Intradiscal transplantation of mesenchymal stromal cells (MSCs) has emerged as a promising therapy for intervertebral disc degeneration (IDD). However, the hostile microenvironment of the intervertebral disc (IVD) may compromise the survival of implanted cells. Interestingly, studies reported that paracrine factors, such as extracellular vesicles (EVs) released by MSCs, may regenerate the IVD. The aim of this study was to investigate the therapeutic effects of Wharton's Jelly MSC (WJ-MSC)-derived EVs on human nucleus pulposus cells (hNPCs) using an in vitro 3D alginate-bead culture model.
Methods
After EV isolation and characterization, hNPCs isolated from surgical specimens were encapsulated in alginate beads and treated with 10, 50, and 100 μg/mL WJ-MSC-EVs. Cell proliferation and viability were assessed by flow cytometry and live/dead staining. Nitrite and glycosaminoglycan (GAG) content was evaluated through Griess and 1,9-dimethylmethylene blue assays. hNPCs in alginate beads were paraffin-embedded and stained for histological analysis (hematoxylin–eosin and Alcian blue) to assess extracellular matrix (ECM) composition. Gene expression levels of catabolic (MMP1, MMP13, ADAMTS5, IL6, NOS2), anabolic (ACAN), and hNPC marker (SOX9, KRT19) genes were analyzed through qPCR. Collagen type I and type II content was assessed with Western blot analysis.
Results
Treatment with WJ-MSC-EVs resulted in an increase in cell content and a decrease in cell death in degenerated hNPCs. Nitrite production was drastically reduced by EV treatment compared to the control. Furthermore, proteoglycan content was enhanced and confirmed by Alcian blue histological staining. EV stimulation attenuated ECM degradation and inflammation by suppressing catabolic and inflammatory gene expression levels. Additionally, NPC phenotypic marker genes were also maintained by the EV treatment.
Conclusions
WJ-MSC-derived EVs ameliorated hNPC growth and viability, and attenuated ECM degradation and oxidative stress, offering new opportunities for IVD regeneration as an attractive alternative strategy to cell therapy, which may be jeopardized by the harsh microenvironment of the IVD.
背景间充质干细胞（MSCs）的椎间盘内移植已成为治疗椎间盘退行性病变（IDD）的一种很有前景的疗法。然而，椎间盘（IVD）恶劣的微环境可能会影响植入细胞的存活。有趣的是，有研究报告称，间充质干细胞释放的细胞外囊泡（EVs）等旁分泌因子可使 IVD 再生。本研究旨在利用体外三维藻酸盐珠培养模型，研究沃顿果冻间充质干细胞（WJ-MSC）衍生的EVs对人髓核细胞（hNPCs）的治疗作用。 方法 在对 EV 进行分离和表征后，将从手术标本中分离出的 hNPCs 封装在藻酸盐珠中，并用 10、50 和 100 μg/mL WJ-MSC-EVs 进行处理。细胞增殖和活力通过流式细胞术和活/死染色进行评估。藻酸盐珠中的 hNPCs 经石蜡包埋并染色后进行组织学分析（苏木精-伊红和阿尔新蓝），以评估细胞外基质（ECM）的组成。通过 qPCR 分析分解代谢基因（MMP1、MMP13、ADAMTS5、IL6、NOS2）、合成代谢基因（ACAN）和 hNPC 标记基因（SOX9、KRT19）的基因表达水平。通过 Western 印迹分析评估 I 型和 II 型胶原蛋白的含量。 结果 用 WJ-MSC-EVs 处理退化的 hNPCs 后，细胞含量增加，细胞死亡减少。与对照组相比，EV 处理大大减少了亚硝酸盐的产生。此外，蛋白多糖含量也得到了提高，并通过阿尔新蓝组织学染色得到了证实。通过抑制分解代谢和炎症基因的表达水平，EV 刺激减轻了 ECM 降解和炎症反应。此外，EV 处理还能维持 NPC 表型标记基因。 结论 WJ-间充质干细胞衍生的 EV 可改善 hNPC 的生长和存活率，减轻 ECM 降解和氧化应激，为 IVD 再生提供了新的机会，是一种极具吸引力的细胞疗法替代策略。
{"title":"Wharton's Jelly mesenchymal stromal cell-derived extracellular vesicles promote nucleus pulposus cell anabolism in an in vitro 3D alginate-bead culture model","authors":"Veronica Tilotta, Gianluca Vadalà, Luca Ambrosio, Giuseppina Di Giacomo, Claudia Cicione, Fabrizio Russo, Adas Darinskas, Rocco Papalia, Vincenzo Denaro","doi":"10.1002/jsp2.1274","DOIUrl":"10.1002/jsp2.1274","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Intradiscal transplantation of mesenchymal stromal cells (MSCs) has emerged as a promising therapy for intervertebral disc degeneration (IDD). However, the hostile microenvironment of the intervertebral disc (IVD) may compromise the survival of implanted cells. Interestingly, studies reported that paracrine factors, such as extracellular vesicles (EVs) released by MSCs, may regenerate the IVD. The aim of this study was to investigate the therapeutic effects of Wharton's Jelly MSC (WJ-MSC)-derived EVs on human nucleus pulposus cells (hNPCs) using an in vitro 3D alginate-bead culture model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>After EV isolation and characterization, hNPCs isolated from surgical specimens were encapsulated in alginate beads and treated with 10, 50, and 100 μg/mL WJ-MSC-EVs. Cell proliferation and viability were assessed by flow cytometry and live/dead staining. Nitrite and glycosaminoglycan (GAG) content was evaluated through Griess and 1,9-dimethylmethylene blue assays. hNPCs in alginate beads were paraffin-embedded and stained for histological analysis (hematoxylin–eosin and Alcian blue) to assess extracellular matrix (ECM) composition. Gene expression levels of catabolic (<i>MMP1, MMP13, ADAMTS5, IL6, NOS2</i>), anabolic (<i>ACAN</i>), and hNPC marker (<i>SOX9, KRT19</i>) genes were analyzed through qPCR. Collagen type I and type II content was assessed with Western blot analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Treatment with WJ-MSC-EVs resulted in an increase in cell content and a decrease in cell death in degenerated hNPCs. Nitrite production was drastically reduced by EV treatment compared to the control. Furthermore, proteoglycan content was enhanced and confirmed by Alcian blue histological staining. EV stimulation attenuated ECM degradation and inflammation by suppressing catabolic and inflammatory gene expression levels. Additionally, NPC phenotypic marker genes were also maintained by the EV treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>WJ-MSC-derived EVs ameliorated hNPC growth and viability, and attenuated ECM degradation and oxidative stress, offering new opportunities for IVD regeneration as an attractive alternative strategy to cell therapy, which may be jeopardized by the harsh microenvironment of the IVD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2023-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.1274","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134944324","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}
Catarina Leite Pereira, Sibylle Grad, Raquel M. Gonçalves
Biomarkers are commonly recognized as objective indicators of a medical state or clinical outcome and have been widely used as clinical and diagnostic tools and surrogate endpoints in many pathological conditions. In the context of intervertebral disc (IVD) and associated back pain, also known as degenerative disc disease (DDD), the use of biomarkers has been poorly explored. DDD is currently diagnosed using imaging techniques and subjective pain scales, limiting an objective association between DDD and pain levels, as well as an evaluation of disease progression. There is a need for objective and reliable measurements for DDD, pain and pathology progression. DDD predictors could also help clinicians in deciding on the optimal treatment for distinct patient groups. This review addresses the current candidate biomarkers in DDD, including imaging, genetic, metabolite and protein-based parameters, both at the tissue and systemic levels, that may become a major advance in the diagnosis and prognosis of the disease, as well as in the management of therapeutic approaches to DDD.
{"title":"Biomarkers for intervertebral disc and associated back pain: From diagnosis to disease prognosis and personalized treatment","authors":"Catarina Leite Pereira, Sibylle Grad, Raquel M. Gonçalves","doi":"10.1002/jsp2.1280","DOIUrl":"10.1002/jsp2.1280","url":null,"abstract":"<p>Biomarkers are commonly recognized as objective indicators of a medical state or clinical outcome and have been widely used as clinical and diagnostic tools and surrogate endpoints in many pathological conditions. In the context of intervertebral disc (IVD) and associated back pain, also known as degenerative disc disease (DDD), the use of biomarkers has been poorly explored. DDD is currently diagnosed using imaging techniques and subjective pain scales, limiting an objective association between DDD and pain levels, as well as an evaluation of disease progression. There is a need for objective and reliable measurements for DDD, pain and pathology progression. DDD predictors could also help clinicians in deciding on the optimal treatment for distinct patient groups. This review addresses the current candidate biomarkers in DDD, including imaging, genetic, metabolite and protein-based parameters, both at the tissue and systemic levels, that may become a major advance in the diagnosis and prognosis of the disease, as well as in the management of therapeutic approaches to DDD.</p>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"6 4","pages":""},"PeriodicalIF":3.7,"publicationDate":"2023-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.1280","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135898788","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}
Intervertebral disc degeneration (IDD) is a common musculoskeletal disorder that contributes significantly to disability and healthcare costs. Serum urate concentration has been implicated in the development of various musculoskeletal conditions. While previous observational studies have suggested an association between the two conditions, it might confound the effect of serum urate concentrations on IDD. This Mendelian randomization (MR) study aimed to investigate the causal relationship between serum urate concentration and IDD.
Methods
We performed a two-sample MR analysis using summary-level data from genome-wide association studies (GWAS) of serum urate concentration (n = 13 585 994 European ancestry) and IDD (n = 16 380 337 European ancestry). Single nucleotide polymorphisms (SNPs) significantly associated with serum urate concentration (p < 5 × 10−8) were selected as instrumental variables. The associations between genetically predicted serum urate concentration and IDD were estimated using the inverse-variance weighted (IVW) method, with sensitivity analyses employing the weighted median, MR-Egger, and MR-PRESSO approaches to assess the robustness of the findings.
Results
In the primary IVW analysis, genetically predicted serum urate concentration was unrelated associated with IDD (odds ratio [OR] = 1.00, 95% confidence interval (CI): 1.00–1.00, p = 0.17)). The results remained consistent across the sensitivity analyses, and no significant directional pleiotropy was detected (MR-Egger intercept: p = 0.15).
Conclusions
This MR study provides evidence that there is no causal relationship between serum urate concentration and IDD. It suggests previous observational associations may be confounded. Serum urate levels are unlikely to be an important contributor to IDD.
{"title":"The non-causative role of abnormal serum uric acid in intervertebral disc degeneration: A Mendelian randomization study","authors":"Yang-Ting Cai, Yong-Xian Li, Li-Ren Wang, Ling Mo, Ying Li, Shun-Cong Zhang","doi":"10.1002/jsp2.1283","DOIUrl":"10.1002/jsp2.1283","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Intervertebral disc degeneration (IDD) is a common musculoskeletal disorder that contributes significantly to disability and healthcare costs. Serum urate concentration has been implicated in the development of various musculoskeletal conditions. While previous observational studies have suggested an association between the two conditions, it might confound the effect of serum urate concentrations on IDD. This Mendelian randomization (MR) study aimed to investigate the causal relationship between serum urate concentration and IDD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed a two-sample MR analysis using summary-level data from genome-wide association studies (GWAS) of serum urate concentration (<i>n</i> = 13 585 994 European ancestry) and IDD (<i>n</i> = 16 380 337 European ancestry). Single nucleotide polymorphisms (SNPs) significantly associated with serum urate concentration (<i>p</i> < 5 × 10<sup>−8</sup>) were selected as instrumental variables. The associations between genetically predicted serum urate concentration and IDD were estimated using the inverse-variance weighted (IVW) method, with sensitivity analyses employing the weighted median, MR-Egger, and MR-PRESSO approaches to assess the robustness of the findings.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the primary IVW analysis, genetically predicted serum urate concentration was unrelated associated with IDD (odds ratio [OR] = 1.00, 95% confidence interval (CI): 1.00–1.00, <i>p</i> = 0.17)). The results remained consistent across the sensitivity analyses, and no significant directional pleiotropy was detected (MR-Egger intercept: <i>p</i> = 0.15).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This MR study provides evidence that there is no causal relationship between serum urate concentration and IDD. It suggests previous observational associations may be confounded. Serum urate levels are unlikely to be an important contributor to IDD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2023-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.1283","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135246700","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}
As the seasons begin to change (at least in the northern hemisphere), we turn our attention to gathering the fruits of our collective labor and start our planning for the coming year. Since the groundwork and planning began in earnest in the fall of 2017, to our first issue in March of 2018, to the present day, the ‘seeds’ that were the JOR Spine concept have come to fruition, and we can now all share in the bounty that is our JOR Spine journal. Over the last six years, the international spine community has come together to support this new effort, and we have steadily progressed though the benchmarks that signify stability and success of a new journal. Last summer we were delighted to receive our first impact factor, a major milestone. This past July, we were even more delighted to find out that our impact factor had held steady, at a 3.7. While impact factor is only one metric, we are happy that all of your labors, and excellent submissions, have had this result, and firmly establish the JOR Spine in the top echelon of Spine related journals.
As we think to the future, we are excited by plans for the coming year. The December issue is slated to be a ‘special issue’, with a compendium of manuscripts from the 2022 ORS/PSRS meeting. We thank the organizers for that great meeting and for assembling an outstanding lineup of papers that are being finalized. Many of you also just finished a race to the finish line for your ORS 2024 abstract submissions. We are excited to see all of the new spine-focused work presented at the meeting, and to see it submitted to the JOR Spine soon! We also look forward to celebrating with all of you our next JOR Spine Early Career Awardee. As you'll recall from past years, this award, developed in collaboration with the ORS Spine Section, is designed to recognize the ‘rising stars’ of our field and highlight their outstanding work published in the JOR Spine. For each of the past four years, awardees have been recognized at the ORS Annual Meeting, and we look forward to continuing this tradition in the coming year. Applications for this highly competitive award are due October 30th, 2023 and information on the award nomination process and eligibility criteria can be found at: https://onlinelibrary.wiley.com/page/journal/25721143/homepage/earlycareeraward. Please consider nominating your colleagues (or yourself) for this Award!
As we move into the fall, we wish you all a bountiful harvest, and look forward to your excellent submissions and suggestions, the seeds that will continue our progress in building JOR Spine into the preeminent spine journal for our community.
{"title":"JOR Spine: Reaping the harvest of a community effort","authors":"Robert L. Mauck, Mauro Alini, Daisuke Sakai","doi":"10.1002/jsp2.1288","DOIUrl":"10.1002/jsp2.1288","url":null,"abstract":"<p>As the seasons begin to change (at least in the northern hemisphere), we turn our attention to gathering the fruits of our collective labor and start our planning for the coming year. Since the groundwork and planning began in earnest in the fall of 2017, to our first issue in March of 2018, to the present day, the ‘seeds’ that were the JOR Spine concept have come to fruition, and we can now all share in the bounty that is our JOR Spine journal. Over the last six years, the international spine community has come together to support this new effort, and we have steadily progressed though the benchmarks that signify stability and success of a new journal. Last summer we were delighted to receive our first impact factor, a major milestone. This past July, we were even more delighted to find out that our impact factor had held steady, at a 3.7. While impact factor is only one metric, we are happy that all of your labors, and excellent submissions, have had this result, and firmly establish the JOR Spine in the top echelon of Spine related journals.</p><p>As we think to the future, we are excited by plans for the coming year. The December issue is slated to be a ‘special issue’, with a compendium of manuscripts from the 2022 ORS/PSRS meeting. We thank the organizers for that great meeting and for assembling an outstanding lineup of papers that are being finalized. Many of you also just finished a race to the finish line for your ORS 2024 abstract submissions. We are excited to see all of the new spine-focused work presented at the meeting, and to see it submitted to the JOR Spine soon! We also look forward to celebrating with all of you our next <b>JOR Spine Early Career Awardee</b>. As you'll recall from past years, this award, developed in collaboration with the ORS Spine Section, is designed to recognize the ‘rising stars’ of our field and highlight their outstanding work published in the <i>JOR Spine</i>. For each of the past four years, awardees have been recognized at the ORS Annual Meeting, and we look forward to continuing this tradition in the coming year. Applications for this highly competitive award are due October 30th, 2023 and information on the award nomination process and eligibility criteria can be found at: https://onlinelibrary.wiley.com/page/journal/25721143/homepage/earlycareeraward. Please consider nominating your colleagues (or yourself) for this Award!</p><p>As we move into the fall, we wish you all a bountiful harvest, and look forward to your excellent submissions and suggestions, the seeds that will continue our progress in building JOR Spine into the preeminent spine journal for our community.</p><p>Rob, Mauro, and Dai.</p>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"6 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2023-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.1288","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41176241","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}
An experimental study was performed to improve the anterior approach model of intervertebral disc degeneration (IVDD).
Objective
The aims of this study were to investigate the anterior approach model of IVDD for the cause of death, phenotypes, and underlying mechanisms of low back pain in mice.
Method
In this study, we conducted an anterior puncture procedure on a cohort of 300 C57BL/6J mice that were 8 weeks old. Our investigation focused on exploring the causes of death in the study population (n = 300) and assessing the time-course changes in various parameters, including radiographical, histological, immunofluorescence, and immunohistochemistry analyses (n = 10). Additionally, we conducted behavioral assessments on a subset of the animals (n = 30).
Results
Transverse vertebral artery rupture is a major factor in surgical death. Radiographical analyses showed that the hydration of the nucleus pulposus began to decrease at 2 weeks after puncture and obviously disappeared over 4 weeks. 3D-CT showed that disc height was significantly decreased at 4 weeks. Osteophyte at the anterior vertebral rims was observed at 2 weeks after the puncture. As the time course increased, histological analyses showed progressive disruption of the destruction of the extracellular matrix and increased secretion of inflammatory cytokines and apoptosis. Behavioral signs of low back pain were increased between the puncture and sham groups at 4 weeks.
Conclusion
The improvement of anterior intervertebral disc approach model in mice will be useful to investigate underlying mechanisms and potential therapeutic strategies for behavior and phenotypes. Furthermore, the application of vibrational pre-treatment can be used to increase the sensitivity of axial back pain in the model, thereby providing researchers with a reliable method for measuring this critical phenotype.
{"title":"Pain behavior and phenotype in a modified anterior lumbar disc puncture mouse model","authors":"Yuming Huang, Linchuan Lei, Jian Zhu, Jinjian Zheng, Zemin Li, Hua Wang, Jianru Wang, Zhaomin Zheng","doi":"10.1002/jsp2.1284","DOIUrl":"10.1002/jsp2.1284","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>An experimental study was performed to improve the anterior approach model of intervertebral disc degeneration (IVDD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The aims of this study were to investigate the anterior approach model of IVDD for the cause of death, phenotypes, and underlying mechanisms of low back pain in mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>In this study, we conducted an anterior puncture procedure on a cohort of 300 C57BL/6J mice that were 8 weeks old. Our investigation focused on exploring the causes of death in the study population (<i>n</i> = 300) and assessing the time-course changes in various parameters, including radiographical, histological, immunofluorescence, and immunohistochemistry analyses (<i>n</i> = 10). Additionally, we conducted behavioral assessments on a subset of the animals (<i>n</i> = 30).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Transverse vertebral artery rupture is a major factor in surgical death. Radiographical analyses showed that the hydration of the nucleus pulposus began to decrease at 2 weeks after puncture and obviously disappeared over 4 weeks. 3D-CT showed that disc height was significantly decreased at 4 weeks. Osteophyte at the anterior vertebral rims was observed at 2 weeks after the puncture. As the time course increased, histological analyses showed progressive disruption of the destruction of the extracellular matrix and increased secretion of inflammatory cytokines and apoptosis. Behavioral signs of low back pain were increased between the puncture and sham groups at 4 weeks.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The improvement of anterior intervertebral disc approach model in mice will be useful to investigate underlying mechanisms and potential therapeutic strategies for behavior and phenotypes. Furthermore, the application of vibrational pre-treatment can be used to increase the sensitivity of axial back pain in the model, thereby providing researchers with a reliable method for measuring this critical phenotype.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2023-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.1284","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135924838","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}
Arnold Y. L. Wong, G. Michael Mallow, Sabina M. Pinto, Alexander L. Hornung, Samuel S. Rudisill, Khaled Aboushaala, Peter M. Udby, Howard S. An, Dino Samartzis
Background
This systematic review and meta-analysis aimed to summarize evidence regarding the effectiveness and safety of oral antibiotic intervention for chronic low back pain (CLBP) patients with/without type-1 Modic changes (MC1).
Methods
AMED, CINAHL, Cochrane Library, Embase, and Medline were searched from inception to March 3, 2023. Randomized controlled trials (RCTs) or non-RCTs that investigated the effectiveness or safety of oral antibiotics in treating CLBP patients were eligible for inclusion. Two independent reviewers screened abstracts, full-text articles, and extracted data. The methodological quality of each included article were evaluated by RoB2 and NIH quality assessment tools. The quality of evidence was appraised by GRADE. Meta-analyses were performed, where applicable. A subgroup analysis was conducted to evaluate the RCTs and case series separately, and to evaluate the effect of removing a low-quality RCT.
Results
Three RCTs and four case series were included. All Amoxicillin-clavulanate/Amoxicillin treatments lasted for approximately 3 months. Moderate- and low-quality evidence suggested that antibiotic was significantly better than placebo in improving disability and quality of life in CLBP patients with MC1 at 12-month follow-up, respectively. Low-quality evidence from meta-analyses of RCTs showed that oral antibiotic was significantly better than placebo in improving pain and disability in CLBP patients with MC1 immediately post-treatment. Very low-quality evidence from the case series suggested that oral Amoxicillin-clavulanate significantly improved LBP/leg pain, and LBP-related disability. Conversely, low-quality evidence found that oral Amoxicillin alone was not significantly better than placebo in improving global perceived health in patients with CLBP at the 12-month follow-up. Additionally, oral antibiotic users had significantly more adverse effects than placebo users.
Conclusions
Although oral antibiotics were statistically superior to placebo in reducing LBP-related disability in patients with CLBP and concomitant MC1, its clinical significance remains uncertain. Future large-scale high-quality RCTs are warranted to validate the effectiveness of antibiotics in individuals with CLBP.
{"title":"The efficacy and safety of oral antibiotic treatment in patients with chronic low back pain and Modic changes: A systematic review and meta-analysis","authors":"Arnold Y. L. Wong, G. Michael Mallow, Sabina M. Pinto, Alexander L. Hornung, Samuel S. Rudisill, Khaled Aboushaala, Peter M. Udby, Howard S. An, Dino Samartzis","doi":"10.1002/jsp2.1281","DOIUrl":"10.1002/jsp2.1281","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>This systematic review and meta-analysis aimed to summarize evidence regarding the effectiveness and safety of oral antibiotic intervention for chronic low back pain (CLBP) patients with/without type-1 Modic changes (MC1).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>AMED, CINAHL, Cochrane Library, Embase, and Medline were searched from inception to March 3, 2023. Randomized controlled trials (RCTs) or non-RCTs that investigated the effectiveness or safety of oral antibiotics in treating CLBP patients were eligible for inclusion. Two independent reviewers screened abstracts, full-text articles, and extracted data. The methodological quality of each included article were evaluated by RoB2 and NIH quality assessment tools. The quality of evidence was appraised by GRADE. Meta-analyses were performed, where applicable. A subgroup analysis was conducted to evaluate the RCTs and case series separately, and to evaluate the effect of removing a low-quality RCT.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Three RCTs and four case series were included. All Amoxicillin-clavulanate/Amoxicillin treatments lasted for approximately 3 months. Moderate- and low-quality evidence suggested that antibiotic was significantly better than placebo in improving disability and quality of life in CLBP patients with MC1 at 12-month follow-up, respectively. Low-quality evidence from meta-analyses of RCTs showed that oral antibiotic was significantly better than placebo in improving pain and disability in CLBP patients with MC1 immediately post-treatment. Very low-quality evidence from the case series suggested that oral Amoxicillin-clavulanate significantly improved LBP/leg pain, and LBP-related disability. Conversely, low-quality evidence found that oral Amoxicillin alone was not significantly better than placebo in improving global perceived health in patients with CLBP at the 12-month follow-up. Additionally, oral antibiotic users had significantly more adverse effects than placebo users.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Although oral antibiotics were statistically superior to placebo in reducing LBP-related disability in patients with CLBP and concomitant MC1, its clinical significance remains uncertain. Future large-scale high-quality RCTs are warranted to validate the effectiveness of antibiotics in individuals with CLBP.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2023-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.1281","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135015291","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}
Rebecca Kritschil, Vivian Li, Dong Wang, Qing Dong, Prashanta Silwal, Toren Finkel, Joon Lee, Gwendolyn Sowa, Nam Vo
<div> <section> <h3> Background</h3> <p>Intervertebral disc degeneration (IDD) is a leading contributor to low back pain (LBP). Autophagy, strongly activated by hypoxia and nutrient starvation, is a vital intracellular quality control process that removes damaged proteins and organelles to recycle them for cellular biosynthesis and energy production. While well-established as a major driver of many age-related diseases, autophagy dysregulation or deficiency has yet been confirmed to cause IDD.</p> </section> <section> <h3> Methods</h3> <p>In vitro, rat nucleus pulposus (NP) cells treated with bafilomycin A1 to inhibit autophagy were assessed for glycosaminoglycan (GAG) content, proteoglycan synthesis, and cell viability. In vivo, a transgenic strain (<i>Col2a1-Cre</i>; <i>Atg7</i><sup><i>fl/fl</i></sup>) mice were successfully generated to inhibit autophagy primarily in NP tissues. <i>Col2a1-Cre</i>; <i>Atg7</i><sup><i>fl/fl</i></sup> mouse intervertebral discs (IVDs) were evaluated for biomarkers for apoptosis and cellular senescence, aggrecan content, and histological changes up to 12 months of age.</p> </section> <section> <h3> Results</h3> <p>Here, we demonstrated inhibition of autophagy by bafilomycin produced IDD features in the rat NP cells, including increased apoptosis and cellular senescence (<i>p21</i><sup><i>CIP1</i></sup>) and decreased expression of disc matrix genes <i>Col2a1</i> and <i>Acan</i>. H&E histologic staining showed significant but modest degenerative changes in NP tissue of <i>Col2a1-Cre; Atg7</i><sup><i>fl/fl</i></sup> mice compared to controls at 6 and 12 months of age. Intriguingly, 12-month-old <i>Col2a1-Cre; Atg7</i><sup><i>fl/fl</i></sup> mice did not display increased loss of NP proteoglycan. Moreover, markers of apoptosis (cleaved caspase-3, TUNEL), and cellular senescence (p53, <i>p16</i><sup><i>INK4a</i></sup><i>,</i> IL-1β, TNF-α) were not affected in 12-month-old <i>Col2a1-Cre; Atg7</i><sup><i>fl/fl</i></sup> mice compared to controls. However, <i>p21</i><sup><i>CIP1</i></sup>and <i>Mmp13</i> gene expression were upregulated in NP tissue of 12-month-old <i>Col2a1-Cre; Atg7</i><sup><i>fl/fl</i></sup> mice compared to controls, suggesting <i>p21</i><sup><i>CIP1</i></sup>-mediated cellular senescence resulted from NP-targeted <i>Atg7</i> knockout might contribute to the observed histological changes.</p> </section> <section> <h3> Conclusion</h3> <p>The absence of overt IDD features from disrupting <i>Atg7</i>-mediated macroautophagy in NP tissue implicates other compensatory mechanisms, highlighting additiona
{"title":"Impact of autophagy inhibition on intervertebral disc cells and extracellular matrix","authors":"Rebecca Kritschil, Vivian Li, Dong Wang, Qing Dong, Prashanta Silwal, Toren Finkel, Joon Lee, Gwendolyn Sowa, Nam Vo","doi":"10.1002/jsp2.1286","DOIUrl":"10.1002/jsp2.1286","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Intervertebral disc degeneration (IDD) is a leading contributor to low back pain (LBP). Autophagy, strongly activated by hypoxia and nutrient starvation, is a vital intracellular quality control process that removes damaged proteins and organelles to recycle them for cellular biosynthesis and energy production. While well-established as a major driver of many age-related diseases, autophagy dysregulation or deficiency has yet been confirmed to cause IDD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In vitro, rat nucleus pulposus (NP) cells treated with bafilomycin A1 to inhibit autophagy were assessed for glycosaminoglycan (GAG) content, proteoglycan synthesis, and cell viability. In vivo, a transgenic strain (<i>Col2a1-Cre</i>; <i>Atg7</i><sup><i>fl/fl</i></sup>) mice were successfully generated to inhibit autophagy primarily in NP tissues. <i>Col2a1-Cre</i>; <i>Atg7</i><sup><i>fl/fl</i></sup> mouse intervertebral discs (IVDs) were evaluated for biomarkers for apoptosis and cellular senescence, aggrecan content, and histological changes up to 12 months of age.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Here, we demonstrated inhibition of autophagy by bafilomycin produced IDD features in the rat NP cells, including increased apoptosis and cellular senescence (<i>p21</i><sup><i>CIP1</i></sup>) and decreased expression of disc matrix genes <i>Col2a1</i> and <i>Acan</i>. H&E histologic staining showed significant but modest degenerative changes in NP tissue of <i>Col2a1-Cre; Atg7</i><sup><i>fl/fl</i></sup> mice compared to controls at 6 and 12 months of age. Intriguingly, 12-month-old <i>Col2a1-Cre; Atg7</i><sup><i>fl/fl</i></sup> mice did not display increased loss of NP proteoglycan. Moreover, markers of apoptosis (cleaved caspase-3, TUNEL), and cellular senescence (p53, <i>p16</i><sup><i>INK4a</i></sup><i>,</i> IL-1β, TNF-α) were not affected in 12-month-old <i>Col2a1-Cre; Atg7</i><sup><i>fl/fl</i></sup> mice compared to controls. However, <i>p21</i><sup><i>CIP1</i></sup>and <i>Mmp13</i> gene expression were upregulated in NP tissue of 12-month-old <i>Col2a1-Cre; Atg7</i><sup><i>fl/fl</i></sup> mice compared to controls, suggesting <i>p21</i><sup><i>CIP1</i></sup>-mediated cellular senescence resulted from NP-targeted <i>Atg7</i> knockout might contribute to the observed histological changes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The absence of overt IDD features from disrupting <i>Atg7</i>-mediated macroautophagy in NP tissue implicates other compensatory mechanisms, highlighting additiona","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2023-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.1286","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135690070","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}
Samuel King, John Magnussen, James Elliott, Mark Jonathan Hancock
Background
Lumbar disc degeneration (DD) is widely regarded as a likely contributor to low back pain (LBP), but the association between DD and LBP is relatively weak. No known studies have normalized quantitative measures of DD severity relative to multiple variables such as age, height, and disc level. This study developed normalized quantitative measures (z-scores) of disc signal intensity (DSI) and disc height (DH) to rate relative severity of DD.
Methods
Raw (unnormalized) quantitative measures of DSI and DH alongside potential normalization variables were acquired from MRI scans and clinical data of 76 patients. The associations between the raw quantitative measures and potential normalization variables were investigated to develop the normalized quantitative measures (z-scores) of DSI and DH. Construct validity was assessed by comparing the normalized measures to an experienced radiologist's subjective measures of relative severity of DSI and DH loss.
Results
CSF signal intensity, age, and disc level were significantly associated with raw DSI (R2 = 0.06, 0.25, and 0.09, respectively). Lumbar height and disc level were significantly associated with raw DH (R2 = 0.13 and 0.31). Normalizing DSI and DH by these variables resulted in stronger relationships (R2 = 0.39 and 0.37) than raw DSI and DH (R2 = 0.24 and 0.31) with the radiologist's subjective measures. Normalized DSI and DH were both normally distributed (p = 0.32 and 0.12).
Conclusions
Construct validity and the distributions suggested that normalized quantitative measures of DSI and DH are better than existing measures of DSI and DH at rating relative DD severity. Determining whether normalized quantitative measures are more predictive of clinical outcomes is important future research.
{"title":"Development of normalized quantitative measures of lumbar disc degeneration","authors":"Samuel King, John Magnussen, James Elliott, Mark Jonathan Hancock","doi":"10.1002/jsp2.1278","DOIUrl":"10.1002/jsp2.1278","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Lumbar disc degeneration (DD) is widely regarded as a likely contributor to low back pain (LBP), but the association between DD and LBP is relatively weak. No known studies have normalized quantitative measures of DD severity relative to multiple variables such as age, height, and disc level. This study developed normalized quantitative measures (z-scores) of disc signal intensity (DSI) and disc height (DH) to rate relative severity of DD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Raw (unnormalized) quantitative measures of DSI and DH alongside potential normalization variables were acquired from MRI scans and clinical data of 76 patients. The associations between the raw quantitative measures and potential normalization variables were investigated to develop the normalized quantitative measures (z-scores) of DSI and DH. Construct validity was assessed by comparing the normalized measures to an experienced radiologist's subjective measures of relative severity of DSI and DH loss.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>CSF signal intensity, age, and disc level were significantly associated with raw DSI (<i>R</i><sup>2</sup> = 0.06, 0.25, and 0.09, respectively). Lumbar height and disc level were significantly associated with raw DH (<i>R</i><sup>2</sup> = 0.13 and 0.31). Normalizing DSI and DH by these variables resulted in stronger relationships (<i>R</i><sup>2</sup> = 0.39 and 0.37) than raw DSI and DH (<i>R</i><sup>2</sup> = 0.24 and 0.31) with the radiologist's subjective measures. Normalized DSI and DH were both normally distributed (<i>p</i> = 0.32 and 0.12).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Construct validity and the distributions suggested that normalized quantitative measures of DSI and DH are better than existing measures of DSI and DH at rating relative DD severity. Determining whether normalized quantitative measures are more predictive of clinical outcomes is important future research.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"6 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2023-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/34/85/JSP2-6-e1278.PMC10540817.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41132069","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}
Emily E. McDonnell, Niamh Wilson, Marcos N. Barcellona, Tara Ní Néill, Jessica Bagnall, Pieter A. J. Brama, Gráinne M. Cunniffe, Stacey L. Darwish, Joseph S. Butler, Conor T. Buckley
<div> <section> <h3> Background</h3> <p>A significant hurdle for potential cell-based therapies is the subsequent survival and regenerative capacity of implanted cells. While many exciting developments have demonstrated promise preclinically, cell-based therapies for intervertebral disc (IVD) degeneration fail to translate equivalent clinical efficacy.</p> </section> <section> <h3> Aims</h3> <p>This work aims to ascertain the clinical relevance of both a small and large animal model by experimentally investigating and comparing these animal models to human from the perspective of anatomical scale and their cellular metabolic and regenerative potential.</p> </section> <section> <h3> Materials and Methods</h3> <p>First, this work experimentally investigated species-specific geometrical scale, native cell density, nutrient metabolism, and matrix synthesis rates for rat, goat, and human disc cells in a 3D microspheroid configuration. Second, these parameters were employed in silico to elucidate species-specific nutrient microenvironments and predict differences in temporal regeneration between animal models.</p> </section> <section> <h3> Results</h3> <p>This work presents in silico models which correlate favorably to preclinical literature in terms of the capabilities of animal regeneration and predict that compromised nutrition is not a significant challenge in small animal discs. On the contrary, it highlights a very fine clinical balance between an adequate cell dose for sufficient repair, through de novo matrix deposition, without exacerbating the human microenvironmental niche.</p> </section> <section> <h3> Discussion</h3> <p>Overall, this work aims to provide a path towards understanding the effect of cell injection number on the nutrient microenvironment and the “time to regeneration” between preclinical animal models and the large human IVD. While these findings help to explain failed translation of promising preclinical data and the limited results emerging from clinical trials at present, they also enable the research field and clinicians to manage expectations on cell-based regeneration.</p> </section> <section> <h3> Conclusion</h3> <p>Ultimately, this work provides a platform to inform the design of clinical trials, and as computing power and software capabilities increase in the future, it is conceivable that generation of patient-specific
{"title":"Preclinical to clinical translation for intervertebral disc repair: Effects of species-specific scale, metabolism, and matrix synthesis rates on cell-based regeneration","authors":"Emily E. McDonnell, Niamh Wilson, Marcos N. Barcellona, Tara Ní Néill, Jessica Bagnall, Pieter A. J. Brama, Gráinne M. Cunniffe, Stacey L. Darwish, Joseph S. Butler, Conor T. Buckley","doi":"10.1002/jsp2.1279","DOIUrl":"10.1002/jsp2.1279","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>A significant hurdle for potential cell-based therapies is the subsequent survival and regenerative capacity of implanted cells. While many exciting developments have demonstrated promise preclinically, cell-based therapies for intervertebral disc (IVD) degeneration fail to translate equivalent clinical efficacy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This work aims to ascertain the clinical relevance of both a small and large animal model by experimentally investigating and comparing these animal models to human from the perspective of anatomical scale and their cellular metabolic and regenerative potential.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>First, this work experimentally investigated species-specific geometrical scale, native cell density, nutrient metabolism, and matrix synthesis rates for rat, goat, and human disc cells in a 3D microspheroid configuration. Second, these parameters were employed in silico to elucidate species-specific nutrient microenvironments and predict differences in temporal regeneration between animal models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>This work presents in silico models which correlate favorably to preclinical literature in terms of the capabilities of animal regeneration and predict that compromised nutrition is not a significant challenge in small animal discs. On the contrary, it highlights a very fine clinical balance between an adequate cell dose for sufficient repair, through de novo matrix deposition, without exacerbating the human microenvironmental niche.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>Overall, this work aims to provide a path towards understanding the effect of cell injection number on the nutrient microenvironment and the “time to regeneration” between preclinical animal models and the large human IVD. While these findings help to explain failed translation of promising preclinical data and the limited results emerging from clinical trials at present, they also enable the research field and clinicians to manage expectations on cell-based regeneration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Ultimately, this work provides a platform to inform the design of clinical trials, and as computing power and software capabilities increase in the future, it is conceivable that generation of patient-specific","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"6 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2023-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.1279","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41129726","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}
Micah Blais, Bahar Shahidi, Brad Anderson, Eli O'Brien, Courtney Moltzen, Tina Iannacone, Robert K. Eastlack, Gregory M. Mundis Jr
Purpose
It is unknown whether the biomechanics of the posterior ligamentous complex (PLC) are impaired in individuals undergoing surgery for adult spinal deformity (ASD). Characterizing these properties may improve our understanding of proximal junctional kyphosis (PJK; defined as proximal junctional angle [PJA] of >10 deg from UIV-1 to UIV + 2), as well as proximal junctional failure (PJF; symptomatic PJK requiring revision). The purpose of this prospective observational study is to compare biomechanical properties of the PLC in individuals with ASD who do, and do not develop PJK or PJF within 1 year of spinal fusion surgery.
Methods
Intraoperative biopsies of PLC were obtained from 32 consecutive patients undergoing spinal fusions for ASD (>4 levels). Ligament peak force, tensile stress, tensile strain, and elastic modulus (EM) were measured with a materials testing system. Biomechanical properties and tissue dimensions were correlated with age, gender, BMI, vitamin D level, osteoporosis, sagittal alignment, PJA and change in PJA preoperatively, within 3 months, and at 1 year postoperatively.
Results
Longer ligaments were associated with greater PJA change at 3 months (p = 0.04), and thinner ligaments were associated with greater PJA change at 1 year (r = 0.57, p = 0.01). Greater EM was associated with greater PJA at both 3 months and 1 year (p = 0.03). Five participants had a change in PJA of >10 1 year postoperatively, and three participants demonstrated PJF. EM was significantly higher in individuals who required revision surgery (p = 0.003), and ligament length was greater (p = 0.03). Preoperative sagittal alignment was not related to incidence of revision surgery (p > 0.10).
Conclusions
The biomechanical properties of the PLC may be associated with higher risk for proximal failure. Ligaments that are longer, thinner, and less elastic are associated with higher postoperative PJA. Furthermore stiffer EM of the ligament is associated with the need for revision surgery.
{"title":"The influence of ligament biomechanics on proximal junctional kyphosis and failure in patients with adult spinal deformity","authors":"Micah Blais, Bahar Shahidi, Brad Anderson, Eli O'Brien, Courtney Moltzen, Tina Iannacone, Robert K. Eastlack, Gregory M. Mundis Jr","doi":"10.1002/jsp2.1277","DOIUrl":"10.1002/jsp2.1277","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>It is unknown whether the biomechanics of the posterior ligamentous complex (PLC) are impaired in individuals undergoing surgery for adult spinal deformity (ASD). Characterizing these properties may improve our understanding of proximal junctional kyphosis (PJK; defined as proximal junctional angle [PJA] of >10 deg from UIV-1 to UIV + 2), as well as proximal junctional failure (PJF; symptomatic PJK requiring revision). The purpose of this prospective observational study is to compare biomechanical properties of the PLC in individuals with ASD who do, and do not develop PJK or PJF within 1 year of spinal fusion surgery.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Intraoperative biopsies of PLC were obtained from 32 consecutive patients undergoing spinal fusions for ASD (>4 levels). Ligament peak force, tensile stress, tensile strain, and elastic modulus (EM) were measured with a materials testing system. Biomechanical properties and tissue dimensions were correlated with age, gender, BMI, vitamin D level, osteoporosis, sagittal alignment, PJA and change in PJA preoperatively, within 3 months, and at 1 year postoperatively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Longer ligaments were associated with greater PJA change at 3 months (<i>p</i> = 0.04), and thinner ligaments were associated with greater PJA change at 1 year (<i>r</i> = 0.57, <i>p</i> = 0.01). Greater EM was associated with greater PJA at both 3 months and 1 year (<i>p</i> = 0.03). Five participants had a change in PJA of >10 1 year postoperatively, and three participants demonstrated PJF. EM was significantly higher in individuals who required revision surgery (<i>p</i> = 0.003), and ligament length was greater (<i>p</i> = 0.03). Preoperative sagittal alignment was not related to incidence of revision surgery (<i>p</i> > 0.10).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The biomechanical properties of the PLC may be associated with higher risk for proximal failure. Ligaments that are longer, thinner, and less elastic are associated with higher postoperative PJA. Furthermore stiffer EM of the ligament is associated with the need for revision surgery.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"6 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2023-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.1277","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41129526","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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