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

Background and Purpose. Non-specific chronic low back pain (NSCLBP) poses a significant disability and economic burden worldwide. Fear avoidance is suggested to contribute to its chronicity and reduced treatment effect. National guidelines recommend exercise as a component of multidisciplinary rehabilitation but its interaction with fear avoidance is ambiguous. This systematic review examined the effect of exercise-based interventions (EBIs) on fear avoidance NSCLBP. Methods and Results. RCTs comparing EBIs to usual care in adults with NSCLBP were included. A systematic search of CINAHL, Medline, EMBASE, Web of Science, Scopus and Cochrane Library (up to January 2019) revealed 10 eligible trials. Following risk of bias assessment, 6 studies were included for data extraction and narrative synthesis. EBIs were not found superior to usual care in reducing fear avoidance at any follow-up. There was evidence that reducing fear avoidance is probably not the mechanism through which EBIs affect pain and disability. In adherent patients, EBIs did not result in greater clinically relevant improvements in pain or disability than usual care, in the short- or intermediate-term. Conclusion. Addition of EBIs as part of multidisciplinary rehabilitation is not more beneficial than that of usual care in reducing fear avoidance in NSCLBP patients. However, the findings of this review are based on heterogenous studies presenting with methodological limitations. Further high-quality research is required to examine the review's findings and investigate current physiotherapy management of fear avoidance in NSCLBP. No conflicts of interest. No funding obtained

A statement of the purposes of the study and background. Lower back pain (LBP) is one of the ten leading causes of disease burden globally, producing significant detrimental effects on physical and emotional wellbeing whilst having a substantial economic burden for society. There is an inverse relationship between socio-economic status and pain prevalence. The effectiveness of a locally run ‘Back to Fitness Programme’ (6-week education and exercise programme) in the most deprived local authority area in England was evaluated. A summary of the methods used and the results. Patients at Blackpool Hospitals NHS Trust over a 6-month timeframe were included. Initial data were collected from 49 patients (mean age 53.4 years, 67% female). The amount of final data collected varied per outcome measure due to a range of factors. Participants reported the programme had helped with their understanding of pain (n=16, 100%), ability to move around and function (n=15, 94%), and level of pain (n=14, 88%). Looking at Roland Morris Disability Questionnaire scores (n=17), 88% (n=15) of patients indicated a reduction (n=12, 71%) or no change (n=3, 18%) in perceived disability. The Pain Self Efficacy Questionnaire (n=18) showed that 78% (n=14) of participants perceived an increase in their average level of confidence to move despite pain. There was an overall improvement in understanding of pain reflected by Revised Neurophysiology of Pain Questionnaire scores (n=44): 89% (n=39) improved (n=36, 82%) or did not change (n=3, 7%). Regarding lumbar flexion post-programme (n=17), 77% (n=13) of participants demonstrated an improvement (n=9, 53%) or no change (n=4, 24%). Conclusion. The majority of clinical outcomes improved following participation, predominantly in relation to understanding of pain. Conflicts of interest: No conflicts of interest. Sources of funding: This study is supported by The University of Central Lancashire in partnership with The Blackpool Teaching Hospitals NHS Foundation Trust

Purpose. This review aims to explore the methodologies used for estimating the direct and indirect costs attributed to back pain in developed countries. Methods. Six databases were searched to uncover studies about the direct and indirect costs of back pain published in English upto November 2016. Data extracted included study characteristics, cost categories and analysis methods. Results were synthesised descriptively. Results. The search identified 8009 potential studies, of which 40 were included for data extraction. The included studies reported data from 14 industrialised countries with considerably varying methodologies. Most of the studies (n=25) followed a retrospective study design and cost perspective was largely societal (n=26). Nearly half of the selected studies included indirect costs in their analysis as well as direct costs; and the proportion of indirect costs in most of the studies far outweighed the direct costs (3:1 ratio). The analysis method used most frequently was the top-down approach (n=13) followed by bottom-up approach (n=7) and econometric methods (n=7). Inpatient costs and absenteeism costs were the most important cost drivers accounting for 12%−35% of the direct costs and 5%−67% of the indirect costs respectively. The healthcare costs associated with back pain in the UK were estimated at £1.6 billion in 1998 while the indirect costs ranged from £5 billion to £10.7 billion. Conclusions. This is the first methodological systematic review assessing the costs of back pain. Despite differences in methodology, the economic burden of back pain is significant. Development of guideline and standardisation of methodologies is needed for future studies. Conflict of interest: None. Sources of funding: None

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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.

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This study was performed to explore the effect of melatonin on pyroptosis in nucleus pulposus cells (NPCs) and the underlying mechanism of that effect.

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This study aimed, through bioinformatics analysis and in vitro experiment validation, to identify the key extracellular proteins of intervertebral disc degeneration (IDD).