Intervertebral disc degeneration produced by vertebral body fracture associated with microcirculation disruption of the sub-endplate.

BACKGROUND: Among the causes of the progression of intervertebral disc (IVD) degeneration (IDD) is the loss of nutrient intake to the IVD through the microcirculation disruption of the sub-endplate. Also, the vertebral body fracture intervenes in degenerating the adjacent IVD. This research aimed to create an animal model of IDD using these two strategies. METHODS: 30 male Sprague-Dawley rats were split into 3 groups: a control group, a middle vertebral body injury (MI) associated with ethanol injection (MI+EtOH) group, and an MI associated with phosphate-buffered saline injection (MI+PBS) group. A vertebral body fracture with or without endplate injection of ethanol was generated by either drilling a hole in the center of a caudal rat vertebral body to form a fracture with an unabated endplate or drilling a hole in the center of a rat coccygeal vertebral body with endplate injection of ethanol to establish a vertebral body fracture with endplate damage. X-ray, macroscopic, histologic, and biochemical evaluations were utilized to assess IDD at weeks 3 and 6. RESULTS: According to X-ray findings, the MI+EtOH group demonstrated a significant decrease in intervertebral space height over time in comparison to the 2 other groups. The water content also was significantly decreased. Macroscopic and histological analysis demonstrated progressive degenerative changes in the IVD of the MI+EtOH group. CONCLUSION: The caudal vertebra fracture with ethanol injection is more likely to induce degeneration of adjacent IVD. This model effectively repreduced IDD, which may serve as a theoretical basis for future clinical intervention for IDD.

Optimizing Disc and Cartilage Endplate Preparation in Full-Endoscopic Lumbar Interbody Fusion: An In-Depth Exploration of Surgical Instruments with a Technique Note and Narrative Review.

Full-endoscopic lumbar interbody fusion (FELIF) is a critical yet challenging procedure. However, extensive analyses of discectomy and cartilage endplate preparation techniques are limited. This can be attributed to the lack of universal protocols owing to diverse surgical practices and equipment preferences. Therefore, this narrative review presents a comprehensive overview of discectomy and cartilage endplate preparation techniques in FELIF. A literature search of the PubMed, Embase, and Google Scholar databases in December 2023 retrieved 490 studies, of which 53 met the predefined inclusion criteria, and 1373 patients were included in the analyses. Spinal endoscopic disc and cartilage endplate removal can be categorized into 2 main types: removal under direct endoscopic visualization and removal under radiographic guidance with the protection of a working sheath following the endoscope's removal. Removal under direct visualization ensures the safety and precision of the procedure. Radiographic guidance can enhance the efficiency of the removal process. Specially designed instruments can be utilized through the narrow working channels of spinal endoscopes for the scraping surgery. Moreover, many traditional spinal endoscopic instruments, through specific techniques and manipulations, can also aid in cartilage removal. The approaches and techniques vary significantly among physicians, but overall, these instruments and techniques aim to achieve a safe and efficient disc-scraping outcome. Thus, this review may offer a comprehensive guidance to surgeons in selecting the most efficient practices for FELIF. Uniform procedural protocols are needed to ensure broader adoption and standardized practice.

Senescence of endplate osteoclasts induces sensory innervation and spinal pain.

Spinal pain affects individuals of all ages and is the most common musculoskeletal problem globally. Its clinical management remains a challenge as the underlying mechanisms leading to it are still unclear. Here, we report that significantly increased numbers of senescent osteoclasts (SnOCs) are observed in mouse models of spinal hypersensitivity, like lumbar spine instability (LSI) or aging, compared to controls. The larger population of SnOCs is associated with induced sensory nerve innervation, as well as the growth of H-type vessels, in the porous endplate. We show that deletion of senescent cells by administration of the senolytic drug Navitoclax (ABT263) results in significantly less spinal hypersensitivity, spinal degeneration, porosity of the endplate, sensory nerve innervation, and H-type vessel growth in the endplate. We also show that there is significantly increased SnOC-mediated secretion of Netrin-1 and NGF, two well-established sensory nerve growth factors, compared to non-senescent OCs. These findings suggest that pharmacological elimination of SnOCs may be a potent therapy to treat spinal pain.

Evolution characteristics and performance evaluation of extended end-plate joints with single and double side connections under cyclic loading.

Experimental studies were conducted on four extended end-plate joints subjected to cyclic loading at the column top, investigating the evolving patterns of the joints' mechanical performance. The paper provides a detailed analysis and discussion of the test joints' failure modes, ductility, stiffness degradation, and energy dissipation capacity. The Mann-Kendall (M - K) trend analysis tool was applied to the mechanical response curves, identifying key performance evolution points (evolution initiation point P and overall yield point Q). The trends in bolt forces, deformations, and strains at critical joints were effectively validated, revealing the transition of the energy system from quantitative to qualitative changes and the component's failure process from stability to instability. Additionally, based on the experimental joints' hysteresis curves and energy dissipation capacity, a theoretical hysteresis model was established to predict the joint's hysteresis curve and cumulative dissipated energy accurately. According to EC3 requirements, joints were classified as partially rigid connections. The experimental results of the initial rotational stiffness and plastic moment were further used to evaluate the calculated values in existing standards EN 1993-1-8, ANSI/AISC 358-16, and GB 51017-2017. The results indicate that extended end-plate connections possess sufficient strength, joint rotational stiffness, ductility, and energy dissipation capacity, making them suitable for seismic moment frames.

Insights into the mechanical microenvironment within the cartilaginous endplate: An emerging role in maintaining disc homeostasis and normal function.

Biomechanical factors are strongly linked with the emergence and development of intervertebral disc degeneration (IVDD). The intervertebral disc (IVD), as a unique enclosed biomechanical structure, exhibits distinct mechanical properties within its substructures. Damage to the mechanical performance of any substructure can disrupt the overall mechanical function of the IVD. Endplate degeneration serves as a significant precursor to IVDD. The endplate (EP) structure, especially the cartilaginous endplate (CEP), serves as a conduit for nutrient and metabolite transport in the IVD. It is inevitably influenced by its nutritional environment, mechanical loading, cytokines and extracellular components. Currently, reports on strategies targeting the CEP for the prevention and treatment of IVDD are scarce. This is due to two primary reasons: first, limited knowledge of the biomechanical microenvironment surrounding the degenerated CEP cells; and second, innovative biological treatment strategies, such as implanting active cells (disc or mesenchymal stem cells) or modulating natural cell activity through the addition of therapeutic factors or genes to treat IVDD often overlook a critical aspect-the restoration of the nutrient supply function and mechanical microenvironment of the endplate. Therefore, restoring the healthy structure of the CEP and maintaining a stable mechanical microenvironment within the EP are crucial for the prevention of IVDD and the repair of degenerated IVDs. We present a comprehensive literature review on the mechanical microenvironment characteristics of cartilage endplates and their associated mechanical signaling pathways. Our aim is to provide valuable insights into the development and implementation of strategies to prevent IVDD by delaying or reversing CEP degeneration.

Predictive value of different site-specific MRI-based assessments of bone quality for cage subsidence among patients undergoing oblique lumbar interbody fusion.

OBJECTIVE: The aim of this study was to investigate the predictive value of different site-specific MRI-based assessments of bone quality for cage subsidence among patients undergoing oblique lumbar interbody fusion (OLIF) with or without posterior internal fixation. METHODS: The authors retrospectively reviewed the records of patients who underwent OLIF between 2017 and 2022. Endplate bone quality (EBQ), mean vertebral bone quality (MVBQ), and vertebral bone quality (VBQ) scores were measured using preoperative non-contrast-enhanced T1-weighted MRI of the lumbar spine. Logistic regression analysis was used to identify factors associated with cage subsidence. Receiver operating characteristic curve analysis was used to evaluate the value of different site-specific MRI-based assessments of bone quality in predicting cage subsidence. RESULTS: Of the 124 patients who underwent OLIF, subsidence was found in 42 (33.9%). The VBQ, MVBQ, and EBQ scores were higher in the subsidence group than in the no-subsidence group. In the stand-alone OLIF (SA-OLIF) group, logistic regression analysis showed that the EBQ score was significantly associated with subsidence (OR 13.656, 95% CI 2.561-72.806; p = 0.002). Furthermore, the areas under the curve (AUCs) for using the VBQ, MVBQ, and EBQ scores and T-score to predict cage subsidence were 0.684, 0.683, 0.745, and 0.685, respectively. In the OLIF with posterior internal fixation (OLIF-PF) group, logistic regression analysis showed that the MVBQ score was significantly associated with subsidence (OR 8.301, 95% CI 2.064-33.385; p = 0.003). The AUCs for using the VBQ score, MVBQ score, and T-score to predict cage subsidence were 0.757, 0.774, and 0.685, respectively. CONCLUSIONS: There are significant differences in the predictive value of different site-specific bone quality assessments for cage subsidence among patients undergoing OLIF. For SA-OLIF, the EBQ score is recommended, while for OLIF-PF, the VBQ score is preferable.

Vertebral Endplate Defects Induced Mechanical Alterations and Disc Calcification.

STUDY DESIGN: Cross sectional comparative study. OBJECTIVES: The current study aims to explore the calcification potential (BMP2 expression) of intervertebral discs and its association with the presence of vertebral endplate defects visible on MRI. METHODS: Forty-seven herniated lumbar disc samples obtained from patients aged 20-76 (31 M/16F) undergoing surgery. Five-µm thin sections were stained with H&E in order to assign a histological degeneration score (HDS) from 0-15 on the basis of cell density (0-5), structural alterations (0-4), granular changes (0-3) and mucus degeneration (0-3). Sections were immuno-stained with anti BMP-2 antibodies to observe the calcification potential in these discs. In addition, pre-operativeT2-T1 W MRI images of the lumbar spine were analyzed for the presence and type (typical or atypical) of vertebral endplate defects, grade of disc degeneration (Pfirrmann grade I-V), presence of high intensity zones (HIZ), and Modic changes at the operated level. RESULTS: Vertebral endplate defects, Modic changes & HIZ were observed in 81%, 29% and 21% of patients respectively. Mean HDS & BMP-2 expression was 9 ± 2 and mean 71 ± 36 spots/mm2 respectively. Discs with adjacent vertebral endplate defects showed increased cell density (P = .004), mucus degeneration (P = .002), HDS (P = .01) and BMP-2 expression (P = .01). Discs with HIZ also had increased HDS, but significance was seen with increased BMP2 expression (P = .006). HDS showed a positive correlation with BMP 2 expression (r = .30, P = .04). CONCLUSION: These findings suggest that the altered mechanical environment of discs is strongly associated with BMP-2 expression which is an important marker of intervertebral disc calcification.

Endplate weakening during cage bed preparation significantly reduces endplate load capacity.

PURPOSE: To analyze the effect of endplate weakness prior to PLIF or TLIF cage implantation and compare it to the opposite intact endplate of the same vertebral body. In addition, the influence of bone quality on endplate resistance was investigated. METHODS: Twenty-two human lumbar vertebrae were tested in a ramp-to-failure test. One endplate of each vertebral body was tested intact and the other after weakening with a rasp (over an area of 200 mm2). Either a TLIF or PLIF cage was then placed and the compression load was applied across the cage until failure of the endplate. Failure was defined as the first local maximum of the force measurement. Bone quality was assessed by determining the Hounsfield units (HU) on CT images. RESULTS: With an intact endplate and a TLIF cage, the median force to failure was 1276.3N (693.1-1980.6N). Endplate weakening reduced axial endplate resistance to failure by 15% (0-23%). With an intact endplate and a PLIF cage, the median force to failure was 1057.2N (701.2-1735.5N). Endplate weakening reduced axial endplate resistance to failure by 36.6% (7-47.9%). Bone quality correlated linearly with the force at which endplate failure occurred. Intact and weakened endplates showed a strong positive correlation: intact-TLIF: r = 0.964, slope of the regression line (slope) = 11.8, p < 0.001; intact-PLIF: r = 0.909, slope = 11.2, p = 5.5E-05; weakened-TLIF: r = 0.973, slope = 12.5, p < 0.001; weakened-PLIF: r = 0.836, slope = 6, p = 0.003. CONCLUSION: Weakening of the endplate during cage bed preparation significantly reduces the resistance of the endplate to subsidence to failure: endplate load capacity is reduced by 15% with TLIF and 37% with PLIF. Bone quality correlates with the force at which endplate failure occurs.

Trabecular Bone Remodeling after Posterior Lumbar Interbody Fusion: Comparison of the Osseointegration in Three-Dimensional Porous Titanium Cages and Polyether-Ether-Ketone Cages.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: Imaging changes in the vertebral body after posterior lumbar interbody fusion (PLIF) are determined to be trabecular bone remodeling (TBR). This study aimed to investigate the influence of cage materials on TBR and segment stabilization in PLIF by studying image changes. METHODS: This was a retrospective study reviewing 101 cases who underwent one-level PLIF with three-dimensional porous titanium (3DTi) cages (53 patients) or polyether-ether-ketone (PEEK) cages (48 patients). Computed tomography images obtained 3 months, 1 year, and 2 years postoperatively were examined for TBR, vertebral endplate cyst formation as an instability sign, cage subsidence, and clear zone around pedicle screw (CZPS). RESULTS: No significant differences in the TBR-positivity rates were observed between the two cages at 3 months, 1 year, and 2 years postoperatively. However, all 3DTi cage segments that were TBR-positive at 3 months postoperatively showed no CZPS and fewer final instability segments than the TBR-negative segments (0% vs 9%). In contrast, although the PEEK cage segments that were TBR-positive at 3 months postoperatively were not associated with future segmental stabilization, those that were TBR-positive at 1 year postoperatively had fewer final instability segments than the TBR-negative segments (0% vs 33%). CONCLUSIONS: The 3DTi cage segments with TBR 3 months postoperatively showed significant final segmental stabilization, whereas TBR at 1 year rather than 3 months postoperatively was useful in determining final segmental stabilization for the PEEK cage segments. The timing of TBR, a new osseointegration assessment, were associated with the cage material.

Chondrocyte-targeted exosome-mediated delivery of Nrf2 alleviates cartilaginous endplate degeneration by modulating mitochondrial fission.

BACKGROUND: Cartilaginous endplate (CEP) degeneration, which is an important contributor to intervertebral disc degeneration (IVDD), is characterized by chondrocyte death. Accumulating evidence has revealed that dynamin-related protein 1 (Drp1)-mediated mitochondrial fission and dysfunction lead to apoptosis during CEP degeneration and IVDD. Exosomes are promising agents for the treatment of many diseases, including osteoporosis, osteosarcoma, osteoarthritis and IVDD. Despite their major success in drug delivery, the full potential of exosomes remains untapped. MATERIALS AND METHODS: In vitro and in vivo models of CEP degeneration were established by using lipopolysaccharide (LPS). We designed genetically engineered exosomes (CAP-Nrf2-Exos) expressing chondrocyte-affinity peptide (CAP) on the surface and carrying the antioxidant transcription factor nuclear factor E2-related factor 2 (Nrf2). The affinity between CAP-Nrf2-Exos and CEP was evaluated by in vitro internalization assays and in vivo imaging assays. qRT‒PCR, Western blotting and immunofluorescence assays were performed to examine the expression level of Nrf2 and the subcellular localization of Nrf2 and Drp1. Mitochondrial function was measured by the JC-1 probe and MitoSOX Red. Mitochondrial morphology was visualized by MitoTracker staining and transmission electron microscopy (TEM). After subendplate injection of the engineered exosomes, the degree of CEP degeneration and IVDD was validated radiologically and histologically. RESULTS: We found that the cargo delivery efficiency of exosomes after cargo packaging was increased by surface modification. CAP-Nrf2-Exos facilitated chondrocyte-targeted delivery of Nrf2 and activated the endogenous antioxidant defence system in CEP cells. The engineered exosomes inhibited Drp1 S616 phosphorylation and mitochondrial translocation, thereby preventing mitochondrial fragmentation and dysfunction. LPS-induced CEP cell apoptosis was alleviated by CAP-Nrf2-Exo treatment. In a rat model of CEP degeneration, the engineered exosomes successfully attenuated CEP degeneration and IVDD and exhibited better repair capacity than natural exosomes. CONCLUSION: Collectively, our findings showed that exosome-mediated chondrocyte-targeted delivery of Nrf2 was an effective strategy for treating CEP degeneration.

Impact of Osteoporosis on Short-Term Surgical Outcomes in Lumbar Degenerative Disease Patients Undergoing Lateral Lumbar Interbody Fusion: A Retrospective Analysis.

OBJECTIVE: This retrospective study assesses the influence of osteoporosis on the short-term clinical outcomes of lateral lumbar interbody fusion (LLIF) surgery in patients with lumbar degenerative diseases (LDDs), focusing on complications, pain intensity, and quality of life (QOL) improvements. The primary aim of this study is to investigate the impact of osteoporosis on the short-term clinical outcomes following LLIF surgery in LDD patients, with a particular focus on the incidence of cage subsidence (CS) and overall patient well-being postoperatively. METHODS: A retrospective review was conducted on 73 patients who underwent LLIF for LDD. Patients were categorized into 2 groups based on osteoporosis status determined by dual-energy X-ray absorptiometry scans: those with osteoporosis (n = 20) and those without osteoporosis (n = 53). Data collection included demographics, surgical details, complications, magnetic resonance imaging analysis, pain intensity, and QOL (Japanese Orthopaedic Association Back Pain Evaluation Questionnaire). RESULTS: The groups had no significant differences regarding operative time, estimated blood loss, and hospital stay duration. However, the incidence of CS was 40% in patients with osteoporosis, compared to 17% in nonosteoporotic patients. Despite this, significant improvements in spinal canal dimensions were observed in both groups. Both groups experienced significant reductions in pain intensity, with notable improvements in functional outcomes assessed by the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire, indicating the overall effectiveness of LLIF in enhancing patient well-being and functionality, irrespective of osteoporosis status. CONCLUSIONS: Osteoporosis increases the risk of CS in LLIF surgery for LDD patients but does not affect short-term pain relief and QOL improvements.

MRI-based endplate bone quality score predicts cage subsidence following oblique lumbar interbody fusion.

BACKGROUND CONTEXT: Cage subsidence is a common complication after lumbar interbody fusion surgery, with low bone mineral density (BMD) being a significant risk factor. ໿Endplate bone quality (EBQ) obtained from clinical MRI scans has been deemed reliable in determining regional BMD. However, the association between EBQ score and cage subsidence following oblique lumbar interbody fusion (OLIF) has not been clearly established. PURPOSE: This study aims to assess the relationship between EBQ score and cage subsidence in patients who underwent single-level OLIF. STUDY DESIGN/SETTING: A retrospective study. PATIENT SAMPLE: The study included adults with degenerative spinal conditions who underwent single-level OLIF at our institution. OUTCOME MEASURES: Cage subsidence, disc height, EBQ score, fusion rate. METHODS: This retrospective study analyzed data from patients who underwent single-level OLIF surgery at our institution between October 2017 and August 2022. Postoperative CT scans were used to measure cage subsidence, while the EBQ score was calculated using preoperative non-contrast T1-weighted MRI. To determine the predictive ability of the EBQ score, receiver operating characteristic (ROC) curve analysis was conducted. Additionally, univariable and multivariable logistic regression analyses were performed. RESULTS: In this study, a total of 88 patients were included and followed up for an average of 15.8 months. It was observed that 32.9% (n=29/88) of the patients experienced cage subsidence. The post-surgery disc height was significantly higher in patients who experienced subsidence compared to those who did not. The mean EBQ scores for patients with non-subsidence and subsidence were 2.31±0.6 and 3.48±1.2, respectively, and this difference was statistically significant. The ROC curve analysis showed that the AUC for the EBQ score was 0.811 (95% CI: 0.717-0.905). The most suitable threshold for the EBQ score was determined to be 2.318 (sensitivity: 93.1%, specificity: 55.9%). Additionally, the multivariate logistic regression analysis revealed a significant association between a higher EBQ score and an increased risk of subsidence (odds ratio [OR]=6.204, 95% CI=2.520-15.272, p<.001). CONCLUSIONS: Our findings indicate that higher preoperative EBQ scores are significantly linked to cage subsidence following single-level OLIF. Preoperative measurement of MRI can serve as a valuable tool in predicting cage subsidence.

Regional structure-function relationships of lumbar cartilage endplates.

Cartilage endplates (CEPs) act as protective mechanical barriers for intervertebral discs (IVDs), yet their heterogeneous structure-function relationships are poorly understood. This study addressed this gap by characterizing and correlating the regional biphasic mechanical properties and biochemical composition of human lumbar CEPs. Samples from central, lateral, anterior, and posterior portions of the disc (n = 8/region) were mechanically tested under confined compression to quantify swelling pressure, equilibrium aggregate modulus, and hydraulic permeability. These properties were correlated with CEP porosity and glycosaminoglycan (s-GAG) content, which were obtained by biochemical assays of the same specimens. Both swelling pressure (142.79 ± 85.89 kPa) and aggregate modulus (1864.10 ± 1240.99 kPa) were found to be regionally dependent (p = 0.0001 and p = 0.0067, respectively) in the CEP and trended lowest in the central location. No significant regional dependence was observed for CEP permeability (1.35 ± 0.97 * 10-16 m4/Ns). Porosity measurements correlated significantly with swelling pressure (r = -0.40, p = 0.0227), aggregate modulus (r = -0.49, p = 0.0046), and permeability (r = 0.36, p = 0.0421), and appeared to be the primary indicator of CEP biphasic mechanical properties. Second harmonic generation microscopy also revealed regional patterns of collagen fiber anchoring, with fibers inserting the CEP perpendicularly in the central region and at off-axial directions in peripheral regions. These results suggest that CEP tissue has regionally dependent mechanical properties which are likely due to the regional variation in porosity and matrix structure. This work advances our understanding of healthy baseline endplate biomechanics and lays a groundwork for further understanding the role of CEPs in IVD degeneration.

Association between vertebral endplate defects and patient-reported symptoms: an immunohistochemical study investigating the COX-2/PGE-2/EP-4 axis.

BACKGROUND CONTEXT: Vertebral endplate defects are often implicated in degenerative disc disorders, yet their connection to patient-reported symptoms remains unclear. COX-2 and PGE-2 are known for their roles in inflammation and pain, with EP-4 receptor involvement in pain signaling. Examining their expression in vertebral endplate tissues may provide insights into pathomechanism of low back pain. PURPOSE: To investigate the association between endplate defects and patient-reported symptoms and to further clarify the role of the COX-2/PGE-2/EP-4 axis in the pathogenesis of chronic low back pain. STUDY DESIGN/SETTING: Retrospective study. PATIENT SAMPLE: A total of 71 patients who had undergone single-level L4/5 or L5/S1 modified laminectomy decompression preserving proximal upper laminae and transforaminal lumbar interbody fusion surgery were included in this study, including 18 patients diagnosed with lumbar disc herniation, 19 with lumbar disc herniation accompanied by degenerative lumbar spinal stenosis, and 34 with degenerative spondylolisthesis. OUTCOME MEASURES: Demographic data, Pfirrmann grade, Modic changes, endplate defect score, visual analog scale (VAS) for back and leg pain, and Oswestry Disability Index (ODI) before surgery, 3-month and 6-month follow-up, and the percentage of immune-positive cells (COX-2, PGE-2, and EP-4) in endplate tissue sections. METHODS: Patients were divided into defect and nondefect groups according to endplate morphology on lumbar MR. All intraoperative endplate specimens were immediately fixed in 10% formaldehyde, and then embedded in paraffin 3 days later for tissue sections. The outcome measures were compared between the defect group and nondefect group. Data were analyzed using independent t-tests and χ² tests. Pearson's rank correlation test was used to assess correlations between patient-reported symptoms and the percentage of immune-positive cells in the groups. Multivariable logistic regression models using the forward stepwise likelihood ratio method were used to identify the factors that were independently associated with endplate defects. RESULTS: The age of Defect group was significantly higher than that of nondefect group (52.5±7.7 vs 57.2±9.1. p=.024). There were no significant differences in gender, diagnosis, BMI, comorbidities, or surgical level between the two groups. Modic changes (Type Ⅱ/Type Ⅲ) were more common in patients of Defect group than nondefect group (38.5% vs 11.1%, p<.001), and so was disc degeneration (Pfirrmann grade Ⅳ/Ⅴ) (69.2% vs 33.3%, p<.001). Defect group had significantly higher VAS-Back (6.5±2.0 vs 4.9±1.6, p<.001) and ODI scores (62.9±10.7 vs 45.2±14.8, p<.001) than nondefect group, while there was no significant differences between the two groups during the 3 and 6-month follow-up after surgery. Histologically, Defect group was characterized by upregulation of COX-2, PGE-2, and EP-4 in endplate tissue sections. Both in defect and nondefect groups, VAS-Back showed moderate positive correlations with the expressions of COX-2 (r=0.643; r=0.558, p both<.001), PGE-2 (r=0.611; r=0.640, p both<.001), and EP-4 (r=0.643; r=0.563, p both<.001). Multivariate regression analyses reveled that percentage of COX-2-positive cells was associated with endplate defects (OR=1.509, 95%CI [1.048-2.171], p=.027), as well as percentage of PGE-2-positive (OR=1.291, 95%CI [1.106-1.508], p=.001) and EP-4-positive cells (OR=1.284, 95%CI [1.048∼2.171], p=.003). CONCLUSIONS: Patients with endplate defects had worse quality of life, more severe disc degeneration and Modic changes, and up-regulated COX-2/PGE-2/EP-4 axis expression in cartilage endplates in patients with defected endplates. Inflammatory factors may significantly contribute to the onset and progression of chronic low back pain in patients with endplate defects, consequently impacting patient-reported symptoms.

Role of Galectin-3 in intervertebral disc degeneration: an experimental study.

BACKGROUND: This study investigated the role of Galectin-3 in the degeneration of intervertebral disc cartilage. METHODS: The patients who underwent lumbar spine surgery due to degenerative disc disease were recruited and divided into Modic I, Modic II, and Modic III; groups. HE staining was used to detect the pathological changes in endplates. The changes of Galectin-3, MMP3, Aggrecan, CCL3, and Col II were detected by immunohistochemistry, RT-PCR, and Western blot. MTT and flow cytometry were used to detect cartilage endplate cell proliferation, cell cycle, and apoptosis. RESULTS: With the progression of degeneration (from Modic I to III), the chondrocytes and density of the cartilage endplate of the intervertebral disc decreased, and the collagen arrangement of the cartilage endplate of the intervertebral disc was broken and calcified. Meanwhile, the expressions of Aggrecan, Col II, Galectin-3, Aggrecan, and CCL3 gradually decreased. After treatment with Galectin-3 inhibitor GB1107, the proliferation of rat cartilage end plate cells was significantly reduced (P < 0.05). GB1107 (25 µmol/L) also significantly promoted the apoptosis of cartilage endplate cells (P < 0.05). Moreover, the percentage of cartilage endplate cells in the G1 phase was significantly higher, while that in the G2 and S phases was significantly lower (P < 0.05). Additionally, the mRNA and protein expression levels of MMP3, CCL3, and Aggrecan in rat cartilage end plate cells were lower than those in the control group. CONCLUSIONS: Galectin-3 decreases with the progression of the cartilage endplate degeneration of the intervertebral disc. Galectin-3 may affect intervertebral disc degeneration by regulating the degradation of the extracellular matrix.

Surgical management of lower limb radiculopathy following acute singe-level osteoporotic vertebral fracture of lower lumbar spine in geriatric patient: a retrospective study.

BACKGROUND: Radiculopathy of the lower limb after acute osteoporotic vertebral fractures (OVFs) in the lower lumbar spine is uncommon in geriatric patients. Moreover, surgical intervention is generally recommended in patients who are irresponsive to conservative treatment. Determining an optimum surgical strategy is challenging considering the poor general condition of this population. Thus, herein, we established an algorithm for surgically managing this clinical scenario, hoping to provide a reference for making a surgical decision. METHODS: We retrospectively studied patients who suffered from new-onset radiculopathy of the lower limb after acute single-level OVFs in the lower lumbar spine and eventually underwent surgical intervention at our department. Information on the demographics, bone quality, AO spine classification of the vertebral fracture, pre-existing degenerative changes, including foraminal stenosis and lumbar disc herniation, and surgical intervention type was collected. Additionally, clinical outcomes, including preoperative and postoperative visual analog scale (VAS) scores for back and leg pain, Oswestry disability index (ODI), and MacNab criterion for response to surgery, were evaluated. RESULTS: From September 2019 to December 2021, a total of 22 patients with a mean age of 68.59 ± 9.74 years were analyzed. The most involved vertebra was L5 (54.5%), followed by L4 (27.3%) and L3 (18.2%). Among the 22 patients, 15 (68.2%) were diagnosed with the A1 type fracture of AO classification, and among them, 11 (73.3%) were characterized by the collapse of the inferior end plate (IEP). Three patients (13.6%) suffered from A2-type fractures, whereas four patients (18.2%) suffered from A3-type fractures. Pre-existing degenerative changes were observed in 12 patients (54.5%) of the patients. A total of 16 patients (72.7%) were treated by percutaneous kyphoplasty (PKP). Additionally, three patients underwent posterior instrumentation and fusion, two patients underwent a secondary endoscopic foraminoplasty, and one patient underwent a secondary radiofrequency ablation. The mean follow-up period was 17.42 ± 9.62 months. The mean VAS scores for leg and back pain and ODI decreased significantly after the surgery (P < 0.05). The total satisfaction rate at the last follow-up was 90.9% per the Macnab criterion. CONCLUSION: Patients with OVFs in the IEP are predisposed to suffer from radiculopathy of the lower limb. PKP alone or in combination with other minimally invasive surgical strategies is safe and effective in treating stable fractures. Additionally, aggressive surgical intervention should be considered in patients with unstable fractures or severe foraminal encroachment.

Relation between sagittal pelvic and thoracolumbar parameters in supine position - Pelvic parameters and their predictive value for spinal Cobb angles.

Introduction: Predicting the pre-morbid sagittal profile of the spine or segmental angles could enhance the process of planning the extent of fracture reduction. There is evidence that spinopelvic parameters may be suitable for this purpose. Research question: Is it possible to determine the inflection point and the mono- and bi-segmental endplate angles (EPA) in the thoracolumbar transition (from Th9 to L2) based on age, gender, spinopelvic parameters, and the adjacent EPA in the supine position? Material and methods: Based on Polytrauma CT scans in the supine position, the following spinopelvic parameters were measured using non-fractured spines: pelvic incidence (PI), sacral slope (SS), lumbar lordosis (LL), and the apex of the LL. Results: In this study, a total of 287 patients with a mean age of 42±16 years were included. Age-related changes were observed, where LL, thoracic kyphosis (TK), and PI increase with age. Gender-related comparisons showed that females had a more pronounced LL and reduced TK. Significant correlations between IP and spinopelvic parameters, with the apex of LL providing the best prediction, were found. However, the overall model quality remained low. Predicting mEPA and bEPA showed positive correlations. The prediction for mEPA L2/3 demonstrated the highest correlation. For bisegmental angles, the most caudal bEPA (L2) exhibited the highest correlation, albeit with some notable absolute differences in the values between measured and predicted values. Discussion and conclusion: While this study highlights the complexity of the relationship between the pelvis and thoracolumbar parameters, finding a predictive tool for thoracolumbar reduction and stabilization was not possible.

GDF5 as a rejuvenating treatment for age-related neuromuscular failure.

Sarcopenia involves a progressive loss of skeletal muscle force, quality and mass during ageing, which results in increased inability and death; however, no cure has been established thus far. Growth differentiation factor 5 (GDF5) has been described to modulate muscle mass maintenance in various contexts. For our proof of concept, we overexpressed GDF5 by AAV vector injection in Tibialis Anterior (TA) muscle of adult aged (20 months) mice and performed molecular and functional analysis of skeletal muscle. We analysed human Vastus Lateralis muscle biopsies from adult young (21-42 years) and aged (77-80 years) donors, quantifying the molecular markers modified by GDF5 overexpression (OE) in mouse muscle. We validated the major effects of GDF5 overexpression using human immortalized myotubes and Schwann Cells (SCs). We established a pre-clinical study by treating chronically (for 4 months) aged mice using recombinant GDF5 protein (rGDF5) in systemic administration and evaluated the long-term effect of this treatment on muscle mass and function. Here, we demonstrated that GDF5 OE in the old TAs promoted an increase of 16.5% of muscle weight (P = 0.0471) associated with a higher percentage of 5000-6000 µm2 large fibres (P = 0.0211), without the induction of muscle regeneration. Muscle mass gain was associated with an amelioration of 26.8% of rate of force generation (P = 0.0330) and a better neuromuscular connectivity (P = 0.0098). Moreover, GDF5 OE preserved neuromuscular junction (NMJ) morphology (38.5% of nerve terminal area increase, P < 0.0001) and stimulated the expression of re-innervation-related genes, in particular markers of SCs (fold change 3.19 for S100b gene expression, P = 0.0101). To further characterize the molecular events induced by GDF5 OE during ageing, we performed a genome-wide transcriptomic analysis of treated muscles and showed that this factor leads to a "rejuvenating" transcriptomic signature in aged mice, as 42% of the transcripts dysregulated by ageing reverted to youthful expression levels upon GDF5 OE (P < 0.05). Towards a pre-clinical approach, we performed a long-term systemic treatment using rGDF5 and showed its effectiveness in counteracting age-related muscle wasting, improving muscle function (17,8% of absolute maximal force increase, P = 0.0079), ensuring neuromuscular connectivity and preventing NMJ degeneration (7,96% of AchR area increase, P = 0.0125). In addition, in human muscle biopsies, we found the same age-related alterations than those observed in mice and improved by GDF5 and reproduced its major effects on human cells, suggesting this treatment as efficient in humans. Overall, these data provide a foundation to examine the curative potential of GDF5 drug in clinical trials for sarcopenia and, eventually, other neuromuscular diseases.

A novel repair strategy using knotless squeeze anchors for lumbar disc herniation with endplate junction lesions under biportal endoscopic spinal surgery.

BACKGROUND: Annulus fibrosus-endplate (AF-EP) junction lesions are important determinants for lumbar disc herniation (LDH). Utilizing biportal endoscopic spinal surgery (BESS), we introduce a novel repair method using bioabsorbable PushLock anchors with suture fibers to stretch disconnected AF tissues to the vertebral cortex. METHODS: The viewing and working portals are established to excise herniated disc materials causing radiculopathy. Through the working portal, a suture strand is passed through the intact AF tissue near the lesion and retrieved using the Suture Crossing Device. Then, the knotless suture limbs are secured into the cortical bone socket of the vertebral body with a PushLock anchor. CONCLUSION: The procedure is a simple, safe, and feasible knotless suturing technique for the treatment of LDH with AF-EP junction lesions.

Preoperative MRI-based endplate quality: a novel tool for predicting cage subsidence after anterior cervical spine surgery.

PURPOSE: The objective of this study was to examine the predictive value of a newly developed MRI-based Endplate Bone Quality (EBQ) in relation to the development of cage subsidence following anterior cervical discectomy and fusion (ACDF). METHODS: Patients undergoing ACDF for degenerative cervical diseases between January 2017 and June 2022 were included. Correlation between EBQ scores and segmental height loss was analyzed using Pearson's correlation. ROC analyses were employed to ascertain the EBQ cut-off values that predict the occurrence of cage subsidence. Multivariate logistic regression analyses were conducted to identify the risk factors associated with postoperative cage subsidence. RESULTS: 23 individuals (14.56%) exhibited the cage subsidence after ACDF. In the nonsubsidence group, the average EBQ and lowest T-score were determined to be 4.13 ± 1.14 and - 0.84 ± 1.38 g/cm2 respectively. In contrast, the subsidence group exhibited a mean EBQ and lowest T-score of 5.38 ± 0.47 (p < 0.001) and - 1.62 ± 1.34 g/cm2 (p = 0.014), respectively. There was a significant positive correlation (r = 0.798**) between EBQ and the segmental height loss. The EBQ threshold of 4.70 yielded optimal sensitivity (73.9%) and specificity (93.3%) with AUC of 0.806. Furthermore, the lowest T-score (p = 0.045, OR 0.667) and an elevated cervical EBQ score (p < 0.001, OR 8.385) were identified as significant risk factors for cage subsidence after ACDF. CONCLUSIONS: The EBQ method presents itself as a promising and efficient tool for surgeons to assess patients at risk of cage subsidence and osteoporosis prior to cervical spine surgery, utilizing readily accessible patient data.