JOR Spine最新文献_第7页

Comparative Performance of Calcium Phosphate Grafts and Iliac Crest Autograft in Posterolateral Spinal Fusion in Rabbits 磷酸钙移植物与自体髂骨移植物在兔后外侧脊柱融合术中的性能比较

IF 3.9 3区医学 Q1 ORTHOPEDICS

JOR Spine

Pub Date : 2025-07-30 DOI: 10.1002/jsp2.70101

William R. Walsh, Rema A. Oliver, Matthew H. Pelletier, Tian Wang, Chris Christou, Emma R. Walsh, Jonathan M. Page, Chase T. Davis, Gregory M. Williams

Background

Calcium phosphate (CaP) biomaterials are widely used in surgical applications such as spinal fusion to substitute for or extend autogenous bone graft. Preclinical testing in standardized animal models is useful for evaluating the relative performance of materials differing in composition and structure, including a newer generation of submicron-structured CaP (sCaP) with surface features uniformly smaller than 1 μm. The purpose of this study was to compare three clinically available CaP-based materials and iliac crest autograft in the rabbit posterolateral fusion (PLF) model.

Methods

A novel sCaP with bovine collagen type I (sCaP/Col I) and two clinically established materials, sCaP with alkylene oxide copolymer (sCaP/AOC) and microstructured CaP with bovine collagen type I (mCaP/Col I), were evaluated in a skeletally mature, single-level, non-instrumented, bilateral rabbit PLF model. Iliac crest autograft served as a control. Endpoints included radiographic, mechanical, and histological evaluation at postoperative 6, 9, and 12 weeks.

Results

Fusion progressed with postoperative time with all grafts, and the CaP materials yielded fusion rates by micro-CT and manual palpation similar to those of the autograft control at each time point. When tested as autograft extenders, sCaP/Col I and sCaP/AOC demonstrated equivalent results for all endpoints. When hydrated with bone marrow aspirate and used as bone graft substitutes, sCaP/Col I supported earlier fusion than mCaP/Col I with an increased radiographic fusion rate at 9 weeks (p = 0.032) and increased bone tissue content by histomorphometry at 12 weeks (p = 0.006). New bone was observed to form with all materials, and no adverse local biological reactions were seen.

Conclusions

Differences in the composition and structure of clinically available CaP-based materials influenced the achievement of spinal fusion in a standardized rabbit PLF model. These results may help guide the selection and use of materials in clinical applications and the future development of biomaterials with improved performance.

磷酸钙（CaP）生物材料广泛应用于外科手术，如脊柱融合，以替代或延长自体骨移植。标准化动物模型的临床前测试有助于评估不同成分和结构材料的相对性能，包括表面特征均匀小于1 μm的新一代亚微米结构CaP （sCaP）。本研究的目的是比较三种临床可用的cap基材料和髂骨自体移植物在兔后外侧融合（PLF）模型中的应用。方法采用一种新型牛I型胶原蛋白sCaP （sCaP/Col I）和两种临床建立的材料，氧化亚烯共聚物sCaP （sCaP/AOC）和牛I型胶原微结构CaP (mCaP/Col I)，在骨骼成熟、单水平、无固定的双侧兔PLF模型中进行评估。自体髂骨移植作为对照。终点包括术后6、9和12周的放射学、力学和组织学评估。结果所有移植物的融合均随术后时间的推移而进展，micro-CT和手工触诊显示，CaP材料在每个时间点的融合率与自体移植物对照组相似。当作为自体接枝扩展剂进行测试时，sCaP/Col I和sCaP/AOC在所有端点上都显示出相同的结果。当用骨髓抽液水化并用作骨移植替代品时，sCaP/Col I比mCaP/Col I支持更早的融合，在9周时放射学融合率增加（p = 0.032），在12周时组织形态学测量增加骨组织含量（p = 0.006）。所有材料均可形成新骨，未见局部不良生物反应。结论临床上可用的cap基材料的组成和结构的差异影响了标准化兔PLF模型脊柱融合的实现。这些结果可能有助于指导临床应用中材料的选择和使用，以及未来性能更好的生物材料的开发。

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引用次数: 0

Animal Models of Disc Degeneration Using Puncture Injury: A 20 Year Perspective 穿刺损伤椎间盘退变的动物模型：20年的观察

IF 3.4 3区医学 Q1 ORTHOPEDICS

JOR Spine

Pub Date : 2025-07-28 DOI: 10.1002/jsp2.70093

Charu Jain, Jonathan J. Huang, Yunsoo Lee, Saad Chaudhary, Andrew C. Hecht, Alon Lai, Koichi Masuda, James Kang, James C. Iatridis

Background

Intervertebral disc (IVD) degeneration (IVDD) is a major cause of global disability. Three papers on puncture models of IVDD were published 20 years ago, transforming the application of preclinical animal models for pathophysiology and therapeutic screening studies.

Methods

Narrative review describing historic and current usage of preclinical puncture models of IVDD, documenting their introduction to induce slow, progressive IVDD and evolution to include many injury types broadly called “puncture models.” IVDD puncture models were reviewed for variability in species, needle gauge, puncture depth, IVD compartment, injectates, angle of puncture, motion of needle, and IVDD phenotype mimicked.

Results

IVD puncture models gained prominence following seminal 2005 publications describing needle puncture to induce slow, progressive IVDD for screening therapies. Specific details of puncture methods were described for controlling injury severity to induce IVDD phenotypes, including slow progressive IVDD, severe IVDD, chronic IVDD, disc herniation, and Modic-like changes. Common measurements for characterizing IVDD were also described.

Conclusions

Surgically induced IVD puncture injury animal models have evolved over decades to include many variations simulating distinct clinical phenotypes of IVDD. To facilitate cross-study comparisons, we recommend reporting a common set of injury features including needle gauge, puncture depth, injectates, puncture angle changes, needle motion, involvement of endplate and surrounding tissues, and phenotypes of IVDD mimicked. Surgically induced “outside-in” puncture injury models are valuable tools to test specific hypotheses and screening therapies.

背景椎间盘退变（IVDD）是全球致残的主要原因之一。20年前发表了三篇关于IVDD穿刺模型的论文，改变了临床前动物模型在病理生理和治疗筛选研究中的应用。方法对IVDD临床前穿刺模型的历史和当前使用情况进行叙述性回顾，记录其引入诱发缓慢、进行性IVDD的过程，并演变为包括许多被广泛称为“穿刺模型”的损伤类型。回顾了IVDD穿刺模型在物种、针距、穿刺深度、IVD室、注射剂、穿刺角度、针的运动和IVDD表型模拟方面的可变性。结果：IVD穿刺模型在2005年的开创性出版物中获得了突出的地位，这些出版物描述了针穿刺诱导缓慢，进行性IVDD的筛查治疗。我们描述了针刺方法的具体细节，以控制损伤严重程度，诱导IVDD表型，包括缓慢进行性IVDD、严重IVDD、慢性IVDD、椎间盘突出和modic样改变。描述了IVDD的常见测量方法。手术诱导的IVD穿刺损伤动物模型已经发展了几十年，包括许多模拟IVDD不同临床表型的变异。为了便于交叉研究比较，我们建议报告一组常见的损伤特征，包括针规、穿刺深度、注射剂、穿刺角度变化、针的运动、终板和周围组织的累及以及模拟IVDD的表型。手术诱导的“由外而内”穿刺损伤模型是检验特定假设和筛选疗法的宝贵工具。

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引用次数: 0

Development and Validation of a Machine Learning-Based Online Prognostic Model for Cervical Spondylosis Patients After Anterior Cervical Discectomy and Fusion: A Multicenter Study 基于机器学习的颈椎病患者前路椎间盘切除术和融合后在线预后模型的开发和验证：一项多中心研究

IF 3.4 3区医学 Q1 ORTHOPEDICS

JOR Spine

Pub Date : 2025-07-28 DOI: 10.1002/jsp2.70090

Sitan Feng, Shengsheng Huang, Zhongxian Zhou, Bin Zhang, Chengqian Huang, Tianyou Chen, Chenxing Zhou, Shaofeng Wu, Jichong Zhu, Jiarui Chen, Jiang Xue, Xinli Zhan, Chong Liu

Background

Cervical spondylosis (CS) is a degenerative condition often requiring surgical intervention, such as anterior cervical discectomy and fusion (ACDF), to alleviate symptoms. However, postoperative outcomes can vary significantly. This study aimed to develop and validate a predictive model for 1-year outcomes in CS patients after ACDF using multiple machine learning algorithms.

Methods

Data from 973 patients across three clinical centers, including 872 patients in the retrospective cohort and 101 patients in the prospective cohort, were utilized. A variety of clinical and laboratory features were identified using LASSO regression. Various machine learning algorithms were employed to develop predictive models. The models' performance was assessed and compared using metrics such as receiver operating characteristic (ROC) curves, area under the curve (AUC), calibration analysis, and decision curve analysis (DCA). Model interpretation and feature importance analysis were carried out using the SHapley Additive exPlanations (SHAP) method. Finally, the model was deployed on the web by using the Shiny app.

Results

The model was constructed using 10 essential predictors. Ten machine learning models were evaluated, with the stacking ensemble learning model demonstrating superior predictive performance (AUC = 0.81 in the internal validation set, 0.80 in the external validation set, and 0.82 in the prospective cohort). Furthermore, CRP, MONO, ESR, and age were highlighted as critical predictors.

Conclusions

This predictive tool offers a robust framework for personalized postoperative management in CS patients, potentially improving clinical outcomes.

背景颈椎病（CS）是一种退行性疾病，通常需要手术干预，如前路颈椎椎间盘切除术和融合（ACDF），以缓解症状。然而，术后结果可能有很大差异。本研究旨在利用多种机器学习算法开发并验证ACDF后CS患者1年预后的预测模型。方法采用来自三个临床中心的973例患者的数据，其中回顾性队列872例，前瞻性队列101例。使用LASSO回归识别各种临床和实验室特征。使用各种机器学习算法来开发预测模型。采用受试者工作特征（ROC）曲线、曲线下面积（AUC）、校准分析和决策曲线分析（DCA）等指标对模型的性能进行评估和比较。采用SHapley加性解释（SHAP）方法进行模型解释和特征重要性分析。最后，使用Shiny应用程序将模型部署到web上。结果使用10个基本预测因子构建模型。对10种机器学习模型进行了评估，其中堆叠集成学习模型表现出更优越的预测性能（内部验证集的AUC = 0.81，外部验证集的AUC = 0.80，前瞻性队列的AUC = 0.82）。此外，CRP、MONO、ESR和年龄被强调为关键预测因子。该预测工具为CS患者的个性化术后管理提供了一个强有力的框架，有可能改善临床结果。

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引用次数: 0

Evaluation of a Force-Control Experimental Method to Perform Unconstrained Load-Induced Subsidence Testing of Spinal Interbody Implants 脊柱椎体间植入物无约束载荷诱导沉降试验的力控制实验方法评价

IF 3.4 3区医学 Q1 ORTHOPEDICS

JOR Spine

Pub Date : 2025-07-25 DOI: 10.1002/jsp2.70087

Rémy Benais, Richard Barina, Stewart McLachlin

Introduction

Intervertebral body fusion devices (“interbody cages”) used in spinal surgeries are susceptible to axial and/or rotational subsidence into the underlying vertebral bone. Experimental testing standards to examine implant subsidence, such as ASTM F2267, simplify the implant loading conditions and vertebral bone materials for ease of use and repeatability. Yet, the ability to assess clinically relevant risk of rotational subsidence with these methods is limited.

Methods

The present work aimed to develop and evaluate a novel force-control (FC) test method for performing unconstrained load-induced implant subsidence into a heterogeneous material interface. The developed method was compared to the ASTM F2267 method, which uses a lubricated ball-and-socket joint, using the AMTI VIVO joint motion simulator to apply unconstrained loading up to 4 kN. Subsidence testing was performed on two different polyurethane (PU) foam densities (rigid 20 and 30 PCF) sandwiched together providing a heterogeneous boundary interface to induce implant rotation into the less dense foam.

Results

Axial and rotational subsidence values varied significantly between the two test methods (p < 0.05). Unconstrained axial compression up to 4 kN yielded, on average, 2.5 ± 0.4 mm of axial subsidence for ASTM-based setup compared to 4.8 ± 0.6 mm for the FC setup. The ASTM-based setup had an average implant rotation of 2.8° ± 0.5°, in contrast to the FC setup, with an average of 18.0° ± 0.9°. Additionally, the experimental FC results had good agreement with a computational finite element model of the same FC setup and PU foam materials.

Conclusions

This new FC method for unconstrained load-induced subsidence testing demonstrates potential improvements in consideration for rotational implant subsidence and the associated clinical burden in spinal surgery.

脊柱手术中使用的椎体间融合装置（“椎体间固定器”）容易轴向和/或旋转沉降到下面的椎骨。用于检查植入物下沉的实验测试标准，如ASTM F2267，简化了植入物加载条件和椎体骨材料，便于使用和可重复性。然而，用这些方法评估旋转沉陷的临床相关风险的能力是有限的。方法本工作旨在开发和评估一种新的力控制（FC）测试方法，用于在非均质材料界面中进行无约束载荷诱导的植入物沉降。将开发的方法与ASTM F2267方法进行了比较，该方法使用润滑球窝关节，使用AMTI VIVO关节运动模拟器施加高达4 kN的无约束载荷。研究人员将两种不同密度的聚氨酯（PU）泡沫（刚性20pcf和30pcf）夹在一起进行沉降测试，以形成非均质边界界面，诱导植入物旋转进入密度较低的泡沫中。结果两种试验方法的轴向和旋转沉降值差异显著（p < 0.05）。在高达4kn的无约束轴向压缩条件下，astm装置的轴向沉降平均为2.5±0.4 mm，而FC装置的轴向沉降平均为4.8±0.6 mm。基于astm的装置平均种植体旋转2.8°±0.5°，而FC装置平均为18.0°±0.9°。此外，实验结果与相同FC设置和PU泡沫材料的计算有限元模型吻合较好。结论：这种用于无约束载荷诱导沉降试验的新型FC方法在考虑脊柱手术中旋转植入物沉降和相关临床负担方面具有潜在的改进潜力。

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引用次数: 0

Effect of Vertebral Body Tether Tensioning on Vertebral Body Growth Modulation 椎体系索张紧对椎体生长调节的影响

IF 3.4 3区医学 Q1 ORTHOPEDICS

JOR Spine

Pub Date : 2025-07-24 DOI: 10.1002/jsp2.70098

Taylor J. Jackson, Craig Louer, Ron El-Hawary, Jennifer Hurry, Hui Nian, Christine Farnsworth, Carrie E. Bartley, Tracey P. Bryan, Michael P. Kelly, Peter O. Newton, Stefan Parent, Pediatric Spine Study Group, Vidyadhar V. Upasani

Background

The relationship between tether tension and spinal growth modulation following vertebral body tethering (VBT) has not been studied in growing children.

Aims

This study aims to explore the relationship between vertebral body growth modulation under varying tether tension.

Materials and Methods

A retrospective, multicenter pediatric registry was queried for idiopathic scoliosis patients treated with right-sided VBT, with recorded intraoperative tension (using an ordinal scale of 0–3), and 3D reconstructions from biplanar radiographs at the first erect (FE) and 2-year post-operative visits. Custom MATLAB code was used to calculate vertebral height (mm) on the untethered and tethered sides from T5-T12. Generalized linear mixed models were used to analyze the effect of tension on vertebral body growth.

Results

Fifty-two subjects (47 female) were included with a mean age of 12.5 ± 1 years. Patients were skeletally immature (triradiate cartilage open in 23 patients) with Proximal Femoral Maturity Index scores of 2 (nine patients), 3 (21 patients), 4 (20 patients), and 5 (two patients). A total of 330 vertebral bodies were analyzed. Mean height change of the vertebral bodies from FE to 2 years was 1.6 + 1.9 mm (untethered) and 1.2 + 1.8 mm (tethered). On the tethered side, greater tension resulted in less height change, with the greatest differential growth observed between maximal tension and no tension (0.8 mm vs. 0.2 mm, p = 0.02). Greater tension resulted in less vertebral body growth and greater differential growth. Future studies should quantify forces applied during VBT surgery, as well as the forces maintained in the post-operative period with spinal motion.

Conclusion

Intraoperative intervertebral tensioning significantly affects vertebral body growth over 2 years.

背景：尚未对正在发育的儿童进行椎体系留术（VBT）后系留张力与脊柱生长调节之间的关系进行研究。目的探讨不同系索张力下椎体生长调节的关系。材料和方法回顾性的、多中心的儿童登记查询了接受右侧VBT治疗的特发性脊柱侧凸患者，记录了术中张力（使用0-3的顺序量表）、首次勃起（FE）时双平面x线片的3D重建和术后2年的随访。使用自定义MATLAB代码从T5-T12计算未系缚侧和系缚侧的椎体高度（mm）。采用广义线性混合模型分析张力对椎体生长的影响。结果纳入52例患者，其中女性47例，平均年龄12.5±1岁。患者骨骼未成熟（23例患者为三放射软骨开放），股骨近端成熟度指数评分分别为2（9例）、3（21例）、4（20例）和5（2例）。共分析了330个椎体。从FE到2年，椎体平均高度变化为1.6 + 1.9 mm（未系留）和1.2 + 1.8 mm（系留）。在系绳一侧，较大的张力导致高度变化较小，最大张力和无张力之间的差异最大（0.8 mm vs. 0.2 mm, p = 0.02）。较大的张力导致椎体生长减少和差异生长增加。未来的研究应该量化VBT手术期间施加的力，以及术后脊柱运动期间保持的力。结论术中椎间张紧对2年内椎体生长有显著影响。

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引用次数: 0

Short-Term Dynamic Unloading of Bovine Tail Discs in Culture Partially Mitigates Induced Degeneration After One-Strike Trigger 短期动态卸载培养牛尾盘部分减轻一击触发后诱导的退变

IF 3.4 3区医学 Q1 ORTHOPEDICS

JOR Spine

Pub Date : 2025-07-16 DOI: 10.1002/jsp2.70092

Astrid Soubrier, Hermann Kasper, Nadja Vonlanthen, Ilse Jonkers, Sibylle Grad

Introduction

Intervertebral disc (IVD) degeneration is driven by a vicious circle of interrelated biological and biomechanical factors. Dynamic unloading, defined as dynamic partial decompression, promotes water and metabolite flow, which is essential for IVD homeostasis. However, the mechanobiological effects of unloading remain poorly understood. IVD organ cultures offer a valuable model for studying IVD degeneration and regeneration at the molecular level. This study investigated the biological and biomechanical effects of induced degeneration and the subsequent short-term dynamic unloading of bovine tail IVDs in a bioreactor culture system.

Methods

We applied a one-strike degenerative trigger on Day 0 and assessed its immediate effects after 1 day of culture under bioreactor loading (Timepoint 1). The impact of dynamic unloading for three additional days (Timepoint 2) was evaluated in comparison to continued loading. We evaluated biological outcomes, namely cell viability, gene expression, water/sulfated glycosaminoglycan (sGAG) ratio, and sGAG release. Mechanical readouts included disc height, slope of the elastic zone, area under the curve, and neutral zone characteristics.

Results

On Timepoint 1, we demonstrated degeneration in the nucleus pulposus with altered viability, increased inflammatory and catabolic gene expression, elevated sGAG release, a decreased slope of the elastic zone, and an increased area under the curve. On Timepoint 2, we noticed a sustained degenerative cascade in both degeneration groups. However, unloading showed a trend towards partial mitigation of the induced degeneration with decreased iNOS and TRPV4 expression, an increased water/sGAG ratio, reduced sGAG release, and recovery of the disc height.

Conclusion

This first ex vivo study on unloading mechanobiology of bovine degenerated IVDs unveils encouraging preliminary insights. The findings suggest potential benefits of unloading and, more broadly, therapeutic movement as regenerative strategies for degenerated IVDs. These results underscore the need for further studies and encourage research combining mechanical and biological approaches in organ culture models.

椎间盘（IVD）退变是由相互关联的生物学和生物力学因素的恶性循环驱动的。动态卸载，定义为动态部分减压，促进水和代谢物流动，这是IVD稳态所必需的。然而，卸载的机械生物学效应仍然知之甚少。IVD器官培养为在分子水平上研究IVD变性和再生提供了一个有价值的模型。本研究在生物反应器培养系统中研究了牛尾ivd诱导变性和随后的短期动态卸载的生物学和生物力学效应。方法我们在第0天使用一击退行性触发，并在生物反应器加载培养1天后（时间点1）评估其即时效果。与持续加载相比，对另外三天（时间点2）动态卸载的影响进行了评估。我们评估了生物学结果，即细胞活力、基因表达、水/硫酸糖胺聚糖（sGAG）比率和sGAG释放。机械读数包括阀瓣高度、弹性区斜率、曲线下面积和中性区特征。结果在时间点1，我们发现髓核变性，活力改变，炎症和分解代谢基因表达增加，sGAG释放增加，弹性区斜率减小，曲线下面积增加。在时间点2，我们注意到两个退化组中持续的退化级联。然而，卸载显示出部分缓解诱导退变的趋势，iNOS和TRPV4表达降低，水/sGAG比增加，sGAG释放减少，椎间盘高度恢复。结论本研究首次对牛退化IVDs的卸载力学生物学进行了体外研究，揭示了令人鼓舞的初步见解。研究结果表明，卸载和更广泛地说，治疗运动作为退化ivd的再生策略有潜在的好处。这些结果强调了进一步研究的必要性，并鼓励在器官培养模型中结合机械和生物学方法的研究。

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引用次数: 0

Impact of Habitual Flexion on Bone Formation After Spinal Fusion Surgery: An In Silico Study 习惯性屈曲对脊柱融合术后骨形成的影响：一项计算机研究

IF 3.4 3区医学 Q1 ORTHOPEDICS

JOR Spine

Pub Date : 2025-07-14 DOI: 10.1002/jsp2.70075

Siddarth Ananth Swaminathan, Nima Taheri, Luis Becker, Matthias Pumberger, Hendrik Schmidt, Sara Checa

Background

Lumbar spinal fusion is currently regarded as one of the most effective surgical treatments for patients with spinal deformities, degenerative disc disease, and degenerative spondylolisthesis. However, the procedure still faces a high incidence of non-unions. A key factor contributing to non-union is stress shielding effects related to unfavorable mechanical signals at the fusion site. Mechanical conditions at the fusion site are determined by the loading conditions that result from daily activities. Recent studies have reported that humans spend most of the day with their spine in a flexed position. The role of flexion loading in the progression of bone fusion remains poorly understood. This study explores the influence of habitual flexion loading on the spinal fusion process using a computational modeling framework that integrates finite element analysis with bone healing algorithms to simulate bone regeneration following fusion surgery.

Methods

A finite element model of the lumbar spine based on a healthy subject was developed and validated with in vitro experimental data. Thereafter, a virtual posterior lumbar interbody fusion was performed where 2 intervertebral cages were inserted at the L4-L5 level together with posterior fixation. The influence of two loading conditions on the predicted fusion process were investigated: (1) A compression load (2) A hybrid (compression + flexion) loading protocol simulating habitual flexion encountered during daily living.

Results

Bone bridging was predicted to occur 14 weeks after surgery. At week 14, for the hybrid loading, the model predicted a bone volume of 70%, whereas for compression load, the bone volume prediction was 59%. Computer model predictions showed that habitual flexion loading can promote bone formation in the anterior and peripheral regions by inducing a mechanical environment favorable for bone formation.

Conclusion

Flexion loading may enhance bone healing by promoting mechanically advantageous conditions. The computational framework could guide the development of optimized rehabilitation protocols to improve fusion outcomes.

背景腰椎融合术目前被认为是治疗脊柱畸形、退行性椎间盘疾病和退行性椎体滑脱最有效的手术方法之一。然而，该手术仍然面临着高发生率的不愈合。导致骨不愈合的一个关键因素是应力屏蔽效应，这与融合部位的不利机械信号有关。核聚变现场的机械条件是由日常活动产生的负荷条件决定的。最近的研究表明，人类一天中的大部分时间都处于脊椎弯曲的状态。屈曲载荷在骨融合进展中的作用仍然知之甚少。本研究探讨了习惯性屈曲载荷对脊柱融合过程的影响，使用了一个将有限元分析与骨愈合算法相结合的计算建模框架来模拟融合手术后的骨再生。方法建立健康人腰椎有限元模型，并用体外实验数据进行验证。之后，进行虚拟后路腰椎椎体间融合术，在L4-L5水平插入2个椎间笼并进行后路固定。研究了两种加载条件对预测融合过程的影响：(1)压缩加载；(2)模拟日常生活中遇到的习惯性屈曲的混合（压缩+屈曲）加载方案。结果术后14周可出现骨桥。在第14周，对于混合载荷，模型预测骨体积为70%，而对于压缩载荷，骨体积预测为59%。计算机模型预测表明，习惯性屈曲载荷可以通过诱导有利于骨形成的机械环境来促进前区和外周区的骨形成。结论屈曲载荷可通过促进有利的机械条件来促进骨愈合。计算框架可以指导优化康复方案的发展，以改善融合结果。

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引用次数: 0

Demographic and Biomedical Characteristics of an Observational Cohort With Chronic Low Back Pain: A Descriptive Analysis 慢性腰痛观察队列的人口统计学和生物医学特征：描述性分析

IF 3.4 3区医学 Q1 ORTHOPEDICS

JOR Spine

Pub Date : 2025-07-14 DOI: 10.1002/jsp2.70094

Sara R. Piva, Clair Smith, William Anderst, Kevin M. Bell, Jessa Darwin, Anthony Delitto, Corey Flynn, Carol M. Greco, Gina P. McKernan, Michael J. Schneider, Gwendolyn A. Sowa, Meenakshi Sundaram, Nam V. Vo, Leming Zhou, Charity G. Patterson

Background

The chronic low back pain (cLBP) literature rarely includes comprehensive characterization of demographic and biomedical factors in a large sample of individuals. The University of Pittsburgh Mechanistic Research Center, entitled, “Low Back Pain: Biological, Biomechanical, Behavioral Phenotypes (LB³P),” is part of the National Institutes of Health's Helping to End Addiction Long-term Initiative. The LB³P conducted a prospective, observational cohort study to identify phenotypes of people with cLBP. Here, we report demographic and biomedical characteristics of a large cohort of individuals with cLBP, stratified by sex and age, collected at the in-person enrollment visit.

Methods

The key eligibility criteria were adults with cLBP, English speakers, and identified in the electronic health record of our medical center. Recruitment strategies were through clinical partners who invited their patients to join the study and research registries. Participants completed demographic and biomedical surveys. Descriptive statistics were computed for the sample overall, and for the subgroups (male/female and age < 60/≥ 60).

Results

N = 1007 individuals (60% female) were enrolled, with an average age of 59 ± 17 years. Most participants were non-Hispanic (90%), White (75%), and 53% attained college or higher education. 54% were married or had a partner, 43% were employed, 38% retired, 41% had an annual household income < $50 000, 20% had been off work for more than 30 days due to low back pain (LBP), 16% had applied for or received disability, and 6% were on worker's compensation. The majority were obese (average BMI of 31.5 kg/m²), 61% had back pain for > 5 years, and pain had been ongoing every or nearly every day in 76% of the sample. The participants reported a high prevalence of osteoarthritis (58%), anxiety (40%), depression (40%), vision impairment (35%), and balance problems/falls (31%). Among the chronic overlapping pain conditions, the most common were migraine or headache (29%), irritable bowel syndrome (16%), and temporomandibular joint dysfunction (12%). Previous low back surgery was reported by 25%. The most frequently reported LBP treatments during the previous month were exercise routine done on their own (58%), physical therapy, occupational therapy, or chiropractic care (33%), mindfulness, meditation, or relaxation (22%), and diet or nutrition counseling (21%). Medication intake during the last month was 43% for nonsteroidal anti-inflammatory drugs, 18% for gabapentin, 13% for opioid, a

背景：关于慢性腰痛（cLBP）的文献很少包括对大样本个体的人口统计学和生物医学因素的全面描述。匹兹堡大学机械研究中心，题为“腰痛：生物学，生物力学，行为表型（LB3P）”，是美国国立卫生研究院帮助结束成瘾长期倡议的一部分。LB3P进行了一项前瞻性、观察性队列研究，以确定cLBP患者的表型。在这里，我们报告了一大批cLBP患者的人口统计学和生物医学特征，按性别和年龄分层，收集于现场登记访问中。方法主要入选标准为患有cLBP的成年人，英语使用者，并在本医疗中心的电子健康记录中确认。招募策略是通过临床合作伙伴邀请他们的患者加入研究和研究登记。参与者完成了人口和生物医学调查。对总体样本和亚组（男性/女性和年龄60岁/≥60岁）进行描述性统计。结果入组1007例，女性60%，平均年龄59±17岁。大多数参与者是非西班牙裔（90%），白人（75%），53%接受过大学或高等教育。54%的人已婚或有伴侣，43%的人有工作，38%的人退休，41%的人家庭年收入超过5万美元，20%的人因为腰痛（LBP）而离开工作超过30天，16%的人申请或接受残疾，6%的人领取工人补偿。大多数人肥胖（平均BMI为31.5 kg/m2）， 61%的人背痛5年，76%的人每天或几乎每天都有疼痛。参与者报告了高患病率的骨关节炎（58%）、焦虑（40%）、抑郁（40%）、视力障碍（35%）和平衡问题/跌倒（31%）。在慢性重叠疼痛疾病中，最常见的是偏头痛或头痛（29%），肠易激综合征（16%）和颞下颌关节功能障碍（12%）。有25%的患者曾做过腰背部手术。在前一个月，最常见的LBP治疗方法是自己进行常规运动（58%），物理治疗，职业治疗或脊椎按摩护理（33%），正念，冥想或放松（22%），饮食或营养咨询（21%）。上个月服用非甾体类抗炎药占43%，加巴喷丁占18%，阿片类药物占13%，抗抑郁药占10%。根据性别和年龄对cLBP患者进行全面的人口学和生物医学特征的描述，将为临床医生和研究计划提供参考，特别是在cLBP的合并症和治疗利用方面。这些数据将有助于未来对cLBP进行全面表型分析。

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引用次数: 0

Chondrodystrophic Dogs as a Preclinical Large Animal Model of Discogenic Back Pain 软骨营养不良犬作为椎间盘源性背痛的临床前大型动物模型

IF 3.4 3区医学 Q1 ORTHOPEDICS

JOR Spine

Pub Date : 2025-07-14 DOI: 10.1002/jsp2.70082

Mary K. Heimann, Shirley N. Tang, Gilian Gunsch, Kyle Kuchynsky, Brett Klamer, Fangli Zhao, Megan Co, Maciej Pietrzak, Justin Richards, Jake Klausner, Adam Smith, Kaitlyn Cimney, Sara McBride-Gagyi, Brad Youngblood, Kara Corps, Candice Askwith, Benjamin A. Walter, Sarah A. Moore, Devina Purmessur

<div> <section> <h3> Background</h3> <p>Intervertebral disc (IVD) degeneration is a major cause of low back pain (LBP) in humans and canines. IVD degeneration affects the structure and function of both the disc and the innervating dorsal root ganglion (DRG) neurons. Preclinical animal models are necessary for elucidating the mechanisms of IVD degeneration (IVDD) and the pain signaling pathways involved in discogenic back pain. The chondrodystrophic (CD) dog exhibits similar characteristics to the clinical population affected by IVDD-associated LBP. However, further investigation of the translational tools to study these conditions and the efficacy of novel treatments is needed in this canine model. The objectives of the present study are to: (1) assess the changes in the structure and function of the IVD and DRG, including pain behaviors, in response to injury using a comprehensive set of outcome measures and (2) evaluate the efficacy of potential therapeutics in mitigating these pathologic changes due to injury in the CD canine model.</p> </section> <section> <h3> Methods</h3> <p>Retired female research beagles underwent spinal surgery where T11/T12, T12/T13, and T13/L1 IVDs were identified and punctured with a needle containing either a protease-activated receptor 2 antagonist (PAR2A) and cromolyn sodium (CS) solution (<i>N</i> = 3) or phosphate-buffered saline (PBS) (<i>N</i> = 3). Pain phenotyping and related outcomes were assessed longitudinally or at the 12-week endpoint via RNA-seq on the DRG, von Frey analysis, FitBark activity, and C-reactive protein plasma levels. Changes in the structure/function of the IVD were assessed via MRI, mechanics, dimethylmethylene blue assay (DMMB), histological staining using picrosirius red/alcian blue (PR/AB) and fluoroscopy, and electrophysiology on the DRG neurons.</p> </section> <section> <h3> Results</h3> <p>We evaluated a comprehensive series of outcome measures to determine the effects of IVD injury on the structure/function of the canine IVD and DRG, and pain in the in vivo CD dog model of IVDD and back pain. Specifically, we established methods to obtain high-quality messenger RNA from canine DRGs to perform bulk RNA-seq. We demonstrated that injury to the disc resulted in significant upregulation of inflammatory and pain-signaling genes, and downregulation of developmental genes in the adjacent innervating DRG neurons. Additionally, we isolated and cultured viable neurons from canine DRGs and found through whole-cell patch-clamp that DRGs innervating the injured disc demonstrated altered voltage-gated sodium channel activity compared to controls. Using T2-weighted MRI, we demonstrated that relaxati

背景：椎间盘（IVD）退变是人类和犬腰痛（LBP）的主要原因。IVD变性影响椎间盘和支配背根神经节（DRG）神经元的结构和功能。临床前动物模型对于阐明椎间盘源性腰痛的机制和疼痛信号通路是必要的。软骨营养不良（CD）犬表现出与临床人群相似的特征，受ivdd相关的LBP影响。然而，在这种犬模型中，需要进一步研究翻译工具来研究这些条件和新治疗的疗效。本研究的目的是：(1)使用一套全面的结果测量方法评估损伤后IVD和DRG结构和功能的变化，包括疼痛行为；(2)评估潜在治疗方法在减轻CD犬模型损伤引起的这些病理变化方面的疗效。方法对接受脊柱手术的退休雌性研究小猎犬进行T11/T12、T12/T13和T13/L1 ivd鉴定，并用含有蛋白酶激活受体2拮抗剂（PAR2A）和色钼酸钠（CS）溶液（N = 3）或磷酸盐缓冲盐水（PBS）（N = 3）的针穿刺。通过DRG、von Frey分析、FitBark活性和c反应蛋白血浆水平的RNA-seq，纵向或在12周终点评估疼痛表型和相关结果。通过MRI、力学、二甲基亚甲基蓝（DMMB）、小天狼星红/阿利新蓝（PR/AB）和荧光染色及DRG神经元电生理观察观察IVD结构/功能的变化。我们评估了一系列综合的结局指标，以确定IVD损伤对犬IVD和DRG结构/功能的影响，以及IVD和背部疼痛的体内CD犬模型的疼痛。具体来说，我们建立了从犬DRGs中获得高质量信使RNA的方法来进行批量RNA测序。我们证明椎间盘损伤导致炎症和疼痛信号基因的显著上调，以及邻近支配DRG神经元的发育基因的下调。此外，我们从犬DRGs中分离培养活神经元，并通过全细胞膜片钳发现，与对照组相比，支配受损椎间盘的DRGs表现出改变的电压门控钠通道活性。通过t2加权MRI，我们证明，与内控椎间盘相比，6只狗中有4只狗被刺破椎间盘的松弛时间缩短，这表明这些受伤的ivd的潜在成分发生了变化。在这个小队列中没有观察到PAR2A和CS治疗的显著效果，需要进一步研究。结论：本研究评估了一系列严格的结果指标，以确定IVD损伤对CD犬背部疼痛模型的椎间盘关节和疼痛的影响。这是首次研究椎间盘损伤对犬DRG转录组的影响以及全细胞贴片夹紧对犬DRG神经元的影响。研究结果支持CD犬作为研究IVDD和LBP的临床相关转化模型，以及评估新疗法在缓解这些疾病相关变化方面的潜在疗效。

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引用次数: 0

Mechanistic Interactions Driving Nucleus Pulposus Cell Senescence in Intervertebral Disc Degeneration: A Multi-Axial Perspective of Mechanical, Immune, and Metabolic Pathways 椎间盘退变中驱动髓核细胞衰老的机制相互作用：机械、免疫和代谢途径的多轴视角

IF 3.4 3区医学 Q1 ORTHOPEDICS

JOR Spine

Pub Date : 2025-07-02 DOI: 10.1002/jsp2.70089

Yunbo Yang, Haoming Li, Junhui Zuo, Fei Lei

Background

The senescence of nucleus pulposus cells (NPCs) at the heart of the pathogenesis of intervertebral disc degeneration (IVDD), which causes low back pain. Abnormal mechanical stress causes intracellular Ca²⁺ overload by activating the Piezo-type mechanosensitive ion channel component 1 (PIEZO1) channel.

Aims

This creates a positive feedback loop of oxidative-inflammatory damage by inducing endoplasmic reticulum stress and mitochondrial reactive oxygen species (ROS) bursts, as well as directly activating the NLRP3 inflammasome/NF-кB axis to promote the release of pro-inflammatory factors like IL-1β.

Results

Energy metabolism collapsed as a result of mechanistic cause that caused excessive activation of mitophagy via the ROS-PINK1/Parkin pathway, and SIRT1 functional suppression further compromised mitochondrial quality control. The inflammatory nucleus pulposus (NP) brought on by mechanical stimulation caused macrophages to polarize toward the M1 type, and the p38MAPK pathway was activated by the TNF-α/IL-1β released, which in turn increased senescence markers like p16/p21. Notably, ROS both triggers mitophagy and activates the p53 pathway. On the one hand, oxidative damage-induced ATM/ATR kinase activation leads to p53 phosphorylation, which triggers p21-mediated cell-cycle block. On the other hand, p53 exacerbates mitochondrial dysfunction by inhibiting SIRT1 expression, creating a triangular amplification loop of p53-ROS-mitophagy. Furthermore, p53 stimulates apoptosis by altering the Bax/Bcl-2 balance and works in concert with inflammatory substances secreted by M1-type macrophages to cause the development of senescence-associated secretory phenotype (SASP).

Conclusion

This interaction network reveals the dynamic coupling of mechano-immune-metabolic pathways in the course of IVDD, providing a theoretical basis for the development of multi-targeted intervention strategies, such as PIEZO1 inhibitors combined with M2-type macrophage polarization modulation, which are expected to delay disease progression by blocking key nodes.

髓核细胞（NPCs）的衰老是导致腰痛的椎间盘退变（IVDD）发病机制的核心。异常机械应力通过激活压电型机械敏感离子通道组分1 （PIEZO1）通道导致细胞内Ca2+过载。通过诱导内质网应激和线粒体活性氧（ROS）爆发，以及直接激活NLRP3炎性小体/NF-кB轴，促进IL-1β等促炎因子的释放，形成氧化炎症损伤的正反馈循环。结果能量代谢崩溃是通过ROS-PINK1/Parkin通路导致线粒体自噬过度激活的机制原因，SIRT1功能抑制进一步损害线粒体质量控制。机械刺激引起的炎性髓核（NP）使巨噬细胞向M1型极化，释放的TNF-α/IL-1β激活了p38MAPK通路，从而增加了p16/p21等衰老标志物。值得注意的是，ROS既触发有丝分裂又激活p53通路。一方面，氧化损伤诱导的ATM/ATR激酶激活导致p53磷酸化，从而触发p21介导的细胞周期阻滞。另一方面，p53通过抑制SIRT1表达加剧线粒体功能障碍，形成p53- ros -mitophagy的三角形扩增环。此外，p53通过改变Bax/Bcl-2平衡刺激细胞凋亡，并与m1型巨噬细胞分泌的炎症物质协同作用，导致衰老相关分泌表型（SASP）的发展。结论该相互作用网络揭示了IVDD过程中机械-免疫-代谢途径的动态耦合，为开发多靶向干预策略提供了理论基础，如PIEZO1抑制剂联合m2型巨噬细胞极化调节，有望通过阻断关键节点来延缓疾病进展。

{"title":"Mechanistic Interactions Driving Nucleus Pulposus Cell Senescence in Intervertebral Disc Degeneration: A Multi-Axial Perspective of Mechanical, Immune, and Metabolic Pathways","authors":"Yunbo Yang, Haoming Li, Junhui Zuo, Fei Lei","doi":"10.1002/jsp2.70089","DOIUrl":"https://doi.org/10.1002/jsp2.70089","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The senescence of nucleus pulposus cells (NPCs) at the heart of the pathogenesis of intervertebral disc degeneration (IVDD), which causes low back pain. Abnormal mechanical stress causes intracellular Ca<sup>2+</sup> overload by activating the Piezo-type mechanosensitive ion channel component 1 (PIEZO1) channel.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This creates a positive feedback loop of oxidative-inflammatory damage by inducing endoplasmic reticulum stress and mitochondrial reactive oxygen species (ROS) bursts, as well as directly activating the NLRP3 inflammasome/NF-кB axis to promote the release of pro-inflammatory factors like IL-1β.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Energy metabolism collapsed as a result of mechanistic cause that caused excessive activation of mitophagy via the ROS-PINK1/Parkin pathway, and SIRT1 functional suppression further compromised mitochondrial quality control. The inflammatory nucleus pulposus (NP) brought on by mechanical stimulation caused macrophages to polarize toward the M1 type, and the p38MAPK pathway was activated by the TNF-α/IL-1β released, which in turn increased senescence markers like p16/p21. Notably, ROS both triggers mitophagy and activates the p53 pathway. On the one hand, oxidative damage-induced ATM/ATR kinase activation leads to p53 phosphorylation, which triggers p21-mediated cell-cycle block. On the other hand, p53 exacerbates mitochondrial dysfunction by inhibiting SIRT1 expression, creating a triangular amplification loop of p53-ROS-mitophagy. Furthermore, p53 stimulates apoptosis by altering the Bax/Bcl-2 balance and works in concert with inflammatory substances secreted by M1-type macrophages to cause the development of senescence-associated secretory phenotype (SASP).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This interaction network reveals the dynamic coupling of mechano-immune-metabolic pathways in the course of IVDD, providing a theoretical basis for the development of multi-targeted intervention strategies, such as PIEZO1 inhibitors combined with M2-type macrophage polarization modulation, which are expected to delay disease progression by blocking key nodes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70089","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144524892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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