Miranda Daniel L, Putman Melissa, Kandah Ruby, Cubria Maria, Suarez Sebastian, Nazarian Ara, Snyder Brian
Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
Division of Endocrinology, Boston Children׳s Hospital and Harvard Medical School, Boston, MA, USA.
J Biomech. 2016 Oct 3;49(14):3549-3554. doi: 10.1016/j.jbiomech.2016.08.018. Epub 2016 Aug 24.
Prolonged immobilization in hospitalized children can lead to fragility fractures and muscle contractures and atrophy. The purpose of this study was to develop a lower-extremity disuse rabbit model with musculoskeletal changes similar to those observed in children subjected to prolonged immobilization. Six-week-old rabbits were randomly assigned to control (CTRL, n=4) or bilateral sciatic and femoral neurectomy (bSFN, n=4) groups. Trans-axial helical CT scans of each rabbit׳s hind limbs were acquired after eight weeks. The rabbits were then euthanized and the tibiae and calcanea were harvested from each rabbit. μCT imaging was performed on the tibiae and calcanea mid-diaphysis. Four-point bending, gas pycnometry, and ashing were then performed on each tibia. All comparisons reflect the differences between the bSFN and CTRL rabbits. Significant decreases in tibiae bone mineral density (≥9.41%, p≤0.006), axial rigidity (≥50.47%, p≤0.02), and soft tissue mass (55.25%, p=0.006) were observed from the trans-axial helical CT scans. The μCT results indicated significant detriments in tibia and calcaneus cortical thickness and bone volume fraction (p≤0.011). Significant changes in stiffness, yield load, ultimate load, and ultimate displacement (≥30.05%, p≤0.025) were observed from mechanical testing. These data indicate that limb disuse at a time of rapid musculoskeletal growth severely impairs muscle and bone development, reflecting the musculoskeletal complications observed in children with chronic medical conditions causing immobilization. Interventions to reduce these musculoskeletal complications in children are urgently needed. This disuse rabbit model will be useful in pre-clinical studies evaluating novel interventions for improving pediatric musculoskeletal health.
住院儿童长期制动可导致脆性骨折、肌肉挛缩和萎缩。本研究的目的是建立一种下肢废用兔模型，其肌肉骨骼变化与长期制动儿童所观察到的相似。将6周龄的兔子随机分为对照组（CTRL，n = 4）或双侧坐骨神经和股神经切除术组（bSFN，n = 4）。8周后对每只兔子的后肢进行横轴位螺旋CT扫描。然后对兔子实施安乐死，并从每只兔子身上采集胫骨和跟骨。对胫骨和跟骨的骨干中部进行显微CT成像。然后对每根胫骨进行四点弯曲、气体比重测定和灰化处理。所有比较均反映了bSFN组和CTRL组兔子之间的差异。横轴位螺旋CT扫描显示胫骨骨密度显著降低（≥9.41%，p≤0.006）、轴向刚度显著降低（≥50.47%，p≤0.02）和软组织质量显著降低（55.25%，p = 0.006）。显微CT结果表明胫骨和跟骨的皮质厚度和骨体积分数显著减小（p≤0.011）。力学测试显示刚度、屈服载荷、极限载荷和极限位移有显著变化（≥30.05%，p≤0.025）。这些数据表明，在肌肉骨骼快速生长时期肢体废用会严重损害肌肉和骨骼发育，这反映了患有导致制动的慢性疾病的儿童所出现的肌肉骨骼并发症。迫切需要采取干预措施来减少儿童的这些肌肉骨骼并发症。这种废用兔模型将有助于评估改善儿童肌肉骨骼健康的新型干预措施的临床前研究。
