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Establishing an Animal Model of Secondary Osteoporosis by Using a Gonadotropin-releasing Hormone Agonist
Nur-Vaizura Mohamad1, Muhammad Afiq Amani Che Zulkepli1, Krystine May Theseira1
1Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, 56000 Cheras, Kuala Lumpur, Malaysia.
Abstract:
Introduction: Orchidectomy is currently the preferred method to induce bone loss in preclinical male osteoporosis model. Gonadotropin-releasing hormone (GnRH) agonists used in prostate cancer treatment can induce testosterone deficiency but its effects on bone in preclinical male osteoporosis model are less studied. Objective: This study aimed to evaluate the skeletal effect of buserelin (a GnRH agonist) in male rats and compare it with orchidectomy. Methods: Forty-six three-month-old male Sprague-Dawley rats were divided into three experimental arms. The baseline arm (n=6) was sacrificed at the onset of the study. In the buserelin arm, the rats received a daily subcutaneous injection of either normal saline (n=8), buserelin acetate at 25 µg/kg (n=8) or 75 µg/kg (n=8). In the orchidectomy arm, the rats were either sham-operated (n=8) or orchidectomized (n=8). All groups underwent in-vivo X-ray micro-computed tomography scanning at the left proximal tibia every month. Blood was collected at the beginning and the end of the study for testosterone level evaluation. The rats were euthanized after the three-month treatment. The femurs were harvested for biomechanical strength and bone calcium determination. Results: The results showed that buserelin at both doses caused a significant decline in testosterone level and deterioration in bone microstructure (p<0.05), but did not affect bone calcium content (p>0.05). Buserelin at 25 µg/kg decreased displacement and strain of the femur significantly (p<0.05). Similar changes were observed in the orchidectomized group compared to the sham-operated group but without any significant changes in biomechanical strength (p>0.05). Conclusion: Buserelin can induce testosterone deficiency and the associated deterioration of bone microarchitecture similar to orchidectomy in three months. However, it may require a longer time to show significant effects on bone strength and mineral content.
Insights
Buserelin, a GnRH agonist, effectively reduces testosterone and bone microarchitecture in male rats, mimicking orchidectomy effects. Longer studies may reveal impacts on bone strength and mineral content.
Area of Science:
- Endocrinology
- Osteoporosis Research
- Preclinical Animal Models
Background:
- Orchidectomy is the standard for inducing bone loss in male osteoporosis models.
- Gonadotropin-releasing hormone (GnRH) agonists, used in prostate cancer treatment, cause testosterone deficiency but their skeletal effects in preclinical models are less explored.
Purpose of the Study:
- To evaluate the skeletal effects of buserelin (a GnRH agonist) in male rats.
- To compare buserelin's skeletal effects with those of orchidectomy.
Main Methods:
- Male Sprague-Dawley rats were divided into baseline, buserelin (25 or 75 µg/kg), and orchidectomy (or sham) groups.
- In-vivo micro-CT scanning, blood testosterone level analysis, and femur biomechanical testing were performed over three months.
Main Results:
- Buserelin significantly decreased testosterone levels and deteriorated bone microstructure, similar to orchidectomy.
- Buserelin treatment affected femur biomechanical properties, while orchidectomy did not show significant changes in strength within three months.
- Bone calcium content remained unaffected by buserelin treatment.
Conclusions:
- Buserelin effectively induces testosterone deficiency and bone microarchitectural deterioration in rats within three months, comparable to orchidectomy.
- Extended treatment duration might be necessary to observe significant effects on bone strength and mineral content.
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