Disc Degeneration Research Articles

Clinical Outcomes Following Treatment of Cervical Spondylotic Radiculopathy With Cervical Posterior Decompression Using Unilateral Biportal Endoscopic Technique: A Single Center Retrospective Series of 20 Patients.

Unilateral biportal endoscopy (UBE) is a minimally invasive approach to treat cervical spondylotic radiculopathy (CSR), which is a common condition caused secondary to disc herniation, disc degeneration, uncal osteophytes, and other conditions manifesting as neuropathic radicular pain. Anterior cervical discectomy and fusion (ACDF) is the gold standard surgical technique for treating CSR. However, it has several disadvantages, including loss of mobile segment, adjacent segment degeneration (ASD), implant- and approach-related complications, and high hospitalization costs. The current study aimed to evaluate the safety and efficacy of UBE decompression for CSR. After obtaining IRB approval, a single-center retrospective study was undertaken. Included patients underwent UBE decompression for CSR with a minimum of 6 months of follow-up. Patient demographics, perioperative data, and length of hospital stay were reviewed. Clinical outcomes were assessed using VAS scores for neck and arm pain, and NDI scores were measure preoperatively and at 1 and 6 months after UBE decompression. A repeated analysis of variance test was performed to measure the difference between VAS and NDI scores. Twenty patients (M: 15, F: 5) with a mean age of 56.7 ± 10.2 years were included. The mean follow-up period was 8.4 ± 1.8 months. The mean surgical time was 64.3±10.6 minutes. The average length of hospital stay was 1 day. At the final follow-up, the mean VAS for arm pain improved from 6.4 ± 0.7 to 0.6 ± 0.5 (92% improvement) and the mean VAS for neck pain improved from 3.3 ± 0.4 to 2.0 ± 0.2 (40% improvement). NDI score improved from 23.2 ± 1.95 to 5.7 ± 0.6 at the final follow-up (75% improvement). There were no complications. UBE is a safe and effective surgical treatment option for patients with CSR with excellent clinical outcomes. Clinical relevance of this case series study is to demonstrate the safety and efficacy of the novel unilateral biportal endoscopic decompression of cervical spondylotic radiculopathy and its short term clinical outcomes.

Effectiveness of robot-assisted minimally invasive and open freehand transforaminal lumbar interbody fusion in treatment of single-level degenerative lumbar spondylolisthesis and the influence on adjacent segment degeneration

To compare the effectiveness of robot-assisted minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) and open freehand TLIF for the treatment of single-level degenerative lumbar spondylolisthesis (DSL) and analyse the influence on postoperative adjacent segmental degeneration (ASD). The clinical data of 116 patients with L 4、5 DLS who were admitted between November 2019 and October 2021 and met the selection criteria were retrospectively analyzed. According to the surgical methods, they were divided into the robotic group (45 cases, who underwent robot-assisted MIS-TLIF) and the open group (71 cases, who underwent open freehand TLIF). There was no significant difference in baseline data such as gender, age, body mass index, DLS Meyerding grading, and preoperative Pfirrmann grading, Weishaupt grading, L 3, 4 intervertebral disc height (DH), L 3, 4 intervertebral mobility, sagittal parameters [including pelvic incidence (PI), lumbar lordosis (LL), sacral slope (SS), pelvic tilt (PT)], and Cage height ( P>0.05). The grade of facet joint violation (FJV) by pedicle screws on the superior articular process was assessed postoperatively. Sagittal parameters, L 3, 4 DH, L 3, 4 DH loss, and L 3, 4 intervertebral mobility were measured preoperatively and at last follow-up in order to determine whether ASD occurred. Based on the occurrence of postoperative ASD, logistic regression analysis was used to identify the risk factors for ASD after TLIF. Patients in both groups were followed up 21-47 months, with a mean of 36.1 months; there was no significant difference in the follow-up time between the two groups ( P>0.05). The occurrence of postoperative FJV was significantly better in the robotic group than in the open group ( P<0.05). At last follow-up, the difference in the change values of sagittal parameters PI, PT, SS, and LL was not significant when comparing the two groups of patients ( P>0.05); the change values of L 3, 4 DH and L 3, 4 DH loss in the robotic group were smaller than those in the open group, and the change value of L 3, 4 intervertebral mobility was larger than that in the open group, and the differences were significant ( P<0.05). At last follow-up, ASD occurred in 8 patients (17.8%) in the robotic group and 35 patients (49.3%) in the open group, and the difference in ASD incidence between the two groups was significant ( P<0.05). logistic regression analysis showed that open surgery, preoperative Pfirrmann grading Ⅳ-Ⅴ, preoperative Weishaupt grading ≥2, and postoperative FJV grading ≥1 were risk factors for the development of ASD after TLIF ( P<0.05). Compared with traditional open surgery, orthopedic robot-assisted MIS-TLIF in the treatment of single-level DLS can more accurately insert pedicle screws, reduce the loss of DH and the occurrence of FJV, and effectively reduce the incidence of mid-postoperative ASD. Preoperative disc and synovial joint degeneration in adjacent segments, nonrobotic-assisted minimally invasive therapy, and FJV are risk factors for ASD after TLIF.

The association of limited or painful spinal range of motion with lumbar disc degeneration: the back complaints in older adults (BACE) study.

We currently lack clear definitions for structural and symptomatic spinal osteoarthritis (OA). To define spinal OA and create diagnostic criteria for this condition, it is necessary to determine the relationship between clinical signs and symptoms of back pain and radiographic features of OA. Notably, recent studies suggest a defining sign of spinal OA could be a limited or painful spinal range of motion (ROM). Therefore, our objective was to assess the association between restricted or painful active spinal ROM, and multilevel structural features of lumbar disc degeneration (LDD) (i.e., disc space narrowing, osteophytes) on radiographs. We used the baseline data from the'Back Complaints in Older Adults' (BACE) study. The association between a limited or painful active spinal ROM, and multilevel disc space narrowing or osteophytes was assessed using multivariable logistic regression adjusted for age, mean pain intensity in the previous week, sex, BMI, and the Fear Avoidance Belief Questionnaire score. Primary analyses were performed on imputed datasets. We included 675 patients with a mean age of 66.52years (SD 7.69). Limited latero-flexion (fingertip that at best reached halfway up the upper leg) was associated with increased odds of having multilevel osteophytes (OR 1.85; 95% CI: 1.13 to 3.01). However, a limited or painful ROM in other directions (i.e., rotation, ante-flexion) was not associated with multilevel osteophytes, and a limited or painful active ROM in any direction was found to have no association with multilevel disc space narrowing. Our study indicates that a restricted ROM in latero-flexion could potentially be a defining sign in future definitions of symptomatic spinal OA. However, since our results partially differ from previous studies, further research is needed to explore the association between active ROM and LDD.

"Elucidating the immunomodulatory role of endocannabinoids in intervertebral disc degeneration".

The endocannabinoid system (ECS) has been well-established to play a crucial role in the regulation of several physiological processes as well as many inflammatory disease conditions. However, its role in intervertebral disc degeneration has been least explored. We aim to investigate the immunomodulatory role of endocannabinoids in regulating IVD health. The study population included 20 healthy volunteers (controls) and 40 patients with disc degeneration (disease group) (20 Modic and 20 Non Modic). 16S metagenome sequencing of the V3-V4 region was performed for the DNA extracted from NP tissue samples of both control and disease groups. Sequencing was carried out using the Novaseq 6000 platform using 250bp paired-end chemistry. A global metabolic profile was obtained using the uHPLC system coupled with Q Exactive Plus Hybrid Quadrupole-Orbitrap mass spectrometer. Our study revealed a higher prevalence of gram-negative bacteria, particularly opportunistic pathogens like Pseudomonas, in diseased discs (71-81%) compared to healthy controls (54%). Further investigation using metabolomics identified significant changes in the lipid profiles of diseased discs. We found that the signalling molecules of the ECS, 2-arachidonylglycerol (2-AG) and N-arachidonoylethanolamine (AEA), were significantly lower in diseased discs compared to controls (Log2FC -2.62 for 2-AG and -3.15 for AEA). Conversely, pro-inflammatory metabolites like LTA4, HPETE, HETE, and Prostaglandin G2 were elevated in diseased discs, with a Log2 fold increase greater than 2.5. The study reveals that the endocannabinoid metabolites (2-AG and AEA) of the ECS could be a significant molecule influencing susceptibility to infection and inflammation within the intervertebral discs, which could be a potential target for improving disc health. Diagnostic: individual cross-sectional studies with consistently applied reference standard and blinding.

Melatonin attenuates degenerative disc degression by downregulating DLX5 via the TGF/Smad2/3 pathway in nucleus pulposus cells.

Intervertebral disc degeneration (IVDD) is the leading cause of low back pain, and apoptosis plays a key role in its pathogenesis. Distal-less homeobox 5 (Dlx5) has been reported to induce cell apoptosis. Melatonin, as a powerful antiapoptotic agent, has been widely reported. This study aimed to investigate the role of DLX5 in the pathogenesis of IVDD and the potential therapeutic role of melatonin in targeting DLX5 in IVDD. Western blotting, RT-qPCR, immunohistochemistry, si-DLX5, Ex-DLX5, flow cytometry, and immunofluorescence were used to examine the regulatory effect of DLX5 on apoptosis. Therapeutic efficacy was assessed by the intraperitoneal injection of melatonin into IVDD mice. The expression level of DLX5 is significantly increased in IVDD, and the expression levels were positively correlated with the grade of IVDD. DLX5 was significantly upregulated in TNF-α-induced degenerative NP cells. Degenerative NP cells transfected with si-DLX5 exhibited significantly less apoptosis than control cells. Melatonin significantly alleviated IVDD in surgically induced IVDD model mice. The results revealed that the expression of DLX5 was positively correlated with the severity of IVDD and that melatonin ameliorated DLX5-induced apoptosis and extracellular matrix imbalance by inhibiting the TGF-β/Smad signaling pathway. This study may provide therapeutic strategies to alleviate inflammation-induced apoptosis IVDD-associated inflammation-induced apoptosis. DLX5 plays an important role in IVDD progression by promoting apoptosis, and melatonin represents a promising therapeutic strategy for alleviating IVDD-associated inflammation and apoptosis.

Percutaneous endoscopic lumbar discectomy versus open fenestration discectomy for lumbar disc herniation: a retrospective propensity score-matched study with more than 5 years of follow-up.

We compared the long-term outcomes of percutaneous endoscopic lumbar discectomy (PELD) with those of open fenestration discectomy (OFD) in treating lumbar disc herniation (LDH). 281 patients were included from January 2013 to December 2018, of whom 228 underwent PELD and 53 underwent OFD. General information of patients was collected and imbalances in covariates between groups were corrected using propensity score matching (PSM). Then, the clinical function scores, imaging data, and complications were compared. Among participants, 102 patients were successfully matched and were followed for 62-128 months. Compared to the OFD group, the PELD group indicated greater improvements in visual analog scale score of low back pain (VAS-BP), Japanese orthopedic association (JOA), and Oswestry disability index (ODI) at 7 days postoperatively and the last follow-up (P < 0.05). At 24 months postoperatively and the last follow-up, the disc height index (DHI), ratio of grays (RVG), and range of motion (ROM) were higher and the compass value was lower (P < 0.05) in the PELD group compared to the OFD group, suggesting that the PELD procedure better maintained the mobility and stability of the responsible segment after surgery. The recurrence rates between the PELD (9.80%) and OFD (7.84%) groups did not reveal statistical differences (P > 0.05). PELD and OFD both provide acceptable clinical outcomes for LDH. However, PELD is superior to OFD in terms of relieving low back pain, delaying disc degeneration, and maintaining segmental stability.

BMSC Derived Exosomes Attenuate Apoptosis of Temporomandibular Joint Disc Chondrocytes in TMJOA via PI3K/AKT Pathway.

Bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos) are crucial means of intercellular communication and can regulate a range of biological processes by reducing inflammation, decreasing apoptosis and promoting tissue repair. We treated temporomandibular joint (TMJ) disc chondrocytes with TNF-α and performed local injection of sodium iodoacetate (MIA) in the TMJ of rats to establish in vitro and in vivo models of TMJ osteoarthritis (TMJOA). BMSC-Exos were isolated and extracted to evaluate their proliferation and trilineage differentiation abilities, and their antiapoptotic and chondroprotective effects were assessed. This study revealed that BMSC-Exos can be endocytosed by TMJ disc chondrocytes in vitro and that BMSC-Exos pretreatment strongly attenuated the inhibitory effect of TNF-α on the proliferative and chondrogenic potential of TMJ disc chondrocytes. The administration of BMSC-Exos significantly suppressed TNF-α-induced apoptosis in TMJ disc chondrocytes by increasing the phosphorylation level of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB/AKT) pathway-related proteins, whereas the PI3K inhibitor LY294002 neutralized this antiapoptotic effect. Intradiscal injection of BMSC-Exos alleviated the degeneration and inflammation of TMJ discs in a rat model of TMJOA. Our study revealed that BMSC-Exos can attenuate the apoptosis of TMJ disc chondrocytes and destruction of TMJ discs partially by inhibiting the apoptotic pathway and activating the PI3K/AKT pathway, thereby providing a promising treatment strategy for the regeneration of damaged TMJ discs.

PH-Responsive Modified HAMA Microspheres Regulate the Inflammatory Microenvironment of Intervertebral Discs.

Currently, intervertebral disc (IVD) degeneration is believed to lead to local accumulation of lactic acid in the IVD, a decrease in pH, activation of the inflammatory pathway, and continued destruction of homeostasis of the IVD. To address these issues, the intelligent and accurate release of drugs is particularly important. In this study, acid-sensitive release methacrylated hyaluronic acid (HAMA) microspheres were constructed by using microfluidic technology, which can be used as a targeted drug delivery system for intervertebral disc degeneration (IVDD) through Schiff base chemical bonding on the surface of the microspheres to achieve intelligent drug release. Interleukin-1 receptor antagonist (IL-1 Ra) is a naturally occurring anti-inflammatory antagonist of the interleukin-1 family of pro-inflammatory cytokines. Despite its outstanding broad-spectrum anti-inflammatory effects, IL-1 Ra has a short biological half-life (4-6 h). The slow-release performance of IL-1 Ra can be greatly improved using bovine serum albumin nanoparticles (BNP). In addition, the modified HAMA microspheres exhibited good injectability and porosity, and efficient and uniform loading of nanoparticles was achieved via the Schiff base bond. The inflammatory microenvironment can be significantly reversed by transporting the modified HAMA microspheres-BNPs (Modified MS) to the degenerative nucleus pulposus.

Single-cell sequencing reveals cellular heterogeneity of nucleus pulposus in intervertebral disc degeneration

The nucleus pulposus (NP) plays a vital role in intervertebral disc degeneration (IVDD). Previous studies have revealed cellular heterogeneity in NP tissue during IVDD progression. However, the cellular and molecular alterations of diverse cell clusters during IVDD remain to be fully elucidated. NP tissues were isolated from patients with different grades of IVDD undergoing discectomy, and then subjected to single-cell RNA sequencing (scRNA-seq). Cell subsets were identified based on unbiased clustering of gene expression profiles. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to determine the molecular features of diverse cell clusters. Monocle analysis was used to illustrate the differentiation trajectories of chondrocytes. Additionally, CellPhoneDB analysis revealed potential interactions between chondrocytes and other cells during IVDD. Based on the expression profiles of 47,610 individual cells, eight putative clusters including chondrocytes, endothelial cells, fibroblasts, macrophages, mural cells, osteoclasts, proliferating stromal cells and T cells were identified. The chondrocyte cluster was classified into three subsets, C1-C3, which were associated with stress-resistance, fibrosis and inflammatory responses, respectively. Pseudo-time trajectories suggested that chondrocytes gradually differentiated into fibroblasts during IVDD. Immune cells including cDC2s, macrophages and monocytes were identified. Further analysis showed that chondrocytes might communicate with immune cells via the MIF, TNFSF9, SPP1 and CCL4L2 signaling pathways. In addition, we found that invading endothelial cells might interact with chondrocytes through the COL4A1, CXCL12, VEGFA and SEMA3E signaling pathways. Our results reveal the cellular complexity and phenotypic characteristics of NP tissues at single-cell resolution, which will contribute to the in-depth investigation of preventative and regenerative strategies for IVDD.

S1P regulates intervertebral disc aging by mediating endoplasmic reticulum-mitochondrial calcium ion homeostasis.

As the aging process progresses, age-related intervertebral disc degeneration (IVDD) is becoming an emerging public health issue. Site-1 protease (S1P) has recently been found to be associated with abnormal spinal development in patients with mutations and has multiple biological functions. Here, we discovered a reduction of S1P in degenerated and aging intervertebral discs, primarily regulated by DNA methylation. Furthermore, through drug treatment and siRNA-mediated S1P knockdown, nucleus pulposus cells were more prone to exhibit degenerative and aging phenotypes. Conditional KO of S1P in mice resulted in spinal developmental abnormalities and premature aging. Mechanistically, S1P deficiency impeded COP II-mediated transport vesicle formation, which leads to protein retention in the endoplasmic reticulum (ER) and subsequently ER distension. ER distension increased the contact between the ER and mitochondria, disrupting ER-to-mitochondria calcium flow and resulting in mitochondrial dysfunction and energy metabolism disturbance. Finally, using 2-APB to inhibit calcium ion channels and the senolytic drug dasatinib and quercetin (D + Q) partially rescued the aging and degenerative phenotypes caused by S1P deficiency. In conclusion, our findings suggest that S1P is a critical factor in causing IVDD in the process of aging and highlight the potential of targeting S1P as a therapeutic approach for age-related IVDD.

The Impact of Changes in Paraspinal Muscle Tissue on Lumbar Percutaneous Intradiscal Radiofrequency Therapy

Background/Objectives: This study aimed to assess whether fatty changes in paraspinal muscle tissue negatively affect pain relief and functional outcomes, measured by the Oswestry Disability Index (ODI), in patients undergoing intradiscal bipolar radiofrequency thermocoagulation for lumbar degenerative disc (LDD) disease. Fatty changes in paraspinal muscles, often associated with sarcopenia, are known to negatively influence treatment outcomes. However, there is limited research on how these changes affect pain and functional capacity following intradiscal procedures. Methods: In this study, data from 59 patients treated for LDD were analyzed. Pain severity was measured using the Numerical Rating Scale (NRS), and the ODI was recorded before the procedure and at 1, 3, and 6 months post-procedure. Fatty changes in the paraspinal muscle tissue were evaluated using the Goutallier classification based on pre-procedure T2-weighted MRI scans, while disc degeneration was assessed using the Pfirrmann classification. Results: The results showed significant positive correlations between the Goutallier and Pfirrmann classifications and pain levels at all time points post-procedure (p &lt; 0.05). Notably, the relationship between NRS scores and Goutallier classification was stronger than that with Pfirrmann classification (p &lt; 0.05). ODI scores were also significantly correlated with both Goutallier and Pfirrmann classifications at each time point, with a stronger association observed between ODI and Goutallier classification than with NRS (p &lt; 0.05). Conclusions: These findings suggest that fatty changes in the paraspinal muscle tissue may significantly influence treatment outcomes and should be considered during pre-treatment evaluations. Further research is needed to explore this relationship more comprehensively.

Effect of chondroitin sulfate and bone marrow-derived mesenchymal stem cells on intervertebral disc degeneration treatment in rabbits

The present study evaluated the influence of bone marrow-derived stem cells (BM-SC) and chondroitin sulfate (CS) on histological changes in intervertebral disc (IVD). A randomized clinical trial was conducted, thirty-six healthy New Zealand rabbits were randomly distributed into four different groups (n=9): con-trol group (A), stem cell group (B), chondroitin sulfate group (C), and associa-tion of stem cells with chondroitin sulfate group (D). All animals underwent the experimental disc degeneration procedure. Group A received two intradiscal applications of DEM (Dulbecco’s modified eagle’s medium), one and two weeks after intervertebral disc degeneration (IVDD), while group B received two intradiscal applications of 1.2 x 106 BM-SC at the same time interval as group A. After IVDD, group C received eight subcutaneous applications of CS at a dose of 5 mg/kg, one application every seven days. In contrast, group D received the association of the techniques used in groups B and C. Sixty days after the end of the interventions, all animals were euthanized, then the crani-ocaudal thickness of the IVD was measured, and IVDD was classified in scores according to the histological grading model. All groups that received CS had thicker IVDs, and all the treated groups presented better scores on several items and a better overall score. It was possible to conclude that in the species studied, the isolated use of CS or BM-SC was statistically significant in improv-ing the histopathological aspects of IVDD, however, the combination of treat-ments did not prove to be more efficient.

The muscle-intervertebral disc interaction mediated by L-BAIBA modulates extracellular matrix homeostasis and PANoptosis in nucleus pulposus cells.

Upon engaging in physical activity, skeletal muscle synthesizes myokines, which not only facilitate crosstalk with various organs, including the brain, adipose tissue, bone, liver, gut, pancreas, and skin but also promote intramuscular signaling. Crosstalk is vital for maintaining various physiological processes. However, the specific interactions between skeletal muscle and intervertebral discs remain largely unexplored. β-Aminoisobutyric acid (BAIBA), an exercise-induced myokine and a metabolite of branched-chain amino acids in skeletal muscle, has emerged as a key player in this context. Our study demonstrated that exercise significantly elevates BAIBA levels in skeletal muscle, plasma, and nucleus pulposus (NP) tissues. Moreover, exercise enhances extracellular matrix (ECM) synthesis in NP tissues and upregulates L-BAIBA synthase in skeletal muscle. Both in vivo and in vitro evidence revealed that L-BAIBA impedes PANoptosis and ECM degradation in NP cells by activating the AMPK/NF-κB signaling pathway. These findings suggest that exercise, coupled with the resulting increase in L-BAIBA, may serve as an effective intervention to decelerate the progression of intervertebral disc degeneration (IDD). Consequently, L-BAIBA, which originates from skeletal muscle, is a promising new therapeutic approach for IDD.

Stem Cell Membrane-Camouflaged Biomimetic Nanoparticles Inhibiting Leptin Pathway for Intervertebral Disc Degeneration Therapy.

Leptin, a kind of adipokine, with its receptor in which the long isoform plays a crucial role in signal transduction, has been identified in intervertebral disc (IVD) tissues, especially showing an increased expression in degenerated discs. Initially identified as a metabolic sensor, leptin has recently been found able to regulate inflammation into imbalance, which favors catabolic degradative processes, thus contributing to progressive intervertebral disc degeneration (IDD). Therefore, efficiently inhibiting the leptin pathway may provide a new strategy to treat IDD. In this study, we introduced an innovative drug delivery system (DDS) that employs stem cell membranes (SCM) to encapsulate (Zeolitic imidazolate frameworks-8) ZIF-8 nanoparticles. These nanoparticles are used to transport a plasmid containing shRNA targeting the leptin receptor (LEPR), with the aim of facilitating repair in IDD. The regenerative performances of this DDS in IDD were verified through a combination of the in vitro western blot and immunofluorescence with the in vivo radiologic examination and histological staining. The DDS demonstrated excellent cell adhesion properties and gene transfection efficiency in vitro, along with impressive treatment outcomes in vivo. Both in vitro and in vivo studies revealed that the DDS effectively reduced leptin receptor expression and alleviated the inflammatory environment, thereby promoting regeneration in degenerated IVDs. We propose that the DDS represents a promising novel approach for treating IDD and may also be beneficial for other degenerative diseases linked to leptin pathway dysfunction.

The Effect of L5 Morphology on Prevention of L5-S1 Degeneration Following Floating Fusion for Degenerative Spine Disorders.

Retrospective Study. The selection of floating fusion or lumbosacral fusion arises when treating patients with instability or stenosis of the lower lumbar spine concomitantly radiographic degeneration of L5-S1. This study aimed to investigate the preoperative anatomical or morphological factors affecting the survivorship of the L5-S1 after floating fusion. This study included 77 patients who had undergone floating fusion surgery through the TLIF approach. Preoperative radiographic parameters were evaluated using anteroposterior and lateral lumbar spine radiographs. The patients were divided into two groups according to the Modified Pfirrmann Grading and total endplate score. Multivariable regression analysis was performed to explore the relationships between the anatomical or morphological characteristics of L5 and the degeneration of L5-S1. The disc degeneration group exhibited a smaller height ratio of the iliac crest (Hi) and a less L5 deep position. Furthermore, the right/left height of L4 (Hr/Hl) and the right/left width of transverse process of L5 (CRt/CLt) were significantly higher in the disc and endplate degeneration groups. Multiple logistic regression analysis revealed that Hi and CRt were independently associated with L5-S1 disc degeneration, whereas Hr was a significant risk factor for L5-S1 endplate degeneration. Anatomical and morphological characteristics of L5, such as smaller Hi, higher CRt and Hr, were associated with an increased risk of L5-S1 degeneration in patients after floating fusion. These findings may indicate the fusion level when addressing lower lumbar degenerative diseases and the concurrent radiographic degeneration of L5-S1.

Comparison of the efficacy of autologous Lp-PRP and Lr-PRP for treating intervertebral disc degeneration: in vitro and in vivo study

BackgroundIntervertebral disc degeneration (IDD) was the most common cause of low back pain. Platelet rich plasma (PRP) has the potential to repair IDD, however, there is still no conclusion on whether Leukocyte-poor platelet rich plasma (Lp-PRP) or Leukocyte-rich platelet rich plasma (Lr-PRP) is better for the treatment of IDD.MethodsFirst, we conducted an in vitro study to compare the effects of autologous Lp-PRP and Lr-PRP on human degenerated nucleus pulposus (NP) cells. Then we verified the in vivo effects of autologous Lp-PRP and Lr-PRP in treating disc degeneration through a rabbit IDD model.ResultsThe in vitro study showed both autologous Lp-PRP and Lr-PRP can promote the cell proliferation, the synthesis of COL II and Aggrecan of human degenerated NP cells, while Lp-PRP are better than Lr-PRP (P<0.05). In addition, only Lp-PRP can inhibit the apoptosis of human degenerated NP cells (P<0.05), whereas Lr-PRP activates the catabolism on the contrary (P<0.05). Further, the in vivo study through the rabbit IDD model verified that autologous Lp-PRP has better effects than autologous Lr-PRP in repairing IDD according to X-ray, MRI, histological, and immunohistochemical assessment (P<0.05, respectively). And the caspase-3 IHC results also showed that only autologous Lp-PRP treatment could inhibit apoptosis of NP cells in the rabbit IDD model (P<0.05).ConclusionCombining in vivo and in vitro studies, the present study confirmed that autologous Lp-PRP has a better effect than autologous Lr-PRP in repairing IDD, which may be due to the inflammatory factors (TNFα, IL-1β, etc.) in Lr-PRP antagonizing part of the repair effects and promoting the catabolism additionally. Therefore, our findings suggest that Lp-PRP may provide better results than Lr-PRP for treating IDD. Further randomized clinical trials will provide evidence to guide practice.

Multifidus Degeneration: The Key Imaging Predictor of Adjacent Segment Disease.

Retrospective cohort study. To identify imaging predictors on pre- and perioperative imaging that are associated with a future revision surgery for adjacent segment disease (ASD) following lumbar fusion. Patients undergoing open posterior lumbar fusion between 2014-2022 were followed-up for >2-year. The initial MRI was evaluated for disc degeneration by Pfirrmann (grade 1-5); Modic changes (0-3); as well as fatty infiltration and functional cross-sectional area (fCSA) of the multifidus, erector spinae, and psoas. Spinopelvic alignment was measured pre- and postoperatively. Of 216 patients, 14.8% (n = 32) required revision surgery for ASD in the further course. There were no significant differences in Modic changes or Pfirrmann grades between the ASD group and controls. Fatty infiltration was significantly higher in the ASD group for both the erector spinae (40.5% vs 36.9%, P = 0.043) and multifidus muscles (61.0% vs 53.9%, P = 0.003). Additionally, the multifidus fCSA was smaller in patients who developed ASD (5.7cm2 vs 6.7cm2). Pre- and postoperative spinopelvic parameters were not significantly different between groups, and no other MRI measurements showed a significant difference. In a multivariable logistic regression model adjusting for age and sex, multifidus fatty infiltration emerged as the only significant predictor of ASD revision surgery (P = 0.004). Patients with more than 58% multifidus fatty infiltration had over double the risk of developing ASD (OR 2.7, 95% CI: 1.1-6.5, P = 0.032). Multifidus fatty infiltration is the key imaging predictor for the development of ASD requiring surgical revision. Disc degeneration and spinopelvic alignment appear to have less impact.

CILP-2 expression in the intervertebral discs of patients with lumbar radiculopathy

BackgroundIntervertebral disc (IVD) degeneration (IVDD) is one of the main causes of low back pain. One of the most important features of IVDD is the loss of extracellular matrix (ECM) with its structural components. Cartilage intermediate layer proteins (CILPs), minor glycoproteins residing in ECM, have been found to be increased in IVD as degeneration and aging progresses. The aim of the present study was to evaluate the expression of CILP-2 in the IVD of patients with lumbar radiculopathy.MethodsThe IVD samples were collected from 25 patients during spinal surgery (interlaminectomy, herniated disc removal). The control IVD samples were obtained from nine patients who underwent lateral corpectomies in the thoracic region. CILP-2 expression was detected by immunohistochemistry. The patients were divided into two groups – aged under or over 50 years. A standardized clinical examination with assessment of radicular signs and deficits was performed. Subjective disability and pain were assessed using the visual analogue scale and Oswestry Disability Index (ODI). The pre-operative MRI was graded for the degree of IVD degeneration by Pfirrmann grading system. IVD samples obtained during operations were subjected to the standardized histopathological analysis applying modified Boos classification. The data were analysed by t-test, Mann-Whitney U-test, and Spearman correlation test.ResultsBoth histopathology scores and Pfirrmann grades did not differ between patients’ groups. Also, no correlations were found between histopathology and Pfirrmann grades, neither were any differences seen when correlating both grades to ODI, back pain or leg pain scores. CILP-2 staining was noted in all studied samples, notably strong staining was seen around large cell clusters. However, no differences in CILP-2 staining were seen between the age groups of patients. No correlations were found between CILP-2 staining and Pfirrmann grades. Grading of CILP-2 immunostaining in nine control patient samples resulted in significantly lower values. The difference is statistically significant (P = 0.002) compared to CILP-2 staining scores of all 25 patients’ samples.ConclusionIn this study, we detected increased CILP-2 expression in the human IVD as compared to the control group patients. CILP-2 can be a possible IVDD marker; however, as knowledge about the role of CILP-2 is limited, further studies are required.

Causal effects of plasma proteome on intervertebral disc degeneration: a comprehensive mendelian randomization study.

Intervertebral disc degeneration (IVDD) considerably impacts global disability and quality of life. Although potential links between plasma proteins and IVDD exist, their causal correlation remains undefined. This study explored the causal links between plasma proteins and IVDD employing genome-wide association study data. For this observational study, summary statistics for plasma proteins were derived from an Icelandic population, paralleled with genome-wide data on IVDD obtained from the FinnGen consortium. Using two-sample Mendelian randomization, we assessed the causal relationship between 4,907 plasma proteins and IVDD. Standard sensitivity analyses encompassing heterogeneity, pleiotropy, and leave-one-out cross-validation tests confirmed the stability and robustness of the findings. Subsequently, through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and protein interaction analyses, we delved into the functional interrelation among identified plasma proteins. A causal association with IVDD was identified for 47 plasma proteins; myoneurin, intersectin 1, and eukaryotic translation initiation factor 4 gamma 3 maintained significant correlations post multiple correction tests (P < 1.02 × 10- 5), influencing IVDD development positively. GO/KEGG pathway analyses confirmed that multiple pathways may be involved in IVDD development. The study underscores the causal correlation between plasma protein levels and IVDD risk. These identified proteins could emerge as unique biomarkers for IVDD, contributing to its predictive measures. The findings further our understanding of IVDD pathomechanisms and prospective therapeutic targets.

Efficacy of Stand-Alone Anterior Lumbar Interbody Fusion With PEEK Cages, BMP-2, and Allografts for Treating Discogenic Low Back Pain: Assessing Clinical and Radiographic Outcomes.

Chronic low back pain secondary to degenerative disc disease is a significant public health issue worldwide, contributing to substantial health care burdens and patient disability. Anterior lumbar interbody fusion (ALIF) has emerged as a promising surgical solution, offering benefits such as disc height restoration, reduced neural compression, and improved spinal alignment. This study evaluates the efficacy of stand-alone ALIF using polyetheretherketone (PEEK) cages, structural femoral head allografts, and recombinant human bone morphogenetic protein-2 (rhBMP-2) in treating discogenic low back pain caused by degenerative disc disease. This prospective case series study included 1335 patients who underwent stand-alone ALIF by a single surgeon. The surgical construct involved PEEK cages with structural femoral allograft dowels and rhBMP-2, supplemented by anterior fixation. Patient-reported outcome measures, including the visual analog scale for back and leg pain, the Oswestry Disability Index, the Roland-Morris Disability Questionnaire, and patient satisfaction, were monitored over 12 months. The overall fusion rate was 99.6%, with pseudoarthrosis occurring in 0.2% of patients. Lower fusion rates were observed in patients older than 65 years and those using the Brantigan cage. Significant improvements were seen in visual analog scale for back and leg pain, Oswestry Disability Index, and Roland-Morris Disability Questionnaire scores from baseline, with most scores exceeding the substantial clinical benefit thresholds. More than 85% of patients reported "Excellent" or "Good" outcomes. Stand-alone ALIF, augmented with rhBMP-2 and structural femoral head allografts, can enhance mechanical stability, fusion rates, and radiographic assessment. This integrated approach achieves successful spinal fusion and positive clinical outcomes for patients with refractory discogenic low back pain. Stand-alone ALIF with PEEK cages, structural femoral head allografts, and rhBMP-2 demonstrates high fusion rates and significant clinical improvements in patients with discogenic low back pain. This approach enhances spinal stability and promotes biological healing, making it a reliable and effective surgical option.