High-dose risedronate treatment partially preserves cancellous bone mass and microarchitecture during long-term disuse
High-dose risedronate treatment partially preserves cancellous bone mass and microarchitecture during long-term disuse
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DOI：
10.1016/j.bone.2005.04.041
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发表时间：
2005-09-01
期刊：
影响因子：
4.1
通讯作者：
Schaffler, MB
中科院分区：
文献类型：
--
作者：
Li, CY;Majeska, RJ;Schaffler, MB
在大型哺乳动物中，由于破骨细胞吸收大大增加，停用会导致快速和严重的骨质流失。在这项研究中，我们测试了利塞膦酸盐（RIS），一种有效的破骨细胞活性抑制剂，是否能有效防止雌性比格犬（5-7岁，N = 28）在单前肢固定（IM） 12个月后的松质骨丢失。年龄匹配的非im狗作为对照（Con）。每组一半的动物每天服用RIS 1 mg/kg （Con + RIS, IM + RIS）。其余犬接受无菌水（Con， IM）。组织形态学分析显示，IM导致第二掌骨远端松质骨量急剧减少（-71%），骨小梁宽度（-51%）和数量（-41%）明显减少，骨吸收指标（侵蚀面、破骨细胞数量和表面）增加4倍。骨形成指标（钙黄素标记表面、类骨表面和骨形成率）IM组也显著高于对照组。IM的激活频率比对照水平增加了约4倍。RIS治疗减少了，但没有消除由于固定造成的松质骨丢失。RIS治疗的IM动物松质骨量减少了近50%，而小梁宽度和数量分别减少了31%和25%。在ris处理的对照和IM动物中，总体骨形成参数（矿化骨表面分数和骨形成率）大致保持在完整对照水平；然而，相对于完整的对照组，ris处理的对照组和ris处理的IM动物的矿物附着率分别降低了40%和86%。这些结果表明，大剂量RIS治疗可能抑制成骨细胞功能，特别是在长期停用的情况下。有趣的是，ris处理的IM动物的骨吸收参数达到甚至高于载体处理的IM动物的水平；侵蚀表面、破骨细胞数量和表面分别比经载体处理的IM值高84%、53%和83%。我们的数据表明，在长期停用期间，利塞膦酸钠治疗在预防松质骨丢失方面部分有效。此外，我们的研究结果表明，双膦酸盐可以损害成熟破骨细胞吸收骨的能力，但不能克服长期停用引起的对破骨细胞募集的强烈刺激。(c) 2005爱思唯尔公司版权所有。
Disuse induces rapid and severe bone loss in larger mammals as a result of greatly elevated osteoclastic resorption. In this study, we tested whether risedronate (RIS), a potent inhibitor of osteoclastic activity, would effectively prevent cancellous bone loss in female beagles (5-7 years old, N = 28) subjected to single forelimb immobilization (IM) for 12 months. Age-matched, non-IM dogs served as controls (Con). Half the animals from each group received RIS 1 mg/kg p.o. daily (Con + RIS, IM + RIS). Remaining dogs received sterile water (Con, IM). Histomorphometry showed that IM caused a dramatic reduction in cancellous bone mass (-71%) of distal 2nd metacarpals, characterized by marked decreases in trabecular width (-51%) and number (-41%), and 4-fold increases in the indices of bone resorption (eroded surface, osteoclast number, and surface). Bone formation indices (calcein-labeled surface, osteoid surface, and bone formation rate) were also significantly higher in IM than in controls. Activation frequency in IM increased about 4-fold beyond control level. RIS treatment reduced, but did not abolish cancellous bone loss due to immobilization. IM animals treated with RIS lost nearly 50% of cancellous bone mass, while trabecular width and number were reduced by 31% and 25%, respectively. In both RIS-treated control and IM animals, overall bone formation parameters (mineralized bone surface fraction and bone formation rate) remained roughly at intact control levels; however, mineral apposition rate relative to intact control was reduced 40% in RIS-treated control and 86% in RIS-treated IM animals. These results indicate that high-dose RIS treatment might suppress osteoblastic function, especially under long-term disuse. Interestingly, bone resorption parameters in RIS-treated IM animals reached levels even higher than in vehicle-treated IM animals; values for eroded surface, osteoclast number, and surface were 84%, 53%, and 83% above vehicle-treated IM values, respectively. Our data indicate that risedronate treatment is partially effective in preventing cancellous bone loss during long-term disuse. Moreover, our results suggest that bisphosphonates can impair the ability of mature osteoclasts to resorb bone, but cannot overcome the strong stimulus for osteoclast recruitment caused by long-term disuse. (c) 2005 Elsevier Inc. All rights reserved.