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

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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.

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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)

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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.

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Authors and Affiliations

  1. Department of Trauma-, Orthopaedic- and Plastic Surgery, University Medical Center Goettingen, Robert Koch St. No. 40, 37075, Goettingen, Germany

    D. B. Hoffmann, M. Komrakova, S. Pflug, M. von Oertzen, D. Saul, L. Weiser, T. A. Walde, A. F. Schilling, W. Lehmann & S. Sehmisch

  2. Department of Medical Microbiology, Subdivision of General Hygiene and Environmental Health, University of Goettingen, Humboldallee 34a, 37073, Goettingen, Germany

    M. Wassmann

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  1. D. B. Hoffmann
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  2. M. Komrakova
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  4. M. von Oertzen
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  5. D. Saul
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Correspondence to D. B. Hoffmann.

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Hoffmann, D.B., Komrakova, M., Pflug, S. et al. Evaluation of ostarine as a selective androgen receptor modulator in a rat model of postmenopausal osteoporosis. J Bone Miner Metab 37, 243–255 (2019). https://doi.org/10.1007/s00774-018-0929-9

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  • DOI: https://doi.org/10.1007/s00774-018-0929-9

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