The Japanese Society for Bone and Mineral Research and Springer Japan KK, part of Springer Nature 2018

Authors and Affiliations

  • D. B. Hoffmann
    • 1
  • M. Komrakova
    • 1
  • S. Pflug
    • 1
  • M. von Oertzen
    • 1
  • D. Saul
    • 1
  • L. Weiser
    • 1
  • T. A. Walde
    • 1
  • M. Wassmann
    • 2
  • A. F. Schilling
    • 1
  • W. Lehmann
    • 1
  • S. Sehmisch
    • 1
  1. 1.Department of Trauma-, Orthopaedic- and Plastic SurgeryUniversity Medical Center GoettingenGoettingenGermany
  2. 2.Department of Medical Microbiology, Subdivision of General Hygiene and Environmental HealthUniversity of GoettingenGoettingenGermany

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