Risedronate does not reduce mechanical loading-related increases in cortical and trabecular bone mass in mice
Risedronate does not reduce mechanical loading-related increases in cortical and trabecular bone mass in mice
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DOI：
10.1016/j.bone.2011.03.775
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发表时间：
2011-07-01
期刊：
影响因子：
4.1
通讯作者：
Price, Joanna S.
中科院分区：
文献类型：
--
作者：
Sugiyama, Toshihiro;Meakin, Lee B.;Price, Joanna S.
为了确定抗骨吸收治疗与机械负荷联合是否对骨结构有负面、附加或协同作用，我们评估了利塞膦酸钠和无创动态负荷对骨小梁和皮质骨的单独和联合作用。17周龄的雌性C57 BL/6小鼠每天皮下注射赋形剂（n = 20）或剂量为0.15、1.5、15或150 μ g/kg/天的利塞膦酸盐（每种n = 10），持续17天。从治疗的第四天开始，右侧胫骨接受单次轴向载荷（40个周期/天），每周交替三天，持续两周。左侧胫骨用作内部对照。通过高分辨率显微计算机断层扫描和荧光染料标记成像分析胫骨骨小梁和皮质部位。在非负载的tibium中，用15或150 μ g/kg/天的较高剂量的利塞膦酸盐治疗导致比赋形剂治疗的对照组更高的骨小梁体积和骨小梁数量，而这种治疗在任何剂量下都与皮质骨体积没有差异相关。在负荷胫骨中，与对侧对照组相比，负荷诱导的骨小梁和皮质骨体积增加主要是通过增加骨小梁厚度和骨膜扩张，分别与利塞膦酸钠治疗无关。总之，即使在1000倍剂量范围内，利塞膦酸钠短期治疗也不会损害小鼠骨小梁和皮质骨对机械负荷的反应。在考虑骨质疏松症治疗的优化时，抗吸收治疗和机械负荷可以发挥独立的有益作用，这是令人放心的。(C)2011 Elsevier Inc. All rights reserved.
To establish whether the combination of anti-resorptive therapy with mechanical loading has a negative, additive or synergistic effect on bone structure, we assessed the separate and combined effects of risedronate and non-invasive dynamic loading on trabecular and cortical bone. Seventeen-week-old female C57BL/6 mice were given daily subcutaneous injections of vehicle (n = 20) or risedronate at a dose of 0.15, 1.5, 15 or 150 mu g/kg/day (n = 10 in each) for 17 days. From the fourth day of treatment, the right tibiae were subjected to a single period of axial loading (40 cycles/day) for three alternate days per week for two weeks. The left tibiae were used as internal controls. Trabecular and cortical sites in the tibiae were analyzed by high-resolution micro-computed tomography and imaging of fluorochrome labels. In the non-loaded tibiae, treatment with the higher doses of risedronate at 15 or 150 mu g/kg/day resulted in higher trabecular bone volume and trabecular number than in vehicle-treated controls, whereas such treatment was associated with no differences in cortical bone volume at any dose. In the loaded tibiae, loading induced increases in trabecular and cortical bone volume compared with contra-lateral controls primarily through increased trabecular thickness and periosteal expansion, respectively, independently of risedronate treatment. In conclusion, the response to mechanical loading in both trabecular and cortical bone in mice is therefore not impaired by short-term treatment with risedronate, even over a 1000-fold dose range. In considering the optimization of treatments for osteoporosis, it is reassuring that anti-resorptive therapy and mechanical loading can exert independent beneficial effects.This article is part of a Special Issue entitled Bisphosphonates. (C) 2011 Elsevier Inc. All rights reserved.