{"title":"Inactivation of Tnf-α/Tnfr signaling attenuates progression of intervertebral disc degeneration in mice","authors":"Chu Tao, Sixiong Lin, Yujia Shi, Weiyuan Gong, Mingjue Chen, Jianglong Li, Peijun Zhang, Qing Yao, Dongyang Qian, Zemin Ling, Guozhi Xiao","doi":"10.1002/jsp2.70006","DOIUrl":"10.1002/jsp2.70006","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Intervertebral disc degeneration (IVDD) is a major cause of low back pain (LBP), worsened by chronic inflammatory processes associated with aging. Tumor necrosis factor alpha (Tnf-α) and its receptors, Tnf receptor type 1 (Tnfr1) and Tnf receptor type 2 (Tnfr2), are upregulated in IVDD. However, its pathologic mechanisms remain poorly defined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To investigate the role of Tnfr in IVDD, we generated global Tnfr1/2 double knockout (KO) mice and age-matched control C57BL/6 male mice, and analyzed intervertebral disc (IVD)-related phenotypes of both genotypes under physiological conditions, aging, and lumbar spine instability (LSI) model through histological and immunofluorescence analyses and μCT imaging. Expression levels of key extracellular matrix (ECM) proteins in aged and LSI mice, especially markers of cell proliferation and apoptosis, were evaluated in aged (21-month-old) mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>At 4 months, KO and control mice showed no marked differences of IVDD-related parameters. However, at 21 months of age, the loss of Tnfr expression significantly alleviated IVDD-like phenotypes, including a significant increase in height of the nucleus pulposus (NPs) and reductions of endplates (EPs) porosity and histopathological scores, when compared to controls. Tnfr deficiency promoted anabolic metabolism of the ECM proteins and suppressed ECM catabolism. Tnfr loss largely inhibited hypertrophic differentiation, and, in the meantime, suppressed cell apoptosis and cellular senescence in the annulus fibrosis, NP, and EP tissues without affecting cell proliferation. Similar results were observed in the LSI model, where Tnfr deficiency significantly alleviated IVDD and enhanced ECM anabolic metabolism while suppressing catabolism.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The deletion of Tnfr mitigates age-related and LSI-induced IVDD, as evidenced by preserved IVD structure, and improved ECM integrity. These findings suggest a crucial role of Tnf-α/Tnfr signaling in IVDD pathogenesis in mice. Targeting this pathway may be a novel strategy for IVDD prevention and treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11461905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400307","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":"Deep learning-based structure segmentation and intramuscular fat annotation on lumbar magnetic resonance imaging","authors":"Yefu Xu, Shijie Zheng, Qingyi Tian, Zhuoyan Kou, Wenqing Li, Xinhui Xie, Xiaotao Wu","doi":"10.1002/jsp2.70003","DOIUrl":"https://doi.org/10.1002/jsp2.70003","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Lumbar disc herniation (LDH) is a prevalent cause of low back pain. LDH patients commonly experience paraspinal muscle atrophy and fatty infiltration (FI), which further exacerbates the symptoms of low back pain. Magnetic resonance imaging (MRI) is crucial for assessing paraspinal muscle condition. Our study aims to develop a dual-model for automated muscle segmentation and FI annotation on MRI, assisting clinicians evaluate LDH conditions comprehensively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The study retrospectively collected data diagnosed with LDH from December 2020 to May 2022. The dataset was split into a 7:3 ratio for training and testing, with an external test set prepared to validate model generalizability. The model's performance was evaluated using average precision (AP), recall and F1 score. The consistency was assessed using the Dice similarity coefficient (DSC) and Cohen's Kappa. The mean absolute percentage error (MAPE) was calculated to assess the error of the model measurements of relative cross-sectional area (rCSA) and FI. Calculate the MAPE of FI measured by threshold algorithms to compare with the model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 417 patients being evaluated, comprising 216 males and 201 females, with a mean age of 49 ± 15 years. In the internal test set, the muscle segmentation model achieved an overall DSC of 0.92 ± 0.10, recall of 92.60%, and AP of 0.98. The fat annotation model attained a recall of 91.30%, F1 Score of 0.82, and Cohen's Kappa of 0.76. However, there was a decrease on the external test set. For rCSA measurements, except for longissimus (10.89%), the MAPE of other muscles was less than 10%. When comparing the errors of FI for each paraspinal muscle, the MAPE of the model was lower than that of the threshold algorithm.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The models demonstrate outstanding performance, with lower error in FI measurement compared to thresholding algorithms.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142244385","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":"Development and validation of deep learning models for identifying the brand of pedicle screws on plain spine radiographs","authors":"Yu-Cheng Yao, Cheng-Li Lin, Hung-Hsun Chen, Hsi-Hsien Lin, Wei Hsiung, Shih-Tien Wang, Ying-Chou Sun, Yu-Hsuan Tang, Po-Hsin Chou","doi":"10.1002/jsp2.70001","DOIUrl":"https://doi.org/10.1002/jsp2.70001","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>In spinal revision surgery, previous pedicle screws (PS) may need to be replaced with new implants. Failure to accurately identify the brand of PS-based instrumentation preoperatively may increase the risk of perioperative complications. This study aimed to develop and validate an optimal deep learning (DL) model to identify the brand of PS-based instrumentation on plain radiographs of spine (PRS) using anteroposterior (AP) and lateral images.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 529 patients who received PS-based instrumentation from seven manufacturers were enrolled in this retrospective study. The postoperative PRS were gathered as ground truths. The training, validation, and testing datasets contained 338, 85, and 106 patients, respectively. YOLOv5 was used to crop out the screws' trajectory, and the EfficientNet-b0 model was used to develop single models (AP, Lateral, Merge, and Concatenated) based on the different PRS images. The ensemble models were different combinations of the single models. Primary outcomes were the models' performance in accuracy, sensitivity, precision, F1-score, kappa value, and area under the curve (AUC). Secondary outcomes were the relative performance of models versus human readers and external validation of the DL models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The Lateral model had the most stable performance among single models. The discriminative performance was improved by the ensemble method. The AP + Lateral ensemble model had the most stable performance, with an accuracy of 0.9434, F1 score of 0.9388, and AUC of 0.9834. The performance of the ensemble models was comparable to that of experienced orthopedic surgeons and superior to that of inexperienced orthopedic surgeons. External validation revealed that the Lat + Concat ensemble model had the best accuracy (0.9412).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The DL models demonstrated stable performance in identifying the brand of PS-based instrumentation based on AP and/or lateral images of PRS, which may assist orthopedic spine surgeons in preoperative revision planning in clinical practice.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142244386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
JOR SpinePub Date : 2024-09-04DOI: 10.1002/jsp2.70000
Milad I. Markhali, John M. Peloquin, Kyle D. Meadows, Harrah R. Newman, Dawn M. Elliott
{"title":"Neural network segmentation of disc volume from magnetic resonance images and the effect of degeneration and spinal level","authors":"Milad I. Markhali, John M. Peloquin, Kyle D. Meadows, Harrah R. Newman, Dawn M. Elliott","doi":"10.1002/jsp2.70000","DOIUrl":"10.1002/jsp2.70000","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Magnetic resonance imaging (MRI) noninvasively quantifies disc structure but requires segmentation that is both time intensive and susceptible to human error. Recent advances in neural networks can improve on manual segmentation. The aim of this study was to establish a method for automatic slice-wise segmentation of 3D disc volumes from subjects with a wide range of age and degrees of disc degeneration. A U-Net convolutional neural network was trained to segment 3D T1-weighted spine MRI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Lumbar spine MRIs were acquired from 43 subjects (23–83 years old) and manually segmented. A U-Net architecture was trained using the TensorFlow framework. Two rounds of model tuning were performed. The performance of the model was measured using a validation set that did not cross over from the training set. The model version with the best Dice similarity coefficient (DSC) was selected in each tuning round. After model development was complete and a final U-Net model was selected, performance of this model was compared between disc levels and degeneration grades.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Performance of the final model was equivalent to manual segmentation, with a mean DSC = 0.935 ± 0.014 for degeneration grades I–IV. Neither the manual segmentation nor the U-Net model performed as well for grade V disc segmentation. Compared with the baseline model at the beginning of round 1, the best model had fewer filters/parameters (75%), was trained using only slices with at least one disc-labeled pixel, applied contrast stretching to its input images, and used a greater dropout rate.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study successfully trained a U-Net model for automatic slice-wise segmentation of 3D disc volumes from populations with a wide range of ages and disc degeneration. The final trained model is available to support scientific use.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11372286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
JOR SpinePub Date : 2024-08-14DOI: 10.1002/jsp2.1364
Seyed Mehrad Razavi, Danial Khayatan, Zahra Najafi Arab, Yasamin Hosseini, Maryam Khanahmadi, Saeideh Momtaz, Tannaz Jamialahmadi, Thomas P. Johnston, Amir Hossein Abdolghaffari, Amirhossein Sahebkar
{"title":"Protective effects of curcumin against spinal cord injury","authors":"Seyed Mehrad Razavi, Danial Khayatan, Zahra Najafi Arab, Yasamin Hosseini, Maryam Khanahmadi, Saeideh Momtaz, Tannaz Jamialahmadi, Thomas P. Johnston, Amir Hossein Abdolghaffari, Amirhossein Sahebkar","doi":"10.1002/jsp2.1364","DOIUrl":"https://doi.org/10.1002/jsp2.1364","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>In parallel with population aging, the prevalence of neurological and neurodegenerative diseases has been dramatically increasing over the past few decades. Neurodegenerative diseases reduce the quality of life of patients and impose a high cost on the health system. These slowly progressive diseases can cause functional, perceptual, and behavioral deficits in patients. Therefore, neurodegenerative impairments have always been an interesting subject for scientists and clinicians. One of these diseases is spinal cord injury (SCI). SCI can lead to irreversible damage and is classified into two main subtypes: traumatic and non-traumatic, each with very different pathophysiological features.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This review aims to gather relevant information about the beneficial effects of curcumin (Cur), with specific emphasis on its anti-inflammatory properties towards spinal cord injury (SCI) patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials & Methods</h3>\u0000 \u0000 <p>The review collates data from extensive in-vitro, in-vivo, and clinical trials documenting the effects of CUR on SCI. It examines the modulation of pathophysiological pathways and regulation of the inflammatory cascades after CUR administration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Various pathophysiological processes involving the nuclear factor erythroid 2-related factor 2 (Nrf2), nuclear factor kappa B (NF-kB), and transforming growth factor beta (TGF-β) signaling pathways have been suggested to exacerbate damages resulting from SCI. CUR administration showed to modulate these signaling pathways which lead to attenuation of SCI complications.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>Anti-inflammatory compounds, particularly CUR, can modulate these pathophysiological pathways and regulate the inflammatory cascades. CUR, a well-known natural product with significant anti-inflammatory effects, has been extensively documented in experimental and clinical trials.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Curcumin's potential to alter key steps in the Nrf2, NF-kB, and TGF-β signaling pathways suggests that it may play a role in attenuating SCI complications.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.1364","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141980246","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":"Clinical implications of linking microstructure, spatial biochemical, spatial biomechanical, and radiological features in ligamentum flavum degeneration","authors":"Azril Azril, Kuo-Yuan Huang, Hsin-Yi Liu, Wei-An Liao, Wen-Lung Liu, Jonathan Hobley, Yeau-Ren Jeng","doi":"10.1002/jsp2.1365","DOIUrl":"10.1002/jsp2.1365","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The ligamentum flavum (LF) degeneration is a critical factor in spinal stenosis, leading to nerve compression and pain. Even with new treatment options becoming available, it is vital to have a better understanding of LF degeneration to ensure the effectiveness of these treatments.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aimed to provide insight into LF degeneration by examining the connections between various aspects of LF degeneration, including histology, microstructure, chemical composition, and biomechanics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>We analyzed 30 LF samples from 27 patients with lumbar vertebrae, employing magnetic resonance imaging (MRI) to link lumbar disc degeneration grades with fibrosis levels in the tissue. X-ray diffraction (XRD) analysis assessed microstructural alterations in the LF matrix component due to degeneration progression. Instrumented nanoindentation combined with Raman spectroscopy explored the spatial microbiomechanical and biochemical characteristics of the LF's ventral and dorsal regions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our outcomes revealed a clear association between the severity of LF fibrosis grades and increasing LF thickness. XRD analysis showed a rise in crystalline components and hydroxyapatite molecules with progressing degeneration. Raman spectroscopy detected changes in the ratio of phosphate, proteoglycan, and proline/hydroxyproline over the amide I band, indicating alterations in the extracellular matrix composition. Biomechanical testing demonstrated that LF tissue becomes stiffer and less extensible with increasing fibrosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>Notably, the micro-spatial assessment revealed the dorsal side of the LF experiencing more significant mechanical stress, alongside more pronounced biochemical and biomechanical changes compared to the ventral side. Degeneration of the LF involves complex processes that affect tissue histology, chemical composition, and biomechanics. It is crucial to fully understand these changes to develop new and effective treatments for spinal stenosis. These findings can improve diagnostic accuracy, identify potential biomarkers and treatment targets, guide personalized treatment strategies, advance tissue engineering approaches, help make informed clinical decisions, and educate patients about LF degeneration.</p>\u0000 </section>\u0000 </di","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11310575/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
JOR SpinePub Date : 2024-08-06DOI: 10.1002/jsp2.1345
Imke Rudnik-Jansen, Sanda van Kruining Kodele, Laura Creemers, Bert Joosten
{"title":"Biomolecular therapies for chronic discogenic low back pain: A narrative review","authors":"Imke Rudnik-Jansen, Sanda van Kruining Kodele, Laura Creemers, Bert Joosten","doi":"10.1002/jsp2.1345","DOIUrl":"10.1002/jsp2.1345","url":null,"abstract":"<p>Chronic low back pain caused by intervertebral disc (IVD) degeneration, also termed chronic discogenic low back pain (CD-LBP), is one of the most prevalent musculoskeletal diseases. Degenerative processes in the IVD, such as inflammation and extra-cellular matrix breakdown, result in neurotrophin release. Local elevated neurotrophin levels will stimulate sprouting and innervation of sensory neurons. Furthermore, sprouted sensory nerves that are directly connected to adjacent dorsal root ganglia have shown to increase microglia activation, contributing to the maintenance and chronification of pain. Current pain treatments have shown to be insufficient or inadequate for long-term usage. Furthermore, most therapeutic approaches aimed to target the underlying pathogenesis of disc degeneration focus on repair and regeneration and neglect chronic pain. How biomolecular therapies influence the degenerative IVD environment, pain signaling cascades, and innervation and excitability of the sensory neurons often remains unclear. This review addresses the relatively underexplored area of chronic pain treatment for CD-LBP and summarizes effects of therapies aimed for CD-LBP with special emphasis on chronic pain. Approaches based on blocking pro-inflammatory mediators or neurotrophin activity have been shown to hamper neuronal ingrowth into the disc. Furthermore, the tissue regenerative and neuro inhibitory properties of extracellular matrix components or transplanted mesenchymal stem cells are potentially interesting biomolecular approaches to not only block IVD degeneration but also impede pain sensitization. At present, most biomolecular therapies are based on acute IVD degeneration models and thus do not reflect the real clinical chronic pain situation in CD-LBP patients. Future studies should aim at investigating the effects of therapeutic interventions applied in chronic degenerated discs containing established sensory nerve ingrowth. The in-depth understanding of the ramifications from biomolecular therapies on pain (chronification) pathways and pain relief in CD-LBP could help narrow the gap between the pre-clinical bench and clinical bedside for novel CD-LBP therapeutics and optimize pain treatment.</p>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11303450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901879","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":"The potential effect of romosozumab on perioperative management for instrumentation surgery","authors":"Koji Ishikawa, Soji Tani, Tomoaki Toyone, Koki Tsuchiya, Tomoko Towatari, Yusuke Oshita, Ryo Yamamura, Kazuki Wada, Takashi Nagai, Toshiyuki Shirahata, Katsunori Inagaki, Kudo Yoshifumi","doi":"10.1002/jsp2.1356","DOIUrl":"10.1002/jsp2.1356","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Age-related changes in bone health increase the risk for complications in elderly patients undergoing orthopedic surgery. Osteoporosis is a key therapeutic target that needs to be addressed to ensure successful instrumentation surgery. The effectiveness of pharmacological interventions in orthopedic surgery, particularly the new drug romosozumab, is still unknown. We aim to evaluate the effect of 3-month romosozumab treatment on biomechanical parameters related to spinal instrumentation surgery, using the Quantitative Computed Tomography (QCT)-based Finite Element Method (FEM).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This open-labeled, prospective study included 81 patients aged 60 to 90 years, who met the osteoporosis criteria and were scheduled for either romosozumab or eldecalcitol treatment. Patients were assessed using blood samples, dual-energy absorptiometry (DXA), and QCT. Biomechanical parameters were evaluated using FEM at baseline and 3 months post-treatment. The primary endpoints were biomechanical parameters at 3 months, while secondary endpoints included changes in regional volumetric bone mineral density around the pedicle (P-vBMD) and vertebral body (V-vBMD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Romosozumab treatment led to significant gains in P-vBMD, and V-vBMD compared to eldecalcitol at 3 months. Notably, the romosozumab group showed greater improvements in all biomechanical parameters estimated by FEM at 3 months compared to the eldecalcitol group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Romosozumab significantly increased the regional vBMD as well as biomechanical parameters, potentially offering clinical benefits in reducing post-operative complications in patients with osteoporosis undergoing orthopedic instrumentation surgery. This study highlights the novel advantages of romosozumab treatment and advocates further research on its effectiveness in perioperative management.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11299907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
JOR SpinePub Date : 2024-08-05DOI: 10.1002/jsp2.1351
Ward Shalash, Ryan Forcier, Adam Z. Higgins, Morgan B. Giers
{"title":"Cryopreserving the intact intervertebral disc without compromising viability","authors":"Ward Shalash, Ryan Forcier, Adam Z. Higgins, Morgan B. Giers","doi":"10.1002/jsp2.1351","DOIUrl":"10.1002/jsp2.1351","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Tissue cryopreservation requires saturation of the structure with cryoprotectants (CPAs) that are also toxic to cells within a short timeframe unless frozen. The race between CPA delivery and cell death is the main barrier to realizing transplantation banks that can indefinitely preserve tissues and organs. Unrealistic cost and urgency leaves less life-threatening ailments unable to capitalize on traditional organ transplantation systems that immediately match and transport unfrozen organs. For instance, human intervertebral discs (IVD) could be transplanted to treat back pain or used as ex vivo models for studying regenerative therapies, but both face logistical hurdles in organ acquisition and transport. Here we aimed to overcome those challenges by cryopreserving intact IVDs using compressive loading and swelling to accelerate CPA delivery.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>CPAs were tested on bovine nucleus pulposus cells to determine the least cytotoxic solution. Capitalizing on our CPAs Computed Tomography (CT) contrast enhancement, we imaged and quantified saturation time in intact bovine IVDs under different conditions in a bioreactor. Finally, the entire protocol was tested, including 1 week of frozen storage, to confirm tissue viability in multiple IVD regions after thawing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Results showed cryopreserving medium containing dimethyl sulfoxide and ethylene glycol gave over 7.5 h before cytotoxicity. While non-loaded IVDs required over 3 days to fully saturate, a dynamic loading protocol followed by CPA addition and free-swelling decreased saturation time to <5 h. After cryopreserving IVDs for 1 week with the optimized CPA and permeation method, all IVD regions had 85% cell viability, not significantly different from fresh unfrozen controls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study created a novel solution to a roadblock in IVD research and development. Using post-compression swelling CPA can be delivered to an intact IVD over 20× more quickly than previous methods, enabling cryopreservation of the IVD with no detectable loss in cell viability.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11299906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
JOR SpinePub Date : 2024-08-05DOI: 10.1002/jsp2.1363
Alikhan B. Fidai, Byumsu Kim, Marianne Lintz, Sertac Kirnaz, Pravesh Gadjradj, Blake I. Boadi, Maho Koga, Ibrahim Hussain, Roger Härtl, Lawrence J. Bonassar
{"title":"Flexible support material maintains disc height and supports the formation of hydrated tissue engineered intervertebral discs in vivo","authors":"Alikhan B. Fidai, Byumsu Kim, Marianne Lintz, Sertac Kirnaz, Pravesh Gadjradj, Blake I. Boadi, Maho Koga, Ibrahim Hussain, Roger Härtl, Lawrence J. Bonassar","doi":"10.1002/jsp2.1363","DOIUrl":"10.1002/jsp2.1363","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Mechanical augmentation upon implantation is essential for the long-term success of tissue-engineered intervertebral discs (TE-IVDs). Previous studies utilized stiffer materials to fabricate TE-IVD support structures. However, these materials undergo various failure modes in the mechanically challenging IVD microenvironment. FlexiFil (FPLA) is an elastomeric 3D printing filament that is amenable to the fabrication of support structures. However, no present study has evaluated the efficacy of a flexible support material to preserve disc height and support the formation of hydrated tissues in a large animal model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We leveraged results from our previously developed FE model of the minipig spine to design and test TE-IVD support cages comprised of FPLA and PLA. Specifically, we performed indentation to assess implant mechanical response and scanning electron microscopy to visualize microscale damage. We then implanted FPLA and PLA support cages for 6 weeks in the minipig cervical spine and monitored disc height via weekly x-rays. TE-IVDs cultured in FPLA were also implanted for 6 weeks with weekly x-rays and terminal T2 MRIs to quantify tissue hydration at study endpoint.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Results demonstrated that FPLA cages withstood nearly twice the deformation of PLA without detrimental changes in mechanical performance and minimal damage. In vivo, FPLA cages and stably implanted TE-IVDs restored native disc height and supported the formation of hydrated tissues in the minipig spine. Displaced TE-IVDs yielded disc heights that were superior to PLA or discectomy-treated levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>FPLA holds great promise as a flexible and bioresorbable material for enhancing the long-term success of TE-IVD implants.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11299905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893486","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}