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The Selective Androgen Receptor Modulator Ostarine Improves Bone Healing in Ovariectomized Rats

Abstract

Non-steroidal selective androgen receptor modulators, including ostarine, have been developed as an alternative to steroidal hormones. Ostarine has shown a beneficial effect on bone in experimental studies, but no data regarding the effect of ostarine on bone healing have yet been reported. We investigated effects of ostarine on bone healing in ovariectomized rats. Sprague-Dawley rats (3 months old) were ovariectomized (Ovx, n = 46) or left intact (Non-Ovx, n = 10). After 8 weeks, an osteotomy of the tibia metaphysis was created in all rats, and the Ovx rats were divided into four groups: untreated Ovx (n = 10) and three Ovx groups (each of 12 rats) treated with ostarine at doses of 0.04, 0.4, or 4 mg/kg BW (OS-0.04, OS-0.4, and OS-4 groups). Five weeks later, bone healing was analyzed. The OS-4 dose enhanced callus formation, increased callus density, accelerated bridging time of the osteotomy, and elevated alkaline phosphatase gene expression in callus and its protein expression in serum. In the Ovx group, most of the callus parameters were diminished. All OS treatments increased the weight of the gastrocnemius muscle, but only partly enhanced uterus weight in OS-0.4 and OS-4. Serum cholesterol level was reduced, and serum phosphorus was elevated in OS-0.04 and OS-4. Ostarine appeared to have a positive effect on early bone healing in ovariectomized rats. Considering its favorable effect on non-osteotomized bone and muscle, this treatment could be further explored as a therapy for osteoporosis. However, possible metabolic side effects should first be evaluated.

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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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Correspondence to Marina Komrakova.

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Marina Komrakova, Judith Furtwängler, Daniel Bernd Hoffmann, Wolfgang Lehmann, Arndt Friedrich Schilling, and Stephan Sehmisch declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

The animal study protocol was approved by the local regional government (14/1396, Oldenburg, Germany) in accordance with German animal protection laws prior to performing the study.

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Komrakova, M., Furtwängler, J., Hoffmann, D.B. et al. The Selective Androgen Receptor Modulator Ostarine Improves Bone Healing in Ovariectomized Rats. Calcif Tissue Int 106, 147–157 (2020). https://doi.org/10.1007/s00223-019-00613-1

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Keywords

  • Selective androgen receptor modulator
  • Ostarine
  • Enobosarm, ovariectomy
  • Bone healing
  • Rat model