Background

The association between lumbar intervertebral disc degeneration (LDD) and low back pain (LBP) is modest. We have recently shown that genetic propensity to pain is an effect modifier of the LDD-LBP relationship when LDD is defined as a summary score of LDD (LSUM), suggesting the association may be driven by individuals with the greatest genetic predisposition to pain. This study examined the association between individual spine magnetic resonance imaging (MRI)-determined LDD features and LBP in subgroups defined by genetic predisposition to pain.

Background

Chronic back pain (CBP) is a major cause of disability globally and its causes are multifactorial. Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) are human herpes viruses usually acquired in early life. About 50% and over 90% of the population worldwide have been infected with CMV and EBV, respectively. This study investigated a potential causal relationship between CMV infection and CBP.

Introduction

Multiple studies have identified Cutibacterium acnes (C.acnes) and other microbes in intervertebral disc tissue using 16S DNA Sequencing and microbial cultures. However, it remains unclear whether these bacteria are native to the discs or result from perioperative contamination. Our study aimed to detect Gram-positive bacteria in non-herniated human disc samples and explore correlations with Toll-like receptors (TLR) 2, TLR4, NLRP3, and Gasdermin D.

A key cause of low back pain is the degeneration of the intervertebral disc (IVD). Causality between infection of the IVD and its degenerative process gained great interest over the last decade. Granville Smith et al. (2021) identified 36 articles from 34 research studies investigating bacteria in human IVDs. Bacteria was identified in 27 studies, whereas 9 attributed bacterial presence to contamination. Cutibacterium acnes was the most abundant, followed by coagulase-negative staphylococcus. However, whether bacteria identified were present in vivo or represent perioperative contamination remains unclear. This study investigated whether bacteria are present in IVDs and what potential effects they may have on native disc cells.

Immunohistochemical staining for Gram positive bacteria was performed on human IVD tissue to identify presence and characterise bacterial species. Nucleus pulposus (NP) cells in monolayer and 3D alginate were stimulated with LPS and Peptidoglycan (0.1-50 µg/ml) for 48hrs. Following stimulation qPCR for factors associated with disc degeneration including matrix genes, matrix degrading enzymes, cytokines, neurotrophic factors and angiogenic factors and conditioned media collected for ELISA and luminex analysis

Gram positive bacteria was detected within human IVD tissue. Internalisation of bacteria by NP cells influenced the cell and nuclei morphology. Preliminary results of exposure of NP cells to bacterial components indicate that LPS as well as Peptidoglycan increase IL-8 and ADAMTS-4 gene expression following 48 hours of stimulation with a dose response seen for IL-8 induction by peptidoglycan compared to the control group. Underlining these results, IL-8 protein release was increased for treated groups compared to non-treated control. Further analysis is underway investigating other output measures and additional biological repeats.

This study has demonstrated bacteria are present within IVD cells within IVD tissue removed from degenerate IVD and is determining the potential influence of these on disc degeneration.

Objectives

This study aims to investigate whether bacteria are present in intervertebral discs (IVDs) and their influence. Causality between chronic infection of the IVD and its degenerative process gained great interest recently. Granville Smith et al. (2021) identified 36 articles from 34 research studies investigating bacteria in IVDs, from these 27 studies found, Cutibacterium acnes being the most abundant. However, whether bacteria identified were present in vivo or if they represent contamination remains unclear.

Background

Intervertebral disc degeneration (DD) is a complex age-related condition that constitutes the main risk factor for disabling back pain. DD is assessed using different traits extracted from MR imaging (MRI), normally combined to give summary measures (e.g. Pfirmann score). The aetiology of DD is poorly understood and despite its high heritability (75%), the precise genetic predisposition is yet to be defined. Genome wide association study (GWAS) is used to discover genetic variants associated with a disease or phenotype. It tests variants across the whole genome. It requires large samples to provide adequate but unfortunately there is poor availability of spine imaging data due to the high cost of MRI. We have adopted new methods to examine different MRI traits independently and use the information of those traits to boost GWAS power using specialized statistical software for jointly analyse correlated traits.

Objective

Modic changes (MC) is a form of intervertebral disc degeneration visible as subchondral and vertebral bone marrow changes on spine magnetic resonance (MR). Their etiology is not understood, but microbial infection may be involved for some subtypes. This study set out to test for an association between MC and gut microbiome in a population sample.

Objective

Low back pain (LBP) is a common debilitating condition with great socioeconomic impact. Identifying individuals at risk of LBP is challenging. We have shown IgG N-glycans are associated with LBP. Herewith, we used polygenic risk scores (PRS) from IgG-glycome to test predictability for LBP.

Objective

Modic changes (MC), a form of intervertebral disc degeneration visible as subchondral and vertebral bone marrow changes on spine magnetic resonance (MR), are known to be associated with low back pain. This study aimed to identify genes contributing to the development of MC using genome-wide association study.

Purpose

Back pain is the primary cause of disability worldwide yet surprisingly little is known of the underlying pathobiology. We conducted a genome-wide association study (GWAS) meta-analysis of chronic back pain (CBP). Adults of European ancestry from 15 cohorts in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and UK Biobank were studied.

Background

Endplate defect is an MRI trait, found to be associated with intervertebral disc degeneration. There is a lack of understanding regarding the mechanism underlying lumbar disc degeneration (LDD). This large-scale longitudinal population-based study aimed to determine the order of appearance of degenerative change in the vertebral body and intervertebral disc, the influence of endplate degeneration on LBP and whether there is a genetic influence on endplate damage.

Objectives

A single degenerate intervertebral disc is suggested to promote rapid degeneration in its adjacent discs. We validated this hypothesis using discordant co-twin case-control design.

Background and aims:

T2D is postulated to be an important aetiological factor for lumbar disc degeneration (LDD), which itself has a well documented relationship with low back pain. Obesity increases risk of both T2D, low back pain and LDD. Connective tissue modification has been reported in hyperglycaemia, but the epidemiology of LDD in T2D has not been described to date.

Background and purpose of study:

Modic change (MC) describes vertebral endplate and bone marrow lesions visible on MRI. MC has been associated with disc degeneration (DD). Independent association of MC with low back pain (LBP) is unclear. The objectives of this study were to assess the relationship between MC and severe, disabling LBP; prevalence and features of DD and incident MC during 10-year follow-up.

Background

The factors influencing normal spine curvature in midlife are unknown. We performed an MR and plain radiograph study on well characterised, unselected twin volunteers from the TwinsUK register (www.twinsuk.ac.uk) to determine the relative contributions of genetic and environmental factors to spine curve.

Introduction: Osteoporosis is a skeletal disorder characterised by decreased bone mineral density (BMD) and a subsequent increased risk of fragility fractures. This disease is commonly associated with postmenopausal females with an increasing incidence into later life, over 50% of females over 80 have osteoporosis. At the opposite spectrum of life, decreased BMD is traditionally associated with the female athletic triad, with hormonal imbalance leading to skeletal insufficiency. Considered a “silent disease” until a fracture occurs, as orthopaedic surgeons we must be able to identify those at risk of osteoporosis and refer promptly for dual energy x-ray absorptiometry (DEXA) scanning to prevent future fragility fractures in this specific patient cohort.

Methods: We carried out an epidemiological analysis of all female patients under the age of 30 referred for DEXA scanning in a university teaching hospital over a 3 year period. We analysed mode of referral, risk factors, T-score and subsequent fractures with an aim to highlight an underestimated level of osteopenia/osteoporosis in the younger patient.

Results: We identified 102 patients eligible for our study, with a mean age of 25.34 (Range- 17–29). As per the World Health Organisation (WHO) osteopenia was defined as osteopenia as a T-Score between −1 and −2.5, with osteoporosis below −2.5. The mean T score of these patients was −1.037 (range −3.2 to 2.4). Medical teams initiated the majority of referrals (77%), followed by General Practitioners (17%), Gynaecologists (4%), Paediatricians (1%) and Surgeons(1%). Risk factors included excess steroid use for medical conditions (41%), decreased body mass index (BMI) (27%), ceoliac disease (12%) and radiological evidence of osteopenia (7%). 34% of these patients had suffered a fall with 12% of patients suffering from a fragility fracture.

Conclusion: We identified a definite cohort of young female patients who had a mean T-score within the levels for osteopenia. Over one third had suffered a fall and 12% had suffered a fragility fracture despite a young age. With ever increasing patient numbers in both fracture and orthopaedic clinics and increased pressure on resources, it is imperative that we still take thorough histories to identify those young female patients that are at risk of osteoporosis. With appropriate follow up and investigations, they can be started on necessary treatment and prevent subsequent fragility fractures, the incidence of which appears to be underestimated.

Computerised tomography (CT) was performed in 30 patients with herniated lumbar discs; this was done both before chemonucleolysis and three months after. In 20 of the 28 patients who were CT positive, the compression produced by the herniated disc was eliminated or reduced. Twenty-three of the 28 patients developed diffuse bulging of the annulus. There was good correlation between the clinical results at three months and the alteration in compression as shown by the CT scan. No evidence of alteration in the bony relationship was seen in the scan and none of the patients developed epidural fibrosis. Chemonucleolysis has thus been shown to be an effective treatment of herniated lumbar discs, but it is definitely not indicated in cases where compression of the nerve root or dural sac is due to a bulging annulus.