Ankylosing spondylitis (AS) is a progressive multisystem chronic inflammatory disorder. The hallmark of this pathological process is a progressive fusion of the zygapophyseal joints and disc spaces of the axial skeleton, leading to a rigid kyphotic deformity and positive sagittal balance. The ankylosed spine is unable to accommodate normal mechanical forces, rendering it brittle and susceptible to injury. Traumatic hyperextension injury of the cervical spine leading to atlantoaxial subluxation (AAS) in AS patients can often be fatal. We report a non-traumatic mechanism of injury in AS progressing to AAS attributable to persistent hyperextension, which resulted in fatal migration of C2 through the foramen magnum. Cite this article: Bone Joint J 2013;95-B:206–9

Introduction. Although the association between osteoporosis and adolescent idiopathic scoliosis (AIS) has become widely accepted, the mechanism behind the development of osteoporosis and AIS remains unknown. To elucidate this relationship, we investigated the radiological and histological changes in a model of scoliosis in chickens, focusing on the cervical vertebrae that are not affected by scoliosis. Methods. 40 newly hatched broiler chickens were divided randomly into four equal groups: sham-operated chickens serving as control (CNT); pinealectomised chickens (PNX); and sham-operated (CNT+MLT) and pinealectomized chickens (PNX+MLT) that received intraperitoneal administration of MLT (8 mg/kg) at 2200 h daily. Pinealectomies were done at the age of 3 days. Before killing the chickens at 2 months of age, blood samples were collected at midnight and MLT concentrations were measured by radioimmunoassay. Post-mortem radiographs were examined for the presence of scoliosis, and microcomputed tomography (micro-CT) images were taken to assess the microstructure of the cervical vertebrae. Histological specimens of the scanned cervical vertebra were prepared, and a mid-sagittal section was stained with haematoxylin and eosin (HE) and tartrate-resistant acid phosphatase (TRAP) to assess the numbers of osteoblasts and osteoclasts, respectively. Results. Scoliosis developed at the thoracic spine in all chickens in the PNX group and in two of the PNX+MLT group. MLT concentrations in the PNX group were substantially reduced, whereas normal concentrations were restored in the PNX+MLT group and were normal in the CNT and CNT+MLT groups. Micro-CT data showed that chickens in the PNX group had a greater degree of generalised osteoporosis than did those in the other groups. The number of osteoblasts was significantly decreased in the PNX group, whereas we recorded no significant difference between the CNT, CNT+MLT, and PNX+MLT groups. The number of osteoclasts was similar in all groups. Conclusions. Our results suggest that MLT deficiency reduces osteoblast proliferation and leads to the development of scoliosis and osteoporosis. The restoration of MLT prevented the development of scoliosis and osteoporosis, indicating that MLT concentrations might be crucial to the development of scoliotic deformity and osteoporosis in AIS

Introduction

Children with early-onset scoliosis (EOS) with rib hump chest-wall distortion or fused/absent ribs have thoracic insufficiency syndrome (TIS). Commonly, respiration is adversely affected by loss of lung volume from chest-wall constriction and clinical loss of active rib cage expansion. The dynamic thoracic components of diaphragm or rib cage lung expansion during respiration is poorly characterised by radiograph or CT scan. Pulmonary function tests indicate only hemithorax performance. Dynamic lung MRI, however, can visualise both chest-wall and diaphragm motion, allowing assessment of each individual hemithorax performance, so that a dynamic classification system of the thoracic function can be developed.

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. Methods. An in vitro model for oxidative stress-induced injury in NPCs was developed to elucidate the mechanisms underlying the upregulation of DDIT4 expression, activation of the reactive oxygen species (ROS)-thioredoxin-interacting protein (TXNIP)-NLRP3 signalling pathway, and nucleus pulposus pyroptosis. Furthermore, the mechanism of action of small interfering DDIT4 (siDDIT4) on NPCs in vitro was validated. A triplex hydrogel named siDDIT4@G5-P-HA was created by adsorbing siDDIT4 onto fifth-generation polyamidoamine (PAMAM) dendrimer using van der Waals interactions, and then coating it with hyaluronic acid (HA). In addition, we established a rat puncture IVDD model to decipher the hydrogel’s mechanism in IVDD. Results. A correlation between DDIT4 expression levels and disc degeneration was shown with human nucleus pulposus and needle-punctured rat disc specimens. We confirmed that DDIT4 was responsible for activating the ROS-TXNIP-NLRP3 axis during oxidative stress-induced pyroptosis in rat nucleus pulposus in vitro. Mitochondria were damaged during oxidative stress, and DDIT4 contributed to mitochondrial damage and ROS production. In addition, siDDIT4@G5-P-HA hydrogels showed good delivery activity of siDDIT4 to NPCs. In vitro studies illustrated the potential of the siDDIT4@G5-P-HA hydrogel for alleviating IVDD in rats. Conclusion. DDIT4 is a key player in mediating pyroptosis and IVDD in NPCs through the ROS-TXNIP-NLRP3 axis. Additionally, siDDIT4@G5-P-HA hydrogel has been found to relieve IVDD in rats. Our research offers an innovative treatment option for IVDD. Cite this article: Bone Joint Res 2024;13(5):247–260

This review provides a concise outline of the advances made in the care of patients and to the quality of life after a traumatic spinal cord injury (SCI) over the last century. Despite these improvements reversal of the neurological injury is not yet possible. Instead, current treatment is limited to providing symptomatic relief, avoiding secondary insults and preventing additional sequelae. However, with an ever-advancing technology and deeper understanding of the damaged spinal cord, this appears increasingly conceivable. A brief synopsis of the most prominent challenges facing both clinicians and research scientists in developing functional treatments for a progressively complex injury are presented. Moreover, the multiple mechanisms by which damage propagates many months after the original injury requires a multifaceted approach to ameliorate the human spinal cord. We discuss potential methods to protect the spinal cord from damage, and to manipulate the inherent inhibition of the spinal cord to regeneration and repair. Although acute and chronic SCI share common final pathways resulting in cell death and neurological deficits, the underlying putative mechanisms of chronic SCI and the treatments are not covered in this review

Purpose. The purpose of this study was to discover if student led clinics (SLC) are feasible delivery mechanisms for Low back pain (LBP) self-management support and to develop a service model. Background. LBP is the most commonly reported musculoskeletal disorder worldwide. The increasing service and workforce demands of LBP are challenging for providers and policy makers. self-management is appropriate for many people living with LBP yet guidance for self-management is lacking. One potential delivery mechanism is through SLC. These are ‘clinics’ run by students, supervised by clinicians. Methods and Results. A scoping review has found that SLC can be effective for supporting self-management of various long-term conditions and can provide cost benefits compared with traditional clinical services. In principle, their use for providing LBP services could have similar advantages as well as mitigating the clinical placement shortage. A further scoping review of self-management support for LBP was used to develop a model for student-led LBP clinics. The proposed model is a student led LBP supported self-management service. The service users will be triaged using the Psychosocial Flags Framework to identify obstacles to participation, followed by 1–6 sessions of self-management support comprising of; 1) empathetic listening and education to build a therapeutic relationship and to dispel LBP myths; 2) collaboratively setting meaningful goals; 3) imparting knowledge and skills to overcome the identified obstacles; 4) developing an evidence-informed plan for self-management, agreed with relevant stakeholders. Conclusion. Previous experience and the evidence-base suggest that SLC are feasible for delivering self-management support for LBP. Conflicts of interest: No conflicts of interest. Sources of funding: No funding obtained

Background. Chronic low back pain (CLBP) is the leading cause of disability worldwide. Immersive virtual reality (IVR) can be delivered using head mounted display (HMD) to interact with 3D virtual environment (VE). IVR has shown promising results in management of chronic pain conditions, using different mechanisms (e.g., exposure to movement and distraction). However, it has not been widely tested for CLBP. Future development of IVR intervention needs inputs from gatekeepers to determine key considerations, facilitators and barriers. This qualitative study aimed to explore views and opinions of physiotherapists about IVR intervention for adults with CLBP. Methods. Four focus groups were conducted online, with 16 physiotherapists. A demonstration of existing IVR mechanisms was presented. The data were transcribed and analysed through descriptive thematic analysis. Results. IVR was thought to be a suitable adjunct for a subgroup of patients who are reluctant to engage with standard care. Motivation to perform challenging physical tasks was believed to be a potential benefit. Safety, possibility of addiction, and transferability of acquired skills from VE to ‘real world’ and hygiene were concerns and the intervention was preferred to be used under clinical supervision. VE personalisation to patient's goal and preference with delivery and progression being gradual depending upon patient's abilities was suggested. Technical knowledge was seen as a facilitator, while cost and technology acceptance were barriers for future implementation. Conclusion. Future studies would need to consider the reported views of physiotherapists to inform development and implementation of IVR intervention for CLBP. Conflicts of interest: No conflict of interest. Sources of funding: Funded by the government of Saudi Arabia

Aims. This study was performed to explore the effect of melatonin on pyroptosis in nucleus pulposus cells (NPCs) and the underlying mechanism of that effect. Methods. This experiment included three patients diagnosed with lumbar disc herniation who failed conservative treatment. Nucleus pulposus tissue was isolated from these patients when they underwent surgical intervention, and primary NPCs were isolated and cultured. Western blotting, reverse transcription polymerase chain reaction, fluorescence staining, and other methods were used to detect changes in related signalling pathways and the ability of cells to resist pyroptosis. Results. Western blot analysis confirmed the expression of cleaved CASP-1 and melatonin receptor (MT-1A-R) in NPCs. The cultured NPCs were identified by detecting the expression of CD24, collagen type II, and aggrecan. After treatment with hydrogen peroxide, the pyroptosis-related proteins NLR family pyrin domain containing 3 (NLRP3), cleaved CASP-1, N-terminal fragment of gasdermin D (GSDMD-N), interleukin (IL)-18, and IL-1β in NPCs were upregulated, and the number of propidium iodide (PI)-positive cells was also increased, which was able to be alleviated by pretreatment with melatonin. The protective effect of melatonin on pyroptosis was blunted by both the melatonin receptor antagonist luzindole and the nuclear factor erythroid 2–related factor 2 (Nrf2) inhibitor ML385. In addition, the expression of the transcription factor Nrf2 was up- or downregulated when the melatonin receptor was activated or blocked by melatonin or luzindole, respectively. Conclusion. Melatonin protects NPCs against reactive oxygen species-induced pyroptosis by upregulating the transcription factor Nrf2 via melatonin receptors. Cite this article: Bone Joint Res 2023;12(3):202–211

Aims. Degenerative cervical spondylosis (DCS) is a common musculoskeletal disease that encompasses a wide range of progressive degenerative changes and affects all components of the cervical spine. DCS imposes very large social and economic burdens. However, its genetic basis remains elusive. Methods. Predicted whole-blood and skeletal muscle gene expression and genome-wide association study (GWAS) data from a DCS database were integrated, and functional summary-based imputation (FUSION) software was used on the integrated data. A transcriptome-wide association study (TWAS) was conducted using FUSION software to assess the association between predicted gene expression and DCS risk. The TWAS-identified genes were verified via comparison with differentially expressed genes (DEGs) in DCS RNA expression profiles in the Gene Expression Omnibus (GEO) (Accession Number: GSE153761). The Functional Mapping and Annotation (FUMA) tool for genome-wide association studies and Meta tools were used for gene functional enrichment and annotation analysis. Results. The TWAS detected 420 DCS genes with p < 0.05 in skeletal muscle, such as ribosomal protein S15A (RPS15A) (PTWAS = 0.001), and 110 genes in whole blood, such as selectin L (SELL) (PTWAS = 0.001). Comparison with the DCS RNA expression profile identified 12 common genes, including Apelin Receptor (APLNR) (PTWAS = 0.001, PDEG = 0.025). In total, 148 DCS-enriched Gene Ontology (GO) terms were identified, such as mast cell degranulation (GO:0043303); 15 DCS-enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were identified, such as the sphingolipid signalling pathway (ko04071). Nine terms, such as degradation of the extracellular matrix (R-HSA-1474228), were common to the TWAS enrichment results and the RNA expression profile. Conclusion. Our results identify putative susceptibility genes; these findings provide new ideas for exploration of the genetic mechanism of DCS development and new targets for preclinical intervention and clinical treatment. Cite this article: Bone Joint Res 2023;12(1):80–90

Aims. Lumbar spinal stenosis (LSS) is a common skeletal system disease that has been partly attributed to genetic variation. However, the correlation between genetic variation and pathological changes in LSS is insufficient, and it is difficult to provide a reference for the early diagnosis and treatment of the disease. Methods. We conducted a transcriptome-wide association study (TWAS) of spinal canal stenosis by integrating genome-wide association study summary statistics (including 661 cases and 178,065 controls) derived from Biobank Japan, and pre-computed gene expression weights of skeletal muscle and whole blood implemented in FUSION software. To verify the TWAS results, the candidate genes were furthered compared with messenger RNA (mRNA) expression profiles of LSS to screen for common genes. Finally, Metascape software was used to perform enrichment analysis of the candidate genes and common genes. Results. TWAS identified 295 genes with permutation p-values < 0.05 for skeletal muscle and 79 genes associated for the whole blood, such as RCHY1 (PTWAS = 0.001). Those genes were enriched in 112 gene ontology (GO) terms and five Kyoto Encyclopedia of Genes and Genomes pathways, such as ‘chemical carcinogenesis - reactive oxygen species’ (LogP value = −2.139). Further comparing the TWAS significant genes with the differentially expressed genes identified by mRNA expression profiles of LSS found 18 overlapped genes, such as interleukin 15 receptor subunit alpha (IL15RA) (PTWAS = 0.040, PmRNA = 0.010). Moreover, 71 common GO terms were detected for the enrichment results of TWAS and mRNA expression profiles, such as negative regulation of cell differentiation (LogP value = −2.811). Conclusion. This study revealed the genetic mechanism behind the pathological changes in LSS, and may provide novel insights for the early diagnosis and intervention of LSS. Cite this article: Bone Joint Res 2023;12(6):387–396

The aim of this study is to clarify the implication of ciliary pathway on the onset of the spinal curvature that occurs in Adolescent Idiopathic Scoliosis (AIS) patients through functional studies of two genes: POC5 and TTLL11. Since the genetic implication for AIS is accepted, many association and candidate gene analysis revealed the implication of ciliary genes. The characterisation of these two proteins was assessed by qPCR, WB and immunofluorescence in vitro using control cells and cells derived from AIS patients. The impact of genetic modification of these genes on the functionality of the proteins in vitro and in vivo was analysed in zebrafish model created by CRISPR/Cas9 using microCT and histologic analysis. Our study revealed that mutant cells, for both gene, were less ciliated and the primary cilia was significantly shorter compared to control cells. We also observed a default in cilia glutamylation by immunofluorescence and Western Blot. Moreover, we observed in both zebrafish model, a 3D spine curvature similar to the spinal deformation in AIS. Interestingly, our preliminary results of immunohistology showed a retinal defect, especially at the cone cell layer level. This study strongly supports the implication of the ciliary pathway in the onset of AIS and this is the first time that a mechanism is described for AIS. Indeed, we show that shorter cilia could be less sensitive to environmental factors due to lower glutamylation and result in altered signalling pathway. Identifying the biological mechanism involved is crucial for elucidating AIS pathogenesis

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. Methods. We investigated the effects of mCRP and the signalling pathways that are involved in cultured human primary annulus fibrosus (AF) cells and in the human nucleus pulposus (NP) immortalized cell line HNPSV-1. We determined messenger RNA (mRNA) and protein levels of relevant factors involved in inflammatory responses, by quantitative real-time polymerase chain reaction (RT-qPCR) and western blot. We also studied the presence of mCRP in human AF and NP tissues by immunohistochemistry. Results. We demonstrated that mCRP increases nitric oxide synthase 2 (NOS2), cyclooxygenase 2 (COX2), matrix metalloproteinase 13 (MMP13), vascular cell adhesion molecule 1 (VCAM1), interleukin (IL)-6, IL-8, and Lipocalin 2 (LCN2) expression in human AF and NP cells. We also showed that nuclear factor-κβ (NF-κβ), extracellular signal-regulated kinase 1/2 (ERK1/2), and phosphoinositide 3-kinase (PI3K) are at play in the intracellular signalling of mCRP. Finally, we demonstrated the presence of mCRP in human AF and NP tissues. Conclusion. Our results indicate, for the first time, that mCRP can be localized in IVD tissues, where it triggers a proinflammatory and catabolic state in degenerative and healthy IVD cells, and that NF-κβ signalling may be implicated in the mediation of this mCRP-induced state. Cite this article: Bone Joint Res 2023;12(3):189–198

Background. Mobile apps have shown promise in helping people to self-manage conditions like chronic low back pain (CLBP). However, it is unclear who benefits most, why, and under what circumstances. This limits our understanding of how to maximize the potential of mobile app technology. Aim. This study aimed to test and refine programme theories about how mobile apps support people to self-manage CLBP in a real-world setting. The theories were based on a previously published realist review. Methods. A realist evaluation was conducted using one-to-one realist interviews by telephone with participants who had used the Curable app to self-manage their CLBP for three months. The interviews were guided by programme theories from the realist review. Analysis of the interviews used abductive and retroductive logic to create chains of inferences, which were then developed into context-mechanism-outcome configurations (CMOCs). These CMOCs offered causal explanations about who might benefit from a mobile app to self-manage CLBP, why and in what circumstances. Results. Ten interviews were conducted (nine with people with CLBP who trialled the app and one with a founding member of Curable LLC). Twenty CMOCs were created that identified key mechanisms such as agency, control and reassurance that interact with contextual factors such as acceptance, internal capacity, and a biopsychosocial approach to pain management. These factors influence whether a person with CLBP will benefit from a mobile app for self-management. Conclusions. Twenty CMOCs were created to support three programme theories centering around concepts of empowerment, burden of care, and timing. Conflicts of interest. None. Sources of funding. R Hunter's work was supported by the Inverness and Highland City-Region Deal Studentship Award [2018]. Presented at: 13th Congress of the European Pain Federation (EFIC), September 2023, Budapest, Hungary

Introduction. Vertebral compression fractures are the most common type of osteoporotic fracture. Though 89% of clinical fractures occur anteriorly, it is challenging to replicate these ex vivo with the underlying intervertebral discs (IVDs) present. Furthermore, the role of disc degeneration in this mechanism is poorly understood. Understanding how disc morphology alters vertebral strain distributions may lead to the utilisation of IVD metrics in fracture prediction, or inform surgical decision-making regarding instrumentation type and placement. Aim. To determine the effect of disc degeneration on the vertebral trabecular bone strain distributions in axial compression and flexion loading. Methods. Eight cadaveric thoracolumbar segments (T11-L3) were prepared (N=4 axial compression, N=4 flexion). µCT-based digital volume correlation was used to quantify trabecular strains. A bespoke loading device fixed specimens at the resultant displacement when loaded to 50N and 800N. Flexion was achieved by adding 6° wedges. Disc degeneration was quantified with Pfirrmann grading and T2 relaxation times. Results. Anterior axial strains were 80.9±39% higher than the posterior region in flexion (p<0.01), the ratio of which was correlated with T2 relaxation time (R. 2. =0.80, p<0.05). In flexion, the central-to-peripheral axial strain ratio in the endplate region was significantly higher when the underlying IVDs were non-degenerated relative to degenerated (+38.1±12%, p<0.05). No significant differences were observed in axial compression. Conclusion. Disc degeneration is a stronger determinant of the trabecular strain distribution when flexion is applied. Load transfer through non-degenerate IVDs under flexion appears to be more centralised, suggesting that disc degeneration predisposes flexion-type compression fractures by shifting high strains anteriorly. Conflicts of interest. The authors declare none. Sources of funding. This work was funded by the Engineering & Physical Sciences Research Council (EP/V029452/1), and Back-to-Back

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

Background. Involving research users in setting priorities for research is essential to ensure research outcomes are patient-centred and to maximise research value and impact. The Musculoskeletal (MSK) Disorders Research Advisory Group Versus Arthritis led a research priority setting exercise across MSK disorders. Methods. The Child Health and Nutrition Research Initiative (CHRNI) method of setting research priorities with a range of stakeholders were utilised. The MSKD RAG identified, through consensus, four research Domains: Mechanisms of Disease; Diagnosis and Impact; Living Well with MSK disorders and Successful Translation. Following ethical approval, the research priority exercise involved four stages and two surveys, to: 1) gather research uncertainties; 2) consolidate these; 3) score uncertainties using agreed criteria of importance and impact on a score of 1–10; and 4) analyse scoring, for prioritisation. Results. The first survey had 209 respondents, who described 1290 research uncertainties, which were refined into 68 research questions. 285 people responded to the second survey. The largest group of respondents represented patients and carers, followed by researchers and healthcare professionals. A ranked list was produced, with scores ranging between 12 and 18. Key priorities included developing and testing new treatments, better targeting of treatments, early diagnosis, prevention and better understanding and management of pain, with an emphasis on understanding underpinning mechanisms. Conclusions. For the first time, we have summarised priorities for research across MSKD, from discovery science to applied clinical and health research, including translation. We present a call to action to researchers and funders to target these priorities. Conflict of Interest: None. Sources of funding: We thank the funder, Versus Arthritis for their support of the research advisory groups and this activity

Background. Specifically designed control interventions can account for expectation effects in clinical trials. For the interpretation of efficacy trials of physical, psychological, and self-management interventions for people living with pain, the design, conduct, and reporting of control interventions is crucial. Objectives. To establish a quality standard in the field, core recommendations are presented alongside additional considerations and a reporting checklist for control interventions. Methods. Three Delphi rounds with 64 experts in placebo research and/or non-pharmacological clinical trials were conducted. The panel was presented with a systematic review and meta-analysis of control and blinding methods. A draft guidance document included 63 consensus items (≥80% agreement) and was discussed with patient partners. Finally, the draft guidance and results from stakeholder interviews were discussed at consensus meetings with Delphi participants and patient representatives. Results. Forty-four experts completed the process. When treatment efficacy or mechanisms are to be studied, the advocated principle is to design control interventions as similar as possible to the tested intervention, apart from the components that the study examines. Structured reasoning in the planning phase, early engagement with stakeholders, feasibility work, and piloting will enhance the quality and acceptability of control interventions. With participant blinding being a primary objective, blinding effectiveness should be routinely assessed and reported. Transparent and detailed reporting will improve interpretability and repeatability of clinical trials. Conclusion. This guideline provides the much-needed standards to enhance the quality of efficacy clinical trials in physical, psychological, and self-management intervention research, ultimately improving patient care. Study registration: . https://osf.io/jmyhq/. Conflict of interest: The authors declare no competing interests. Sources of Funding: Alain and Sheila Diamond Charitable Trust PhD Studentship

Background. Intervertebral disc degeneration (DD) is a complex age-related condition that constitutes the main risk factor for disabling back pain. DD is assessed using different traits extracted from MR imaging (MRI), normally combined to give summary measures (e.g. Pfirmann score). The aetiology of DD is poorly understood and despite its high heritability (75%), the precise genetic predisposition is yet to be defined. Genome wide association study (GWAS) is used to discover genetic variants associated with a disease or phenotype. It tests variants across the whole genome. It requires large samples to provide adequate but unfortunately there is poor availability of spine imaging data due to the high cost of MRI. We have adopted new methods to examine different MRI traits independently and use the information of those traits to boost GWAS power using specialized statistical software for jointly analyse correlated traits. Methods/Results. We examined DD MRI features disc narrowing, disc bulge, disc signal intensity and osteophyte formation in the TwinsUK cohort who had undergone T2-weighted sagittal spine MRI. GWAS were performed on the four traits. MTAG software was used to boost single trait GWAS power using the information in the other trait GWAS. 9 different loci were identified. Conclusions. Preliminary results suggest genes GDF6, SP1/SP7 are associated with individual trait signal intensity. In addition, novel associated genes with potential for shedding new light on pathogenic mechanisms are identified. Additional cohorts will be included in the design as a replication to test reproducibility of the results. Conflicts of interest: No conflicts of interest. Sources of funding: Funded by Disc4All, EU Horizon 2020, MSCA-2020-ITN-ETN GA: 955735

Purpose and Background. Patients’ engagement with self-management strategies (SMS) is key when managing low back pain (LBP) and relies on appropriate information being delivered by the treating Clinician. However, patients have differing coping mechanisms which may affect success with SMS. This study aimed to determine Patient and Physiotherapist's perceptions of coping responses and SMS in patients with LBP. Methods. Patient completed a Pain Coping strategies questionnaire, before and after LBP treatment. Semi-structured interviews gathered data from of 10 patients (6 males; and 6 physiotherapists. Questionnaire data was described descriptively, and qualitative data was transcribed/analysed thematically. Results. 5 patients were categorized as ‘active copers’ and 5 as ‘passive copers’ before treatment. SMS success appeared to be impacted by patient coping strategies they adopted. Spiritual religious coping strategies linked to cultural beliefs was a common strategy for all patients. However, the active copers were more likely to engage with active strategies compared to passive copers. All patients felt they had not received full education/details about the home exercises. One patient became an ‘active coper’ following treatment demonstrating high self-confidence to self-manage pain and accepted exercises as a lifestyle. Physiotherapists did not use a valid method for screening purposes for coping, although they referred to ascertaining this verbally and they did tailor exercises differently for passive and active copers. Conclusion. Screening for individual coping strategies would enhance targeting treatments and all patients would benefit from full exercise programmes for self- management and pain self-efficacy approaches to change patients ‘behaviour and enhance patients’ self-confidence. Conflicts of interest: No conflicts of interest. Sources of funding: The study is sponsored by Kuwait Government

Background. Serious traumatic injury is a leading cause of death and disability globally, with the majority of survivors developing chronic pain. Methods. The aims of this study were to describe early predictors of poor long-term outcome for post-trauma pain. We conducted a prospective observational study, recruiting patients admitted to a Major Trauma Centre hospital in England within 14 days of their injuries, and followed them for 12 months. We defined a poor outcome as Chronic Pain Grade ≥ II and measured this at both 6-months and 12-months. A broad range of candidate predictors were used, including surrogates for pain mechanisms, quantitative sensory testing, and psychosocial factors. Univariate models were used to identify the strongest predictors of poor outcome, which were entered into multivariate models. Results. 124 eligible participants were recruited. At 6-months, 19 (23.2%) of 82 respondents reported a good outcome, whereas at 12-months 27 (61.4%) of 44 respondents reported a good outcome. The multivariate model for 6-months produced odds ratios for a unit increase in: number of fractures, 3.179 (0.52 to 19.61); average pain intensity, 1.611 (0.96 to 2.7); pain extent, 1.138 (0.92 to 1.41) and post-traumatic stress symptoms, 1.044 (0.10 to 1.10). At 12-months, equivalent values were: number of fractures, 1.653 (0.77 to 3.55); average pain intensity, 0.967 (0.67 to 1.40); pain extent, 1.062 (0.92 to 1.23) and post-traumatic stress symptoms, 1.025 (0.99 to 1.07). Conclusion. A poor long-term pain outcome from musculoskeletal traumatic injuries can be predicted by measures recorded within days of injury. Conflicts of interest: No conflicts of interest. Sources of funding: This study was funded by the National Institute for Health Research (NIHR) Surgical Reconstruction and Microbiology Research Centre (SRMRC)