JOR Spine最新文献

{"title":"From Concept to Clinic: Pre-Clinical Testing and Regulatory Considerations in Spine Implant Development","authors":"Amit Benady,&nbsp;Jerrin Thadathil Varghese,&nbsp;Ryan David Quarrington,&nbsp;Morsi Khashan,&nbsp;B. Gangadhara Prusty,&nbsp;Ashish Diwan","doi":"10.1002/jsp2.70176","DOIUrl":"https://doi.org/10.1002/jsp2.70176","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Spinal implant development demands integration of biomechanical rigor with regulatory compliance. For surgeons, researchers, and biomedical engineers engaged in translational research, understanding the regulatory pathway, from the <i>Design History File</i> (DHF) through post-market surveillance, is essential to smoothly transform an innovative idea into a safe and effective clinical product.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This paper reviews the major regulatory frameworks governing spinal implants, including the <i>United States Food and Drug Administration</i> (FDA) pathways such as <i>Premarket Notification</i> [510(k)] and <i>Premarket Approval</i> (PMA), as well as the <i>European Union Medical Device Regulation</i> (EU MDR) leading to <i>Conformité Européenne</i> (CE) marking. International standards such as ISO 13485 for quality systems, ISO 14971 for risk management, ISO 10993 for biocompatibility, and ASTM mechanical testing standards are discussed. Particular attention is given to how biomechanics, including <i>Finite Element Analysis</i> (FEA), bench testing, and fatigue studies, are integrated into the pre-market submission dossier.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>Key elements of the regulatory process include design controls and documentation (DHF/technical file), <i>Chemistry, Manufacturing, and Controls</i> (CMC), preclinical validation through simulation, bench, cadaver, and animal testing, regulatory submissions across FDA and EU systems, and post-market surveillance and lifecycle management. Common pitfalls involve overreliance on simulations without validation, inadequate risk management, and insufficient traceability. Emerging trends such as <i>in silico</i> trials, digital twins, and smart implants show promise, while global differences in classification, clinical requirements, and post-market expectations highlight the ongoing challenge of regulatory divergence.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Understanding the biomechanical foundations of the development process is crucial for the safe and successful translation of spine implants into clinical use. Surgeons and implant designers should engage early, understand the critical steps, and advocate for rigorous validation aligned with regulatory expectations to deliver safer and more effective implants to clinical practice.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"9 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70176","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147668589","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":"A Decade of Leadership and Impact: Celebrating 10 Years of the ORS Spine Section","authors":"Neharika Bhadouria,&nbsp;Rahul Gawri,&nbsp;Gabriela Graziani,&nbsp;Dennis E. Anderson,&nbsp;Ana V. Chee,&nbsp;Chitra L. Dahia,&nbsp;Ashish Diwan,&nbsp;Morgan B. Giers,&nbsp;Svenja Illien-Junger,&nbsp;Anthony Kirilusha,&nbsp;David J. Nuckley,&nbsp;Derek H. Rosenzweig,&nbsp;Cheryle Séguin,&nbsp;Dmitriy Sheyn,&nbsp;Graciosa Q. Teixeira,&nbsp;Mauro Alini,&nbsp;Keita Ito,&nbsp;Robert L. Mauck,&nbsp;Daisuke Sakai,&nbsp;Jeannie Bailey,&nbsp;Aaron J. Fields,&nbsp;Sibylle Grad,&nbsp;Sarah E. Gullbrand,&nbsp;Nilsson Holguin,&nbsp;Rita Kandel,&nbsp;Zhen Li,&nbsp;Joshua Li,&nbsp;John T. Martin,&nbsp;Fackson Mwale,&nbsp;Grace D. O'Connell,&nbsp;Devina Purmessur,&nbsp;Nam Vo,&nbsp;Uruj Zehra,&nbsp;Nadeen O. Chahine,&nbsp;Lisbet Haglund,&nbsp;Judith A. Hoyland,&nbsp;Christine L. Le Maitre,&nbsp;Jeffrey C. Lotz,&nbsp;Makarand V. Risbud,&nbsp;Lachlan J. Smith,&nbsp;Simon Tang,&nbsp;James C. Iatridis,&nbsp;Karin Wuertz-Kozak,&nbsp;Dino Samartzis","doi":"10.1002/jsp2.70180","DOIUrl":"10.1002/jsp2.70180","url":null,"abstract":"&lt;p&gt;As we celebrate the 10th anniversary of the Spine Section of the Orthopaedic Research Society (ORS), we reflect on a decade defined by visionary leadership, scientific excellence, and a steadfast commitment to advancing spine research. What began as a focused initiative within the ORS to unify spine investigators has grown into a vibrant, international community of scientists and clinicians at all career stages dedicated to transforming musculoskeletal health through collaboration, education, discovery, and translation. Since its inception, the ORS Spine Section has expanded not only in membership but also in scientific scope, global engagement, and leadership development. This growth is a testament to the dedication of past and present Chairs and Officers, whose selfless contributions and countless hours of service cemented the foundation on which the Section proudly stands today.&lt;/p&gt;&lt;p&gt;The first ORS Spine Research Interest Group (RIG) was organized in 2011 by its founding organizers: Fackson Mwale, Daisuke Sakai, Makarand V. Risbud, Rita Kandel, and Sibylle Grad. Their vision was to create a collaborative platform for researchers dedicated to advancing spine science within the ORS. Following the initial success of the RIG, leadership and participation steadily expanded over the subsequent years with the support and contributions of many members of the spine research community. Among those who played important roles in its early growth were James C. Iatridis, Mauro Alini, Lisbet Haglund, Christine L. Le Maitre, Nam Vo, Devina Purmessur, Judith A. Hoyland, and Jeffrey C. Lotz, along with many other dedicated researchers and ORS staff, such as Bailey McMurray and others who contributed to the development and success of the group (Figure 1).&lt;/p&gt;&lt;p&gt;The RIG played a pivotal role in building a collaborative network and achieving early scientific milestones, including a consensus article on nucleus pulposus cell phenotypic markers [&lt;span&gt;1&lt;/span&gt;], a &lt;i&gt;Journal of Orthopaedic Research&lt;/i&gt; “virtual issue” highlighting key spine publications [&lt;span&gt;2, 3&lt;/span&gt;], and a review on spinal aging [&lt;span&gt;4&lt;/span&gt;]. Building on this momentum, the Section was formally established in 2016 with James C. Iatridis serving as its first Chair (2016–2017). During this formative period, the leadership clarified the Section's mission, launched its website and newsletter, initiated webinars, introduced social events at the ORS Annual Meeting and implemented member surveys to guide priorities. These foundational efforts, anchored in collaboration, mentorship, and scientific excellence, helped establish a vibrant and inclusive spine research community. From its inception, the Section embraced broad scientific integration, bringing together expertise in intervertebral disc biology, pain, spine biomechanics, mechanobiology, tissue engineering, biomaterials, inflammation research, computational modeling, imaging sciences, and clinical translation. This interdisciplinary appr","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"9 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70180","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147668490","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":"Inhibition of PLA2G15 Alleviates Palmitic Acid-Induced Lysosomal Membrane Permeabilization in Human Nucleus Pulposus Cells During Intervertebral Disc Degeneration","authors":"Liqun Duan,&nbsp;Jiang Jiang,&nbsp;Shuangshuang Tu,&nbsp;Chuanfu Li,&nbsp;Yijun Dong,&nbsp;Yongjin Li,&nbsp;Wenzhi Zhang,&nbsp;Xi Chen","doi":"10.1002/jsp2.70178","DOIUrl":"10.1002/jsp2.70178","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Intervertebral disc degeneration (IDD) imposes substantial economic and healthcare burdens, yet its mechanisms remain incompletely understood and effective pharmacological treatments are lacking. This study aimed to elucidate key factors driving IDD progression, specifically investigating lysosomal dysfunction and lysosomal membrane permeability (LMP) in human nucleus pulposus (NP) cells, and to identify potential therapeutic targets.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We employed an integrative multiomics approach (transcriptomics, proteomics, metabonomics, and lipomics) combined with functional validation. Luciferase reporter assays investigated transcriptional regulation. The role of PLA2G15 in palmitic acid (PA)-induced lysosomal dysfunction was assessed in vitro and in vivo.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Integrated analysis identified lysosomal dysfunction and increased LMP as the key molecular features in human NP cells during IDD. PLA2G15 expression was significantly upregulated under PA overload conditions. PLA2G15-mediated PA-induced alterations in lysosomal membrane lipid composition and subsequent LMP by hydrolyzing lysosomal membrane phospholipids. The transcription factor C/EBPα directly bound the PLA2G15 promoter, regulating its transcription under PA overload conditions. Crucially, in vivo inhibition of PLA2G15 mitigated PA-induced LMP by restoring normal lysosomal membrane lipid composition, thereby attenuating IDD progression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study demonstrates that PLA2G15 inhibition mitigates PA-induced IDD progression by preventing lysosomal dysfunction and LMP. Our findings reveal the significance of lysosomal membrane lipid composition alterations in human NP cells and identify PLA2G15 as a potential therapeutic target for IDD treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"9 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70178","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147668426","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":"Patients With Chronic Low Back Pain Without Advanced Disk Degeneration Exhibit Gut Microbiome Dysbiosis: Evidence From an Age-, Sex-, and BMI-Matched Pilot Study","authors":"Stone Sima,&nbsp;Thomas Jeffries,&nbsp;Alisha Sial,&nbsp;Suhani Sharma,&nbsp;Neha Chopra,&nbsp;Fan Zhang,&nbsp;Georgina Hold,&nbsp;Wentian Li,&nbsp;Ji Tu,&nbsp;Victor Chen,&nbsp;Ashish Diwan","doi":"10.1002/jsp2.70174","DOIUrl":"10.1002/jsp2.70174","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Chronic low back pain (LBP) is the leading cause of disability worldwide, yet its underlying pathophysiology remains poorly understood. Current diagnostic techniques rely heavily on imaging, which is insufficient for identifying inflammatory or systemic contributors. Emerging evidence suggests a role for gut microbiome dysbiosis in inflammatory pain pathways, yet its specific contribution to chronic LBP remains unclear. The aim of this study is to investigate gut microbiome alterations in chronic LBP patients compared to healthy controls.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Twenty-eight patients with chronic LBP (&gt; 3 months) without advanced disk degeneration (Pfirrmann grade &lt; 4) and 28 age-, sex-, and BMI-matched healthy controls were recruited. Stool samples were analyzed using 16S rRNA V4 gut microbiome analysis. Alpha diversity and beta diversity were assessed to determine microbial diversity differences. Taxonomic composition was compared at the phylum and genus levels.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;There were no significant differences in age, sex, BMI, and race between the two groups. Patients with chronic LBP exhibited significantly reduced alpha diversity compared to controls (&lt;i&gt;U&lt;/i&gt; = 517, &lt;i&gt;p&lt;/i&gt; = 0.003, &lt;i&gt;r&lt;/i&gt; = 0.395). Beta diversity analysis demonstrated distinct clustering between groups, suggesting significant shifts in microbial composition (PERMANOVA, &lt;i&gt;p&lt;/i&gt; &lt; 0.05). At the phylum level, &lt;i&gt;Proteobacteria&lt;/i&gt; (&lt;i&gt;U&lt;/i&gt; = 91, &lt;i&gt;p&lt;/i&gt; &lt; 0.001, &lt;i&gt;r&lt;/i&gt; = 0.659) and &lt;i&gt;Desulfobacterota&lt;/i&gt; (&lt;i&gt;U&lt;/i&gt; = 73, &lt;i&gt;p&lt;/i&gt; &lt; 0.001, &lt;i&gt;r&lt;/i&gt; = 0.718) were significantly elevated in chronic LBP patients, while &lt;i&gt;Bacteroidota&lt;/i&gt; was significantly reduced (&lt;i&gt;U&lt;/i&gt; = 524, &lt;i&gt;p&lt;/i&gt; = 0.031, &lt;i&gt;r&lt;/i&gt; = 0.289). At the genus level, &lt;i&gt;Prevotella&lt;/i&gt; (&lt;i&gt;U&lt;/i&gt; = 272, &lt;i&gt;p&lt;/i&gt; = 0.045, &lt;i&gt;r&lt;/i&gt; = 0.268) and &lt;i&gt;Faecalibacterium&lt;/i&gt; (&lt;i&gt;U&lt;/i&gt; = 254, &lt;i&gt;p&lt;/i&gt; = 0.024, &lt;i&gt;r&lt;/i&gt; = 0.302) were increased in chronic LBP patients, whereas &lt;i&gt;Parabacteroides&lt;/i&gt; was depleted (&lt;i&gt;U&lt;/i&gt; = 621, &lt;i&gt;p&lt;/i&gt; &lt; 0.001, &lt;i&gt;r&lt;/i&gt; = 0.500).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusion&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;These findings indicate that gut microbiome dysbiosis may play a key role in chronic LBP among patients without identifiable surgical pathologies, likely through systemic inflammation, reinforcing the “gut–disk axis” hypothesis. Given the limitations of conventional diagnostic tools and management strategies, microbiome profiling may provide novel biomarkers for LBP and inform microbiome-targeted ","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"9 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70174","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147668877","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":"Secretome and Pathway Analysis of Stress Induced Disc Degeneration In Vitro","authors":"Exarchos Kanelis,&nbsp;Andrea Nüesch,&nbsp;Joseph Snuggs,&nbsp;Christine Lyn Le Maitre,&nbsp;Leonidas G. Alexopoulos","doi":"10.1002/jsp2.70165","DOIUrl":"10.1002/jsp2.70165","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Intervertebral disc degeneration (IDD) involves complex inflammatory and oxidative stress pathways within nucleus pulposus (NP) cells, leading to catabolic remodeling and loss of disc function. Traditional single-analyte assays capture only a small part of these coordinated networks. Leveraging the multiplex capability of Luminex, this study uses targeted immunoassays to simultaneously quantify 73 extracellular proteins and 21 intracellular signaling molecules in primary human NP cells stimulated with IL-1β, Pam2CSK4, or hydrogen peroxide, enabling comparison of shared and stimulus-specific responses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Human NP cells isolated from patients undergoing spine surgery were plated in monolayer or encapsulated in alginate and stimulated for 1 week with either: 100 pg/mL or 1 ng/mL Interleukin (IL)-1β, or the Toll-Like Receptor (TLR) 2/6 agonist Pam2CSK4 at 100 ng/mL, or 50 μM Hydrogen Peroxide (H₂O₂). The role of the stimuli was investigated using mRNA expression analysis and Luminex multiplex immunoassays.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>TLR2/6 agonist and IL-1β stimulation significantly up-regulated IL-6, IL-8, IL-1β, and MMP-3 mRNA expression, while H₂O₂ failed to induce any changes. The secretome showed that IL-8, IL-6, MMP-7, Intercellular Adhesion Molecule 1 (ICAM-1), and Growth-Regulated Oncogene-α (GRO-α) were the most responsive proteins across treatments and culture conditions. Intracellularly, phosphorylation of Jun Proto-Oncogene AP-1 Transcription Factor Subunit (cJUN), Nuclear Factor Kappa B (NF-kB), and Inhibitor of Nuclear Factor Kappa B Alpha (IKBA) was observed following IL-1β and Pam2CSK4 stimulation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Across inflammatory and innate immune activation and under both monolayer and 3D culture, a concise five-marker panel, namely IL-6, IL-8, GRO-α (CXCL-1), ICAM-1, and MMP-7 captured NP cell responses with high consistency, while phosphoproteomics demonstrated convergence on NF-κB/AP-1 signaling. These markers are well established within disc-degeneration pathways (inflammation, innate immunity, and ECM remodeling); thus, they offer practical, reusable readouts for comparative pharmacology, assay qualification, and early biomarker development in translational spine research.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"9 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70165","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147579813","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":"A Network-Based Approach to Understanding Key Signaling Pathways in Intervertebral Disc Biology","authors":"Sofia Tseranidou,&nbsp;Zerihun G. Workineh,&nbsp;Maria Segarra-Queralt,&nbsp;Francis Kiptengwer Chemorion,&nbsp;Paola Bermudez-Lekerika,&nbsp;Exarchos Kanelis,&nbsp;Katherine B. Crump,&nbsp;Benjamin Gantenbein,&nbsp;Leonidas G. Alexopoulos,&nbsp;Christine L. Le Maitre,&nbsp;Janet Piñero,&nbsp;Jérôme Noailly","doi":"10.1002/jsp2.70172","DOIUrl":"10.1002/jsp2.70172","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Intervertebral disc degeneration (IDD) reflects a poorly characterized shift from anabolic matrix renewal to catabolic breakdown. Fragmentary experimental and modeling efforts leave many signaling routes unresolved; a consolidated map is required to guide hypothesis-driven studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A literature-curated regulatory network model (RNM) for human nucleus pulposus (NP) cells was assembled from PubMed and enriched with interactions from STRING, KEGG and R&amp;D Systems. The static graph was converted to a semi-quantitative dynamical system. Simulations examined responses to interleukin-1β (IL-1β) and the Toll-like receptor (TLR) and were benchmarked against time-resolved proteomics from 2D NP monolayers and 3D alginate cultures representing healthy and degenerated discs. Single-node perturbations assessed the impact of targeted inhibition on catabolic output.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The final network contains 82 proteins and 193 directed edges; 41.4% of supporting evidence derives from NP-specific studies, the highest for any cell type. Baseline activity depicts a non-degenerate disc, with high expression of anabolic mediators and low expression of catabolic enzymes. Both IL-1β and TLR elicited strong c-Jun and p65 NF-κB activation in silico and in vitro. The model simulated IκBα depletion, whereas its increase in the experimental study shows the biological agreement among in silico and in vitro simulations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This RNM unifies scattered IDD data into a validated dynamic framework that mirrors NP signaling. The publicly available model provides a foundation for multiscale studies linking molecular events to disc mechanics and for prioritizing therapeutic interventions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"9 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70172","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147579812","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":"Viscoelastic and Morphologic Changes in the Lumbar Intervertebral Discs of the 5xFAD Mouse Model of Alzheimer's Disease","authors":"C. E. Gonzalez,&nbsp;C. A. Schurman,&nbsp;K. A. Wilson,&nbsp;B. Schilling,&nbsp;L. M. Ellerby,&nbsp;S. Y. Tang","doi":"10.1002/jsp2.70171","DOIUrl":"https://doi.org/10.1002/jsp2.70171","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Chronic low back pain, commonly associated with intervertebral disc (IVD) degeneration, is highly prevalent in patients with Alzheimer's disease (AD), and the severity of the pain is correlated with the severity of the dementia. While incidences of both afflictions increase dramatically in the elderly population, it is unknown whether AD exacerbates the health of the IVD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>The aim of this study is to examine how AD-related mutations affect the structure and mechanics of the IVD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>Utilizing one-year-old male and female 5xFAD mice that constitutively express human APP and PSEN1 transgenes with five AD-linked mutations, we measured the lumbar IVD's extracellular matrix composition, the three-dimensional structure, histopathological degeneration, and mechanical behaviour.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The amount of collagen, glycosaminoglycans, and advanced glycation end-products in the IVD did not differ in the 5xFAD animals. Likewise, the 5xFAD IVDs were not histopathologically degenerated. However, the IVD volume, measured by contrast-enhanced microCT, was larger in the 5xFAD animals (<i>p</i> = 0.046; 1–β = 0.53; Cohen's d = 1.19). Morphologically, the 5xFAD IVD heights were homogeneous and flatter than the WT IVDs (<i>p</i> = 0.043; 1–β = 0.60; Cohen's d = 1.41). Finally, dynamic micro compression revealed that 5xFAD IVDs have higher loss tangent (<i>p</i> = 0.0062; 1–β = 0.85; Cohen's d = 1.60) and greater energy dissipation (<i>p</i> = 0.0379; 1–β = 0.55; Cohen's d = 1.21).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>Shifts in viscoelastic behaviour and disc morphology are associated with early tissue degradation and affect the IVD's ability to efficiently recover from mechanical loading, predisposing the IVD to eventual degeneration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This work suggests that IVD's structure, morphology, and mechanics are affected by AD. Future work will focus on defining the molecular mechanisms of these changes in the IVD and their consequences in individuals with AD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"9 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70171","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147615376","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":"Viscoelastic and Morphologic Changes in the Lumbar Intervertebral Discs of the 5xFAD Mouse Model of Alzheimer's Disease","authors":"C. E. Gonzalez,&nbsp;C. A. Schurman,&nbsp;K. A. Wilson,&nbsp;B. Schilling,&nbsp;L. M. Ellerby,&nbsp;S. Y. Tang","doi":"10.1002/jsp2.70171","DOIUrl":"https://doi.org/10.1002/jsp2.70171","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Chronic low back pain, commonly associated with intervertebral disc (IVD) degeneration, is highly prevalent in patients with Alzheimer's disease (AD), and the severity of the pain is correlated with the severity of the dementia. While incidences of both afflictions increase dramatically in the elderly population, it is unknown whether AD exacerbates the health of the IVD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>The aim of this study is to examine how AD-related mutations affect the structure and mechanics of the IVD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>Utilizing one-year-old male and female 5xFAD mice that constitutively express human APP and PSEN1 transgenes with five AD-linked mutations, we measured the lumbar IVD's extracellular matrix composition, the three-dimensional structure, histopathological degeneration, and mechanical behaviour.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The amount of collagen, glycosaminoglycans, and advanced glycation end-products in the IVD did not differ in the 5xFAD animals. Likewise, the 5xFAD IVDs were not histopathologically degenerated. However, the IVD volume, measured by contrast-enhanced microCT, was larger in the 5xFAD animals (<i>p</i> = 0.046; 1–β = 0.53; Cohen's d = 1.19). Morphologically, the 5xFAD IVD heights were homogeneous and flatter than the WT IVDs (<i>p</i> = 0.043; 1–β = 0.60; Cohen's d = 1.41). Finally, dynamic micro compression revealed that 5xFAD IVDs have higher loss tangent (<i>p</i> = 0.0062; 1–β = 0.85; Cohen's d = 1.60) and greater energy dissipation (<i>p</i> = 0.0379; 1–β = 0.55; Cohen's d = 1.21).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>Shifts in viscoelastic behaviour and disc morphology are associated with early tissue degradation and affect the IVD's ability to efficiently recover from mechanical loading, predisposing the IVD to eventual degeneration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This work suggests that IVD's structure, morphology, and mechanics are affected by AD. Future work will focus on defining the molecular mechanisms of these changes in the IVD and their consequences in individuals with AD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"9 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70171","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147615357","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":"Feasibility of Smartphone-Derived Short-Interval Walking Tests for Monitoring Functional Recovery After Spine Surgery","authors":"J. Puhakka,&nbsp;M. Jung,&nbsp;T. Fekete,&nbsp;M. Loibl,&nbsp;F. Kleinstück,&nbsp;F. Porchet,&nbsp;M. Ropelato,&nbsp;M. Gocevic,&nbsp;F. Galbusera,&nbsp;A. Cina,&nbsp;D. O'Riordan,&nbsp;J. Kosola,&nbsp;D. Haschtmann","doi":"10.1002/jsp2.70173","DOIUrl":"https://doi.org/10.1002/jsp2.70173","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Traditional assessments of functional recovery after spine surgery rely on patient-reported outcomes, which are prone to bias. Wearables and smartphone activity tracking offer objective monitoring but may be unreliable if devices are not carried continuously. Capacity-oriented measures, such as the 1-min walk test (1MWT) and 6-min walk test (6MWT), may be more reliable. This study evaluated smartphone-derived interval metrics after lumbar spine surgery retrospectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>iPhone Health exports from 41 patients were analyzed. A sliding-window algorithm parsed daily distances to simulate 1MWT and 6MWT. Step counts and active time were extracted. Activity was compared across four intervals: 6-month baseline, final 2 weeks preoperatively, early postoperative (0–2 weeks), and late postoperative (2–6 weeks). Paired <i>t</i>-tests or Wilcoxon signed-rank tests were used, with Simes–Hochberg adjustment for multiple comparisons. Day-to-day stability was summarized by the coefficient of variation (CV). Pearson correlations were calculated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Median 1MWT fell from 98 m at baseline to 82 m in the final two preoperative weeks (<i>p</i> &lt; 0.05) and increased to 105 m by late recovery (<i>p</i> &lt; 0.05 vs. preoperative). Median 6MWT declined from 403 to 345 m preoperatively, with this decline not reaching significance (<i>p</i> = 0.07), and increased to 407 m by late recovery (<i>p</i> &lt; 0.05 vs. preoperative). Steps declined from 5030 to 3825 preoperatively (<i>p</i> &lt; 0.05) and rose to 5538 at 2–6 weeks (<i>p</i> &lt; 0.05 vs. preoperative). The 1MWT and 6MWT were strongly correlated. CV was lower for 1MWT and 6MWT than for steps.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Smartphone-derived 1MWT and 6MWT improved significantly from the immediate preoperative period to late postoperative recovery, showed lower day-to-day variability than longitudinal activity metrics, and were strongly correlated with each other. These findings support smartphone-derived interval metrics as a feasible method to monitor recovery following lumbar spine surgery.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"9 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70173","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147615181","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":"Modic Change Bone Marrow Neutrophils Are Activated and Degrade Cartilage Endplates","authors":"Irina Heggli,&nbsp;Tamara Mengis,&nbsp;Jan Devan,&nbsp;Nick Herger,&nbsp;Mazda Farshad,&nbsp;Mohamed Habib,&nbsp;Christopher P. Ames,&nbsp;Oliver Distler,&nbsp;Aaron J. Fields,&nbsp;Stefan Dudli","doi":"10.1002/jsp2.70170","DOIUrl":"https://doi.org/10.1002/jsp2.70170","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Vertebral endplate bone marrow lesions (Modic changes, MC) are linked to vertebrogenic pain and to structural defects of the bony and cartilaginous endplates (CEP). However, the immune mechanisms that may perpetuate CEP damage in MC remain unclear.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Objective&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;To (i) characterize neutrophils in MC bone marrow and (ii) test whether activated neutrophils can degrade human CEP tissue.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;In low back pain patients undergoing lumbar fusion, paired bone marrow aspirates were collected intraoperatively from an MC level and an adjacent non-MC vertebra (intra-patient control). MC neutrophils were characterized by bulk RNA sequencing of sorted CD45&lt;sup&gt;+&lt;/sup&gt;CD66b&lt;sup&gt;+&lt;/sup&gt; cells (&lt;i&gt;n&lt;/i&gt; = 7), flow cytometry (activation (CD66b); neutrophil maturation subsets), and neutrophil elastase (NE) activity in short-term culture supernatants. To model CEP degradation, conditioned media from healthy-donor blood neutrophils incubated ± neutrophil activator phorbol 12-myristate 13-acetate (PMA) (12.5 or 25 Mio cells/mL) were applied to human CEP explants (18 h). Proteoglycan loss (sGAG) and collagen loss (hydroxyproline) were quantified as release fractions, normalized to media-only controls.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;MC neutrophils showed an activated, pro-inflammatory transcriptomic signature, including enrichment of calcium-associated processes consistent with degranulation. Flow cytometry demonstrated higher CD66b intensity in MC neutrophils versus intra-patient controls (125.4 ± 34.2%, &lt;i&gt;p&lt;/i&gt; = 0.022) and a trend toward increased band neutrophils (126.7 ± 33.4%, &lt;i&gt;p&lt;/i&gt; = 0.069). NE release was higher in 4/6 patients (191.2 ± 142.7%, &lt;i&gt;p&lt;/i&gt; = 0.178) and correlated with band neutrophil abundance (&lt;i&gt;r&lt;/i&gt; = 0.67, &lt;i&gt;p&lt;/i&gt; = 0.033). PMA activation markedly increased NE activity in conditioned media and was cell-number dependent. CEP exposure to activated neutrophil conditioned media induced significant sGAG release (25 Mio/mL: 380.1 ± 177.0%, &lt;i&gt;p&lt;/i&gt; = 0.012; 12.5 Mio/mL: 123.7 ± 22.3%, &lt;i&gt;p&lt;/i&gt; = 0.048), while hydroxyproline release was not significantly increased.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Neutrophils within MC bone marrow have an activated pro-inflammatory phenotype, and activated neutrophils can degrade CEP proteoglycans ex vivo. These findings support a potential immune-mediated mechanism con","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"9 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70170","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147566975","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}