Establishing an animal model of secondary osteoporosis by using a gonadotropin-releasing hormone agonist

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

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)300-308
Number of pages9
JournalInternational Journal of Medical Sciences
Volume15
Issue number4
DOIs
Publication statusPublished - 19 Jan 2018

Fingerprint

Buserelin
Gonadotropin-Releasing Hormone
Osteoporosis
Orchiectomy
Animal Models
Testosterone
Bone and Bones
Femur
X-Ray Microtomography
Subcutaneous Injections
Tibia
Bone Density
Sprague Dawley Rats
Prostatic Neoplasms
Calcium
Therapeutics

Keywords

  • Androgen
  • Bone
  • Gonadotropin-releasing hormone agonists
  • Male osteoporosis
  • Testosterone

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Mohamad, N. V., Che Zulkepli, M. A. A., Theseira, K. M., Zulkifli, N., Shahrom, N. Q., Ridzuan, N. A. M., ... Kok Yong, C. (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

Establishing an animal model of secondary osteoporosis by using a gonadotropin-releasing hormone agonist. / Mohamad, Nur Vaizura; Che Zulkepli, Muhammad Afiq Amani; Theseira, Krystine May; Zulkifli, Norain; Shahrom, Nur Quraisha; Ridzuan, Nurul Amni Mohamad; Jamil @ A. Wahab, Nor Aini; Soelaiman, Ima Nirwana; Kok Yong, Chin.

In: International Journal of Medical Sciences, Vol. 15, No. 4, 19.01.2018, p. 300-308.

Research output: Contribution to journalArticle

Mohamad, Nur Vaizura ; Che Zulkepli, Muhammad Afiq Amani ; Theseira, Krystine May ; Zulkifli, Norain ; Shahrom, Nur Quraisha ; Ridzuan, Nurul Amni Mohamad ; Jamil @ A. Wahab, Nor Aini ; Soelaiman, Ima Nirwana ; Kok Yong, Chin. / Establishing an animal model of secondary osteoporosis by using a gonadotropin-releasing hormone agonist. In: International Journal of Medical Sciences. 2018 ; Vol. 15, No. 4. pp. 300-308.
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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.",
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N2 - 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.

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