Reduced skeletal loading leads to marked bone loss. Animal models of hindlimb suspension are widely used to assess alterations in skeleton during the course of complete unloading. More recently, the effects of partial unloading on the musculoskeletal system have been interrogated in mice and rats, revealing dose-dependent effects of partial weight bearing (PWB) on the skeleton and skeletal muscle. Here, we extended these studies to determine the structural and functional skeletal alterations in 14-week-old male Wister rats exposed to 20%, 40%, 70%, or 100% of body weight for 1, 2, or 4 weeks (n = 11-12/group). Using in vivo pQCT, we found that trabecular bone density at the proximal tibia declined in proportion to the degree of unloading and continued progressively with time, without evidence of a plateau by 4 weeks. Ex vivo measurements of trabecular microarchitecture in the distal femur by microcomputed tomography revealed deficits in bone volume fraction, 2 and 4 weeks after unloading. Histologic analyses of trabecular bone in the distal femur revealed the decreased osteoblast number and mineralizing surface in unloaded rats. Three-point bending of the femoral diaphysis indicated modest or no reductions in femoral stiffness and estimated modulus due to PWB. Our results suggest that this rat model of PWB leads to trabecular bone deterioration that is progressive and generally proportional to the degree of PWB, with minimal effects on cortical bone.

中文翻译：

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由于大鼠机械负荷的不同减少而导致的剂量依赖性骨骼缺陷。

骨骼负荷减少会导致明显的骨质流失。后肢悬吊的动物模型被广泛用于评估完全卸载过程中骨骼的变化。最近，已经在小鼠和大鼠中研究了部分卸载对肌肉骨骼系统的影响，揭示了部分负重（PWB）对骨骼和骨骼肌的剂量依赖性作用。在这里，我们扩展了这些研究，以确定暴露于20％，40％，70％或100％体重，持续1、2或4周的14周龄雄性Wister大鼠的结构和功能骨骼改变（n = 11-12 /组）。使用体内pQCT，我们发现胫骨近端的小梁骨密度与卸载程度成比例下降，并随时间逐渐增加，没有证据表明到4周时出现平台期。通过微型计算机断层扫描对股骨远端的小梁微结构进行离体测量，结果显示在卸载后2周和4周骨量分数不足。股骨远端小梁骨的组织学分析显示，空载大鼠的成骨细胞数量和矿化表面减少。股骨干physi端的三点弯曲表明，由于PWB导致股骨硬度和估计模量适度降低或没有降低。我们的结果表明，这种PWB大鼠模型导致小梁骨退化，这种退化是进行性的，通常与PWB的程度成正比，对皮质骨的影响最小。股骨远端小梁骨的组织学分析显示，空载大鼠的成骨细胞数量减少，矿化表面减少。股骨干physi端的三点弯曲表明，由于PWB导致股骨硬度和估计模量适度降低或没有降低。我们的结果表明，这种PWB大鼠模型导致小梁骨退化，这种退化是进行性的，通常与PWB的程度成正比，对皮质骨的影响最小。股骨远端小梁骨的组织学分析显示，空载大鼠的成骨细胞数量减少，矿化表面减少。股骨干physi端的三点弯曲表明，由于PWB导致股骨硬度和估计模量适度降低或没有降低。我们的结果表明，这种PWB大鼠模型导致小梁骨退化，这种退化是进行性的，通常与PWB的程度成正比，对皮质骨的影响最小。