Department of Mechanical and Manufacturing Engineering, University of Calgary, 2500 University Drive, NW, Calgary, AB T2N1N4, Canada.
Osteoporos Int. 2011 Mar;22(3):931-42. doi: 10.1007/s00198-010-1283-5. Epub 2010 May 18.
Bone loss and recovery in a receptor activator for nuclear factor κ B ligand (RANKL)-administered rat model was assessed. Microarchitecture, mineralization and strength deteriorated faster than ovariectomy (OVX). Recovery was dependent on the loss of trabecular elements and connections. Early recovery suggests a natural mechanism in rats to overcome excess RANKL, and may have implications for long-term bone loss.
To compare a model for experimental osteoporosis that induces bone loss by injecting RANKL into rats to an OVX rat model, and measure subsequent recovery of bone architecture, mineralization, and mechanics after stopping injections.
Mature, healthy, female Wistar rats were divided into high-dose RANKL, low-dose RANKL, OVX, and vehicle control groups. The right proximal tibiae were micro-computed tomography (micro-CT) scanned in vivo every 2 weeks from week 0 to week 12 and every 4 weeks from week 12 to week 20. Bone architectural, mineralization, and mechanical changes were determined. Serum calcium, RANKL, anti-RANKL, and osteoprotegerin were measured at weeks 0, 6, and 20.
High-dose RANKL administration resulted in severe deterioration of the trabecular architecture (39% of baseline BV/TV), and modest decreases in tissue mineralization, bone mass, and stiffness. Bone loss occurred more rapidly than in the OVX and low-dose RANKL group, and recovery occurred prior to stopping RANKL injections. Full recovery of trabecular thickness, tissue mineralization, and cortical bone mass, partial recovery of trabecular bone volume (55% of baseline), structural model index, bone mass (69% of baseline), and stiffness (90% of baseline) but no improvement in connectivity density or trabecular number was observed.
RANKL administration resulted in rapid and dose-dependent bone loss. The recovery of trabecular bone volume and stiffness appeared to be dependent on the number of remaining trabecular elements and their interconnections. Uncontrolled recovery suggests that further investigation into the RANKL-injected rat as a model of bone loss is required.
比较一种通过向大鼠注射 RANKL 诱导骨丢失的实验性骨质疏松模型与去卵巢大鼠模型，并测量停止注射后骨结构、矿化和力学的后续恢复情况。
成熟、健康的雌性 Wistar 大鼠分为高剂量 RANKL、低剂量 RANKL、去卵巢和载体对照组。从第 0 周开始，每隔 2 周对右侧胫骨近端进行一次活体 micro-CT 扫描，持续至第 12 周，然后每隔 4 周扫描一次，直至第 20 周。确定骨结构、矿化和力学变化。在第 0、6 和 20 周测量血清钙、RANKL、抗 RANKL 和护骨素。
高剂量 RANKL 给药导致骨小梁结构严重恶化（基线 BV/TV 的 39%），组织矿化、骨量和刚度适度降低。骨丢失比去卵巢和低剂量 RANKL 组发生得更快，并且在停止 RANKL 注射之前就已经开始恢复。观察到骨小梁厚度、组织矿化和皮质骨量完全恢复，骨小梁体积（基线的 55%）、结构模型指数、骨量（基线的 69%）和刚度（基线的 90%）部分恢复，但连接密度或骨小梁数量没有改善。
RANKL 给药导致快速且剂量依赖性的骨丢失。骨小梁体积和刚度的恢复似乎依赖于剩余的骨小梁数量及其相互连接。未经控制的恢复表明，需要进一步研究 RANKL 注射大鼠作为骨丢失模型。
