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Effect of Selective Androgen Receptor Modulator Enobosarm on Bone Healing in a Rat Model for Aged Male Osteoporosis
Marina Komrakova1, Janek Nagel2, Daniel Bernd Hoffmann2
1Department of Trauma Surgery, Orthopaedics and Plastic Surgery, University Medical Center Goettingen, Robert-Koch Str. 40, 37075, Goettingen, Germany. marina.komrakova@med.uni-goettingen.de.
Abstract:
Enobosarm (ostarine, MK-2866, or GTx-024) is a non-steroidal selective androgen receptor modulator. This study evaluated the effect of various regimens of enobosarm (EN) on bone healing in an orchiectomized rat model for aged male osteoporosis and compared it to testosterone (T) treatment. Ninety eight-month-old male Sprague Dawley rats were either orchiectomized (Orx) or left intact (Non-Orx) and divided into groups (n = 15/group): (1) Non-Orx; (2) Orx; (3) Orx+T-th; (4) Orx+EN-th; (5) Orx+T-pr; and (6) Orx+EN-pr. Prophylaxis (Pr) treatments were applied immediately after Orx for up to 18 weeks. Therapy (Th) treatments were applied 12 weeks after Orx for up to 6 weeks. Bilateral tibia osteotomy with plate osteosynthesis was performed 12 weeks after Orx in all groups. EN and T were mixed with the diet; the daily dosage was 0.35 ± 0.06 and 41 ± 8 mg/kg BW, respectively. Both T treatments improved bone healing by increasing callus volume and area, bone volume and density, and cortical width; they had no effect on prostate or levator ani weight. EN-pr increased the callus area and callus density and decreased cortical density, but increased prostate weight. The effect of T-pr and T-th on bone was stronger than EN-pr. EN-th affected bone healing negatively by reducing callus density and area and delaying osteotomy bridging. Levator ani weight was increased in both EN groups. EN treatment after fracture is not advisable in aged males. EN-pr treatment as a therapy for bone healing in men could be further investigated; endocrinological side effects must be closely monitored.
Insights
Enobosarm (EN) showed mixed results for bone healing in aged male rats. While prophylactic EN improved some bone healing markers, therapeutic EN worsened outcomes, suggesting it is not advisable after fracture in aged males.
Area of Science:
- Endocrinology
- Orthopedics
- Pharmacology
Background:
- Aging male osteoporosis presents a significant challenge, impacting bone health and fracture healing.
- Selective Androgen Receptor Modulators (SARMs) like enobosarm (EN) are being investigated for therapeutic potential.
- Testosterone (T) is a common treatment for age-related bone loss, but has side effects.
Purpose of the Study:
- To evaluate the efficacy of different enobosarm (EN) regimens on bone healing in an aged male osteoporosis rat model.
- To compare the effects of EN with testosterone (T) treatment on bone healing and potential side effects.
- To determine the optimal timing and regimen for EN administration in the context of bone repair.
Main Methods:
- Ninety 8-month-old male Sprague Dawley rats underwent orchiectomy (Orx) or were left intact (Non-Orx).
- Groups received either testosterone (T) or enobosarm (EN) treatments, either prophylactically (Pr) or therapeutically (Th) after induced osteotomy.
- Bone healing was assessed by measuring callus volume, area, density, cortical width, and osteotomy bridging.
Main Results:
- Both T treatments significantly improved bone healing, increasing callus and bone volume, density, and cortical width.
- Prophylactic EN (EN-pr) increased callus area and density but decreased cortical density, with increased prostate weight.
- Therapeutic EN (EN-th) negatively impacted bone healing, reducing callus density/area and delaying bridging; T treatments were more effective than EN-pr.
Conclusions:
- Testosterone (T) demonstrates superior efficacy in improving bone healing compared to enobosarm (EN) in this aged male osteoporosis model.
- Enobosarm (EN) treatment after fracture is not recommended for aged males due to negative effects on bone healing.
- Prophylactic enobosarm (EN-pr) warrants further investigation for bone healing in men, but careful monitoring of endocrinological side effects is crucial.
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