JOR SpinePub Date : 2026-07-08DOI: 10.1002/jsp2.70203
Siegmund Lang, Stefan Motov, Jonas Krueckel, Julian Scherer, Victor E. Staartjes, Karin Wuertz-Kozak
{"title":"Large Language Models in Preclinical Spine Research: A Scoping Review and Expert Perspective on Evidence-Aware Experimental Workflows","authors":"Siegmund Lang, Stefan Motov, Jonas Krueckel, Julian Scherer, Victor E. Staartjes, Karin Wuertz-Kozak","doi":"10.1002/jsp2.70203","DOIUrl":"10.1002/jsp2.70203","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Preclinical spine research is limited by heterogeneous experimental reporting, fragmented documentation, and barriers to reproducibility and translational alignment. Large language models (LLMs) and related artificial intelligence (AI) technologies may support semantic interpretation, structured data extraction, and reasoning over biomedical text, but their role in experimental spine science remains unclear. This focused scoping review and expert perspective mapped current AI/LLM applications in spine research, quantified the preclinical evidence gap, and identified responsible integration opportunities.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A structured search of PubMed, Embase, and Web of Science was performed for studies published from January 2020 to January 2026 evaluating LLM, AI, chatbot, or advanced natural language processing applications in spine-related contexts. The search intentionally captured both LLM-specific and broader AI/chatbot applications to map the translational landscape. For this preclinical-focused analysis, the corpus was re-examined for experimental and translational use cases, supplemented by expert synthesis of methodologically relevant adjacent biomedical literature.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of 792 records identified, 166 unique studies met inclusion criteria. Publication activity increased markedly over time. The literature was dominated by conversational assessment/patient-reported outcome measure applications (82/166; 49.4%), patient education/information quality studies (53/166; 31.9%), and other LLM/AI applications (19/166; 11.4%). Preclinical/basic science applications were rare (3/166; 1.8%) and used classical machine learning, deep learning, or broader AI frameworks rather than generative LLMs. The most credible near-term opportunities include schema-constrained data extraction, protocol completeness checking, ontology-aligned data structuring, and evidence-grounded workflow support under human supervision.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In preclinical spine research, LLMs are best positioned as human-supervised workflow instruments for structuring fragmented experimental knowledge. Spine-specific validation and robust governance are essential for responsible translational use.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"9 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13344227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148411782","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}
{"title":"Lost in Translation: Why Biologic Therapies for Intervertebral Disc Degeneration and Low Back Pain Have Not Reached the Clinic (Yet)","authors":"Luca Ambrosio, Jordy Schol, Clara Ruiz-Fernandez, Vincenzo Denaro, Gianluca Vadalà, Daisuke Sakai","doi":"10.1002/jsp2.70187","DOIUrl":"https://doi.org/10.1002/jsp2.70187","url":null,"abstract":"<p>Low back pain (LBP) is the leading cause of disability worldwide, imposing substantial social and economic burdens and affecting more than 600 million individuals globally. According to the Global Burden of Disease 2021 study [<span>1</span>], the prevalence of LBP is projected to increase by 36.4% during the next 25 years, with the most pronounced rises expected in Asia and Africa, largely driven by population growth. This anticipated surge, together with progressive population aging, will further amplify its socioeconomic impact, which is already comparable to that of cardiovascular diseases, cancer, and major mental health disorders [<span>2</span>].</p><p>Although most episodes of LBP are classified as “nonspecific”, intervertebral disc degeneration (IDD) is frequently implicated in discogenic LBP and considered a major contributing factor. In the context of IDD, the intervertebral disc (IVD) undergoes progressive cell loss and senescence, extracellular matrix (ECM) degradation with dehydration and disc height reduction, as well as pronounced neoangiogenesis and neoinnervation, immune cell infiltration, and deterioration of native biomechanical properties [<span>3</span>]. Despite these structural alterations, a substantial proportion of individuals with disc abnormalities remain asymptomatic [<span>4</span>]. While most pain flares resolve spontaneously in symptomatic cohorts, approximately 5%–10% of patients develop chronic LBP, the management of which remains challenging, as no conservative or surgical strategies directly target the underlying pathophysiological processes [<span>3</span>].</p><p>Over the past decades, several biologic therapies have been investigated in both preclinical and clinical settings, with the putative aim of regenerating the degenerative IVDs or, at minimum, inducing local reparative processes presumingly associated with alleviation of discogenic LBP. These approaches include cell-based therapies (particularly mesenchymal stromal cells [MSCs]), platelet-rich plasma (PRP), extracellular vesicles (EVs), biomaterials, growth factors, gene therapy, as well as their various combinations [<span>3, 5, 6</span>]. Although many of these strategies have demonstrated encouraging “regenerative” outcomes, translation from preclinical investigations to clinical trials has been inconsistent and limited to a small number of products. Nonetheless, despite a generally favorable safety profile, the application of these biologic therapies at the bedside has generally yielded only modest improvements in pain and function, with no consistent demonstration of structural repair on imaging [<span>7</span>]. At present, the disconnect between preclinical promise and clinical reality is tempering enthusiasm for biologics in spine care and underscores the need for a critical appraisal of the factors underlying the stalled translational pipeline.</p><p>Rather than revisiting the current literature on biologics (which has been extensively r","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"9 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70187","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148386446","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}
JOR SpinePub Date : 2026-06-23eCollection Date: 2026-06-01DOI: 10.1002/jsp2.70202
Richard A Lindtner, Fabian Krumm, Werner Schmoelz, Julian Benko, Andreas E Ellmerer, Johannes Dominikus Pallua, Romed Hoermann, Anna Spicher
{"title":"Impact of Screw Insertion Technique on Thoracic Pedicle Screw Anchorage: Biomechanical Comparison of the Modified Slide, Slide, Funnel, and Conventional Techniques.","authors":"Richard A Lindtner, Fabian Krumm, Werner Schmoelz, Julian Benko, Andreas E Ellmerer, Johannes Dominikus Pallua, Romed Hoermann, Anna Spicher","doi":"10.1002/jsp2.70202","DOIUrl":"10.1002/jsp2.70202","url":null,"abstract":"<p><strong>Background: </strong>Several techniques have been developed to facilitate safe and accurate thoracic pedicle screw placement. However, their impact on screw anchorage has not been systematically evaluated. This study compared thoracic pedicle screw anchorage following placement using the Modified Slide, Slide, Funnel, and Conventional techniques under cyclic loading.</p><p><strong>Study design: </strong>Cadaveric biomechanical study.</p><p><strong>Methods: </strong>Forty-five fresh-frozen human thoracic vertebrae (T4-T11) were allocated to three experimental groups (<i>n</i> = 15 each). For standardized paired comparisons, one randomly selected pedicle of each vertebra was instrumented using the Modified Slide technique, developed by the authors as a refinement of the original Slide technique, and the contralateral pedicle with one of three established techniques. Screws were subjected to cyclic craniocaudal loading until loosening or a maximum load level of 750 N.</p><p><strong>Results: </strong>Screws placed using the Modified Slide technique withstood 1.9-fold and 1.5-fold more load cycles until loosening than those placed with the Slide and Funnel techniques, respectively (both <i>p</i> < 0.001), but only 0.9-fold that of screws inserted with the Conventional technique (<i>p</i> = 0.008).</p><p><strong>Conclusions: </strong>The Modified Slide technique preserves the advantage of the Funnel and original Slide techniques by allowing direct visualization of the pedicle entry point for accurate screw placement, yet substantially enhances thoracic pedicle screw anchorage compared with those techniques. Although anchorage was lower than that of the Conventional technique, screws placed using the Modified Slide technique still withstood loads substantially exceeding those reported to occur during daily activities.</p>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"9 2","pages":"e70202"},"PeriodicalIF":3.9,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13289838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148317204","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}
{"title":"Pre-Conditioned Bone Marrow Mesenchymal Stromal Cell-Derived Secretome Exerts an Anti-Inflammatory Effect on Degenerative Nucleus Pulposus Cells In Vitro.","authors":"Veronica Tilotta, Gianluca Vadalà, Luca Ambrosio, Giuseppina Di Giacomo, Claudia Cicione, Fabrizio Russo, Rocco Papalia, Vincenzo Denaro","doi":"10.1002/jsp2.70199","DOIUrl":"10.1002/jsp2.70199","url":null,"abstract":"<p><strong>Background: </strong>Intervertebral disc degeneration (IDD) is frequently associated with chronic low back pain (LBP), which contributes significantly to disability, psychological distress, and reduced work capacity. Mesenchymal stromal cell (MSC)-based treatments may offer a promising, less invasive alternative to conventional treatments for IDD. The MSC secretome has shown regenerative potential through paracrine and anti-inflammatory mechanisms. In this study, we investigated the effects of the secretome isolated from interleukin-1β (IL-1β)-preconditioned bone marrow-derived MSCs (BM-MSCs) on human nucleus pulposus cells (hNPCs) adopting a 3D in vitro culture model.</p><p><strong>Methods: </strong>The secretome (BM-MSCsec) was collected from BM-MSCs preconditioned with 10 ng/mL IL-1β. hNPCs were isolated, expanded, encapsulated in alginate beads, and stimulated with IL-1β to mimic a pro-inflammatory environment. These cells were then treated with either standard culture media (control group), IL-1β alone, BM-MSCsec, or IL-1β + BM-MSCsec. We evaluated cell proliferation and viability via flow cytometry, nitrite and reactive oxygen species (ROS) levels using the H2DCFDA assay, glycosaminoglycan (GAG) content with the 1,9-dimethylmethylene blue assay, gene expression of extracellular matrix (ECM) components and inflammatory markers via qPCR, and cell senescence through Western blot and β-galactosidase staining.</p><p><strong>Results: </strong>IL-1β stimulation increased hNPC proliferation, nitrite release, ROS production, catabolic and inflammatory gene expression, and cell senescence. Treatment with BM-MSCsec attenuated these effects, restoring proliferation to baseline levels, significantly reducing ROS and nitrite accumulation. BM-MSCsec also upregulated anabolic genes (<i>ACAN</i>, <i>COL2A1</i>, <i>SOX9</i>, <i>TIMP-1/3</i>), enhanced GAG production, and downregulated <i>IL-1β</i>, <i>IL-6</i>, <i>IL-8</i>, <i>NOS2</i>, <i>MMP-1</i>, and <i>MMP-13</i> expression. Furthermore, senescence was markedly reduced in BM-MSCsec-treated hNPCs, with decreased β-galactosidase activity and lower p16 and p21 expression.</p><p><strong>Conclusions: </strong>Our findings support the potential of BM-MSCsec as a cell-free therapeutic strategy for IDD. The IL-1β-preconditioned secretome reduced hNPC death and senescence, mitigated inflammation and oxidative stress, and promoted ECM preservation, highlighting its potential to counteract key processes driving IDD.</p>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"9 2","pages":"e70199"},"PeriodicalIF":3.9,"publicationDate":"2026-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13282689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148295032","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}
JOR SpinePub Date : 2026-06-20eCollection Date: 2026-06-01DOI: 10.1002/jsp2.70201
Niamh Wilson, Tara Ní Néill, Jake McDonnell, Emily McDonnell, Stacey Darwish, Joseph S Butler, Conor T Buckley
{"title":"Defining the Human Nucleus Pulposus Microenvironment and Its Impact on Cell Matrix Synthesis and Metabolic Activity.","authors":"Niamh Wilson, Tara Ní Néill, Jake McDonnell, Emily McDonnell, Stacey Darwish, Joseph S Butler, Conor T Buckley","doi":"10.1002/jsp2.70201","DOIUrl":"10.1002/jsp2.70201","url":null,"abstract":"<p><strong>Introduction: </strong>Intervertebral disc (IVD) degeneration remains the leading cause of low back pain worldwide. Regenerative therapies focused on restoring extracellular matrix (ECM) composition and disc height often overlook the IVD microenvironment, which remains to be fully characterized. This study first aims to profile the microenvironment of human nucleus pulposus (NP) tissue across degeneration grades from discectomy procedures, quantifying glucose, oxygen, pH, lactate, osmolarity, and 13 cytokines (TNF, IL-1β, IL-6, MMP-3, β-NGF, BNDF, IL-10, TIMP-1, -2, -3, FGF, and ADAMTS4 and 5). Profiling within the same samples enabled correlation analysis between all parameters. Second, this study investigated how clinically relevant microenvironmental conditions influence NP cell matrix synthesis and metabolic activity.</p><p><strong>Materials and methods: </strong>Microenvironmental profiling: NP tissue was obtained via informed consent from patients undergoing discectomy. pH was measured using a fiber optic microsensor. Oxygen was quantified using Image-iT green hypoxia reagent. Glucose and lactate were quantified via colorimetric assays, and osmolarity was measured using a vapor pressure osmometer. Cytokines were analyzed by multiplex and enzyme-linked immunosorbent assay (ELISA). Cellular response: NP cells were formed into microtissues and primed with TGF-β3 for 7 days, followed by 14 days of clinically relevant microenvironmental insult with different combinations of glucose and pH or cytokine exposure and pH. Cell viability, DNA, GAG, collagen, and metabolic rates were assessed.</p><p><strong>Results and discussion: </strong>Across a broad donor cohort, microenvironmental parameters, cytokine concentrations, and ECM were maintained with increasing degeneration grades, despite notable donor variability. NP microtissues demonstrated resilience across clinically relevant ranges of glucose, pH, and cytokine exposure. This study establishes experimentally defined microenvironmental ranges that are representative of the human NP microenvironment and supported by donor-specific in silico modeling. It further demonstrates that human NP cells within a native matrix are not highly sensitive to clinically relevant changes in microenvironmental conditions, an important consideration for cell-based regenerative strategies.</p>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"9 2","pages":"e70201"},"PeriodicalIF":3.9,"publicationDate":"2026-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13282693/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148294981","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}
{"title":"Explainable Supervised Learning Classification Model Using Diffusion Tensor Imaging Predicts Postoperative Outcomes in Cervical Spondylotic Myelopathy: A Preliminary Study.","authors":"Yifei Peng, Zixuan Zhang, Zhikun Zhang, Kaiyi Shi, Ruoyu Wang, Yue Liu, Li Zhang","doi":"10.1002/jsp2.70197","DOIUrl":"10.1002/jsp2.70197","url":null,"abstract":"<p><strong>Background: </strong>Cervical spondylotic myelopathy (CSM) is common in older adults. Some patients may experience incomplete neurological recovery after surgery, or even deterioration. Accurate prognosis is essential for patients, yet current tools use subjective scores and fail to detect early spinal cord microstructural changes.</p><p><strong>Methods: </strong>CSM patients undergoing preoperative cervical MRI and diffusion tensor imaging (DTI) scans between 2024 and 2025 at a single center were included in this retrospective study. Data were retrieved from medical records, and the determination of whether patients achieved minimal clinically important difference (MCID) was based on the change in modified Japanese Orthopaedic Association (mJOA) scores. Three supervised learning classification models, namely extreme gradient boosting (XGB), logistic regression (LR), and support vector machine (SVM), were constructed based on DTI and clinical risk factors. The performance of these models was evaluated using the area under the receiver operating characteristic curve (AUC) and precision-recall curve (AP), and decision curve analysis (DCA). The contribution of each feature to model prediction was visualized by SHapley Additive exPlanations (SHAP).</p><p><strong>Results: </strong>The training set included 163 patients (mean age: 54.43 ± 10.27 years; 57 males), whereas the testing set included 71 patients (mean age: 54.86 ± 12.25 years; 23 males). The AUCs for XGB, LR, and SVM models in the training set were 0.940, 0.791, and 0.908 respectively (<i>p</i> < 0.05). The XGB model showed the best performance in the training set (AUC = 0.940, AP = 0.948), and the results in the testing set demonstrated moderate discriminative ability with good precision (AUC = 0.754; 95% CI, 0.643-0.857, AP = 0.851; 95% CI, 0.742-0.937). DCA showed that the clinical utility of the XGB model was relatively high.</p><p><strong>Conclusion: </strong>An explainable XGB model based on DTI and clinical risk factors provides a foundation for preoperative risk stratification of MCID achievement in postoperative CSM.</p>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"9 2","pages":"e70197"},"PeriodicalIF":3.9,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13250838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148225484","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}
JOR SpinePub Date : 2026-06-08eCollection Date: 2026-06-01DOI: 10.1002/jsp2.70184
Adriana Brenzikofer, Maria Monzon, Fabio Galbusera, Zina-Mary Manjaly, Andrea Cina, Catherine R Jutzeler
{"title":"Uncertainty Quantification of Central Canal Stenosis Deep Learning Classifier From Lumbar Sagittal T2-Weighted MRI.","authors":"Adriana Brenzikofer, Maria Monzon, Fabio Galbusera, Zina-Mary Manjaly, Andrea Cina, Catherine R Jutzeler","doi":"10.1002/jsp2.70184","DOIUrl":"10.1002/jsp2.70184","url":null,"abstract":"<p><strong>Background: </strong>Accurate assessment of the severity of central canal stenosis (CCS) on lumbar spine MRI is critical for clinical decision-making. We evaluated deep learning models for automated CCS grading on sagittal T2-weighted MRI, focusing on uncertainty quantification to improve clinical reliability.</p><p><strong>Methods: </strong>Using a retrospective cohort from the LumbarDISC dataset (1974 patients), we compared multiple deep learning architectures for three-level CCS classification (normal/mild, moderate, severe). To assess model confidence, Monte Carlo (MC) dropout and Test Time Augmentation (TTA) techniques were applied to quantify prediction uncertainty.</p><p><strong>Results: </strong>The fine-tuned Spine Grading Network (SGN) achieved a balanced accuracy of 79.4% and a macro F1 score of 68.8%, with per-class accuracies of 71.3% for moderate and 78.5% for severe stenosis. MC dropout revealed an increase in uncertainty predominantly in moderate and severe cases, while TTA uncertainty was higher for mild stenosis.</p><p><strong>Conclusion: </strong>DL-based CCS grading demonstrates potential to assist radiologists by providing rapid, standardized evaluations. Incorporating uncertainty quantification offers a safeguard to flag ambiguous cases, thus supporting clinical trust and facilitating safer integration of AI tools into the interpretation of spine MRI.</p>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"9 2","pages":"e70184"},"PeriodicalIF":3.9,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13246319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148217793","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}
JOR SpinePub Date : 2026-06-08DOI: 10.1002/jsp2.70188
Virginie Kreutzinger, Katharina Ziegeler, Misung Han, Cynthia T. Chin, Rupsa Bhattacharjee, Isabelle Remick, Emma Bahroos, Sharmila Majumdar
{"title":"Quantitative Disk and Metabolic Bone PET-MRI for Understanding Disk-Endplate Crosstalk in Degeneration of the Lumbar Spine","authors":"Virginie Kreutzinger, Katharina Ziegeler, Misung Han, Cynthia T. Chin, Rupsa Bhattacharjee, Isabelle Remick, Emma Bahroos, Sharmila Majumdar","doi":"10.1002/jsp2.70188","DOIUrl":"10.1002/jsp2.70188","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>The aim of this investigation was to explore the association between disk degeneration, quantified by Pfirrmann grades and T1rho as a marker of hydration, and bone remodeling in the vertebral endplate quantified by Na[<sup>18</sup>F]F uptake on PET.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Subjects for this exploratory, post hoc analysis were selected from a prospective observational study on low back pain. Subjects received simultaneous Na[<sup>18</sup>F]F-PET and spinal MRI (including T1rho mapping) in a hybrid scanner system. Tracer uptake (SUV<sub>max</sub>) was quantified per endplate, and quantitative disk metrics were measured for annulus fibrosus and nucleus pulposus separately. Disk degeneration (Pfirrman grade) and endplate lesions (Modic changes) were assessed by a radiologist. Linear mixed models were used to investigate the association between quantitative disk and metabolic endplate metrics, adjusting for age, sex, body mass index, as well as Pfirrmann grade and Modic changes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Eighty-six endplates from 9 patients (6 women) with median age 58 years (IQR: 53–72) were included. We found a positive association between annular T1rho and endplate Na[<sup>18</sup>F]F uptake (<i>β</i> = 0.088; 95% CI 0.018–0.159). The association was amplified by the presence of Modic changes (interaction <i>p</i> = 0.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings indicate that bone remodeling of vertebral endplates is not associated with disk dehydration, and thus more likely a result of biological disk-endplate crosstalk than a sign of increased mechanical load.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"9 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13244074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148211372","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}
JOR SpinePub Date : 2026-06-07DOI: 10.1002/jsp2.70189
Mary H. Foltz, Alexandra Seidenstein, Wesley M. Durand, Amit Jain, Jill M. Middendorf
{"title":"Application of Statistical Shape Models to Standard Lumbar MRI for Stenosis Treatment Stratification: Severe Versus Normal Stenosis","authors":"Mary H. Foltz, Alexandra Seidenstein, Wesley M. Durand, Amit Jain, Jill M. Middendorf","doi":"10.1002/jsp2.70189","DOIUrl":"10.1002/jsp2.70189","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Lumbar spinal stenosis is a prevalent and debilitating diagnosis, which in severe cases requires surgical treatment to relieve nerve root pressure. Often, treatment plans are based in part on subjective, qualitative, and limited MRI assessment. Statistical shape models (SSMs) have the potential to improve treatment indications by uncovering morphological features that work synergistically but are difficult to assess independently or directly quantify. This study examined whether 2D SSM using standard clinically relevant MRIs can differentiate between severe and normal stenosis patients in a population with low back pain.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 62 patients were analyzed from an open-access Lumbar Spine MRI dataset, with variable parameters, and classified as severe or normal stenosis (at L45). Intervertebral disc (IVD) and posterior element (PE) edges were extracted using the SegNet algorithm, then aligned via generalized Procrustes analysis. Aligned shapes were used for principal component analysis and principal components (PCs) were evaluated for IVD and PE independently and together. To observe if SSMs improved from anatomical measurements, facet angles, spinous process length, IVD, and thecal sac diameters were manually extracted. ANOVA and ROC analysis was run to determine the measurements' ability to discriminate between groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>PC1 explained 38% and 32% of the IVD and combined (IVD & PE) shape variances and had a clear difference between the severe and normal stenosis groups (<i>p</i> < 0.01) with moderate to strong discriminatory power (AUC = 0.89, 0.83). In comparison to anatomical measurements, the combined SSM's ability to distinguish between groups was comparable to the thecal sac diameter (AUC = 0.84) and exceeded all other traditional anatomical measures.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>SSMs were able to distinguish between the severe and normal stenosis groups, specifically PC1 for both IVD and combined SSMs. Hence, this study demonstrates that SSMs could be a quantitative tool to improve stenosis diagnosis and treatment planning using clinical 2D MRIs.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"9 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13243780/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148211317","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}
JOR SpinePub Date : 2026-06-05DOI: 10.1002/jsp2.70198
Tara Ní Néill, Niamh Wilson, Jake McDonnell, Fergal J. O'Brien, Caroline M. Curtin, James E. Dixon, Pieter A. J. Brama, Conor T. Buckley
{"title":"Comparative Analysis of Dual-miRNA Mediated Stimulation of Nucleus Pulposus and Bone Marrow Derived Stem Cells for Intervertebral Disc Repair","authors":"Tara Ní Néill, Niamh Wilson, Jake McDonnell, Fergal J. O'Brien, Caroline M. Curtin, James E. Dixon, Pieter A. J. Brama, Conor T. Buckley","doi":"10.1002/jsp2.70198","DOIUrl":"https://doi.org/10.1002/jsp2.70198","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Intervertebral disc (IVD) degeneration is the primary cause of low back pain (LBP). Disease progression is characterized by a shift in extracellular matrix homeostasis towards degradation over regeneration, a process that is a key target of emerging therapeutic strategies. Our laboratory has previously identified the dual delivery of FLR-miRNA-149-5p mimic and 221-3p inhibitor as being beneficial in generating an anti-catabolic regenerative niche. Cell therapies have likewise demonstrated potential, though the most suitable cell source has been debated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>In this study, we explored the stimulation of nucleus pulposus and bone marrow derived stem cells with our therapeutic miRNA pair, with the aim of identifying the most suitable cell population for delivery to the IVD. Culture systems of increasing complexity ranging from monolayer to ex vivo organ culture were employed using caprine cells and IVD organs due to their physiological relevance to humans.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We demonstrated the maintenance of our previously reported anti-catabolic niche, with significant downregulation of matrix degrading factors, ADAMTS5 and MMP13 and pro-inflammatory cytokines, TNF and IL-1β. Furthermore, delivery of dual-miRNA stimulated nucleus pulposus cells in an organ culture model of mild IVD degeneration significantly upregulated the matrix markers, SOX9 and aggrecan. However, this matrix response was not identified in dual-miRNA-bone marrow derived stem cells delivered to goat IVD organs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Taken together, these findings highlight the potential of nucleus pulposus cells as a regenerative cell source when combined with FLR-miRNA-149-5p mimic and 221-3p inhibitor for the treatment of LBP.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"9 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70198","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148174268","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}