Treatment of osteoporosis using a selective androgen receptor modulator ostarine in an orchiectomized rat model

Abstract

Abstract Purpose: The selective androgen receptor modulator ostarine has been shown to have advantageous effects on skeletal tissue properties, reducing muscle wasting and improving physical function in males. However, data on effects in male osteoporosis remain limited. In this study, the effects of ostarine on osteoporotic bone were evaluated in a rat model of male osteoporosis and compared with those of testosterone treatments. Methods: Eight-month-old male Sprague-Dawley rats were orchiectomized (Orx) and grouped (n=15/group): 1) Orx, 2) Ostarine Therapy, 3) Test. Therapy, 4) Ostarine Prophylaxe and 5) Test. Proph. Fifteen rats were left non-orchiectomized (Non Orx). Proph. treatments were begun directly after orchiectomy and continued for 18 weeks, whereas Therapy treatments were initiated 12 weeks after Orx. Ostarine and Test. were applied orally at daily doses of 0.4 and 50 mg/kg body weight, respectively. The lumbar vertebral bodies and femora were analyzed via biomechanical, micro-CT, ashing, and gene expression analyses. Results: Ostarine Proph. showed positive effects in preventing osteoporotic changes in cortical and trabecular bone; biomechanical parameters were not affected; prostate weight was increased. Ostarine Therapy increased solely the cortical density of the femur; other bone parameters remained unaffected. Test. Proph. positively influenced cortical density in femur; Test. Therapy did not change any bony parameters. Conclusion: Ostarine Proph. could be further investigated as a preventative treatment for male osteoporosis, but an androgenic effect on the prostate comparable to testosterone should be taken into consideration. Combination therapies with other anti-osteoporosis agents should be considered in future studies to strengthen the selective effects on the bone tissue.