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Bone & Joint Research
Vol. 14, Issue 1 | Pages 58 - 68
27 Jan 2025
Pelleg-Kallevag R Borgel S Kedar E Peled N May H

Aims. The development of lumbar lordosis has been traditionally examined using angular measurements of the spine to reflect its shape. While studies agree regarding the increase in the angles during growth, the growth rate is understudied, and sexual dimorphism is debated. In this study, we used a novel method to estimate the shape of the lumbar curve (LC) using the landmark-based geometric morphometric method to explore changes in LC during growth, examine the effect of size and sex on LC shape, and examine the associations between angular measurements and shape. Methods. The study population included 258 children aged between 0 and 20 years (divided into five age groups) who underwent a CT scan between the years 2009 and 2019. The landmark-based geometric morphometric method was used to capture the LC shape in a sagittal view. Additionally, the lordosis was measured via Cobb and sacral slope angles. Multivariate and univariate statistical analyses were carried out to examine differences in shape between males and females and between the age groups. Results. The overall shape of the LC overlapped between males and females in most age groups, except for the nine- to 12-year age group. However, size did not affect LC shape. LC shape changed significantly during growth from straight to curved, reaching its mature shape earlier in females. This corresponded with the results obtained by the lordosis and sacral slope angles. A significant positive correlation was found between the LC shape and angles, although the angles demonstrated poor distinction between age groups, as opposed to the LC shape. Conclusion. New insights into LC shape development were achieved using the geometric morphometric method. The LC shape was sex-independent in most age groups. However, the LC reached its mature shape earlier in females than males. The method and data of this study are beneficial for future studies examining aetiological factors for spinal pathologies and maldevelopment. Cite this article: Bone Joint Res 2025;14(1):58–68


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. 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. Results. Torsion index (TI) and apical vertebral rotation (AVR) were identified as accurate predictors of curve progression in early visits. Initial TI > 3.7° and AVR > 5.8° were predictive of curve progression. Thoracic hypokyphosis was inconsistently observed in progressive curves with weak evidence. While sagittal wedging was observed in mild curves, there is insufficient evidence for its correlation with curve progression. In curves with initial Cobb angle < 25°, Cobb angle was a poor predictor for future curve progression. Prediction accuracy was improved by incorporating serial reconstructions in stepwise layers. However, a lack of post-hoc analysis was identified in studies involving geometrical models. Conclusion. For patients with mild curves, TI and AVR were identified as predictors of curve progression, with TI > 3.7° and AVR > 5.8° found to be important thresholds. Cobb angle acts as a poor predictor in mild curves, and more investigations are required to assess thoracic kyphosis and wedging as predictors. Cumulative reconstruction of radiographs improves prediction accuracy. Comprehensive analysis between progressive and non-progressive curves is recommended to extract meaningful thresholds for clinical prognostication. Cite this article: Bone Jt Open 2024;5(3):243–251


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.


Bone & Joint Open
Vol. 5, Issue 10 | Pages 886 - 893
15 Oct 2024
Zhang C Li Y Wang G Sun J

Aims

A variety of surgical methods and strategies have been demonstrated for Andersson lesion (AL) therapy. In 2011, we proposed and identified the feasibility of stabilizing the spine without curettaging the vertebral or discovertebral lesion to cure non-kyphotic AL. Additionally, due to the excellent reunion ability of ankylosing spondylitis, we further came up with minimally invasive spinal surgery (MIS) to avoid the need for both bone graft and lesion curettage in AL surgery. However, there is a paucity of research into the comparison between open spinal fusion (OSF) and early MIS in the treatment of AL. The purpose of this study was to investigate and compare the clinical outcomes and radiological evaluation of our early MIS approach and OSF for AL.

Methods

A total of 39 patients diagnosed with AL who underwent surgery from January 2004 to December 2022 were retrospectively screened for eligibility. Patients with AL were divided into an MIS group and an OSF group. The primary outcomes were union of the lesion on radiograph and CT, as well as the visual analogue scale (VAS) and Oswestry Disability Index (ODI) scores immediately after surgery, and at the follow-up (mean 29 months (standard error (SE) 9)). The secondary outcomes were total blood loss during surgery, operating time, and improvement in the radiological parameters: global and local kyphosis, sagittal vertical axis, sagittal alignment, and chin-brow vertical angle immediately after surgery and at the follow-up.


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.


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.


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.


Bone & Joint Open
Vol. 4, Issue 11 | Pages 832 - 838
3 Nov 2023
Pichler L Li Z Khakzad T Perka C Pumberger M Schömig F

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.


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.


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.


Bone & Joint Open
Vol. 5, Issue 5 | Pages 435 - 443
23 May 2024
Tadross D McGrory C Greig J Townsend R Chiverton N Highland A Breakwell L Cole AA

Aims

Gram-negative infections are associated with comorbid patients, but outcomes are less well understood. This study reviewed diagnosis, management, and treatment for a cohort treated in a tertiary spinal centre.

Methods

A retrospective review was performed of all gram-negative spinal infections (n = 32; median age 71 years; interquartile range 60 to 78), excluding surgical site infections, at a single centre between 2015 to 2020 with two- to six-year follow-up. Information regarding organism identification, antibiotic regime, and treatment outcomes (including clinical, radiological, and biochemical) were collected from clinical notes.


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.


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.


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.


Bone & Joint Open
Vol. 3, Issue 5 | Pages 348 - 358
1 May 2022
Stokes S Drozda M Lee C

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.


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.


Bone & Joint Open
Vol. 2, Issue 7 | Pages 540 - 544
19 Jul 2021
Jensen MM Milosevic S Andersen GØ Carreon L Simony A Rasmussen MM Andersen MØ

Aims

The aim of this study was to identify factors associated with poor outcome following coccygectomy on patients with chronic coccydynia and instability of the coccyx.

Methods

From the Danish National Spine Registry, DaneSpine, 134 consecutive patients were identified from a single centre who had coccygectomy from 2011 to 2019. Patient demographic data and patient-reported outcomes, including pain measured on a visual analogue scale (VAS), Oswestry Disability Index (ODI), EuroQol five-dimension five-level questionnaire, and 36-Item Short-Form Health Survey questionnaire (SF-36) were obtained at baseline and at one-year follow-up. Patient satisfaction was obtained at follow-up. Regression analysis, including age, sex, smoking status, BMI, duration of symptoms, work status, welfare payment, preoperative VAS, ODI, and SF-36 was performed to identify factors associated with dissatisfaction with results at one-year follow-up.


Bone & Joint Research
Vol. 10, Issue 5 | Pages 328 - 339
31 May 2021
Jia X Huang G Wang S Long M Tang X Feng D Zhou Q

Aims

Non-coding microRNA (miRNA) in extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) may promote neuronal repair after spinal cord injury (SCI). In this paper we report on the effects of MSC-EV-microRNA-381 (miR-381) in a rodent model of SCI.

Methods

In the current study, the luciferase assay confirmed a binding site of bromodomain-containing protein 4 (BRD4) and Wnt family member 5A (WNT5A). Then we detected expression of miR-381, BRD4, and WNT5A in dorsal root ganglia (DRG) cells treated with MSC-isolated EVs and measured neuron apoptosis in culture by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. A rat model of SCI was established to detect the in vivo effect of miR-381 and MSC-EVs on SCI.