Department of Biochemistry Investigation, Instituto de Investigacion Sanitaria Fundación Jimenez Diaz, Madrid, Spain.
Aging Male. 2011 Dec;14(4):220-30. doi: 10.3109/13685538.2010.518176. Epub 2010 Oct 12.
The aim of this study was to investigate the effects of the bisphosphonate ibandronate (IBN) in a male osteoporosis animal model.
Two studies were performed in 9-month-old orchidectomised (ORX) or sham-operated rats. In prevention study, subcutaneous IBN was administered daily (1 μg/kg) or monthly (28 μg/kg every 28 days) starting on day of surgery for 5 months. In treatment study, the same treatment started 6 months after ORX. After sacrifice, bone analyses by dual-energy X-ray absorptiometry, 3-dimensional micro-computed tomography, and 3-point bending were performed in femora or vertebrae. Serum tartrate-resistant acid phosphatase 5b (TRAP-5b) and aminoterminal propeptide of collagen I (PINP) were analysed for resorption and osteocalcin (BGP) for bone formation.
In both studies, ORX resulted in significant femoral and vertebral bone loss and microarchitectural deterioration after 5 months of ORX, and became more pronounced after 11 months. Biomechanical strength was also decreased. Serum levels for TRAP-5b and BGP increased while PINP levels were reduced or unchanged. Both daily and monthly IBN prevented or even restored ORX-induced changes in both studies, with the intermittent regimen showing a improvement in efficacy with respect to many of the biomechanical parameters.
本研究旨在探讨双膦酸盐伊班膦酸盐(IBN)在雄性骨质疏松动物模型中的作用。
本研究在 9 月龄去势(ORX)或假手术大鼠中进行了两项研究。在预防研究中,从手术当天开始,每天(1μg/kg)或每月(28μg/kg,每 28 天一次)皮下给予 IBN,持续 5 个月。在治疗研究中,相同的治疗在 ORX 后 6 个月开始。处死动物后,通过双能 X 射线吸收仪、三维微计算机断层扫描和三点弯曲试验对股骨或椎体进行骨分析。检测血清抗酒石酸酸性磷酸酶 5b(TRAP-5b)、I 型胶原氨基端前肽(PINP)和骨钙素(BGP)以评估骨吸收和骨形成。
在两项研究中,ORX 导致大鼠股骨和椎体在去势 5 个月后出现明显的骨丢失和微结构恶化,在去势 11 个月后更加明显。生物力学强度也降低。血清 TRAP-5b 和 BGP 水平升高,而 PINP 水平降低或不变。每日和每月 IBN 预防或甚至恢复了两项研究中 ORX 引起的变化,间歇性方案在许多生物力学参数方面显示出更好的疗效。