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

Thoracic back pain caused by osteoarthritis of a single costovertebral joint is a poorly recognised condition. We report a series of five patients who were successfully treated by resection arthroplasty of this joint. Each had received a preliminary image-guided injection of local anaesthetic and steroid into the joint to confirm it as the source of pain. The surgical technique is described. There were no complications. The pain improved from a mean of 7.0 (6 to 8) on a visual analogue scale to 2.0 (0 to 4) post-operatively. The final post-operative Oswestry disability index was a mean of 19.4 (9 to 38). Isolated osteoarthritis of a costovertebral joint is a rare but treatable cause of thoracic back pain. It is possible to obtain excellent short- and intermediate-term relief from pain with resection arthroplasty in appropriately selected patients

Purpose and background:. Sacroiliitis identified by MRI is considered as a keystone in the diagnosis of spondyloarthritis. To reduce the number of unnecessary MRI scans it would be ideal if sacroiliac (SI) joint pain provocation tests could be used to identify patients at risk of having sacroiliitis. The aim of the current study was to investigate the diagnostic value of three pain provocation SI-joint tests for sacroiliitis identified by MRI. Methods:. Patients (n=454, mean age 32 years, 54% women) without clinical signs of nerve root compression were selected from a cohort consisting of patients with persistent low back pain referred to an outpatient spine clinic. Data from the Gaenslen's Test, Thigh Thrust Test and Long Dorsal Sacroiliac Ligaments Test and sacroiliitis identified by MRI were analysed. Results:. The prevalence of SI-joints with sacroiliitis was 5%. In the whole study group, only the Thigh Trust Test was associated with sacroiliitis, ROC area 0.58 (95% CI 0.51–0.65), sensitivity 31% (18–47) and specificity 85% (82–87). In men, sacroiliitis was associated with all three SI joint tests and multitest regimens, with the greatest ROC area found for ≥ 1 positive out of 3 tests, (0.68 (0.56–0.80)), sensitivity 56% (31–79) and specificity 81% (77–85). In women, no significant associations were observed between the assessed SI joint tests and sacroiliitis. Conclusions:. Only in men were the performed SI-joint tests found to be associated with sacroiliitis identified by MRI. Although, the diagnostic value was limited, the results indicate that the use of SI joint tests for sacroiliitis may be optimised by gender-separated analyses

Purpose. To study the relationship between Zygoapophysial Joint Tropism and pathologic fractures affecting lumbar and thoracic vertebrae in elderly patients. Methods. The sagittal plane orientation of the Zygoapophysial joints (facets or ZAJ) of 324 vertebrae of 63 patients were measured on MRI scans, stratified into lumbar and thoracic, fractured and non-fractured, and then classified according to the presence of tropism. The correlation between tropism and fractures, demographics pertaining to age, spinal level, and morbidity were studied. Results. From the 415 ZAJ pairs studied, 23 were excluded because of insufficient imaging leaving 388 ZAJ pairs. In 155 Thoracic ZAJ pairs, there 92 with a fracture, 39% demonstrating tropism; and there were 63 with no fracture, 43% demonstrating tropism. In 237 Lumbar ZAJ pairs, there were 144 with a fracture, 73% demonstrating tropism; there were 93 with no fracture, 42% demonstrating tropism. Conclusion. Our study suggests a correlation between the emergence of pathological fractures in the spine and tropism which is statistically significant in the lumbar but not in the thoracic. The authors confirm that this abstract has not been previously published in whole or substantial part nor has it been presented previously at a national meeting. Conflicts of interest: No conflicts of interest. Sources of funding: No funding obtained

Introduction. Percutaneous radiofrequency lesioning of the lateral branches of the sacroiliac joint has become a recognised method of treating chronic pain arising from this joint. Due to the large and varied innervation from the S1-3 lateral branches success has been achieved with large lesions that has a high chance of covering these nerves. Such lesions require specialised and expensive equipment and the NIMBUS needle is a large 17G electrode with expandable tines at the tip. It is compatible with all standard radiofrequency probes and it produces a large lesion at the tip. It has been in use in the USA in over 100 cases and we describe its use in the UK. Methods. Patients were identified as having sacroiliac joint pain by clinical assessment and positive pain response to local anaesthetic sacroiliac joint lateral branch blocks. Under fluoroscopic control, the needle is inserted at the lateral edge of the sacral S1-3 posterior foramen. Three lesions at the lateral edge of the foramen are made at 80°C for 90s. A further lesion is made at the L5 dorsal ramus. Results. 4 patients achieved very good pain relief >50% reduction in pain scores on the NRS scale at 6 weeks follow up. No complications were noted and there were no technical difficulties. Conclusion. Lesioning with the NIMBUS needle is feasible and allows clinicians a method of treating chronic sacroiliac joint pain using existing radiofrequency equipment. Further large, long term studies are warranted to establish clinical efficacy

Purpose. To assess the impact of implementing a joint Neurosurgical/Orthopaedic Spinal on-call rota on the referral patterns to the Neurosurgical Department at James Cook University Hospital, Middlesbrough. Methods. A joint spinal rota was implemented at James Cook University Hospital in April 2008, to provide 24-hour on-call availability of a Spinal specialist. Using the Neurosurgical Referral Database (Microsoft Access), the referrals received for the 12 months prior to, and subsequent to, the implementation were analysed. Results. There was a 13.4% increase in total spinal referrals in the 12 months post-implementation of the new spinal rota, compared with pre-implementation. Total admissions from these referrals increased by 11.7%. There was an increase of 5.5% in lumbar degenerative referrals (including cauda equina referrals), a 10.5% decrease in cervical degenerative referrals, and most significantly, a 42.9% increase in spinal injury referrals, including fractures, and spinal cord injuries. Conclusions. The implementation of a joint Neurosurgical and Spinal Orthopaedic on-call rota for Spinal Surgery has resulted in the availability of a Spinal Consultant on-call 24hrs a day, 7 days a week to cover Spinal emergencies. The resulting change in referrals to the Neurosurgical Department has seen an increase in both referrals and admissions, although it is uncertain whether this is a result of a general increase in referral rate, or a direct result of the change in service provision

We present four patients who had sustained a traumatic dislocation of the atlanto-occipital joint. The diagnosis was initially missed in two patients. One patient, who was neurologically intact, was treated non-operatively. The remaining three recovered neurologically after an occipitocervical fusion. Early recognition of the injury, especially in multiply-injured patients with head injuries, and timely management may improve survival and neurological recovery

Purpose and Background. Leg length discrepancy (LLD) occurs commonly and has been associated with osteoarthritis of the knee and the hip joints. However, the possible association between LLD and degenerative changes in the lumbar spine has not been investigated. Here we correlate the degree of LLD with degenerative changes in the hip joints and the lumbar spine. Methods and Results. A modification of Friberg's method was used to measure LLD and a novel method was devised to exclude magnification errors in standing radiographs of the lumbopelvic region. 5mm of LLD was considered significant. 75 sets (36 female and 39 male) of radiographs from adult patients presenting to chiropractic teaching clinics were used. Degenerative changes at hip and L4/5 and L5/S1 disc spaces were graded on a 4-point scale. Hip degeneration in men with significant LLD was [mean, 95% confidence interval] [1.35, 1.05–1.66], as opposed to men with no significant LLD [0.31, 0.1–0.53]. Degenerative changes at the L5/S1 spinal level in the group with significant LLD demonstrated values of [1.04, 0.75–1.33], compared to the group without significant LLD with values of [0.41, 0.22–0.61]. The association between LLD and lumbar degeneration was particularly strong in men and also in women at or above the age of 25. Conclusion. Here we demonstrate that LLD of 5mm or above, as measured by our method, is associated with significant degenerative changes in the hip joint in men and the L5/S1 motion segment in both men and women, but may be more significant in older women. This abstract has not been previously published in whole or substantial part nor has it been presented previously at a national meeting

We reviewed 15 consecutive patients, 11 women and four men, with a mean age of 48.7 years (37.3 to 62.6), who between July 2004 and August 2007 had undergone percutaneous sacroiliac fusion using hollow modular anchorage screws filled with demineralised bone matrix.

Each patient was carefully assessed to exclude other conditions and underwent pre-operative CT and MR scans. The diagnosis of symptomatic sacroiliac disease was confirmed by an injection of local anaesthetic and steroid under image intensifier control.

The short form-36 questionnaire and Majeed’s scoring system were used for pre- and post-operative functional evaluation. Post-operative radiological evaluation was performed using plain radiographs.

Intra-operative blood loss was minimal and there were no post-operative clinical or radiological complications. The mean follow-up was for 17 months (9 to 39). The mean short form-36 scores improved from 37 (23 to 51) to 80 (67 to 92) for physical function and from 53 (34 to 73) to 86 (70 to 98) for general health (p = 0.037). The mean Majeed’s score improved from 37 (18 to 54) pre-operatively to 79 (63 to 96) post-operatively (p = 0.014). There were 13 good to excellent results. The remaining two patients improved in short form-36 from a mean of 29 (26 to 35) to 48 (44 to 52). Their persistent pain was probably due to concurrent lumbar pathology.

We conclude that percutaneous hollow modular anchorage screws are a satisfactory method of achieving sacroiliac fusion.

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. To investigate the correlations among cytokines and regulatory T cells (T-regs) in ankylosing spondylitis (AS) patients, and their changes after anti-tumour necrosis factor-α (TNF-α) treatment. Methods. We included 72 AS patients with detailed medical records, disease activity score (Bath Ankylosing Spondylitis Disease Activity Index), functional index (Bath Ankylosing Spondylitis Functional Index), and laboratory data (interleukin (IL)-2, IL-4, IL-10, TNF-α, interferon (IFN)-γ, transforming growth factor (TGF)-β, ESR, and CRP). Their peripheral blood mononuclear cells (PBMCs) were marked with anti-CD4, anti-CD25, and anti-FoxP3 antibodies, and triple positive T cells were gated by flow cytometry as T-regs. Their correlations were calculated and the changes after anti-TNF-α therapy were compared. Results. The frequency of T-regs in PBMCs was positively correlated to ESR and CRP in AS (r = 0.35 and 0.43; p = 0.032 and 0.027, respectively), and there was also a significant correlation between serum level of TNF-α and CRP (p = 0.041). The frequency of T-regs in PBMCs positively correlated to serum levels of TNF-α, IL-10, and TGF-β, while IL-2, IL-4, and IFN-γ showed opposite results. After anti-TNF-α treatment, there were significantly lower serum levels of TNF-α, IL-10, TGF-β, and frequency of T-regs in PBMCs among these AS patients (p = 0.026, 0.032, 0.029, and 0.037, respectively). Conclusion. In AS patients, proinflammatory cytokine may give positive feedback to induce more T-reg production and anti-inflammatory cytokine secretion to suppress this inflammatory status, and they can be reversed by anti-TNF-α therapy. However, the detailed interactions among T-regs and complex cytokine networks in autoinflammatory diseases still need more studies and further functional assay. Cite this article: Bone Joint Res 2023;12(2):133–137

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

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

Aims. Implant-related postoperative spondylodiscitis (IPOS) is a severe complication in spine surgery and is associated with high morbidity and mortality. With growing knowledge in the field of periprosthetic joint infection (PJI), equivalent investigations towards the management of implant-related infections of the spine are indispensable. To our knowledge, this study provides the largest description of cases of IPOS to date. Methods. Patients treated for IPOS from January 2006 to December 2020 were included. Patient demographics, parameters upon admission and discharge, radiological imaging, and microbiological results were retrieved from medical records. CT and MRI were analyzed for epidural, paravertebral, and intervertebral abscess formation, vertebral destruction, and endplate involvement. Pathogens were identified by CT-guided or intraoperative biopsy, intraoperative tissue sampling, or implant sonication. Results. A total of 32 cases of IPOS with a mean patient age of 68.7 years (37.6 to 84.1) were included. Diabetes, age > 60 years, and history of infection were identified as risk factors. Patient presentation upon admission included a mean body temperature of 36.7°C (36.1 to 38.0), back pain at rest (mean visual analogue scale (VAS) mean 5/10) and when mobile (mean VAS 6/10), as well as elevated levels of CRP (mean 76.8 mg/l (0.4 to 202.9)) and white blood cell count (mean 9.2 units/nl (2.6 to 32.8)). Pathogens were identified by CT-guided or conventional biopsy, intraoperative tissue sampling, or sonication, and Gram-positive cocci presented as the most common among them. Antibiotic therapy was established in all cases with pathogen-specific treatment in 23 (71.9%) subjects. Overall 27 (84.4%) patients received treatment by debridement, decompression, and fusion of the affected segment. Conclusion. Cases of IPOS are rare and share similarities with spontaneous spondylodiscitis. While procedures such as CT-guided biopsy and sonication are valuable tools in the diagnosis of IPOS, MRI and intraoperative tissue sampling remain the gold standard. Research on known principles of PJI such as implant retention versus implant exchange need to be expanded to the field of spine surgery. Cite this article: Bone Jt Open 2023;4(11):832–838

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. Methods. This was a multicentre retrospective study involving consecutively enrolled patients who underwent L4-L5 LLIF by seven surgeons at seven institutions in three countries over a five-year period. The demographic details of the patients and the details of the surgery, reoperations and complications, including femoral and non-femoral neuropraxia, thigh pain, weakness of hip flexion, and abdominal complications, were analyzed. Neurological and psoas-related complications attributed to LLIF or posterior instrumentation and persistent symptoms were recorded at one year postoperatively. Results. A total of 517 patients were included in the study. Their mean age was 65.0 years (SD 10.3) and their mean BMI was 29.2 kg/m. 2. (SD 5.5). A mean of 1.2 levels (SD 0.6) were fused with LLIF, and a mean of 1.6 (SD 0.9) posterior levels were fused. Femoral neuropraxia occurred in six patients (1.2%), of which four (0.8%) were LLIF-related and two (0.4%) had persistent symptoms one year postoperatively. Non-femoral neuropraxia occurred in nine patients (1.8%), one (0.2%) was LLIF-related and five (1.0%) were persistent at one year. All LLIF-related neuropraxias resolved by one year. A total of 32 patients (6.2%) had thigh pain, 31 (6.0%) were LLIF-related and three (0.6%) were persistent at one year. Weakness of hip flexion occurred in 14 patients (2.7%), of which eight (1.6%) were LLIF-related and three (0.6%) were persistent at one year. No patients had bowel injury, three (0.6%) had an intraoperative vascular injury (not LLIF-related), and five (1.0%) had ileus. Reoperations occurred in five patients (1.0%) within 30 days, 37 (7.2%) within 90 days, and 41 (7.9%) within one year postoperatively. Conclusion. LLIF involving the L4-L5 disc level has a low rate of persistent neurological, psoas-related, and abdominal complications in patients with the appropriate indications and using a standardized surgical technique. Cite this article: Bone Joint J 2024;106-B(1):53–61

Aims. The aim of this study was to compare outcomes after growth-friendly treatment for early-onset scoliosis (EOS) between patients with skeletal dysplasias versus those with other syndromes. Methods. We retrospectively identified 20 patients with skeletal dysplasias and 292 with other syndromes (control group) who had completed surgical growth-friendly EOS treatment between 1 January 2000 and 31 December 2018. We compared radiological parameters, complications, and health-related quality of life (HRQoL) at mean follow-up of 8.6 years (SD 3.3) in the dysplasia group and 6.6 years (SD 2.6) in the control group. Results. Mean major curve correction per patient did not differ significantly between the dysplasia group (43%) and the control group (28%; p = 0.087). Mean annual spinal height increase was less in the dysplasia group (9.3 mm (SD 5.1) than in the control group (16 mm (SD 9.2); p < 0.001). Mean annual spinal growth adjusted to patient preoperative standing height during the distraction period was 11% in the dysplasia group and 14% in the control group (p = 0.070). The complication rate was 1.6 times higher (95% confidence interval (CI) 1.3 to 2.0) in the dysplasia group. The following complications were more frequent in the dysplasia group: neurological injury (rate ratio (RR) 5.1 (95% CI 2.3 to 11)), deep surgical site infection (RR 2.2 (95% CI 1.2 to 4.1)), implant-related complications (RR 2.0 (95% CI 1.5 to 2.7)), and unplanned revision (RR 1.8 (95% CI 1.3 to 2.5)). Final fusion did not provide additional spinal height compared with watchful waiting (p = 0.054). There were no significant differences in HRQoL scores between the groups. Conclusion. After growth-friendly EOS treatment, patients with skeletal dysplasias experienced a higher incidence of complications compared to those with other syndromes. Surgical growth-friendly treatment for skeletal dysplasia-associated EOS should be reserved for patients with severe, progressive deformities that are refractory to nonoperative treatment. Cite this article: Bone Joint J 2024;106-B(6):596–602

Aims. This study aimed, through bioinformatics analysis and in vitro experiment validation, to identify the key extracellular proteins of intervertebral disc degeneration (IDD). Methods. The gene expression profile of GSE23130 was downloaded from the Gene Expression Omnibus (GEO) database. Extracellular protein-differentially expressed genes (EP-DEGs) were screened by protein annotation databases, and we used Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) to analyze the functions and pathways of EP-DEGs. STRING and Cytoscape were used to construct protein-protein interaction (PPI) networks and identify hub EP-DEGs. NetworkAnalyst was used to analyze transcription factors (TFs) and microRNAs (miRNAs) that regulate hub EP-DEGs. A search of the Drug Signatures Database (DSigDB) for hub EP-DEGs revealed multiple drug molecules and drug-target interactions. Results. A total of 56 EP-DEGs were identified in the differential expression analysis. EP-DEGs were enriched in the extracellular structure organization, ageing, collagen-activated signalling pathway, PI3K-Akt signalling pathway, and AGE-RAGE signalling pathway. PPI network analysis showed that the top ten hub EP-DEGs are closely related to IDD. Correlation analysis also demonstrated a significant correlation between the ten hub EP-DEGs (p＜0.05), which were selected to construct TF–gene interaction and TF–miRNA coregulatory networks. In addition, ten candidate drugs were screened for the treatment of IDD. Conclusion. The findings clarify the roles of extracellular proteins in IDD and highlight their potential as promising novel therapeutic targets. Cite this article: Bone Joint Res 2023;12(9):522–535

Aims. To determine the major risk factors for unplanned reoperations (UROs) following corrective surgery for adult spinal deformity (ASD) and their interactions, using machine learning-based prediction algorithms and game theory. Methods. Patients who underwent surgery for ASD, with a minimum of two-year follow-up, were retrospectively reviewed. In total, 210 patients were included and randomly allocated into training (70% of the sample size) and test (the remaining 30%) sets to develop the machine learning algorithm. Risk factors were included in the analysis, along with clinical characteristics and parameters acquired through diagnostic radiology. Results. Overall, 152 patients without and 58 with a history of surgical revision following surgery for ASD were observed; the mean age was 68.9 years (SD 8.7) and 66.9 years (SD 6.6), respectively. On implementing a random forest model, the classification of URO events resulted in a balanced accuracy of 86.8%. Among machine learning-extracted risk factors, URO, proximal junction failure (PJF), and postoperative distance from the posterosuperior corner of C7 and the vertical axis from the centroid of C2 (SVA) were significant upon Kaplan-Meier survival analysis. Conclusion. The major risk factors for URO following surgery for ASD, i.e. postoperative SVA and PJF, and their interactions were identified using a machine learning algorithm and game theory. Clinical benefits will depend on patient risk profiles. Cite this article: Bone Joint Res 2023;12(4):245–255

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. Methods. Between July 2017 and July 2019, 40 patients with cervical OPLL were equally randomized to undergo surgery with an ACOE or a PTLF. The clinical and radiological results were compared between the two groups. Results. The Japanese Orthopaedic Association (JOA) score and recovery rate in the ACOE group were significantly higher than those in the PTLF group during two years postoperatively, provided that the canal occupying ratio (COR) was > 50%, or the K-line was negative. There was no significant difference in JOA scores and rate of recovery between the two groups in those in whom the COR was < 50%, or the K-line was positive. There was no significant difference in the Cobb angle between C2 and C7, sagittal vertical axis, cervical range of motion (ROM), and complications between the two groups. Conclusion. Compared with PTLF, ACOE is a preferred surgical approach for the surgical management of patients with cervical OPLL in that it offers a better therapeutic outcome when the COR is > 50%, or the K-line is negative, and it also preserves better cervical curvature and sagittal balance. The prognosis of ACOE is similar to that of PTLE when the COR is < 50%, or the K-line is positive. Cite this article: Bone Joint J 2023;105-B(4):412–421

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