Surgical and Orthopaedic Research Laboratories, Prince of Wales Clinical School, University of New South Wales, Prince of Wales Hospital, Gate 6, Avoca St, Randwick, Sydney, NSW 2031, Australia.
Neurospine Clinic, Prince of Wales Hospital, University of New South Wales, Barker St, Randwick, Sydney, NSW 2031, Australia.
Spine J. 2018 Oct;18(10):1896-1909. doi: 10.1016/j.spinee.2018.05.022. Epub 2018 May 22.
Degenerative disc disease (DDD) is a common, widespread socioeconomic problem. Appropriate large animal models of DDD are required for improved understanding and to serve as preclinical test beds for therapeutic strategies.
To evaluate the effects of short and medium duration immobilization on the sheep lumbar intervertebral disc (IVD) and facet joints (FJs), and to establish a large animal model for DDD research.
An in vivo sheep model evaluating the effect of short- and medium-term immobilization on disc degeneration.
Eighteen sheep were equally randomized into three groups: short-term (6-week) immobilization (n=6), medium-term (26-week) immobilization (n=6), and control (no surgery) (n=6). Immobilization of L3-L4 was achieved with pedicle screw and rod implantation, the IVD was kept intact, and the annulus and end plates were not disrupted. The IVD and FJs were assessed with planar radiography, computerized tomography (CT), magnetic resonance imaging (MRI), pure moment biomechanical testing, and histologic analysis.
Disc height was reduced for 6- and 26-week immobilization groups. The MRI and histologic analysis demonstrated significant disc degeneration for both immobilized groups compared with control, but no statistical difference was detected between short- and medium-term duration. Progressive degenerative changes in FJs were observed with micro-CT and histologic end points. Immobilization significantly reduced lateral bending and flexion-extension range of motion.
The mechanical environment set up by immobilization alone is capable of inducing lumbar disc degeneration at both 6 and 26 weeks in sheep. Longer duration immobilization did not advance disc degeneration process beyond of that found with short duration. The present model produces a degenerative disc with intact annulus and without acute injury, more closely representing the scenario common in human disc degeneration. This provides a suitable large animal in vivo model for the evaluation of the new therapies for disc degeneration. Further studies would do well to examine the effect of remobilization after immobilization in this model.
退行性椎间盘疾病（DDD）是一种常见的、广泛存在的社会经济问题。需要合适的大动物模型来更好地理解 DDD，并作为治疗策略的临床前试验台。
评估短期和中期固定对绵羊腰椎椎间盘（IVD）和小关节（FJ）的影响，并建立 DDD 研究的大动物模型。
一种评估短期和中期固定对椎间盘退变影响的体内绵羊模型。
18 只绵羊被平均随机分为三组：短期（6 周）固定组（n=6）、中期（26 周）固定组（n=6）和对照组（无手术）（n=6）。通过椎弓根螺钉和棒植入实现 L3-L4 的固定，IVD 保持完整，并且环和终板没有破裂。通过平面射线照相、计算机断层扫描（CT）、磁共振成像（MRI）、纯力矩生物力学测试和组织学分析评估 IVD 和 FJ。
6 周和 26 周固定组的椎间盘高度降低。MRI 和组织学分析显示，与对照组相比，两个固定组的椎间盘均有明显退变，但短期和中期持续时间之间没有统计学差异。微 CT 和组织学终点观察到 FJ 的进行性退行性变化。固定显著降低了侧屈和屈伸运动范围。
单独固定建立的力学环境能够在绵羊中诱导腰椎间盘在 6 周和 26 周时发生退变。更长时间的固定不会使椎间盘退变进程超过短期固定的程度。该模型产生的退变椎间盘具有完整的环和没有急性损伤，更能代表人类椎间盘退变的常见情况。这为评估新的椎间盘退变治疗方法提供了合适的大动物体内模型。进一步的研究最好在该模型中检查固定后的再活动对椎间盘的影响。
