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

J Bone Miner Metab. 2019 Mar;37(2):243-255. doi: 10.1007/s00774-018-0929-9. Epub 2018 May 21.


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: Ostarine; Osteoporosis; Rat model of osteoporosis; SARM.

MeSH terms

  • Alkaline Phosphatase / blood
  • Anilides / pharmacology
  • Anilides / therapeutic use*
  • Animals
  • Biomechanical Phenomena
  • Body Weight / drug effects
  • Bone Density / drug effects
  • Dose-Response Relationship, Drug
  • Female
  • Femur / diagnostic imaging
  • Femur / drug effects
  • Humans
  • Minerals / metabolism
  • Muscles / drug effects
  • Muscles / pathology
  • Organ Size / drug effects
  • Osteoporosis, Postmenopausal / blood
  • Osteoporosis, Postmenopausal / drug therapy*
  • Osteoporosis, Postmenopausal / physiopathology
  • Ovariectomy
  • Phosphorus / blood
  • RANK Ligand / genetics
  • RANK Ligand / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats, Sprague-Dawley
  • Receptors, Androgen / metabolism*
  • Spine / diagnostic imaging
  • Spine / drug effects
  • X-Ray Microtomography


  • Anilides
  • Minerals
  • RANK Ligand
  • RNA, Messenger
  • Receptors, Androgen
  • Phosphorus
  • Alkaline Phosphatase
  • ostarine