gms | German Medical Science

Objectives: Osteoporosis is a worldwide bone disease, which characterized by reduced bone mass and impaired fracture healing. It is widely viewed as a "women's disease", however 20% of the affected patients are men. Recently, the application of non-steroid selective androgen receptor modulators is gaining interest not only for improvement of muscle tissue, but also for treatment of osteoporosis.

Ostarine (OS) reportedly increases muscle mass in patients with tumor cachexia. In our previous studies, OS improved bone parameters as well as bone healing in a female rat model of postmenopausal osteoporosis. The present study was carried out to determine whether OS also influences bone and bone healing in male rat model and could be considered as a treatment option for osteoporosis in men.

Methods: Eight month old male Sprague-Dawley rats were orchiectomized (Orx, n=75) or left intact (Non-Orx, n=15). Orx rats were divided into 5 groups (n=15): 1) Orx, 2) Ostarine treatment for osteoporosis prophylaxis, after Orx onward (OS-Pr, 18 weeks), 3) OS for fracture therapy, after osteotomy (OS-Th, 6 weeks), 4) Testosterone treatment after Orx onward (T-Pr, 18 weeks), 5) Testosterone after osteotomy (T-Th, 6 weeks). OS and T were administered to the rats along with food for the appropriate time periods at the daily doses of 0.4 mg/kg body weight (BW) and 0.45 mg/kg/BW, respectively. Food intake was recorded throughout the experiment. After 12 weeks (when Orx-rats develop osteoporosis) a bilateral transverse osteotomy of the tibia metaphysis with plate osteosynthesis was performed in all rats. 18 weeks after the beginning of the experiments, the rats were sacrificed. The osteotomized tibiae and intact femora were examined by micro-CT, biomechanical and ashing analyses. BW and prostate weight was recorded. Statistical analysis was performed using one-way ANOVA and Tukey-test (p<0.05).

Results and Conclusion: BW and food intake did not differ between the groups.

In the proximal femur, T-Th improved cortical BMD in Orx rats. OS-Pr enhanced cortical density and volume, trabecular density and thickness, as well as the number of trabecular nodes.

In the osteotomized tibia, both testosterone treatments (T-Pr, T-Th) were effective in improving cortical and callus bone parameters such as thickness, density and volume. OS-Pr increased callus density; OS-Th increased total callus volume, whereas other bone parameters remained unaltered.

Prostate weight was the highest in Non-Orx group. In OS-Pr group, it was higher than in the Orx group and both T treated groups.

Our results show that OS treatment is more effective in non-osteotomized femur than in tibia healing. In contrast, T treatments show a stronger effect for the bone healing. Further analyses (histomorphometry, gene expression, serum markers for bone turnover) are currently underway to explain these findings. Whether OS could represent a preventing treatment option for osteoporosis in men, given the side effects on prostate weight will be further investigated.