伊班膦酸盐预防和治疗兔糖皮质激素性骨质疏松症。
Ibandronate for prevention and treatment of glucocorticoid-induced osteoporosis in rabbits.
机构信息
Biomedical Engineering Center of Hebei Medical University, No. 9 Tiyu North Street, Shijiazhuang, 050011 Hebei, China.
出版信息
Rheumatol Int. 2012 Nov;32(11):3405-11. doi: 10.1007/s00296-011-2074-9. Epub 2011 Nov 6.
The objective of this study is to evaluate the efficacy of ibandronate (IBN) in prevention and treatment of glucocorticoid-induced osteoporosis in rabbits. A total of 60 New Zealand white rabbits were randomly allocated into six groups. Twenty rabbits in the control group were injected with saline. Forty rabbits received dexamethasone (DX) treatment at a dose of 3 mg/kg twice weekly during the first 6 weeks, while 10 of these rabbits (group IBN&DX) were injected additionally with IBN at a dose of 2 mg/kg before DX treatment. At week 6, the rabbits from IBN&DX group, 10 rabbits from control group (group CNTR-1) and 10 rabbits treated with DX (group DX6) were killed. Half (10) of the remaining rabbits in DX group were continued for DX treatment at a dose of 3 mg/kg once weekly (group DX12), while the other half (10) rabbits (group DX&IBN) additionally received IBN injection (2 mg/kg) once before continuing DX treatment. The remaining rabbits (10) in an additional of control group (group CNTR-2) continuously received saline. At week 12, all rabbits were killed for bone biomechanical analysis and histological examination. At week 6, the analysis of bone biomechanical and histological results of group CNTR-1 and DX6 showed that GIOP rabbit models were successfully established. Compared with group DX6, bone volume/tissue volume (BV/TV), trabecular number (Tb.N) and trabecular thickness (Tb.Th) of lumbar spine in group IBN&DX were increased by 100, 45.74 and 40.55%, respectively (P < 0.01). Meanwhile, BV/TV and Tb.N of femoral neck were increased by 30.29 and 16.86%, respectively (P < 0.01). The maximum compressive load, the maximum bending stress and the maximum torque were increased by 24.19, 29.91 and 37.24%, respectively (P < 0.01). At week 12, in comparison of the results between group DX12 and group DX6, the histomorphometric and mechanical analysis demonstrated that prolonged DX treatment could lead to further loss of bone mass and strength. Compared with group DX12, BV/TV, Tb.N and Tb.Th of lumbar spine in group DX&IBN were increased by 73.34, 39.02 and 23.87%, respectively (P < 0.05), the parameters of femoral neck were increased by 88.75, 31.29 and 42.01%, respectively (P < 0.01), and the biomechanical parameters were increased by 54.36, 21.38 and 105.75%, respectively (P < 0.05). IBN could effectively prevent and treat high-dosing glucocorticoid-induced loss of bone mass and strength in rabbits.
本研究旨在评估伊班膦酸盐（IBN）在预防和治疗兔糖皮质激素诱导性骨质疏松症中的疗效。将 60 只新西兰大白兔随机分为 6 组。对照组 20 只兔给予生理盐水注射。40 只兔在前 6 周内每周接受 3mg/kg 地塞米松（DX）治疗 2 次，其中 10 只（IBN&DX 组）在 DX 治疗前额外给予 2mg/kg IBN。第 6 周末，IBN&DX 组、对照组的 10 只兔（CNTR-1 组）和接受 DX 治疗的 10 只兔（DX6 组）被处死。DX 组的一半（10 只）兔继续以 3mg/kg 每周 1 次的剂量接受 DX 治疗（DX12 组），而另一半（10 只）兔（DX&IBN 组）则在继续接受 DX 治疗前额外接受 2mg/kg IBN 注射。对照组的其余 10 只兔（CNTR-2 组）继续给予生理盐水。第 12 周末，所有兔均被处死进行骨生物力学分析和组织学检查。第 6 周末，CNTR-1 组和 DX6 组的骨生物力学和组织学分析结果表明，成功建立了糖皮质激素诱导性骨质疏松症兔模型。与 DX6 组相比，IBN&DX 组的腰椎骨体积/组织体积（BV/TV）、骨小梁数量（Tb.N）和骨小梁厚度（Tb.Th）分别增加了 100%、45.74%和 40.55%（P<0.01）。同时，股骨颈的 BV/TV 和 Tb.N 分别增加了 30.29%和 16.86%（P<0.01）。最大压缩载荷、最大弯曲应力和最大扭矩分别增加了 24.19%、29.91%和 37.24%（P<0.01）。第 12 周末，与 DX12 组相比，DX12 组的组织形态计量学和力学分析表明，延长 DX 治疗可导致骨量和骨强度进一步丧失。与 DX12 组相比，IBN&DX 组的腰椎 BV/TV、Tb.N 和 Tb.Th 分别增加了 73.34%、39.02%和 23.87%（P<0.05），股骨颈的参数分别增加了 88.75%、31.29%和 42.01%（P<0.01），生物力学参数分别增加了 54.36%、21.38%和 105.75%（P<0.05）。IBN 可有效预防和治疗兔高剂量糖皮质激素诱导的骨量和骨强度丢失。
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