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Bone & Joint Research
Vol. 13, Issue 9 | Pages 452 - 461
5 Sep 2024
Lee JY Lee HI Lee S Kim NH

Aims

The presence of facet tropism has been correlated with an elevated susceptibility to lumbar disc pathology. Our objective was to evaluate the impact of facet tropism on chronic lumbosacral discogenic pain through the analysis of clinical data and finite element modelling (FEM).

Methods

Retrospective analysis was conducted on clinical data, with a specific focus on the spinal units displaying facet tropism, utilizing FEM analysis for motion simulation. We studied 318 intervertebral levels in 156 patients who had undergone provocation discography. Significant predictors of clinical findings were identified by univariate and multivariate analyses. Loading conditions were applied in FEM simulations to mimic biomechanical effects on intervertebral discs, focusing on maximal displacement and intradiscal pressures, gauged through alterations in disc morphology and physical stress.


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 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 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 Research
Vol. 12, Issue 3 | Pages 199 - 201
7 Mar 2023
Brzeszczyńska J Brzeszczyński F

Cite this article: Bone Joint Res 2023;12(3):199–201.


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 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.


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.


Bone & Joint Research
Vol. 10, Issue 8 | Pages 498 - 513
3 Aug 2021
Liu Z Lu C Shen P Chou S Shih C Chen J Tien YC

Aims. Interleukin (IL)-1β is one of the major pathogenic regulators during the pathological development of intervertebral disc degeneration (IDD). However, effective treatment options for IDD are limited. Suramin is used to treat African sleeping sickness. This study aimed to investigate the pharmacological effects of suramin on mitigating IDD and to characterize the underlying mechanism. Methods. Porcine nucleus pulposus (NP) cells were treated with vehicle, 10 ng/ml IL-1β, 10 μM suramin, or 10 μM suramin plus IL-1β. The expression levels of catabolic and anabolic proteins, proinflammatory cytokines, mitogen-activated protein kinase (MAPK), and nuclear factor (NF)-κB-related signalling molecules were assessed by Western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), and immunofluorescence analysis. Flow cytometry was applied to detect apoptotic cells. The ex vivo effects of suramin were examined using IDD organ culture and differentiation was analyzed by Safranin O-Fast green and Alcian blue staining. Results. Suramin inhibited IL-1β-induced apoptosis, downregulated matrix metalloproteinase (MMP)-3, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4, and ADAMTS-5, and upregulated collagen 2A (Col2a1) and aggrecan in IL-1β-treated NP cells. IL-1β-induced inflammation, assessed by IL-1β, IL-8, and tumour necrosis factor α (TNF-α) upregulation, was alleviated by suramin treatment. Suramin suppressed IL-1β-mediated proteoglycan depletion and the induction of MMP-3, ADAMTS-4, and pro-inflammatory gene expression in ex vivo experiments. Conclusion. Suramin administration represents a novel and effectively therapeutic approach, which could potentially alleviate IDD by reducing extracellular matrix (ECM) deposition and inhibiting apoptosis and inflammatory responses in the NP cells. Cite this article: Bone Joint Res 2021;10(8):498–513


Bone & Joint Research
Vol. 9, Issue 5 | Pages 225 - 235
1 May 2020
Peng X Zhang C Bao J Zhu L Shi R Xie Z Wang F Wang K Wu X

Aims. Inflammatory response plays a pivotal role in the pathophysiological process of intervertebral disc degeneration (IDD). A20 (also known as tumour necrosis factor alpha-induced protein 3 (TNFAIP3)) is a ubiquitin-editing enzyme that restricts nuclear factor-kappa B (NF-κB) signalling. A20 prevents the occurrence of multiple inflammatory diseases. However, the role of A20 in the initiation of IDD has not been elucidated. The aim of the study was to investigate the effect of A20 in senescence of TNF alpha (TNF-α)-induced nucleus pulposus cells (NPCs). Methods. Immunohistochemical staining was performed to observe the expression of A20 in normal and degenerated human intervertebral discs. The NPCs were dissected from the tail vertebrae of healthy male Sprague-Dawley rats and were cultured in the incubator. In the experiment, TNF-α was used to mimic the inflammatory environment of IDD. The cell viability and senescence were examined to investigate the effect of A20 on TNF-α-treated NPCs. The expression of messenger RNA (mRNA)-encoding proteins related to matrix macromolecules (collagen II, aggrecan) and senescence markers (p53, p16). Additionally, NF-κB/p65 activity of NPCs was detected within different test compounds. Results. The expression of A20 was upregulated in degenerate human intervertebral discs. The A20 levels of NPCs in TNF-α inflammatory microenvironments were dramatically higher than those of the control group. TNF-α significantly decreased cell proliferation potency but increased senescence-associated beta-galactosidase (SA-β-Gal) activity, the expression of senescence-associated proteins, the synthesis of extracellular matrix, and G1 cycle arrest. The senescence indicators and NF-κB/p65 expression of A20 downregulated group treated with TNF-α were significantly upregulated compared to TNF-α-treated normal NPCs. Conclusion. A20 has a self-protective effect on the senescence of NPCs induced by TNF-α. The downregulation of A20 in NPCs exacerbated the senescence of NPCs induced by TNF-α. Cite this article:Bone Joint Res. 2020;9(5):225–235


Bone & Joint Research
Vol. 9, Issue 4 | Pages 173 - 181
1 Apr 2020
Schon J Chahla J Paudel S Manandhar L Feltham T Huard J Philippon M Zhang Z

Aims

Femoroacetabular impingement (FAI) is a potential cause of hip osteoarthritis (OA). The purpose of this study was to investigate the expression profile of matrix metalloproteinases (MMPs) in the labral tissue with FAI pathology.

Methods

In this study, labral tissues were collected from four FAI patients arthroscopically and from three normal hips of deceased donors. Proteins extracted from the FAI and normal labrums were separately applied for MMP array to screen the expression of seven MMPs and three tissue inhibitors of metalloproteinases (TIMPs). The expression of individual MMPs and TIMPs was quantified by densitometry and compared between the FAI and normal labral groups. The expression of selected MMPs and TIMPs was validated and localized in the labrum with immunohistochemistry.


The Bone & Joint Journal
Vol. 101-B, Issue 12 | Pages 1526 - 1533
1 Dec 2019
Endler P Ekman P Berglund I Möller H Gerdhem P

Aims

Chronic low back pain due to degenerative disc disease is sometimes treated with fusion. We compared the outcome of three different fusion techniques in the Swedish Spine Register: noninstrumented posterolateral fusion (PLF), instrumented posterolateral fusion (IPLF), and interbody fusion (IBF).

Patients and Methods

A total of 2874 patients who were operated on at one or two lumbar levels were followed for a mean of 9.2 years (3.6 to 19.1) for any additional lumbar spine surgery. Patient-reported outcome data were available preoperatively (n = 2874) and at one year (n = 2274), two years (n = 1958), and a mean of 6.9 years (n = 1518) postoperatively and consisted of global assessment and visual analogue scales of leg and back pain, Oswestry Disability Index, EuroQol five-dimensional index, 36-Item Short-Form Health Survey, and satisfaction with treatment. Statistical analyses were performed with competing-risks proportional hazards regression or analysis of covariance, adjusted for baseline variables.


Bone & Joint 360
Vol. 8, Issue 1 | Pages 40 - 42
1 Feb 2019


The Bone & Joint Journal
Vol. 100-B, Issue 10 | Pages 1289 - 1296
1 Oct 2018
Berliner JL Esposito CI Miller TT Padgett DE Mayman DJ Jerabek SA

Aims

The aims of this study were to measure sagittal standing and sitting lumbar-pelvic-femoral alignment in patients before and following total hip arthroplasty (THA), and to consider what preoperative factors may influence a change in postoperative pelvic position.

Patients and Methods

A total of 161 patients were considered for inclusion. Patients had a mean age of the remaining 61 years (sd 11) with a mean body mass index (BMI) of 28 kg/m2 (sd 6). Of the 161 patients, 82 were male (51%). We excluded 17 patients (11%) with spinal conditions known to affect lumbar mobility as well as the rotational axis of the spine. Standing and sitting spine-to-lower-limb radiographs were taken of the remaining 144 patients before and one year following THA. Spinopelvic alignment measurements, including sacral slope, lumbar lordosis, and pelvic incidence, were measured. These angles were used to calculate lumbar spine flexion and femoroacetabular hip flexion from a standing to sitting position. A radiographic scoring system was used to identify those patients in the series who had lumbar degenerative disc disease (DDD) and compare spinopelvic parameters between those patients with DDD (n = 38) and those who did not (n = 106).


Objectives

Degenerative disc disease (DDD) and osteoarthritis (OA) are relatively frequent causes of disability amongst the elderly; they constitute serious socioeconomic costs and significantly impair quality of life. Previous studies to date have found that aggrecan variable number of tandem repeats (VNTR) contributes both to DDD and OA. However, current data are not consistent across studies. The purpose of this study was to evaluate systematically the relationship between aggrecan VNTR, and DDD and/or OA.

Methods

This study used a highly sensitive search strategy to identify all published studies related to the relationship between aggrecan VNTR and both DDD and OA in multiple databases from January 1996 to December 2016. All identified studies were systematically evaluated using specific inclusion and exclusion criteria. Cochrane methodology was also applied to the results of this study.


The Bone & Joint Journal
Vol. 100-B, Issue 1 | Pages 81 - 87
1 Jan 2018
Peng B Yang L Yang C Pang X Chen X Wu Y

Aims

Cervical spondylosis is often accompanied by dizziness. It has recently been shown that the ingrowth of Ruffini corpuscles into diseased cervical discs may be related to cervicogenic dizziness. In order to evaluate whether cervicogenic dizziness stems from the diseased cervical disc, we performed a prospective cohort study to assess the effectiveness of anterior cervical discectomy and fusion on the relief of dizziness.

Patients and Methods

Of 145 patients with cervical spondylosis and dizziness, 116 underwent anterior cervical decompression and fusion and 29 underwent conservative treatment. All were followed up for one year. The primary outcomes were measures of the intensity and frequency of dizziness. Secondary outcomes were changes in the modified Japanese Orthopaedic Association (mJOA) score and a visual analogue scale score for neck pain.


Bone & Joint Research
Vol. 6, Issue 4 | Pages 245 - 252
1 Apr 2017
Fu M Ye Q Jiang C Qian L Xu D Wang Y Sun P Ouyang J

Objectives

Many studies have investigated the kinematics of the lumbar spine and the morphological features of the lumbar discs. However, the segment-dependent immediate changes of the lumbar intervertebral space height during flexion-extension motion are still unclear. This study examined the changes of intervertebral space height during flexion-extension motion of lumbar specimens.

Methods

First, we validated the accuracy and repeatability of a custom-made mechanical loading equipment set-up. Eight lumbar specimens underwent CT scanning in flexion, neural, and extension positions by using the equipment set-up. The changes in the disc height and distance between adjacent two pedicle screw entry points (DASEP) of the posterior approach at different lumbar levels (L3/4, L4/5 and L5/S1) were examined on three-dimensional lumbar models, which were reconstructed from the CT images.


Bone & Joint Research
Vol. 5, Issue 9 | Pages 412 - 418
1 Sep 2016
Ye S Ju B Wang H Lee K

Objectives. Interleukin 18 (IL-18) is a regulatory cytokine that degrades the disc matrix. Bone morphogenetic protein-2 (BMP-2) stimulates synthesis of the disc extracellular matrix. However, the combined effects of BMP-2 and IL-18 on human intervertebral disc degeneration have not previously been reported. The aim of this study was to investigate the effects of the anabolic cytokine BMP-2 and the catabolic cytokine IL-18 on human nucleus pulposus (NP) and annulus fibrosus (AF) cells and, therefore, to identify potential therapeutic and clinical benefits of recombinant human (rh)BMP-2 in intervertebral disc degeneration. Methods. Levels of IL-18 were measured in the blood of patients with intervertebral disc degenerative disease and in control patients. Human NP and AF cells were cultured in a NP cell medium and treated with IL-18 or IL-18 plus BMP-2. mRNA levels of target genes were measured by real-time polymerase chain reaction, and protein levels of aggrecan, type II collagen, SOX6, and matrix metalloproteinase 13 (MMP13) were assessed by western blot analysis. Results. The serum level of patients (IL-18) increased significantly with the grade of IVD degeneration. There was a dramatic alteration in IL-18 level between the advanced degeneration (Grade III to V) group and the normal group (p = 0.008) Furthermore, IL-18 induced upregulation of the catabolic regulator MMP13 and downregulation of the anabolic regulators aggrecan, type II collagen, and SOX6 at 24 hours, contributing to degradation of disc matrix enzymes. However, BMP-2 antagonised the IL-18 induced upregulation of aggrecan, type II collagen, and SOX6, resulting in reversal of IL-18 mediated disc degeneration. Conclusions. BMP-2 is anti-catabolic in human NP and AF cells, and its effects are partially mediated through provocation of the catabolic effect of IL-18. These findings indicate that BMP-2 may be a unique therapeutic option for prevention and reversal of disc degeneration. Cite this article: S. Ye, B. Ju, H. Wang, K-B. Lee. Bone morphogenetic protein-2 provokes interleukin-18-induced human intervertebral disc degeneration. Bone Joint Res 2016;5:412–418. DOI: 10.1302/2046-3758.59.BJR-2016-0032.R1


Bone & Joint Research
Vol. 3, Issue 9 | Pages 273 - 279
1 Sep 2014
Vasiliadis ES Kaspiris A Grivas TB Khaldi L Lamprou M Pneumaticos SG Nikolopoulos K Korres DS Papadimitriou E

Objectives

The aim of this study was to examine whether asymmetric loading influences macrophage elastase (MMP12) expression in different parts of a rat tail intervertebral disc and growth plate and if MMP12 expression is correlated with the severity of the deformity.

Methods

A wedge deformity between the ninth and tenth tail vertebrae was produced with an Ilizarov-type mini external fixator in 45 female Wistar rats, matched for their age and weight. Three groups were created according to the degree of deformity (10°, 30° and 50°). A total of 30 discs and vertebrae were evaluated immunohistochemically for immunolocalisation of MMP12 expression, and 15 discs were analysed by western blot and zymography in order to detect pro- and active MMP12.


Bone & Joint 360
Vol. 3, Issue 2 | Pages 32 - 65
1 Apr 2014
Adams MA

This short contribution aims to explain how intervertebral disc ‘degeneration’ differs from normal ageing, and to suggest how mechanical loading and constitutional factors interact to cause disc degeneration and prolapse. We suggest that disagreement on these matters in medico-legal practice often arises from a misunderstanding of the nature of ‘soft-tissue injuries’.


We investigated the relationship between spinopelvic parameters and disc degeneration in young adult patients with spondylolytic spondylolisthesis. A total of 229 men with a mean age of 21 years (18 to 26) with spondylolytic spondylolisthesis were identified. All radiological measurements, including pelvic incidence, sacral slope, pelvic tilt, lumbar lordosis, sacral inclination, lumbosacral angle (LSA), and sacrofemoral distance, were calculated from standing lateral lumbosacral radiographs. The degree of intervertebral disc degeneration was classified using a modified Pfirrmann scale. We analysed the spinopelvic parameters according to disc level, degree of slip and disc degeneration.

There were significant positive correlations between the degree of slip and pelvic incidence (p = 0.009), sacral slope (p = 0.003) and lumbar lordosis (p = 0.010). The degree of slip and the LSA were correlated with disc degeneration (p < 0.001 and p = 0.003, respectively). There was also a significant difference between the degree of slip (p < 0.001) and LSA (p = 0.006) according to the segmental level of disc degeneration.

Cite this article: Bone Joint J 2013;95-B:1239–43.


Bone & Joint Research
Vol. 2, Issue 8 | Pages 169 - 178
1 Aug 2013
Rodrigues-Pinto R Richardson SM Hoyland JA

Mesenchymal stem-cell based therapies have been proposed as novel treatments for intervertebral disc degeneration, a prevalent and disabling condition associated with back pain. The development of these treatment strategies, however, has been hindered by the incomplete understanding of the human nucleus pulposus phenotype and by an inaccurate interpretation and translation of animal to human research. This review summarises recent work characterising the nucleus pulposus phenotype in different animal models and in humans and integrates their findings with the anatomical and physiological differences between these species. Understanding this phenotype is paramount to guarantee that implanted cells restore the native functions of the intervertebral disc. Cite this article: Bone Joint Res 2013;2:169–78


Bone & Joint 360
Vol. 1, Issue 1 | Pages 18 - 19
1 Feb 2012


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 9 | Pages 1253 - 1258
1 Sep 2011
Alpantaki K Katonis P Hadjipavlou AG Spandidos DA Sourvinos G

It has been proposed that intervertebral disc degeneration might be caused by low-grade infection. The purpose of the present study was to assess the incidence of herpes viruses in intervertebral disc specimens from patients with lumbar disc herniation. A polymerase chain reaction based assay was applied to screen for the DNA of eight different herpes viruses in 16 patients and two controls. DNA of at least one herpes virus was detected in 13 specimens (81.25%). Herpes Simplex Virus type-1 (HSV-1) was the most frequently detected virus (56.25%), followed by Cytomegalovirus (CMV) (37.5%). In two patients, co-infection by both HSV-1 and CMV was detected. All samples, including the control specimens, were negative for Herpes Simplex Virus type-2, Varicella Zoster Virus, Epstein Barr Virus, Human Herpes Viruses 6, 7 and 8. The absence of an acute infection was confirmed both at the serological and mRNA level. To our knowledge this is the first unequivocal evidence of the presence of herpes virus DNA in intervertebral disc specimens of patients with lumbar disc herniation suggesting the potential role of herpes viruses as a contributing factor to the pathogenesis of degenerative disc disease


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 12 | Pages 1664 - 1668
1 Dec 2010
Ranson CA Burnett AF Kerslake RW

In our study, the aims were to describe the changes in the appearance of the lumbar spine on MRI in elite fast bowlers during a follow-up period of one year, and to determine whether these could be used to predict the presence of a stress fracture of the posterior elements. We recruited 28 elite fast bowlers with a mean age of 19 years (16 to 24) who were training and playing competitively at the start of the study. They underwent baseline MRI (season 1) and further scanning (season 2) after one year to assess the appearance of the lumbar intervertebral discs and posterior bony elements. The incidence of low back pain and the amount of playing and training time lost were also recorded. In total, 15 of the 28 participants (53.6%) showed signs of acute bone stress on either the season 1 or season 2 MR scans and there was a strong correlation between these findings and the later development of a stress fracture (p < 0.001). The prevalence of intervertebral disc degeneration was relatively low. There was no relationship between disc degeneration on the season 1 MR scans and subsequent stress fracture. Regular lumbar MR scans of asymptomatic elite fast bowlers may be of value in detecting early changes of bone stress and may allow prompt intervention aimed at preventing a stress fracture and avoiding prolonged absence from cricket


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 6 | Pages 713 - 719
1 Jun 2009
Denaro V Papalia R Denaro L Di Martino A Maffulli N

Cervical spinal disc replacement is used in the management of degenerative cervical disc disease in an attempt to preserve cervical spinal movement and to prevent adjacent disc overload and subsequent degeneration. A large number of patients have undergone cervical spinal disc replacement, but the effectiveness of these implants is still uncertain. In most instances, degenerative change at adjacent levels represents the physiological progression of the natural history of the arthritic disc, and is unrelated to the surgeon. Complications of cervical disc replacement include loss of movement from periprosthetic ankylosis and ossification, neurological deficit, loosening and failure of the device, and worsening of any cervical kyphosis. Strict selection criteria and adherence to scientific evidence are necessary. Only prospective, randomised clinical trials with long-term follow-up will establish any real advantage of cervical spinal disc replacement over fusion.


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 10 | Pages 1261 - 1270
1 Oct 2008
Hadjipavlou AG Tzermiadianos MN Bogduk N Zindrick MR

The pathophysiology of intervertebral disc degeneration has been extensively studied. Various factors have been suggested as influencing its aetiology, including mechanical factors, such as compressive loading, shear stress and vibration, as well as ageing, genetic, systemic and toxic factors, which can lead to degeneration of the disc through biochemical reactions. How are these factors linked? What is their individual importance? There is no clear evidence indicating whether ageing in the presence of repetitive injury or repetitive injury in the absence of ageing plays a greater role in the degenerative process. Mechanical factors can trigger biochemical reactions which, in turn, may promote the normal biological changes of ageing, which can also be accelerated by genetic factors. Degradation of the molecular structure of the disc during ageing renders it more susceptible to superimposed mechanical injuries. This review supports the theory that degeneration of the disc has a complex multifactorial aetiology. Which factors initiate the events in the degenerative cascade is a question that remains unanswered, but most evidence points to an age-related process influenced primarily by mechanical and genetic factors


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 7 | Pages 841 - 851
1 Jul 2006
Lee EH Hui JHP


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 8 | Pages 1111 - 1116
1 Aug 2005
Ranson CA Kerslake RW Burnett AF Batt ME Abdi S

Low back injuries account for the greatest loss of playing time for professional fast bowlers in cricket. Previous radiological studies have shown a high prevalence of degeneration of the lumbar discs and stress injuries of the pars interarticularis in elite junior fast bowlers. We have examined MRI appearance of the lumbar spines of 36 asymptomatic professional fast bowlers and 17 active control subjects. The fast bowlers had a relatively high prevalence of multi-level degeneration of the lumbar discs and a unique pattern of stress lesions of the pars interarticularis on the non-dominant side. The systems which have been used to classify the MR appearance of the lumbar discs and pars were found to be reliable. However, the relationship between the radiological findings, pain and dysfunction remains unclear.


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 5 | Pages 687 - 691
1 May 2005
Aihara T Takahashi K Ogasawara A Itadera E Ono Y Moriya H

We studied 52 patients, each with a lumbosacral transitional vertebra. Using MRI we found that the lumbar discs immediately above the transitional vertebra were significantly more degenerative and those between the transitional vertebrae and the sacrum were significantly less degenerative compared with discs at other levels. We also performed an anatomical study using 70 cadavers. We found that the iliolumbar ligament at the level immediately above the transitional vertebra was thinner and weaker than it was in cadavers without a lumbosacral transitional vertebra.

Instability of the vertebral segment above the transitional vertebra because of a weak iliolumbar ligament could lead to subsequent disc degeneration which may occur earlier than at other disc levels. Some stability between the transitional vertebra and the sacrum could be preserved by the formation of either an articulation or by bony union between the vertebra and the sacrum through its transverse process. This may protect the disc from further degeneration in the long term.


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 1 | Pages 62 - 67
1 Jan 2005
Peng B Wu W Hou S Li P Zhang C Yang Y

Discogenic low back pain is a common cause of disability, but its pathogenesis is poorly understood. We collected 19 specimens of lumbar intervertebral discs from 17 patients with discogenic low back pain during posterior lumbar interbody fusion, 12 from physiologically ageing discs and ten from normal control discs. We investigated the histological features and assessed the immunoreactive activity of neurofilament (NF200) and neuropeptides such as substance P (SP) and vasoactive-intestinal peptide (VIP) in the nerve fibres.

The distinct histological characteristic of the painful disc was the formation of a zone of vascularised granulation tissue from the nucleus pulposus to the outer part of the annulus fibrosus along the edges of the fissures. SP-, NF- and VIP-immunoreactive nerve fibres in the painful discs were more extensive than in the control discs. Growth of nerves deep into the annulus fibrosus and nucleus pulposus was observed mainly along the zone of granulation tissue in the painful discs. This suggests that the zone of granulation tissue with extensive innervation along the tears in the posterior part of the painful disc may be responsible for causing the pain of discography and of discogenic low back pain.


The Journal of Bone & Joint Surgery British Volume
Vol. 84-B, Issue 2 | Pages 289 - 294
1 Mar 2002
Phillips FM Reuben J Wetzel FT

Our study establishes a rabbit model of disc degeneration which requires neither a chemical nor physical injury to the disc. Disc degeneration similar to that seen in man was created at levels proximal (L4-L5) and caudal (L7-S1) to a simulated lumbar fusion and was studied for up to nine months after arthrodesis.

Loss of the normal parallel arrangement of collagen bundles within the annular lamellae was observed in intervertebral discs adjacent to the fusion at three months. By six months there was further disorganisation as well as loss of distinction between the lamellae themselves. By nine months the structure of the disc had been replaced by disorganised fibrous tissue, and annular tears were seen. There was an initial cellular proliferative response followed by loss of chondrocytes and notochordal cells in the nucleus pulposus. Degeneration was accompanied by a decrease in the monomer size of proteoglycans. Narrowing of the disc space, endplate sclerosis and the formation of osteophytes at adjacent disc spaces were observed radiologically.


The Journal of Bone & Joint Surgery British Volume
Vol. 74-B, Issue 3 | Pages 431 - 435
1 May 1992
Osti O Fraser R

We attempted to correlate the findings of MRI and discography in patients with low back pain, examining 108 lumbar intervertebral discs in 33 consecutive patients. MRI results were assessed from the intensity and shape of the signal obtained from the central part of the disc. Discography was classified according to the pattern of contrast material, the pressure accepted and the pain reproduced. All discs which were abnormal on MRI had altered patterns on discography, but 18 of the 60 discs with normal MRI had abnormal discograms. Of 39 asymptomatic discs, 33 had normal MRI signals and 24 had normal discograms. None of the 15 discs showing severe degeneration on MRI sustained high levels of intradiscal pressure, but only six of the 60 discs giving normal MRI had low pressure. With current techniques, discography is more accurate than MRI for the detection of annular pathology: a normal MRI does not exclude significant changes in the peripheral structure of the intervertebral disc which can produce low back pain.


The Journal of Bone & Joint Surgery British Volume
Vol. 74-B, Issue 3 | Pages 421 - 425
1 May 1992
Hardcastle P Annear P Foster D Chakera T McCormick C Khangure M Burnett A

The action of fast bowling in the game of cricket is known to cause injuries to the lumbar spine. We studied a group of 16- to 18-year-old fast bowlers, selected for special training in Western Australia. All 24 had MR scans of the spine, 22 had radiographs and CT scans; in 20 the bowling technique was analysed biomechanically. There was a high incidence of back pain and this was always associated with a radiological abnormality. Pars interarticularis defects were diagnosed in 54% and intervertebral disc degeneration in 63%. Bowling actions which involved counter-rotation were associated with a higher incidence of both injuries


The Journal of Bone & Joint Surgery British Volume
Vol. 47-B, Issue 2 | Pages 211 - 223
1 May 1965
Sacks S

1. At the present stage of our experience, when 150 patients have been analysed over a period of five years, the conclusion has been reached that anterior interbody fusion in the lower lumbar spine is a procedure which should be added to our surgical armamentarium for use in selected cases. 2. Patients suffering from chronic intervertebral disc degeneration whose main symptoms are recurrent incapacitating backache derive the most benefit from this procedure. 3. When used as a salvage operation in patients who have had previous unsuccessful laminectomy or posterior fusion, good results can be expected. 4. In patients with spondylolisthesis anterior interbody fusion should be confined to cases in which the vertebral bodies have not slipped forward more than one-third


The Journal of Bone & Joint Surgery British Volume
Vol. 38-B, Issue 2 | Pages 485 - 497
1 May 1956
Shaw EG Taylor JG

1. In this series of posterior onlay grafting with fresh autogenous bone and without internal fixation, in the treatment of non-infective structural lesions in the lumbo-sacral area, 71 per cent of the patients were relieved of their symptoms, but bony fusion was obtained in only 60 per cent. 2. It is probable that with this technique twelve weeks' immobilisation in a plaster bed is required. 3. Some failures are ascribed to the use of an insufficient quantity of bone or to poor apposition of the graft to its bed. 4. It is evident that the more vertebrae one attempts to fuse the more difficult it is to succeed. When the diseased area is successfully fused but an unnecessarily long graft has been used, a pseudarthrosis above the level of the pre-operative pathology may be the cause of persisting backache. For these reasons we believe that one should not attempt to graft more vertebrae than is necessary to stabilise the local lesion. 5. The complication rate, particularly from deep vein thrombosis, was high. This major complication could perhaps be overcome by using banked bone. 6. The indications for the operation are assessed as follows. It should be done for low back pain only when there is a definite diagnosis and a limited extent of structural pathology; one can then expect excellent results when successful fusion is achieved and also an appreciably high proportion of satisfied patients even when bony fusion has not been obtained, presumably because there is a fibrous union strong enough to stabilise the affected spine. It is inadvisable to undertake lumbar-lumbo-sacral fusion for intervertebral disc degeneration when there are more than three adjacent vertebrae involved, and in any case operation should be confined to the indicated extent