Response of bone tissue to ostarine treatment and/or treadmill exercise in a healthy adult rat model

Introduction Physical exercise is one of the primary factors associated with bone health, probably due to muscle-bone interactions. Exercise interventions during adolescence and adulthood are capable to mitigate age-related bone loss. The selective androgen receptor modulator ostarine (OS) exerts anabolic effect on musculoskeletal tissue. Here, we investigated whether OS and treadmill exercise (TE) applied alone or in combination affect bone tissue in healthy adult rats.

Methods 3.5-month-old male Wistar rats were trained on a treadmill for 5 min 3 days a week for 2 weeks prior to the experiment. The rats that ran spontaneously were selected and randomly divided into 4 groups (n=10/ group): 1) Control: sedentary rats receiving vehicle, 2) OS: sedentary rats receiving OS, 3) TE: training rats receiving vehicle, 4) TE+OS: training rats receiving OS. TE was applied for 5 min 3 days a week in the Control and OS sedentary groups and for 40 min 5 days per week in the TE and TE+OS groups. The velocity was 25 m/min at a track elevation of 5° for all groups. OS was administered subcutaneously dissolved in polyethylene glycol 300 and dimethyl sulfoxide (80% and 20%) at a daily dose of 0.4 mg/kg body weight. The vehicle groups received only solvent. After 8 weeks of treatments, bone samples were collected for micro-computed tomographical (micro-CT) and biomechanical analyses. Statistical analysis was done using one way analysis of variance and Tukey-test (p<0.05).

Results Body weight, micro-CT 3D and biomechanical parameters of bones were not different between the groups. micro-CT 2D analysis showed that in the distal femur, the number of trabecular nodes (N.Nd) and the cortical density (Ct.Dn) were increased after TE treatment, whereas cortical width (Ct.Wi) was decreased in TE and TE+OS groups. In the proximal femur, N.Nd, trabecular density, trabecular width (Tb.Wi) and trabecular area (Tb.Ar) were higher in OS+TE group than in the Control group. In the lumbar vertebral body, N.Nd was higher in the TE+OS than in the TE group, whereas cortical area was reduced in TE group. In the proximal tibia, Tb.Wi, Tb.Ar and Ct.Dn were higher and Ct.Wi was lower in OS, TE and OS+TE groups than in the Control group.

Discussion All treatments exerted a weak bone response in healthy adult rats that was detected in the 2D analysis. The effect was favorable in trabecular bone, whereas in cortical bone, that is less metabolically active, it was ambiguous and should be further investigated. The effect could be ordered as OS<TE<OS+TE. TE was rather beneficial for bone which supports the notion that a long-term application may delay age-related bone loss. OS alone had less effect than TE alone, whereas in combination with TE there was a subtle favorable synergetic impact on bone. Possible side effects of OS application in adult organisms have to be taken into account.

Keywords treadmill exercise, ostarine, adult rat model, bone tissue

Korrespondenzadresse Marina Komrakova, University Medical Center, Department of Trauma Surgery, Orthopaedics and Plastic Surgery, Robert-Koch-Str. 40, 37075 Göttingen, Deutschland, E-Mail: [e-mail]

Publication History

Article published online:
08 September 2022