Introduction. Low back pain (LBP) is a worldwide leading cause of disability. This preclinical study evaluated the safety of a combined advanced therapy medicinal product developed during the European iPSpine project (#825925) consisting of mesendoderm progenitor cells (MEPC), derived from human induced pluripotent stem cells, in combination with a synthetic poly(N-isopropylacrylamide) hydrogel (NPgel) in an ovine intervertebral disc degeneration (IDD) model. Method. IDD was induced through nucleotomy in 4 adult sheep, 5 lumbar discs each (n=20). After 5 weeks, 3 alternating discs were treated with NPgel (n=6) or NPgel+MEPC (n=6). Before sacrifice, animals were subjected to: MRI of lumbar spines (disc height and Pfirmann grading); blood sampling (hematological, biochemical, metabolic and lymphocyte/monocytes immunological). After 3 months the sheep were sacrificed. The spines were processed for: macroscopic morphology (Thompson grading), microscopic morphology (Histological grading), and glycosaminoglycan content (GAG, DMMB Assay). Furthermore, at sacrifice biodistribution of human MEPC was assessed by Alu-sequences quantification (qPCR) from three tissue samples of heart, liver, spleen, brain, lungs, and kidneys, and PBMCs collected to assess activation of systemic immune cells. To each evaluation, appropriate statistical analysis was applied. Result. Flow cytometry showed no induction of systemic activation of T cells or monocytes. Alu quantification did not give detection of any cells in any organ. Disc height index was slightly increased in discs treated with NPgel+MEPC. Pfirmann's and Thompson's classification showed that treatment with NPgel or NPgel+MEPC gave no adverse reactions. Histological grading showed similar degeneration in vertebrae treated with NPgel+MEPC or with NPgel alone. The amount of GAG was significantly increased in the nucleus pulposus following treatment with NPgel+MEPC compared to NPgel alone, in which a decrease was observed compared to untreated discs in both nucleus pulposus and annulus fibrosus. Conclusion. This study showed the safety of both NPgel+MEPC and NPgel treatments

Introduction. Intervertebral disc degeneration has been associated with low back pain (LBP) which is a major cause of long-term disability worldwide. Observed mechanical and biological modifications have been related to decreased water content. Clinical traction protocols as part of LBP management have shown positive outcomes. However, the underlying mechanical and biological processes are still unknown. The study purpose was to evaluate the impact of unloading through traction on the mechanobiology of healthy bovine tail discs in culture. Method. We loaded bovine tail discs (n=3/group) 2h/day at 0.2Hz for 3 days, either in dynamic compression (-0.01MPa to -0.2MPa) or in dynamic traction (-0.01MPa to 0.024MPa). In between the dynamic loading sessions, we subjected the discs to static compression loading (-0.048MPa). We assessed biomechanical and biological parameters. Result. Over the 3 days of loading, disc height decreased upon dynamic compression loading but increased upon unloading. The neutral zone was restored for all samples at the end of the dynamic unloading. Upon dynamic compression, the stiffness increased over time while the hysteresis decreased. Upon dynamic unloading, sulfated glycosaminoglycan (sGAG) release in the medium was lower at the endpoint. In the outer annulus fibrosus (AFo), we saw a higher water/sGAG of at least 30%. In the nucleus pulposus, COL2 mRNA was expressed more highly upon dynamic unloading while MMP3, iNOS and TRPV4 expression levels were lower. In the AFo of the unloading group, COL2 expression was higher but COL1 was lower. Conclusion. The biomechanical and biological results consistently indicate that dynamic unloading of healthy bovine discs in culture facilitates water uptake and promotes an anti-catabolic response which reflects a function optimization of the disc. This work combines biomechanical and biological results and opens the door to evidence-based improvement of regenerative protocols for degenerated discs and conservative LBP management. This study is funded by AO Foundation and AO Spine

Background. The association between lumbar intervertebral disc degeneration (LDD) and low back pain (LBP) is modest. We have recently shown that genetic propensity to pain is an effect modifier of the LDD-LBP relationship when LDD is defined as a summary score of LDD (LSUM), suggesting the association may be driven by individuals with the greatest genetic predisposition to pain. This study examined the association between individual spine magnetic resonance imaging (MRI)-determined LDD features and LBP in subgroups defined by genetic predisposition to pain. Method. We developed a polygenic risk score (PRS) for “genetic propensity to pain” defined as the number of non-back pain locations (head, face, neck/shoulder, stomach/abdomen, hip, and knee) with duration ≥3 months in 377,538 UK Biobank participants of European ancestry. This PRS was used to stratify TwinsUK MRI samples (n=645) into four strata of genetic propensity to pain. We examined the association between LBP and MRI features of lumbar disc height, disc signal intensity, disc bulge, and osteophytes with adjustments for age, sex, PRS strata, interaction terms for each MRI feature x PRS strata, and twin status. Results. We found significant effect modification of the LDD-LBP relationship by genetic propensity to pain for the lumbar MRI features of disc height (p=0.03 for the interaction term with highest quartile of genetically-predicted propensity to pain) and disc signal intensity (p=0.001), but not for disc bulge and osteophytes. Conclusion. Genetic propensity to pain modifies the association between individual LDD features and LBP and should be considered in LBP clinical studies. Conflicts of interest. No conflicts of interest. Sources of funding. No funding obtained. Acknowledgement. UKBB data were obtained under the project #18219. This paper is submitted to the Spine journal and is under review

Study purpose and background. Kinematic variables have been identified as potential biomarkers for low back pain patients; however, an in-depth comparison between chronic (n=22), acute (n=15), and healthy controls (n=136) has not been done. This retrospective data analysis compared intervertebral lumbar motion parameters, angular range of motion, translation, maximum disc height, motion share inequality (MSI) and variability (MSV), and laxity, between these groups. Methods and results. Kinematic parameters were determined using video tracking techniques utilising quantitative fluoroscopy (QF), during both weight-bearing and recumbent controlled sagittal bending tasks. Data was analysed for normality, and appropriate statistical tests were applied to determine differences between groups. There were no significant differences between the groups for age, height, weight and sex. Whilst few differences were found between acute and healthy groups, differences were shown between both chronic and healthy, and acute and chronic groups for all six parameters. Of particular note were examples of differences in the motion share parameters between the acute and chronic populations, with an increased MSI in the chronic group during recumbent flexion, and MSV during recumbent extension, and inversely an increase in MSV in the acute group during weight-bearing flexion. Conclusion. Analysis of intervertebral lumbar motion provides valuable insights into kinematic differences between chronic, acute, and healthy control populations. These findings suggest that there is variation between the groups which is knowledge that may benefit management strategies. Further exploration of the time varying data is warranted to explore how such differences may relate to the motion share inequalities and variability shown. Conflicts of Interest. No conflicts of interest. Sources of Funding. No funding obtained

Aims

In this investigation, we administered oxidative stress to nucleus pulposus cells (NPCs), recognized DNA-damage-inducible transcript 4 (DDIT4) as a component in intervertebral disc degeneration (IVDD), and devised a hydrogel capable of conveying small interfering RNA (siRNA) to IVDD.

Mechanical loading is important to maintain the homeostasis of the intervertebral disc (IVD) under physiological conditions but can also accelerate cell death and tissue breakdown in a degenerative state. Bioreactor loaded whole organ cultures are instrumental for investigating the effects of the mechanical environment on the IVD integrity and for preclinical testing of new therapies under simulated physiological conditions. Thereby the loading parameters that determine the beneficial or detrimental reactions largely depend on the IVD model and its preparation. Within this symposium we are discussing the use of bovine caudal IVD culture models to reproduce tissue inflammation or matrix degradation with or without bioreactor controlled mechanical loading. Furthermore, the outcome parameters that define the degenerative state of the whole IVD model will be outlined. Besides the disc height, matrix integrity, cell viability and phenotype expression, the tissue secretome can provide indications about potential interactions of the IVD with other cell types such as neurons. Finally, a novel multiaxial bioreactor setup capable of mimicking the six degrees-of-freedom loading environment of IVDs will be introduced that further advances the relevance of preclinical ex-vivo testing

Stand-alone anterior lumbar interbody fusion (ALIF) provides the opportunity to avoid supplemental posterior fixation. This may reduce morbidity and complication rate, which is of special interest in patients with reduced bone mineral density (BMD). This study aims to assess immediate biomechanical stability and radiographic outcome of a stand-alone ALIF device with integrated screws in specimens of low BMD. Eight human cadaveric spines (L4-sacrum) were instrumented with SynFix-LR™ (DePuy Synthes) at L5/S1. Quantitative computed tomography was used to measure BMD of L5 in AMIRA. Threshold values proposed by the American Society of Radiology 80 and 120 mg CaHa/mL were used to differentiate between Osteoporosis, Osteopenia, and normal BMD. Segmental lordosis, anterior and posterior disc height were analysed on pre- and postoperative radiographs (Fig 1). Specimens were tested intact and following instrumentation using a flexibility protocol consisting of three loading cycles to ±7.5 Nm in flexion-extension, lateral bending, and axial rotation. The ranges of motion (ROM) of the index level were assessed using an optoelectronic system. BMD ranged 58–181mg CaHA/mL. Comparison of pre- and postoperative radiographs revealed significant increase of L5/S1 segmental lordosis (mean 14.6°, SD 5.1, p < 0.001) and anterior disc height (mean 5.8mm, SD 1.8, p < 0.001), but not posterior disc height. ROM of 6 specimens was reduced compared to the intact state. Two specimens showed destructive failure in extension. Mean decrease was most distinct in axial rotation up to 83% followed by flexion-extension. ALIF device with integrated screws at L5/S1 significantly increases segmental lordosis and anterior disc height without correlation to BMD. Primary stability in the immediate postoperative situation is mostly warranted in axial rotation. The risk of failure might be increased in extension for some patients with reduced lumbar BMD, therefore additional posterior stabilization could be considered. For any figures or tables, please contact the authors directly

Aims

The aim of this study was to reassess the rate of neurological, psoas-related, and abdominal complications associated with L4-L5 lateral lumbar interbody fusion (LLIF) undertaken using a standardized preoperative assessment and surgical technique.

Low back pain is the single most common cause for disability in individuals aged 45 years or younger, it carries tremendous weight in socioeconomic considerations. Degenerative aging of the structural components of the spine can be associated with genetic aspects, lifetime of tissue exposure to mechanical stress & loads and environmental factors. Mechanical consequences of the disc degenerative include loss of disc height, segment instability and increase the load on facets joints. All these can lead to degenerative changes and osteophytes that can narrow the spinal canal. Surgery is indicated in patients with spinal stenosis who have intractable pain, altered quality of life, substantially diminished functional capacity, failed non-surgical treatment and are not candidates for non-surgical treatment. The aim was to determine the reasons for refusal of surgery in patients with established degenerative lumber spine pathology eligible for surgery. All patients meeting the study criteria, patients older than 18 years, patients with both clinical and radiological established symptomatic degenerative lumbar spine pathology and patients eligible for surgery but refusing it were recruited. Questionnaire used to investigate reasons why they are refusing surgery. Results 59 were recruited, fifty-one (86.4 %) females and eight (13.6 %) males. Twenty (33.8 %) were between the age of 51 and 60 years, followed by nineteen (32.2 %) between 61 and 70 years, and fourteen (23.7 %) between 71 and 80 years. 43 (72 %) patients had lumber spondylosis complicated by lumber spine stenosis, followed by nine (15.2 %) with lumbar spine spondylolisthesis and four (6.7 %) had adjacent level disease. 28 (47.4 %) were scared of surgery, fifteen (25.4 %) claimed that they are too old for surgery and nine (15.2 %) were not ready. Findings from this study outlined that patients lack information about the spinal surgery. Patients education about spine surgery is needed

Using deep learning and image processing technology, a standardized automatic quantitative analysis systerm of lumbar disc degeneration based on T2MRI is proposed to help doctors evaluate the prognosis of intervertebral disc (IVD) degeneration. A semantic segmentation network BianqueNet with self-attention mechanism skip connection module and deep feature extraction module is proposed to achieve high-precision segmentation of intervertebral disc related areas. A quantitative method is proposed to calculate the signal intensity difference (SI) in IVD, average disc height (DH), disc height index (DHI), and disc height-to-diameter ratio (DHR). According to the correlation analysis results of the degeneration characteristic parameters of IVDs, 1051 MRI images from four hospitals were collected to establish the quantitative ranges for these IVD parameters in larger population around China. The average dice coefficients of the proposed segmentation network for vertebral bodies and intervertebral discs are 97.04% and 94.76%, respectively. The designed parameters of intervertebral disc degeneration have a significant negative correlation with the Modified Pfirrmann Grade. This procedure is suitable for different MRI centers and different resolution of lumbar spine T2MRI (ICC=.874~.958). Among them, the standard of intervertebral disc signal intensity degeneration has excellent reliability according to the modified Pfirrmann Grade (macroF1=90.63%~92.02%). we developed a fully automated deep learning-based lumbar spine segmentation network, which demonstrated strong versatility and high reliability to assist residents on IVD degeneration grading by means of IVD degeneration quantitation

Aims

Spinopelvic characteristics influence the hip’s biomechanical behaviour. However, to date there is little knowledge defining what ‘normal’ spinopelvic characteristics are. This study aims to determine how static spinopelvic characteristics change with age and ethnicity among asymptomatic, healthy individuals.

Aims

The optimal procedure for the treatment of ossification of the posterior longitudinal ligament (OPLL) remains controversial. The aim of this study was to compare the outcome of anterior cervical ossified posterior longitudinal ligament en bloc resection (ACOE) with posterior laminectomy and fusion with bone graft and internal fixation (PTLF) for the surgical management of patients with this condition.

Aims

CRP is an acute-phase protein that is used as a biomarker to follow severity and progression in infectious and inflammatory diseases. Its pathophysiological mechanisms of action are still poorly defined. CRP in its pentameric form exhibits weak anti-inflammatory activity. The monomeric isoform (mCRP) exerts potent proinflammatory properties in chondrocytes, endothelial cells, and leucocytes. No data exist regarding mCRP effects in human intervertebral disc (IVD) cells. This work aimed to verify the pathophysiological relevance of mCRP in the aetiology and/or progression of IVD degeneration.

The December 2022 Spine Roundup³⁶⁰ looks at: Deep venous thrombosis prophylaxis protocol on a Level 1 trauma centre patient database; Non-specific spondylodiscitis: a new perspective for surgical treatment; Disc degeneration could be recovered after chemonucleolysis; Three-level anterior cervical discectomy and fusion versus corpectomy- anterior cervical discectomy and fusion “hybrid” procedures: how does the alignment look?; Rivaroxaban or enoxaparin for venous thromboembolism prophylaxis; Surgical site infection: when do we have to remove the implants?; Determination of a neurologic safe zone for bicortical S1 pedicle placement; Do you need to operate on unstable spine fractures in the elderly: outcomes and mortality; Degeneration to deformity: when does the patient need both?

Background. We have previously reported an injectable hydrogel (NPgel), which could deliver patients own stem cells, via small bore needles, decreasing damage to the annulus fibrosus. NPgel drives differentiation to NP cells and can inhibit the degenerate niche. However, clinical success of NPgel is dependent on the capacity to inject NPgel into naturally degenerate human discs, restore mechanical function to the IVD, prevent extrusion during loading and induce regeneration. This study assessed injectability of NPgel into human IVD, influence on mechanical properties, regeneration ability in an ex vivo culture system and retention under failure testing. Methodology. Cadaveric human discs were used to calculate disc height and to determine Youngs Modulus during simulated walking pre and post injection of NPgel, extrusion testing performed. Whole human IVDs were injected with NPgel +/− human BMPCs and maintained in culture under physiological loading regime for 4 weeks. Pre and post culture MRI imaging and in line biomechanical characteristics determined. Histology and immunochemistry performed for anabolic and catabolic factors. Results. NPgel injection significantly increased disc height and Youngs modulus with no extrusion observed during failure testing. T1ρ intensity was increased during culture in those injected with NPgel +/− cells compared to non-injected discs, and biomechanical restoration. Histological analysis has demonstrated excellent tissue attachment to the injected gel, and cellular migration into acellular gel systems. With increased matrix production and decreased catabolic factor expression. Conclusion. These results provide essential proof of concept data supporting the use of NPgel as an injectable therapy for disc regeneration. Conflict of interest: C Le Maitre & C Sammon are inventors on the hydrogel discussed. Funding: This work was funded by MRC and Versus Arthritis

Osteoarthritis (OA) is a painful and disabling chronic condition that constitutes a major challenge to health care worldwide. There is currently no cure for OA and the analgesic pharmaceuticals available do not offer adequate and sustained pain relief, often being associated with significant undesirable side effects. Another disease associated with degenerating joints is Intervertebral disc degeneration (IVDD) which is a leading cause of chronic back pain and loss of function. It is characterized by the loss of extracellular matrix, specifically proteoglycan and collagen, tissue dehydration, fissure development and loss of disc height, inflammation, endplate sclerosis, cell death and hyperinnervation of nociceptive nerve fibers. The adult human IVD seems incapable of intrinsic repair and there are currently no proven treatments to prevent, stop or even retard disc degeneration. Fusion is currently the most common surgical treatment of symptomatic disc disease. However, radiographic follow-up studies have revealed that many patients develop adjacent segment disc degeneration due to altered spine biomechanics. The development of safe and efficacious disease modifying OA drugs (DMOADs) that treat pain and inflammation in joints will improve our ability to control the disease. I addition, a biologic treatment of IVDD is desirable. This presentation will provide an overview of recent advances and future prospects of a multimodal biologic treatment of OA, and IVDD. We will focus on Link N, a naturally occurring peptide representing the N terminal region of link protein and the first 1–8 residues of Link N (short Link N, sLN) responsible for the biologic therapy in question

Aims

To study the associations of lumbar developmental spinal stenosis (DSS) with low back pain (LBP), radicular leg pain, and disability.

Aims. To determine the effectiveness of prone traction radiographs in predicting postoperative slip distance, slip angle, changes in disc height, and lordosis after surgery for degenerative spondylolisthesis of the lumbar spine. Methods. A total of 63 consecutive patients with a degenerative spondylolisthesis and preoperative prone traction radiographs obtained since 2010 were studied. Slip distance, slip angle, disc height, segmental lordosis, and global lordosis (L1 to S1) were measured on preoperative lateral standing radiographs, flexion-extension lateral radiographs, prone traction lateral radiographs, and postoperative lateral standing radiographs. Patients were divided into two groups: posterolateral fusion or posterolateral fusion with interbody fusion. Results. The mean changes in segmental lordosis and global lordosis were 7.1° (SD 6.7°) and 2.9° (SD 9.9°) respectively for the interbody fusion group, and 0.8° (SD 5.1°) and -0.4° (SD 10.1°) respectively for the posterolateral fusion-only group. Segmental lordosis (ρ = 0.794, p < 0.001) corrected by interbody fusion correlated best with prone traction radiographs. Global lumbar lordosis (ρ = 0.788, p < 0.001) correlated best with the interbody fusion group and preoperative lateral standing radiographs. The least difference in slip distance (-0.3 mm (SD 1.7 mm), p < 0.001), slip angle (0.9° (SD 5.2°), p < 0.001), and disc height (0.02 mm (SD 2.4 mm), p < 0.001) was seen between prone traction and postoperative radiographs. Regression analyses suggested that prone traction parameters best predicted correction of slip distance (Corrected Akaike’s Information Criterion (AICc) = 37.336) and disc height (AICc = 58.096), while correction of slip angle (AICc = 26.453) was best predicted by extension radiographs. Receiver operating characteristic (ROC) cut-off showed, with 68.3% sensitivity and 64.5% specificity, that to achieve a 3.0° increase in segmental lordotic angle, patients with a prone traction disc height of 8.5 mm needed an interbody fusion. Conclusion. Prone traction radiographs best predict the slip distance and disc height correction achieved by interbody fusion for lumbar degenerative spondylolisthesis. To achieve this maximum correction, interbody fusion should be undertaken if a disc height of more than 8.5 mm is attained on preoperative prone traction radiographs. Level of Evidence: Level II Prognostic Study. Cite this article: Bone Joint J 2020;102-B(8):1062–1071