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

• Published in: Calcified tissue international Vol. 106; no. 2; pp. 147 - 157
• Main Authors: Komrakova, Marina, Furtwängler, Judith, Hoffmann, Daniel Bernd, Lehmann, Wolfgang, Schilling, Arndt Friedrich, Sehmisch, Stephan
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-02-2020; Springer Nature B.V
• Subjects: Alkaline phosphatase; Androgen receptors; Androgens; Biochemistry; Biomedical and Life Sciences; Bone healing; Callus; Cell Biology; Cholesterol; Endocrinology; Gastrocnemius muscle; Gene expression; Life Sciences; Metaphysis; Original Research; Orthopedics; Osteoporosis; Osteotomy; Ovariectomy; Phosphorus; Rodents; Tibia; Uterus; Ostarine; Rat model; Selective androgen receptor modulator; Enobosarm, ovariectomy; Bone healing
• ISSN: 0171-967X; 1432-0827
• DOI: 10.1007/s00223-019-00613-1

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.