Establishing an Animal Model of Secondary Osteoporosis by Using a Gonadotropin-releasing Hormone Agonist

Mohamad, Nur-Vaizura; Che Zulkepli, Muhammad Afiq Amani; May Theseira, Krystine; Zulkifli, Norain; Shahrom, Nur Quraisha; Ridzuan, Nurul Amni Mohamad; Jamil, Nor Aini; Soelaiman, Ima-Nirwana; Chin, Kok-Yong

doi:10.7150/ijms.22732

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Int J Med Sci 2018; 15(4):300-308. doi:10.7150/ijms.22732 This issue Cite

Research Paper

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, Norain Zulkifli¹, Nur Quraisha Shahrom¹, Nurul Amni Mohamad Ridzuan¹, Nor Aini Jamil², Ima-Nirwana Soelaiman¹, Kok-Yong Chin^1✉

1. Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, 56000 Cheras, Kuala Lumpur, Malaysia.
2. School of Healthcare Sciences, Faculty of Health Science, Universiti Kebangsaan Malaysia, 50300 Kuala Lumpur, Malaysia.

Citation:

Mohamad NV, Che Zulkepli MAA, May Theseira K, Zulkifli N, Shahrom NQ, Ridzuan NAM, Jamil NA, Soelaiman IN, Chin KY. Establishing an Animal Model of Secondary Osteoporosis by Using a Gonadotropin-releasing Hormone Agonist. Int J Med Sci 2018; 15(4):300-308. doi:10.7150/ijms.22732. https://www.medsci.org/v15p0300.htm

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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.

Keywords: androgen, bone, gonadotropin-releasing hormone agonists, male osteoporosis, testosterone

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APA

Mohamad, N.V., Che Zulkepli, M.A.A., May Theseira, K., Zulkifli, N., Shahrom, N.Q., Ridzuan, N.A.M., Jamil, N.A., Soelaiman, I.N., Chin, K.Y. (2018). Establishing an Animal Model of Secondary Osteoporosis by Using a Gonadotropin-releasing Hormone Agonist. International Journal of Medical Sciences, 15(4), 300-308. https://doi.org/10.7150/ijms.22732.

ACS

Mohamad, N.V.; Che Zulkepli, M.A.A.; May Theseira, K.; Zulkifli, N.; Shahrom, N.Q.; Ridzuan, N.A.M.; Jamil, N.A.; Soelaiman, I.N.; Chin, K.Y. Establishing an Animal Model of Secondary Osteoporosis by Using a Gonadotropin-releasing Hormone Agonist. Int. J. Med. Sci. 2018, 15 (4), 300-308. DOI: 10.7150/ijms.22732.

NLM

CSE

Mohamad NV, Che Zulkepli MAA, May Theseira K, Zulkifli N, Shahrom NQ, Ridzuan NAM, Jamil NA, Soelaiman IN, Chin KY. 2018. Establishing an Animal Model of Secondary Osteoporosis by Using a Gonadotropin-releasing Hormone Agonist. Int J Med Sci. 15(4):300-308.

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