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The Bone & Joint Journal
Vol. 106-B, Issue 11 | Pages 1333 - 1341
1 Nov 2024
Cheung PWH Leung JHM Lee VWY Cheung JPY

Aims. Developmental cervical spinal stenosis (DcSS) is a well-known predisposing factor for degenerative cervical myelopathy (DCM) but there is a lack of consensus on its definition. This study aims to define DcSS based on MRI, and its multilevel characteristics, to assess the prevalence of DcSS in the general population, and to evaluate the presence of DcSS in the prediction of developing DCM. Methods. This cross-sectional study analyzed MRI spine morphological parameters at C3 to C7 (including anteroposterior (AP) diameter of spinal canal, spinal cord, and vertebral body) from DCM patients (n = 95) and individuals recruited from the general population (n = 2,019). Level-specific median AP spinal canal diameter from DCM patients was used to screen for stenotic levels in the population-based cohort. An individual with multilevel (≥ 3 vertebral levels) AP canal diameter smaller than the DCM median values was considered as having DcSS. The most optimal cut-off canal diameter per level for DcSS was determined by receiver operating characteristic analyses, and multivariable logistic regression was performed for the prediction of developing DCM that required surgery. Results. A total of 2,114 individuals aged 64.6 years (SD 11.9) who underwent surgery from March 2009 to December 2016 were studied. The most optimal cut-off canal diameters for DcSS are: C3 < 12.9 mm, C4 < 11.8 mm, C5 < 11.9 mm, C6 < 12.3 mm, and C7 < 13.3 mm. Overall, 13.0% (262 of 2,019) of the population-based cohort had multilevel DcSS. Multilevel DcSS (odds ratio (OR) 6.12 (95% CI 3.97 to 9.42); p < 0.001) and male sex (OR 4.06 (95% CI 2.55 to 6.45); p < 0.001) were predictors of developing DCM. Conclusion. This is the first MRI-based study for defining DcSS with multilevel canal narrowing. Level-specific cut-off canal diameters for DcSS can be used for early identification of individuals at risk of developing DCM. Individuals with DcSS at ≥ three levels and male sex are recommended for close monitoring or early intervention to avoid traumatic spinal cord injuries from stenosis. Cite this article: Bone Joint J 2024;106-B(11):1333–1341


Aims. Psychoeducative prehabilitation to optimize surgical outcomes is relatively novel in spinal fusion surgery and, like most rehabilitation treatments, they are rarely well specified. Spinal fusion patients experience anxieties perioperatively about pain and immobility, which might prolong hospital length of stay (LOS). The aim of this prospective cohort study was to determine if a Preoperative Spinal Education (POSE) programme, specified using the Rehabilitation Treatment Specification System (RTSS) and designed to normalize expectations and reduce anxieties, was safe and reduced LOS. Methods. POSE was offered to 150 prospective patients over ten months (December 2018 to November 2019) Some chose to attend (Attend-POSE) and some did not attend (DNA-POSE). A third independent retrospective group of 150 patients (mean age 57.9 years (SD 14.8), 50.6% female) received surgery prior to POSE (pre-POSE). POSE consisted of an in-person 60-minute education with accompanying literature, specified using the RTSS as psychoeducative treatment components designed to optimize cognitive/affective representations of thoughts/feelings, and normalize anxieties about surgery and its aftermath. Across-group age, sex, median LOS, perioperative complications, and readmission rates were assessed using appropriate statistical tests. Results. In all, 65 (43%) patients (mean age 57.4 years (SD 18.2), 58.8% female) comprised the Attend-POSE, and 85 (57%) DNA-POSE (mean age 54.9 years (SD 15.8), 65.8% female). There were no significant between-group differences in age, sex, surgery type, complications, or readmission rates. Median LOS was statistically different across Pre-POSE (5 days ((interquartile range (IQR) 3 to 7)), Attend-POSE (3 (2 to 5)), and DNA-POSE (4 (3 to 7)), (p = 0.014). Pairwise comparisons showed statistically significant differences between Pre-POSE and Attend-POSE LOS (p = 0.011), but not between any other group comparison. In the Attend-POSE group, there was significant change toward greater surgical preparation, procedural familiarity, and less anxiety. Conclusion. POSE was associated with a significant reduction in LOS for patients undergoing spinal fusion surgery. Patients reported being better prepared for, more familiar, and less anxious about their surgery. POSE did not affect complication or readmission rates, meaning its inclusion was safe. However, uptake (43%) was disappointing and future work should explore potential barriers and challenges to attending POSE. Cite this article: Bone Jt Open 2022;3(2):135–144


Bone & Joint Research
Vol. 12, Issue 9 | Pages 522 - 535
4 Sep 2023
Zhang G Li L Luo Z Zhang C Wang Y Kang X

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


Bone & Joint Open
Vol. 5, Issue 9 | Pages 809 - 817
27 Sep 2024
Altorfer FCS Kelly MJ Avrumova F Burkhard MD Sneag DB Chazen JL Tan ET Lebl DR

Aims. To report the development of the technique for minimally invasive lumbar decompression using robotic-assisted navigation. Methods. Robotic planning software was used to map out bone removal for a laminar decompression after registration of CT scan images of one cadaveric specimen. A specialized acorn-shaped bone removal robotic drill was used to complete a robotic lumbar laminectomy. Post-procedure advanced imaging was obtained to compare actual bony decompression to the surgical plan. After confirming accuracy of the technique, a minimally invasive robotic-assisted laminectomy was performed on one 72-year-old female patient with lumbar spinal stenosis. Postoperative advanced imaging was obtained to confirm the decompression. Results. A workflow for robotic-assisted lumbar laminectomy was successfully developed in a human cadaveric specimen, as excellent decompression was confirmed by postoperative CT imaging. Subsequently, the workflow was applied clinically in a patient with severe spinal stenosis. Excellent decompression was achieved intraoperatively and preservation of the dorsal midline structures was confirmed on postoperative MRI. The patient experienced improvement in symptoms postoperatively and was discharged within 24 hours. Conclusion. Minimally invasive robotic-assisted lumbar decompression utilizing a specialized robotic bone removal instrument was shown to be accurate and effective both in vitro and in vivo. The robotic bone removal technique has the potential for less invasive removal of laminar bone for spinal decompression, all the while preserving the spinous process and the posterior ligamentous complex. Spinal robotic surgery has previously been limited to the insertion of screws and, more recently, cages; however, recent innovations have expanded robotic capabilities to decompression of neurological structures. Cite this article: Bone Jt Open 2024;5(9):809–817


Bone & Joint Research
Vol. 12, Issue 1 | Pages 80 - 90
20 Jan 2023
Xu J Si H Zeng Y Wu Y Zhang S Liu Y Li M Shen B

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


Bone & Joint Open
Vol. 4, Issue 9 | Pages 689 - 695
7 Sep 2023
Lim KBL Lee NKL Yeo BS Lim VMM Ng SWL Mishra N

Aims. To determine whether side-bending films in scoliosis are assessed for adequacy in clinical practice; and to introduce a novel method for doing so. Methods. Six surgeons and eight radiographers were invited to participate in four online surveys. The generic survey comprised erect and left and right bending radiographs of eight individuals with scoliosis, with an average age of 14.6 years. Respondents were asked to indicate whether each bending film was optimal (adequate) or suboptimal. In the first survey, they were also asked if they currently assessed the adequacy of bending films. A similar second survey was sent out two weeks later, using the same eight cases but in a different order. In the third survey, a guide for assessing bending film adequacy was attached along with the radiographs to introduce the novel T1-45B method, in which the upper endplate of T1 must tilt ≥ 45° from baseline for the study to be considered optimal. A fourth and final survey was subsequently conducted for confirmation. Results. Overall, 12 (86%) of 14 respondents did not use any criteria to assess the bending film adequacy; the remaining two each described a different invalidated method. In total, 12 (86%) of the respondents felt T1-45B was easy to learn and apply. There was fair to substantial intra-rater reliability (k = 0.25 to 0.88) which improved to fair to almost perfect (k = 0.38 to 0.88) post-introduction of the guide. Inter-rater reliability varied considerably among the rater groups but similarly increased following introduction of the guide (k. S1. = 0.19 to 0.34, k. S2. = 0.33 to 0.43 vs k. S3. = 0.49 to 0.5, k. S4. = 0.35 to 0.43). Conclusion. Many surgeons and radiographers do not assess spinal bending films for adequacy. We propose that the change in the plane of the upper endplate of T1 on side-bending can be used in this evaluation. In the T1-45B method, a change of ≥ 45° on side bending qualifies as an adequate bend effort. Cite this article: Bone Jt Open 2023;4(9):689–695


Bone & Joint Research
Vol. 12, Issue 4 | Pages 245 - 255
3 Apr 2023
Ryu S So J Ha Y Kuh S Chin D Kim K Cho Y Kim K

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


The Bone & Joint Journal
Vol. 105-B, Issue 1 | Pages 64 - 71
1 Jan 2023
Danielsen E Gulati S Salvesen Ø Ingebrigtsen T Nygaard ØP Solberg TK

Aims. The number of patients undergoing surgery for degenerative cervical radiculopathy has increased. In many countries, public hospitals have limited capacity. This has resulted in long waiting times for elective treatment and a need for supplementary private healthcare. It is uncertain whether the management of patients and the outcome of treatment are equivalent in public and private hospitals. The aim of this study was to compare the management and patient-reported outcomes among patients who underwent surgery for degenerative cervical radiculopathy in public and private hospitals in Norway, and to assess whether the effectiveness of the treatment was equivalent. Methods. This was a comparative study using prospectively collected data from the Norwegian Registry for Spine Surgery. A total of 4,750 consecutive patients who underwent surgery for degenerative cervical radiculopathy and were followed for 12 months were included. Case-mix adjustment between those managed in public and private hospitals was performed using propensity score matching. The primary outcome measure was the change in the Neck Disability Index (NDI) between baseline and 12 months postoperatively. A mean difference in improvement of the NDI score between public and private hospitals of ≤ 15 points was considered equivalent. Secondary outcome measures were a numerical rating scale for neck and arm pain and the EuroQol five-dimension three-level health questionnaire. The duration of surgery, length of hospital stay, and complications were also recorded. Results. The mean improvement from baseline to 12 months postoperatively of patients who underwent surgery in public and private hospitals was equivalent, both in the unmatched cohort (mean NDI difference between groups 3.9 points (95% confidence interval (CI) 2.2 to 5.6); p < 0.001) and in the matched cohort (4.0 points (95% CI 2.3 to 5.7); p < 0.001). Secondary outcomes showed similar results. The duration of surgery and length of hospital stay were significantly longer in public hospitals. Those treated in private hospitals reported significantly fewer complications in the unmatched cohort, but not in the matched cohort. Conclusion. The clinical effectiveness of surgery for degenerative cervical radiculopathy performed in public and private hospitals was equivalent 12 months after surgery. Cite this article: Bone Joint J 2023;105-B(1):64–71


Bone & Joint Research
Vol. 12, Issue 3 | Pages 202 - 211
7 Mar 2023
Bai Z Shou Z Hu K Yu J Meng H Chen C

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. 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


Bone & Joint Open
Vol. 5, Issue 8 | Pages 662 - 670
9 Aug 2024
Tanaka T Sasaki M Katayanagi J Hirakawa A Fushimi K Yoshii T Jinno T Inose H

Aims. The escalating demand for medical resources to address spinal diseases as society ages is an issue that requires careful evaluation. However, few studies have examined trends in spinal surgery, especially unscheduled hospitalizations or surgeries performed after hours, through large databases. Our study aimed to determine national trends in the number of spine surgeries in Japan. We also aimed to identify trends in after-hours surgeries and unscheduled hospitalizations and their impact on complications and costs. Methods. We retrospectively investigated data extracted from the Diagnosis Procedure Combination database, a representative inpatient database in Japan. The data from April 2010 to March 2020 were used for this study. We included all patients who had undergone any combination of laminectomy, laminoplasty, discectomy, and/or spinal arthrodesis. Results. This investigation included 739,474 spinal surgeries and 739,215 hospitalizations in Japan. There was an average annual increase of 4.6% in the number of spinal surgeries. Scheduled hospitalizations increased by 3.7% per year while unscheduled hospitalizations increased by 11.8% per year. In-hours surgeries increased by 4.5% per year while after-hours surgeries increased by 9.9% per year. Complication rates and costs increased for both after-hours surgery and unscheduled hospitalizations, in comparison to their respective counterparts of in-hours surgery and scheduled hospitalizations. Conclusion. This study provides important insights for those interested in improving spine care in an ageing society. The swift surge in after-hours spinal surgeries and unscheduled hospitalizations highlights that the medical needs of an increasing number of patients due to an ageing society are outpacing the capacity of existing medical resources. Cite this article: Bone Jt Open 2024;5(8):662–670


Bone & Joint Open
Vol. 4, Issue 11 | Pages 873 - 880
17 Nov 2023
Swaby L Perry DC Walker K Hind D Mills A Jayasuriya R Totton N Desoysa L Chatters R Young B Sherratt F Latimer N Keetharuth A Kenison L Walters S Gardner A Ahuja S Campbell L Greenwood S Cole A

Aims. Scoliosis is a lateral curvature of the spine with associated rotation, often causing distress due to appearance. For some curves, there is good evidence to support the use of a spinal brace, worn for 20 to 24 hours a day to minimize the curve, making it as straight as possible during growth, preventing progression. Compliance can be poor due to appearance and comfort. A night-time brace, worn for eight to 12 hours, can achieve higher levels of curve correction while patients are supine, and could be preferable for patients, but evidence of efficacy is limited. This is the protocol for a randomized controlled trial of ‘full-time bracing’ versus ‘night-time bracing’ in adolescent idiopathic scoliosis (AIS). Methods. UK paediatric spine clinics will recruit 780 participants aged ten to 15 years-old with AIS, Risser stage 0, 1, or 2, and curve size (Cobb angle) 20° to 40° with apex at or below T7. Patients are randomly allocated 1:1, to either full-time or night-time bracing. A qualitative sub-study will explore communication and experiences of families in terms of bracing and research. Patient and Public Involvement & Engagement informed study design and will assist with aspects of trial delivery and dissemination. Discussion. The primary outcome is ‘treatment failure’ (Cobb angle progression to 50° or more before skeletal maturity); skeletal maturity is at Risser stage 4 in females and 5 in males, or ‘treatment success’ (Cobb angle less than 50° at skeletal maturity). The comparison is on a non-inferiority basis (non-inferiority margin 11%). Participants are followed up every six months while in brace, and at one and two years after skeletal maturity. Secondary outcomes include the Scoliosis Research Society 22 questionnaire and measures of quality of life, psychological effects of bracing, adherence, anxiety and depression, sleep, satisfaction, and educational attainment. All data will be collected through the British Spine Registry. Cite this article: Bone Jt Open 2023;4(11):873–880


Bone & Joint Research
Vol. 12, Issue 6 | Pages 387 - 396
26 Jun 2023
Xu J Si H Zeng Y Wu Y Zhang S Shen B

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


Bone & Joint Research
Vol. 12, Issue 3 | Pages 189 - 198
7 Mar 2023
Ruiz-Fernández C Ait Eldjoudi D González-Rodríguez M Cordero Barreal A Farrag Y García-Caballero L Lago F Mobasheri A Sakai D Pino J Gualillo O

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


The Bone & Joint Journal
Vol. 106-B, Issue 3 | Pages 286 - 292
1 Mar 2024
Tang S Cheung JPY Cheung PWH

Aims. To systematically evaluate whether bracing can effectively achieve curve regression in patients with adolescent idiopathic scoliosis (AIS), and to identify any predictors of curve regression after bracing. Methods. Two independent reviewers performed a comprehensive literature search in PubMed, Ovid, Web of Science, Scopus, and Cochrane Library to obtain all published information about the effectiveness of bracing in achieving curve regression in AIS patients. Search terms included “brace treatment” or “bracing,” “idiopathic scoliosis,” and “curve regression” or “curve reduction.” Inclusion criteria were studies recruiting patients with AIS undergoing brace treatment and one of the study outcomes must be curve regression or reduction, defined as > 5° reduction in coronal Cobb angle of a major curve upon bracing completion. Exclusion criteria were studies including non-AIS patients, studies not reporting p-value or confidence interval, animal studies, case reports, case series, and systematic reviews. The GRADE approach to assessing quality of evidence was used to evaluate each publication. Results. After abstract and full-text screening, 205 out of 216 articles were excluded. The 11 included studies all reported occurrence of curve regression among AIS patients who were braced. Regression rate ranged from 16.7% to 100%. We found evidence that bracing is effective in achieving curve regression among compliant AIS patients eligible for bracing, i.e. curves of 25° to 40°. A similar effect was also found in patients with major curve sizes ranging from 40° to 60° when combined with scoliosis-specific exercises. There was also evidence showing that a low apical vertebral body height ratio, in-brace correction, smaller pre-brace Cobb angle, and daily pattern of brace-wear compliance predict curve regression after bracing. Conclusion. Bracing provides a corrective effect on scoliotic curves of AIS patients to achieve curve regression, given there is high compliance rate and the incorporation of exercises. Cite this article: Bone Joint J 2024;106-B(3):286–292


The Bone & Joint Journal
Vol. 104-B, Issue 12 | Pages 1343 - 1351
1 Dec 2022
Karlsson T Försth P Skorpil M Pazarlis K Öhagen P Michaëlsson K Sandén B

Aims. The aims of this study were first, to determine if adding fusion to a decompression of the lumbar spine for spinal stenosis decreases the rate of radiological restenosis and/or proximal adjacent level stenosis two years after surgery, and second, to evaluate the change in vertebral slip two years after surgery with and without fusion. Methods. The Swedish Spinal Stenosis Study (SSSS) was conducted between 2006 and 2012 at five public and two private hospitals. Six centres participated in this two-year MRI follow-up. We randomized 222 patients with central lumbar spinal stenosis at one or two adjacent levels into two groups, decompression alone and decompression with fusion. The presence or absence of a preoperative spondylolisthesis was noted. A new stenosis on two-year MRI was used as the primary outcome, defined as a dural sac cross-sectional area ≤ 75 mm. 2. at the operated level (restenosis) and/or at the level above (proximal adjacent level stenosis). Results. A total of 211 patients underwent surgery at a mean age of 66 years (69% female): 103 were treated by decompression with fusion and 108 by decompression alone. A two-year MRI was available for 176 (90%) of the eligible patients. A new stenosis at the operated and/or adjacent level occurred more frequently after decompression and fusion than after decompression alone (47% vs 29%; p = 0.020). The difference remained in the subgroup with a preoperative spondylolisthesis, (48% vs 24%; p = 0.020), but did not reach significance for those without (45% vs 35%; p = 0.488). Proximal adjacent level stenosis was more common after fusion than after decompression alone (44% vs 17%; p < 0.001). Restenosis at the operated level was less frequent after fusion than decompression alone (4% vs 14%; p = 0.036). Vertebral slip increased by 1.1 mm after decompression alone, regardless of whether a preoperative spondylolisthesis was present or not. Conclusion. Adding fusion to a decompression increased the rate of new stenosis on two-year MRI, even when a spondylolisthesis was present preoperatively. This supports decompression alone as the preferred method of surgery for spinal stenosis, whether or not a degenerative spondylolisthesis is present preoperatively. Cite this article: Bone Joint J 2022;104-B(12):1343–1351


The Bone & Joint Journal
Vol. 105-B, Issue 4 | Pages 400 - 411
15 Mar 2023
Hosman AJF Barbagallo G van Middendorp JJ

Aims

The aim of this study was to determine whether early surgical treatment results in better neurological recovery 12 months after injury than late surgical treatment in patients with acute traumatic spinal cord injury (tSCI).

Methods

Patients with tSCI requiring surgical spinal decompression presenting to 17 centres in Europe were recruited. Depending on the timing of decompression, patients were divided into early (≤ 12 hours after injury) and late (> 12 hours and < 14 days after injury) groups. The American Spinal Injury Association neurological (ASIA) examination was performed at baseline (after injury but before decompression) and at 12 months. The primary endpoint was the change in Lower Extremity Motor Score (LEMS) from baseline to 12 months.


Bone & Joint Open
Vol. 5, Issue 3 | Pages 243 - 251
25 Mar 2024
Wan HS Wong DLL To CS Meng N Zhang T Cheung JPY

Aims

This systematic review aims to identify 3D predictors derived from biplanar reconstruction, and to describe current methods for improving curve prediction in patients with mild adolescent idiopathic scoliosis.

Methods

A comprehensive search was conducted by three independent investigators on MEDLINE, PubMed, Web of Science, and Cochrane Library. Search terms included “adolescent idiopathic scoliosis”,“3D”, and “progression”. The inclusion and exclusion criteria were carefully defined to include clinical studies. Risk of bias was assessed with the Quality in Prognostic Studies tool (QUIPS) and Appraisal tool for Cross-Sectional Studies (AXIS), and level of evidence for each predictor was rated with the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. In all, 915 publications were identified, with 377 articles subjected to full-text screening; overall, 31 articles were included.


Bone & Joint Open
Vol. 5, Issue 7 | Pages 612 - 620
19 Jul 2024
Bada ES Gardner AC Ahuja S Beard DJ Window P Foster NE

Aims

People with severe, persistent low back pain (LBP) may be offered lumbar spine fusion surgery if they have had insufficient benefit from recommended non-surgical treatments. However, National Institute for Health and Care Excellence (NICE) 2016 guidelines recommended not offering spinal fusion surgery for adults with LBP, except as part of a randomized clinical trial. This survey aims to describe UK clinicians’ views about the suitability of patients for such a future trial, along with their views regarding equipoise for randomizing patients in a future clinical trial comparing lumbar spine fusion surgery to best conservative care (BCC; the FORENSIC-UK trial).

Methods

An online cross-sectional survey was piloted by the multidisciplinary research team, then shared with clinical professional groups in the UK who are involved in the management of adults with severe, persistent LBP. The survey had seven sections that covered the demographic details of the clinician, five hypothetical case vignettes of patients with varying presentations, a series of questions regarding the preferred management, and whether or not each clinician would be willing to recruit the example patients into future clinical trials.


Bone & Joint Research
Vol. 12, Issue 2 | Pages 133 - 137
10 Feb 2023
Liao H Tsai C

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.