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在临床相关时间点对Legg-Calvé-Perthes病猪模型进行形态学和组织学评估。

Morphologic and Histologic Assessment of Porcine Model of Legg-Calvé-Perthes Disease at a Clinically Relevant Time Point.

作者信息

Taboada Phillip, Trautmann Daniel, Croley Garrett, Lee Joonoh, Deng Zhuo, Kim Harry K W

机构信息

University of Texas Southwestern Medical Center, Dallas, Texas, USA.

Center of Excellence in Hip, Scottish Rite for Children, Dallas, Texas, USA.

出版信息

J Orthop Res. 2025 Jul;43(7):1336-1343. doi: 10.1002/jor.26093. Epub 2025 May 7.

DOI:10.1002/jor.26093
PMID:40342202
Abstract

Previous studies using the porcine model of Legg-Calvé-Perthes Disease (LCPD) focused on treatments initiated 1 week following osteonecrosis (ON) induction, which represents the early avascular necrosis (AVN) stage (Stage Ia). Most patients, however, present to the clinic during later stages, like the late AVN (Stage Ib) or the early fragmentation stage (Stage IIa), when development of deformity and revascularization is initiated. This study's purpose was to determine the histologic and morphologic changes in the porcine model at 3 weeks after the ON induction. We hypothesized that the 3-week time point better represents a clinically relevant stage of LCPD when patients present to clinic. Eighteen piglets underwent ON induction surgery. Femoral heads were assessed using X-ray, histology, and micro-CT at 3 weeks post-ON. X-ray and histologic assessments revealed subchondral fracture, mild femoral head deformity, variable degree of revascularization (33 ± 30%, range 0%-88%), and early necrotic bone remodeling changes with significantly decreased osteoblast (p < 0.0001) and osteoclast numbers (p < 0.0001) compared to the normal side. Taken together, the results of this study provide comprehensive morphologic and histologic evidence of the late AVN stage (Stage 1b) in the porcine model, which is a clinically relevant time point to develop and test new treatment strategies. A wide variability of revascularization was seen at the 3-week time point, which stresses the importance of evaluating femoral head perfusion and individualizing treatment even in the early stage of AVN.

摘要

以往使用猪Legg-Calvé-Perthes病(LCPD)模型的研究主要关注于骨坏死(ON)诱导后1周开始的治疗,这代表早期无血管坏死(AVN)阶段(Ia期)。然而,大多数患者在后期阶段才到诊所就诊,如晚期AVN(Ib期)或早期碎裂阶段(IIa期),此时畸形发展和再血管化已经开始。本研究的目的是确定ON诱导后3周猪模型的组织学和形态学变化。我们假设3周这个时间点更能代表LCPD患者到诊所就诊时的临床相关阶段。18只仔猪接受了ON诱导手术。在ON后3周,使用X射线、组织学和微型计算机断层扫描(micro-CT)对股骨头进行评估。X射线和组织学评估显示,与正常侧相比,出现了软骨下骨折、轻度股骨头畸形、不同程度的再血管化(33±30%,范围0%-88%)以及早期坏死骨重塑变化,成骨细胞数量(p<0.0001)和破骨细胞数量显著减少(p<0.0001)。综上所述,本研究结果提供了猪模型中晚期AVN阶段(1b期)的全面形态学和组织学证据,这是开发和测试新治疗策略的临床相关时间点。在3周时间点观察到再血管化存在很大差异,这强调了即使在AVN早期评估股骨头灌注和个体化治疗的重要性。

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本文引用的文献

1
Early-Stage Femoral Head Hypoperfusion Correlates with Femoral Head Deformity at Intermediate Follow-up in Legg-Calvé-Perthes Disease.在Legg-Calvé-Perthes病中期随访中,早期股骨头灌注不足与股骨头畸形相关。
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Prolonged non-weightbearing treatment decreases femoral head deformity compared to symptomatic treatment in the initial stage of Legg-Calvé-Perthes disease.
在 Legg-Calvé-Perthes 病的初期,与症状治疗相比,长时间不负重治疗可减少股骨头畸形。
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Dynamic deformation of the femoral head occurs on weightbearing in Legg-Calves-Perthes disease: a translational pilot study.股骨头的动态变形在Legg-Calvé-Perthes病负重时出现:一项转化性初步研究。
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6
Anti-Interleukin-6 Therapy Decreases Hip Synovitis and Bone Resorption and Increases Bone Formation Following Ischemic Osteonecrosis of the Femoral Head.抗白细胞介素-6 治疗可减少缺血性股骨头坏死髋关节滑膜炎和骨吸收,并增加骨形成。
J Bone Miner Res. 2021 Feb;36(2):357-368. doi: 10.1002/jbmr.4191. Epub 2020 Nov 2.
7
Demographics and Clinical Presentation of Early-Stage Legg-Calvé-Perthes Disease: A Prospective, Multicenter, International Study.早期 Legg-Calvé-Perthes 病的人口统计学和临床表现:一项前瞻性、多中心、国际研究。
J Am Acad Orthop Surg. 2021 Jan 15;29(2):e85-e91. doi: 10.5435/JAAOS-D-19-00379.
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Evolution of Legg-Calvé-Perthes disease following proximal femoral varus osteotomy performed in the avascular necrosis stage:a prospective study.在无血管坏死阶段进行股骨近端内翻截骨术后Legg-Calvé-Perthes病的演变:一项前瞻性研究
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