Bentolila V, Boyce T M, Fyhrie D P, Drumb R, Skerry T M, Schaffler M B
Breech Research Laboratory, Bone and Joint Center, Henry Ford Health Sciences Center, Detroit, MI, USA.
Bone. 1998 Sep;23(3):275-81. doi: 10.1016/s8756-3282(98)00104-5.
Intracortical remodeling in the adult skeleton removes and replaces areas of compact bone that have sustained microdamage. Although studies have been performed in animal species in which there is an existing baseline of remodeling activity, laboratory rodents have been considered to have limited suitability as models for cortical bone turnover processes because of a lack of haversian remodeling activity. Supraphysiological cyclic axial loading of the ulna in vivo was used to induce bending with consequent fatigue and microdamage. Right ulnae of adult Sprague-Dawley rats were fatigue-loaded to a prefailure stopping point of 30% decrease in ulnae whole bone stiffness. Ten days after the first loading, left ulnae were fatigued in the same way. Ulnae were harvested immediately to allow comparison of the immediate response of the left ulna to the fatigue loads, and the biological response of the right leg to the fatigue challenge. Histomorphometry and confocal microscopy of basic fuchsin-stained bone sections were used to assess intracortical remodeling activity, microdamage, and osteocyte integrity. Bone microdamage (linear microcracks, as well as patches of diffuse basic fuchsin staining within the cortex) occurred in fatigue-loaded ulnar diaphyses. Ten days after fatigue loading, intracortical resorption was activated in ulnar cortices. Intracortical resorption occurred in preferential association with linear-type microcracks, with microcrack number density reduced almost 40% by 10 days after fatigue. Resorption spaces were also consistently observed within areas of the cortex in which no bone matrix damage could be detected. Confocal microscopy studies showed alterations of osteocyte and canalicular integrity around these resorption spaces. These studies reveal that: (1) rat bone undergoes intracortical remodeling in response to high levels of cyclic strain, which induce microdamage in the cortex; and (2) intracortical resorption is associated both with bone microdamage and with regions of altered osteocyte integrity. From these studies, we conclude that rats can initiate haversian remodeling in long bones in response to fatigue, and that osteocyte death or damage may provide one of the stimuli for this process.
成年骨骼中的皮质内重塑会去除并替换承受微损伤的密质骨区域。尽管已经在具有现有重塑活动基线的动物物种中开展了研究，但由于缺乏哈弗斯系统重塑活动，实验室啮齿动物被认为作为皮质骨周转过程的模型适用性有限。在体内对成年Sprague-Dawley大鼠的尺骨施加超生理水平的周期性轴向负荷，以诱导弯曲并随之产生疲劳和微损伤。成年Sprague-Dawley大鼠的右侧尺骨被疲劳加载至尺骨全骨刚度降低30%的预失效停止点。首次加载10天后，左侧尺骨以相同方式进行疲劳加载。立即采集尺骨，以便比较左侧尺骨对疲劳负荷的即时反应以及右侧尺骨对疲劳挑战的生物学反应。使用碱性品红染色骨切片的组织形态计量学和共聚焦显微镜来评估皮质内重塑活动、微损伤和骨细胞完整性。在疲劳加载的尺骨干中出现了骨微损伤（线性微裂纹以及皮质内弥漫性碱性品红染色斑块）。疲劳加载10天后，尺骨皮质内的吸收被激活。皮质内吸收优先与线性微裂纹相关，到疲劳后10天，微裂纹数量密度降低了近40%。在皮质内未检测到骨基质损伤的区域也始终观察到吸收间隙。共聚焦显微镜研究显示这些吸收间隙周围的骨细胞和小管完整性发生了改变。这些研究表明：（1）大鼠骨骼会因高水平的周期性应变而发生皮质内重塑，这种应变会在皮质中诱导微损伤；（2）皮质内吸收与骨微损伤以及骨细胞完整性改变的区域均相关。从这些研究中，我们得出结论，大鼠可以在长骨中启动哈弗斯系统重塑以应对疲劳，并且骨细胞死亡或损伤可能为此过程提供刺激因素之一。
