Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, 56000 Cheras, Kuala Lumpur, Malaysia.
School of Healthcare Sciences, Faculty of Health Science, Universiti Kebangsaan Malaysia, 50300 Kuala Lumpur, Malaysia.
Int J Med Sci. 2018 Jan 19;15(4):300-308. doi: 10.7150/ijms.22732. eCollection 2018.
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. This study aimed to evaluate the skeletal effect of buserelin (a GnRH agonist) in male rats and compare it with orchidectomy. Forty-six three-month-old male 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. 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). 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.
去势术目前是诱导临床前男性骨质疏松模型骨丢失的首选方法。用于前列腺癌治疗的促性腺激素释放激素（GnRH）激动剂可引起睾酮缺乏，但对临床前男性骨质疏松模型中骨的影响研究较少。本研究旨在评估促黄体生成素释放激素（GnRH）激动剂布舍瑞林（buserelin）对雄性大鼠的骨骼作用，并将其与去势术进行比较。46 只 3 月龄雄性大鼠分为 3 个实验组。基线组（n=6）在研究开始时处死。布舍瑞林组中，大鼠每天接受皮下注射生理盐水（n=8）、25μg/kg 布舍瑞林乙酸盐（n=8）或 75μg/kg 布舍瑞林乙酸盐（n=8）。去势组中，大鼠行假手术（n=8）或去势术（n=8）。所有组均在左胫骨近端进行每月一次的体内 X 射线微计算机断层扫描。在研究开始和结束时采集血液，用于评估睾酮水平。治疗 3 个月后处死大鼠。收集股骨用于生物力学强度和骨钙测定。结果显示，两种剂量的布舍瑞林均导致睾酮水平显著下降和骨微结构恶化（p<0.05），但不影响骨钙含量（p>0.05）。25μg/kg 布舍瑞林显著降低股骨的位移和应变（p<0.05）。与假手术组相比，去势组也观察到类似的变化，但生物力学强度无明显变化（p>0.05）。布舍瑞林可在 3 个月内诱导睾酮缺乏和骨微结构的相关恶化，类似于去势术。然而，它可能需要更长的时间才能对骨强度和矿物质含量产生显著影响。
