Purpose. Cognitive Muscular Therapy (CMT) is a new treatment for low back pain which integrates psychological techniques for pain management alongside training to improve postural control. Rather than focus on postural alignment or strength, CMT aims to improve the regulation of postural tone (low-level activity which supports the body against gravity). This is achieved by teaching patients an awareness of compensatory paraspinal activation, which can be triggered by overactivity of the abdominal muscles. The aim of this study was to understand whether CMT could reduce symptoms associated with low back pain and improve paraspinal muscle activation. Methods and results. Fifteen patients with chronic low back pain received seven weekly sessions of CMT from a physiotherapist. Clinical data was captured at baseline and two weeks after the intervention using the Roland-Morris questionnaire and the pain catastrophising scale. Activation of the erector spinae muscle during walking was also measured at baseline and after the final intervention session. Change data were analysed using paired t-tests. There was a 75% reduction (p<0.001) in the Roland-Morris score from a mean (SD) of 9.3(2.9) to 2.3(2.6), along with a 78% reduction in pain catastrophising (p<0.002) from 16.6(13) to 3.7(4.8). Activation of the contralateral erector spinae muscles reduced by 30% (p<0.01) during the contralateral swing phase of walking. Conclusion. In this small sample, CMT delivered large clinical improvements and reduced activation of the low back muscles during walking. Larger randomised trials are now required to confirm whether CMT could outperform existing physiotherapy treatments for chronic back pain. Conflict of interest. No conflicts of interest. Source of funding. University of Salford

Background. Lateral lumbar spine statistical shape models (SSM) have been used previously to describe associations with osteoarthritis and back pain. However, associations with factors such as osteoporosis, menopause and parity have not been explored. Methods and Results. A 143-point SSM, describing L1 to the top of L5, was applied to lateral spine iDXA scans from UK Biobank. Associations with self-reported osteoporosis, menopause, parity and back pain and the first 10 modes of variation were examined using adjusted binary logistic regression or linear regression (adjusted for age, height, weight and total spine BMD). We report odds ratios with 95% confidence intervals for each standard deviation change in mode. Complete data were available for 2494 women. Mean age was 61.5 (± 7.4) years. 1369 women reported going through menopause, 96 women self-reported osteoporosis and 339 women reported chronic back pain. 80% of women reported at least 1 live birth. Lumbar spine shape was not associated with back pain in this cohort. Two modes were associated with menopause (modes 1 & 2), 1 mode with parity (mode 1) and 2 modes with osteoporosis (modes 3 & 5). Mode 1 (43.6% total variation), describing lumbar curvature was positively associated with both menopause [OR 1.15 95% CI 1.00–1.33, p=0.05] and parity [OR 1.058 95% CI 1.03–1.0, p=0.01]. Mode 3, describing decreased vertebral height was positively associated with osteoporosis [OR 1.40 95% CI 1.14–1.73, p=0.001]. Conclusion. Menopause and parity were associated with a curvier lumbar spine and osteoporosis with decreased vertebral height. Shape was not associated with back pain. No conflicts of interest.  . Sources of funding. Wellcome Trust collaborative award ref 209233

Background. Chronic back pain (CBP) is a major cause of disability globally and its causes are multifactorial. Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) are human herpes viruses usually acquired in early life. About 50% and over 90% of the population worldwide have been infected with CMV and EBV, respectively. This study investigated a potential causal relationship between CMV infection and CBP. Method. UK Biobank participants provided information on CMV seropositivity and CBP status, which were available for both traits in 5,140 participants. We used EBV seropositivity as a negative control to identify confounding and inaccurate causal inference. A one-sample Mendelian randomization (MR) based on independent genetic variants predicting CMV and EBV positivity was conducted in Northern European participants. To validate the association further, the MR study was repeated using a CMV polygenic risk score (PRS). Results. CMV GWAS revealed 86 independent SNPs having p-value < 2 × 10. −4. for the one-sample MR. These SNPs were used to define genetically-predicted categories of CMV infection risk. CMV infection risk categories were significantly associated with CBP (OR = 1.150; 95% CI: 1.005–1.317, p-value = 0.043), findings which were confirmed using the CMV PRS (OR = 1.299; 95% CI: 1.141–1.479, p-value = 0.001). There was no causal association between EBV and CBP (p-value = 0.17). Conclusion. Our results provide further evidence for a causal relationship between CMV infection and CBP. These results suggest a stratified approach to CBP may be useful, particularly in clinical trials and they shed light on underlying mechanisms in CBP. Conflicts of interest. No conflicts of interest. Sources of funding. No funding obtained. Acknowledgement. UKBB data were obtained under the project #18219. Some aspects of this work have been previously presented at The Challenge of Chronic Pain: From Genomics to Therapy in UK and first 1st Danish International Conference on Personalised Medicine in Denmark

Intervertebral disc (IVD) degeneration is a pathological process often associated with chronic back pain and considered a leading cause of disability worldwide. 1. During degeneration, progressive structural and biochemical changes occur, leading to blood vessel and nerve ingrowth and promoting discogenic pain. 2. In the last decades, several cytokines have been applied to IVD cells in vitro to investigate the degenerative cascade. Particularly, IL-10 and IL-4 have been predicted as important anabolic factors in the IVD according to a regulatory network model based in silico approach. 3. Thus, we aim to investigate the potential presence and anabolic effect of IL-10 and IL-4 in human NP cells (in vitro) and explants (ex vivo) under hypoxia (5% O2) after a catabolic induction. Primary human NP cells were expanded, encapsulated in 1.2% alginate beads (4 × 106 cells/ml) and cultured for two weeks in 3D for phenotype recovery while human NP explants were cultured for five days. Afterwards, both alginate and explant cultures were i) cultured for two days and subsequently treated with 10 ng/ml IL-10 or IL-4 (single treatments) or ii) stimulated with 0.1 ng/ml IL-1β for two days and subsequently treated with 10 ng/ml IL-10 or IL-4 (combined treatments). The presence of IL-4 receptor, IL-4 and IL-10 was confirmed in human intact NP tissue (Fig 1). Additionally, IL-4 single and combined treatments induced a significant increase of proinflammatory protein secretion in vitro (Fig. 2A-C) and ex vivo (Fig. 2D and E). In contrast, no significant differences were observed in the secretome between IL-10 single and combined treatments compared to control group. Overall, IL-4 containing treatments promote human NP cell and explant catabolism in contrast to previously reported IL-4 anti-inflammatory performance. 4. Thus, a possible pleiotropic effect of IL-4 could occur depending on the IVD culture and environmental condition. Acknowledgements: This project was supported by the Marie Skłodowska Curie International Training Network “disc4all” under the grant agreement #955735. For any figures and tables, please contact the authors directly

Intervertebral disc (IVD) degeneration is responsible for severe clinical symptoms including chronic back pain. Galectins are a family of carbohydrate-binding proteins, some of which can induce functional disease markers in IVD cells and other musculoskeletal diseases. Galectins −4 and −8 were shown to trigger disease-promoting activity in chondrocytes but their effects on IVD cells have not been investigated yet. This study elucidates the role of galectin-4 and −8 in IVD degeneration. Immunohistochemical evidence for the presence of galectin-4 and −8 in the IVD was comparatively provided in specimens of 36 patients with spondylochondrosis, spondylolisthesis, or spinal deformity. Confocal microscopy revealed co-localization of galectin-4 and −8 in chondrocyte clusters of degenerated cartilage. The immunohistochemical presence of galectin-4 correlated with histopathological and clinical degeneration scores of patients, whereas galectin-8 did not show significant correlations. The specimens were separated into annulus fibrosus (AF), nucleus pulposus (NP) and endplate, which was confirmed histologically. Separate cell cultures of AF and NP (n=20) were established and characterized using cell type-specific markers. Potential binding sites for galectins including sialylated N-glycans and LacdiNAc structures were determined in AF and NP cells using LC/ESI-MS-MS. To assess galectin functions, cell cultures were treated with recombinant galectin-4 or −8, in comparison to IL-1β, and analyzed using RT-qPCR and In-cell Western blot. In vitro, both galectins triggered the induction of functional disease markers (CXCL8 and MMP3) on mRNA level and activated the nuclear factor-kB pathway. NP cells were significantly more responsive to galectin-8 and Il-1β than AF cells. Phosphorylation of p-65 was time-dependently induced by both galectins in both cell types to a comparable extent. Taken together, this study provides evidence for a functional role of glycobiological processes in IVD degeneration and highlights galectin-4 and −8 as regulators of pro-inflammatory and degrative processes in AF and NP cells

Tryfonidou leads the Horizon 2020 consortium (iPSpine; 2019–2023) bringing a transdisciplinary team of 21 partners together to address the challenges and bottlenecks of iPS-based advanced therapies towards their transition to the clinic. Here, chronic back pain due to intervertebral disc degeneration is employed as a show case. The project develops the iPS-technology and designed smart biomaterials to carry, protect and instruct the iPS cells within the degenerate disc environment. This work will be presented including ongoing activities focus on translating the developed methodology and tools towards clinically relevant animal models. The consortium optimized the protocol for the differentiated iPS-notochordal-like cells (iPS-NLCs) and shortlisted two biomaterials shortlisted based on their physicochemical, cytotoxicity, biomechanical and biocompatibility testing. Both were shown to be safe and have been tested with the progenitors of iPS-NLCs. An advanced platform (e.g., the dynamic loading bioreactor for disc tissue) was used to evaluate their performance: the biomaterials supported the iPS-NLC progenitors after injection into the degenerate disc and seem to also support their maturation towards NLCs. Furthermore, we confirmed the capacity of these cells to survive inside degenerated discs at 30 days upon injection in sheep, whereafter we continued with their evaluation at 3 months post-injection. We achieved full evaluation of the sheep spines, including biomechanical analysis using the portable spine biomechanics tester prior analysis at the macro- and microscopic, and biochemical level

This edition of Cochrane Corner looks at some of the work published by the Cochrane Collaboration, covering pharmacological interventions for the prevention of bleeding in people undergoing definitive fixation or joint replacement for hip, pelvic, and long bone fractures; interventions for reducing red blood cell transfusion in adults undergoing hip fracture surgery: an overview of systematic reviews; and pharmacological treatments for low back pain in adults: an overview of Cochrane Reviews

Cite this article: Bone Joint Res 2023;12(3):199–201.

Aims

To develop and internally validate a preoperative clinical prediction model for acute adjacent vertebral fracture (AVF) after vertebral augmentation to support preoperative decision-making, named the after vertebral augmentation (AVA) score.

Chronic low back pain (cLBP) is a complex, multifaceted disorder where biological, psychological, and social factors affect its onset and trajectory. Consequently, cLBP encompasses many different disease variants, with multiple patient-specific mechanisms. The goal of NIH Back Pain Consortium (BACPAC) Research Program is to develop understanding of cLBP mechanisms and to develop algorithms that optimally match specific treatments to individual patients. To accomplish this, one research activity of BACPAC is to develop theoretical models for chronic low back pain based on the current state of knowledge in the scientific community, and to interrogate the relationships implied by the theoretical models using data generated by or available to BACPAC. The models consider biopsychosocial perspectives, and encompass both peripheral (i.e. low back) and central (i.e. spinal and supra-spinal) factors as well as proposed mechanisms of action of cLBP treatments. However, absent explanations, models/algorithms may fall short of regulatory requirements and clinician expectations, and ultimately may not be embraced by physicians and patients. To address this, BACPAC is developing a clinical utility roadmap (CUR) to clarify how models will be used in practice for selecting optimal treatments, monitoring response to treatment, and reducing health care utilization. This presentation will review the goals of BACPAC and how theoretical models and CUR are being used to support computational knowledge networks to integrate data from deeply phenotyped cLBP patients.

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

Introduction

Studies have addressed the issue of increasing prevalence of work-related musculoskeletal (MSK) pain among different occupations. However, contributing factors to MSK pain have not been fully investigated among orthopaedic surgeons. Thus, this study aimed to approximate the prevalence and predictors of MSK pain among Saudi orthopaedic surgeons working in Riyadh, Saudi Arabia.

Advanced osteoarthritis of knee is associated with low-backache in a significant number of patients and adversely affects the quality of life. There is a paucity of literature describing outcomes of backache after total-knee-arthroplasty (TKA). We evaluated backache in patients of advanced knee-osteoarthritis and their functional and radiological outcomes after TKA after approval from Institutional ethics committee. Fifty-nine patients (40 females and 19 males) were included. Mean body-mass index was 28.7. Mean visual analogue score (VAS) for knee-pain was 7.98 preoperatively and 1.6 in follow-up. For chronic backache, the mean VAS score improved from 6.08 to 2.4, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) improved from 67.5 to 37.8, Knee society score (KSS) from 49.8 to 76.6, Oswestry Disability Index (ODI) Score from 55.44 to 34.65 and SF-36 Quality-of-life score from 44.95 to 74.63. There was a significant correlation between in knee and low-back functional scores. Magnetic resonance imaging-based scoring of degenerative changes (Pfirrmann grading) showed improvement only in 13.5% patients; 56% showed no change and 30.5% showed deterioration of scores. Chronic low backache is a significant co-morbidity in advanced knee-osteoarthritis. TKA has the potential to relieve backache along with knee-pain and improves quality of life

Purpose. Back pain is the primary cause of disability worldwide yet surprisingly little is known of the underlying pathobiology. We conducted a genome-wide association study (GWAS) meta-analysis of chronic back pain (CBP). Adults of European ancestry from 15 cohorts in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and UK Biobank were studied. Methods. CBP cases were defined as reporting back pain present for ≥3–6 months; non-cases were included as comparisons (“controls”). Each cohort conducted genotyping followed by imputation. GWAS used logistic regression with additive genetic effects adjusting for age, sex, study-specific covariates, and population substructure. Suggestive (p<5×10. –7. ) & genome-wide significant (p<5×10. –8. ) variants were carried forward for replication in an independent sample of UK Biobank participants. Discovery sample n = 158,025 individuals, including 29,531 CBP cases. Results. Genome-wide significant association was found for intron variant rs12310519 in SOX5 (OR=1.08, p=7.2×10. −10. ). This was replicated in the independent sample n = 283,752, comprising 50,915 cases (OR 1.06, p=5.3×10. −11. ); in joint meta-analysis OR=1.07, p=4.5×10. −19. exceeding genome-wide significance. We found three other suggestive associations in discovery, two of which exceeded genome-wide significance in joint meta-analysis: an intergenic variant rs7833174 located between CCDC26 and GSDMC (OR 1.05, p=4.4×10. −13. ), and an intron variant, rs4384683, in DCC (OR 0.97, p=2.4×10. −10. ). Conclusion. We have identified and replicated a genetic locus associated with CBP (SOX5). We also identified 2 other loci that reached genome-wide significance in a 2-stage joint meta-analysis (CCDC26/GSDMC and DCC) which will shed light on the pathogenic mechanisms underlying CBP. Conflicts of interest: YA and LK are owners of Maatschap PolyOmica. This study was supported by the European Community's Seventh Framework Programme funded project PainOmics (Grant agreement n. 602736) and conducted using the UK Biobank Resource (project # 18219). CHARGE and other cohort-specific funding sources to be submitted- see below

Aims

The aim of this study was to examine whether hips with unilateral osteoarthritis (OA) secondary to developmental dysplasia of the hip (DDH) have significant asymmetry in femoral length, and to determine potential related factors.

Aims

The surgical treatment of tuberculosis (TB) of the spine consists of debridement and reconstruction of the anterior column. Loss of correction is the most significant challenge. Our aim was to report the outcome of single-stage posterior surgery using bone allografts in the management of this condition.

Objectives

Degenerative disc disease (DDD) and osteoarthritis (OA) are relatively frequent causes of disability amongst the elderly; they constitute serious socioeconomic costs and significantly impair quality of life. Previous studies to date have found that aggrecan variable number of tandem repeats (VNTR) contributes both to DDD and OA. However, current data are not consistent across studies. The purpose of this study was to evaluate systematically the relationship between aggrecan VNTR, and DDD and/or OA.