We conducted a prospective follow-up MRI study of originally asymptomatic healthy subjects to clarify the development of Modic changes in the cervical spine over a ten-year period and to identify related factors. Previously, 497 asymptomatic healthy volunteers with no history of cervical trauma or surgery underwent MRI. Of these, 223 underwent a second MRI at a mean follow-up of 11.6 years (10 to 12.7). These 223 subjects comprised 133 men and 100 women with a mean age at second MRI of 50.5 years (23 to 83). Modic changes were classified as not present and types 1 to 3. Changes in Modic types over time and relationships between Modic changes and progression of degeneration of the disc or clinical symptoms were evaluated. A total of 31 subjects (13.9%) showed Modic changes at follow-up: type 1 in nine, type 2 in 18, type 3 in two, and types 1 and 2 in two. Modic changes at follow-up were significantly associated with numbness or pain in the arm, but not with neck pain or shoulder stiffness. Age (≥ 40 years), gender (male), and pre-existing disc degeneration were significantly associated with newly developed Modic changes. In the cervical spine over a ten-year period, type 2 Modic changes developed most frequently. Newly developed Modic changes were significantly associated with age, gender, and pre-existing disc degeneration

Introduction: Modic changes are vertebral endplate changes visible in magnetic resonance imaging (MRI), which associate with degenerative intervertebral disc disease. Twin studies suggest that intervertebral disc degeneration and low back pain may be primarily explained by genetic factors. There are, however, no studies on genetic factors in Modic changes. Materials and methods: Eleven variations in eight genes (COL9A2, COL9A3, COL11A2, IL1A, IL1B, IL6, MMP-3 and VDR) were genotyped in an occupational cohort of 159 male train engineers and 69 male paper mill workers. All the study subjects were MRI scanned and evaluated for Modic changes. Results: Out of 228 subjects studied, 128 (56%) were found to have Modic change at one or more disc levels. 15% of them had exclusively Modic type I while 32% had exclusively Modic II changes. 10% of the subjects had both type I and type II changes. When single nucleotide polymorphisms (SNPs) were analyzed independently, none of them significantly associated with Modic changes. However, when the gene-gene interactions were evaluated IL1A and MMP-3 polymorphisms together associated with type II Modic changes (OR 3.2, 95% CI 1.2–8.5; p = 0.038). Furthermore, IL-1 gene cluster together with MMP-3 polymorphism associated significantly with type II Modic changes (OR = 8.14, 95% CI 1.72–38.44; p = 0.008). Discussion: This is the first study evaluating the role of genetic factors in relation to Modic changes. Genetic variations in IL-1 cluster and MMP-3 gene were found together to associate significantly with type II Modic changes

The study was founded by The Regional Institute of Health Sciences Research. Background: There is a need for identifying specific subgroups of LBP, Modic changes might be one of these subgroups. The aim is to describe the relationship between a previous herniated disc and the following Modic changes. Methods: 181 patients with radicular pain below the knee, leg pain ≥ 3, duration of leg pain between 2 and 52 weeks, and age between 18 and 65 years were included. The patients were randomized into one of two active conservative treatment regimes lasting eight weeks. All included patients were scanned at baseline and again at 14 months follow-up. All MRI evaluation was carried out by the same experienced radiologist using a validated evaluation protocol. Results: The prevalence of Modic changes type 1 increased more than 3 fold from 9 % at baseline to 29 % at follow-up; type 2 was respectively 14 % and 13 %. In patients with Modic changes at baseline, extremely few reduced in size or disappeared, on the contrary new type 1 changes developed after the herniation. In patients with a normal disc, 0 % developed Modic changes at follow-up, whereas in those with extrusions and sequestrations 56–63%. There exist a strong association between Modic changes and LBP, 67 % of those with Modic changes had LBP compared to 21 % of the patients without, OR 6.1, (p< 0.0001). Discussion: A lumbar disc herniation is a strong risk factor for developing Modic changes (especially type 1) during the following year. Furthermore, Modic changes are strongly associated with LBP

Background. Recently, some studies have focused attention on the possibility that anaerobic pathogens of low virulence could constitute an etiological factor in disc herniation. There have been isolated such strains, predominantly Propionibacterium acne, between 7 and 53% of patients undergoing surgery for disc pathology. According to these studies, patients with anaerobic infections of the disc are more likely to develop Modic changes in the adjacent vertebrae. The aim of this work was to test this hypothesis by growing in specific media the disc material extracted in a series of lumbar discectomy and relating this factor with the presence of pre-intervention Modic changes. Methods. A total of 22 consecutive patients undergoing primary unisegmental discectomy for lumbar disc herniation (77.2% male, mean age 40.1 ± 9.1 years) were included. All patients were immunocompetent and none had previously received an epidural steroid injection prior surgery. MRI study confirmed the disc herniation. Following strict antiseptic protocols, the extracted disc material was sent for slow-growth anaerobic enriched culture (>10 days). Results. In total, anaerobic cultures were positive in 7 cases (31.8%) all men. In 5 of these cases, the symptoms developed with an acute onset. The isolated germs were always unique: Propionibacterium acne (3), Streptococcus parasanguinis (1), Actinomyces naeslundii (1), Actinomyces meyeri (1) and methicillin sensitive Staphylococcus epidermidis. Only two (28.6%) of these 7 patients had Modic changes on MRI prior surgery (one type I, one type 2). None of the patients with negative cultures had Modic changes. Conclusions. These findings support the theory that anaerobic infections of low virulence and slow growth may contribute to the pathogenesis of herniated discs. However, these cases do not necessarily develop type 1 Modic changes as previously speculated. Level of evidence. Level IV

Study Design: A retrospective study of the clinical outcome of patients with lumbar discogenic pain with Modic changes on MRI prior to intradiscal steroid injection. Objectives: To determine whether the clinical outcome of patients with discogenic back pain who underwent intradiscal steroid injection could be predicted from MRI Modic changes. Methods: The pre-operative scans were studied by two senior spinal surgeons. The lumbar vertebral end-plate changes were then classified according to the method described by Modic. The intra- and inter-observer ratings were satisfactory. Subjects: 40 patients with discogenic back pain were recruited in this study. The mean age was 43.6 years (23 to 72 years). The male to female ratio was 1 to 1. Outcome Measures: The clinical outcomes at six months post-intradiscal steroid injection were correlated with the Modic changes. The clinical outcomes were assessed using visual analogue scores for back pain as well as Oswestry disability index (ODI). At least a 2-point improvement in visual analogue score and a 20-point improvement in ODI were required to indicate significant symptomatic relief. Results: We found that in those patients without Modic changes there was improvement of the low back pain in 9% (1/11). In those with Modic I changes there were significant relief in 64% (9/14), moderate relief in 29% (4/14) and no relief in 7% (1/14). In those with Modic II changes there were significant relief in 27% (4/15), moderate relief in 27% (4/15) and no relief in 47% (7/15). There were no cases with Modic III changes. Conclusions: Previous studies on intradiscal steroid injections have shown variable results. Two prospective double-blind clinical trials, using intradiscal steroids, identified no significant benefit or improvement in the clinical outcome. Our results however suggest that patients with Modic I changes on MRI are most likely to benefit from intradiscal steroid injection in the short term

Introduction: Modic changes have recently been identified as a pain giving pathoanatomical diagnosis for a considerable percentage (20–30 %) of Low Back Pain (LBP) patients. The causes of these Modic changes have not been determined conclusively. The aim was to evaluate a possible effect of antibiotic treatment in an uncontrolled group of patients with LBP and Modic changes. Methods: A cohort of patients (n=32) participated in this study. The patients had previous sciatic mostly from lumbar disc herniation, all were treated conservatively. At the 14 month follow-up, 43 of the patients had Modic changes, six of whom did not suffer from LBP, five declined participation. The treatment consisted of amoxicillin-clavulanate (500 mg/125 mg) (Spektramox ®) three times a day for 90 days. Results: Twenty-nine patients completed the treatment, of which 15 (52 %) reported that they were much better or cured, 7 (24 %) experienced moderate improvement, and 7 (24 %) remained unchanged. None reported a worsening of symptoms. At the end of treatment and at long term follow-up (mean 10.8 months) there was both a clinically and statistically significant (p< 0.001) improvement found in all outcome parameters, namely; general health, disease and patient specific function, pain in the lumbar area, and number of days with pain. Discussion: The clinical effect of antibiotic treatment was profound in a group of patients suffering from persistent low back pain after experiencing a disc herniation. Our results support the theory that bacterial infection could play a role in LBP with Modic changes

Introduction: In this study we describe Modic changes within treated-lumbar disc levels and levels adjacent-to-Dynamic Neutralisation System for the Spine (Dynesys). Modic changes(M) have been described in association to Degenerative Disc Disease(DDD). Type-I represents the inflammatory phase whereas Type-II describes fatty changes within the vertebral marrow and endplate. Type-III is more advanced degeneration and it indicates marked sclerosis adjacent to endplates. Material & Methods: Postoperative MRI has been compared to preoperative scan in 28 symptomatic patients treated with Dynesys. Parameters assessed were Modic changes within treated disc levels and their adjacent segments. Average time to postoperative MRI was 36 months with a range of 17–66 months. Results: Within Dynesys-treated levels; 16 levels had no Modic change preoperatively of which 13 remained unchanged while 3 developed M2 with treatment. 15 had M2, of which, 7 worsen to M3, 6 continued as M2 and 2 improved to M0. 12 had M3, of which 1 improved to M1 and the rest did not change. Adjacent endplate levels showed worsening of M0 to M2 in 11 patients while no change was seen in 35 levels. Only 4 levels with M2 were seen, of which 3 levels did not change and 1 level continued to M3. 2 M3 improved to M2. Discussion & Conclusion: Compared to recently published studies by Danish group, Modic changes have the tendancy to worsen on conservative treatment. In this study we could show that following Dynesys progress of Modic changes at the treated level(s) was not remarkable though few cases continued with the process of degeneration

Recently there has been considerable interest in the role of inflammatory mediator production by herniated degenerate discs. Modic has described MR endplate changes which have an inflammatory appearance and have been linked with discogenic back pain. To date there has been no biomechanical investigation of discs with associated Modic changes. The aim of this study is to determine if degenerate discs with associated Modic changes have higher levels of pro-inflammatory mediator production than those without Modic changes. Intervertebral disc tissue was obtained from 52 patients undergoing spinal surgery for sciatica [40] and discogram proven discogenic low back pain [12]. The tissue was cultured and the medium analysed for interleukin-6, interleukin-8 and prostaglandin E2 using an enzyme linked immunoabsorbetn assay method. Preoperative MR images of the patients were examined by a double blinded radiologist to determine the Modic status of the cultured disc level. Forty percent of patients undergoing surgery for discogenic low back pain had a Modic 1 change compared to only 12.5% of patients undergoing surgery for sciatica [p< .05] There was a statistically significant difference between levels of IL-6, IL-8 and PGE2 production by both the Modic1 [M1] and Modic2 [M2] groups compared to the Modic negative [NEG] group. IL-6:NEGvM1 p< .001, NEG v M2 p< .05, IL-8: NEG v M1 p< .01, NEG v M2 p> .05, PGE2: NEG v M1 p< 01, NEG v M2 p< .05. Modic changes have been associated with positive provocative discography by a number of authors. Pain generation requires the presence of nerves and hyperalgsia inducing mediators. Both IL-8 and PGE2 are known to induce hyperalgesia. The fact that Modic changes are associated with high levels of production of these mediators supports their role as an objective marker of discogenic low back pain

Introduction. The usefulness of markers of non-specific low back pain (NSLBP), including MRI derived measurements of cross-sectional area (CSA) and functional CSA (FCSA, fat free muscle area) of the lumbar musculature, is in doubt. To our knowledge, such markers remain unexplored in Lumbar Disc Degeneration (LDD), which is significantly associated with NSLBP, Modic change and symptom recurrence. This exploratory 3.0-T MRI study addresses this shortfall by comparing asymmetry and composition in asymptomatic older adults with and without Modic change. Methods. A sample of 21 healthy, asymptomatic subjects participated (mean age 56.9 years). T2-weighted axial lumbar images were obtained (L3/L4 to L5/S1), with slices oriented through the centre of each disc. Scans were examined by a Consultant MRI specialist and divided into 2 groups dependent on Modic presence (M) or absence (NM). Bilateral measurements of the CSA and FCSA of the erector spinae, multifidus, psoas major and quadratus lumborum were made using Image-J software. Muscle composition was determined using the equation [(FCSA/CSA)*100] and asymmetry using the equation [(Largest FCSA-smallest FCSA)/largest FCSA*100]. Data were analysed using Mann-Whitney U tests (p value set at). Intrarater reliability was examined using Intraclass Correlations (ICCs). Results. ICCs ranged between 0.74 and 0.96 for all area measurements, indicating excellent reliability. There was no significant difference in TCSA and FCSA asymmetry (P=0.1–1.0) and muscle composition (P=0.1–1.0) between M and NM groups. Conclusion. Modic change in the absence of pain does not appear to influence cross-sectional asymmetry or composition of the lumbar musculature. CSA remains a controversial marker. No conflicts of interest. Funding: This work is funded by an Allied Health Professional Doctoral Fellowship awarded to Janet Deane by Arthritis Research U.K

Study Design: Prospective cohort study. Summary of Background data: A definite link between Modic end plate changes and discogenic low back pain has yet to be established. However, current prospective data indicates that Modic changes strongly correlate with the pain provocation of lumbar discography and improved clinical outcome following instrumented posterolateral fusion. Consequently, there is recent heightened awareness using this radiological entity in the selection of patients for interbody fusion or total disc replacement. Objective: To prospectively evaluate whether Modic changes can predict improved clinical outcome following antero-posterior lumbar interbody fusion using femoral ring allograft. Methods: A cohort of chronic low back pain patients were investigated with MRI and lumbar discography. Twenty-six patients with disco-graphically-proven concordant pain reproduction were prospectively entered into the study. Clinical results were collected using the Oswestry Disability Index (ODI), Visual Analogue Scale (VAS) and Short Form 36 Health Questionnaire (SF-36) at the pre-operative and two-year follow up. The minimal clinically important difference (MCID) was taken as 10 points for ODI, 2 points for VPAS, and 7 points for the physical function and bodily pain subset of the SF-36 questionnaire. Results: MRI scans evaluated for the level fused revealed 13 patients with no end-plate changes (Type 0), whilst 2 patients had Modic Type I and 11 had Modic Type II changes. MCID in ODI were achieved in Type 0, Type 1 and Type 2, but improvement in VAS only was achieved in the Type 0 and Type 1. For SF-36, the MCID of 7 points was reached in most domains for all types of Modic change. There was no statistical difference in clinical outcome between those patients with Modic Type 0 and those with Modic type I or II. Conclusion: This prospective study shows that Modic changes do not predict improved clinical outcome following antero-posterior interbody fusion using the femoral ring allograft

Study Design: Retrospective review of 55 subjects who for various clinical indications had sequential MRI scans. Summary of Background data: Changes in the vertebral end plate are frequently associated with degenerative disc disease. These are called Modic changes. The changes were first classified into two types. Type I changes include decreased signal intensity on T1-weighted and increased signal intensity on T2-weighted images. In type II, signal intensity is increased in both T1- and T2-weighted sequences. Type I changes are assumed to be a result of fibrovascular replacement of subchondral bone and type II changes are the manifestation of fatty replacement of subchondral bone and are considered to be chronic. These changes can be separated only on magnetic resonance imaging (MRI). If bone sclerosis is extensive, signal intensities are decreased in both T1- and T2- weighted images, and this change in the end plate is called type III change. It is again assumed that these endplate changes represent a process that is progressive (Type I converts to Type II converts to Type III). To our knowledge there is little evidence to support such assumptions. Objective: To investigate the hypothesis that Modic changes are a progressive degenerative process. Subjects: The average time interval between MRI scans was two years. No subjects had had surgical intervention. The lumbar vertebral endplates were classified using the Modic system and the results compiled to provide further data on the natural history of these endplate changes. Results: Of the endplates that had Modic type I changes on the first MRI scan, 6% had reverted to a normal MRI endplate appearance on subsequent scan. Of those with Modic type II appearance 18% were normal or type I on subsequent scan. Conclusions: This data would not support the hypothesis that Modic changes observed on MRI are a progressive degenerative process

The aim of the present study was to record the MRI characteristics of the thoracic spine in asymptomatic adult males and their correlation with age and thoracic level. A cross sectional retrospective study was designed in order to record MRI thoracic spine findings in asymptomatic adult males, 35 to 65 years of age. All study participants were evaluated by MRI. The qualitative and quantitative assessed MRI parameters were as follows: disc degeneration (disk signal intensity), bulging, herniation, disc height, Modic changes, endplate irregularities, osteophytes. Intervertebral disc signal was decreased more in the lower thoracic spine (T6-T12 level). In addition there was a strong correlation between disc degeneration (disc signal loss) and the age of the study participants. Disc bulging was most frequently observed anteriorly than posteriorly with the prevalence increased caudally. Modic changes were not so frequent and there were most commonly seen in the lower thoracic spine (T11-T12 level). In addition osteophytes were larger anteriorly than posteriorly and their prevalence increased caudally. Endplate irregularities (Schmorl nodes) were more common in the upper endplates and in the lower thoracic spine (T6-T12 level). Finally strong positive correlation was noted between osteophytes, anterior and posterior and disc bulging. This study documents the mild to moderate grade of degenerative changes especially in the lower thoracic spine (T6-T12 level) of asymptomatic adult males, 35 to 65 years of age

Aims: MRI changes to the symptomatic intervertebral disc following Intradiscal Electrothermal Therapy (IDET), in particular those relating to the Ç High Intensity Zone È (HIZ) in the posterior annulus, were determined in this prospective study. Methods: MRI images before the IDET procedure were compared to those taken at six months post procedure in 10 patients. The presence and absence of an HIZ, the disc height and hydration, and Modic changes, were determined from the images. Two of the patients also had discography performed post-IDET to supplement the MRI. Results: In 6 out of the 10 patients, an HIZ was present on the MRI images of the disc before the IDET procedure. In all 6 patients, a HIZ was still present six months after the procedure. In all 10 patients, there were no changes to disc height and hydration signal on T2 weighted images. Modic changes were not present in any of the patients on pre or post IDET images. Two patients had signiþ-cant changes to the shape of the posterior annulus compared to the pre-treatment MRI scans. The two patients who had discography after IDET had persistent annular tears. Conclusion: Our þndings question the clinical relevance of the Ç High Intensity Zone È. They also suggest that the main mechanism of action of IDET, may be other than that of sealing the annular tear

Objective: MRI changes to the symptomatic intervertebral disc following Intradiscal Electrothermal Therapy (IDET), in particular those relating to the “High Intensity Zone” (HIZ) in the posterior annulus, were determined in this prospective study. Material and Methods: MRI images before the IDET procedure were compared to those taken at six months post procedure in 10 patients. The presence and absence of an HIZ, the disc height and hydration, and Modic changes, were determined from the images. Two of the patients also had discography performed post-IDET to supplement the MRI. Results: In 6 out of the 10 patients, an HIZ was present on the MRI images of the disc before the IDET procedure. In all 6 patients, a HIZ was still present six months after the procedure. In all 10 patients, there were no changes to disc height and hydration signal on T. 2. weighted images. Modic changes were not present in any of the patients on pre or post IDET images. Two patients had significant changes to the shape of the posterior annulus compared to the pre-treatment MRI scans. The two patients who had discography after IDET had persistent annular tears. Conclusion: Our findings question the clinical relevance of the “High Intensity Zone”. They also suggest that the main mechanism of action of IDET, may be other than that of sealing the annular tear

Background: Many studies have examined magnetic resonance images (MRI) with a view to the anatomy and signaling properties of the intervertebral disc and adjacent tissues in asymptomatic populations. In this study we have examined MRIs of a discrete population of patients undergoing surgery for symptomatic disc herniations. Methods: Sixty patients (aged 23–66 years, mean 41.5±8.4) had sagittal T1 and T2- weighted turbo spin echo imaging of the lumbar spine prior to surgery. One disc was herniated at L2-3, 3 at L3-4, 22 at L4-5 and 31 at L5-S1; 3 patients had herniations at both L4-5 and L5-S1. The images were scored for disc narrowing and signal, degree of anterior and posterior bulging and herniation, and assessed for Modic I and II endplate changes and fatty degeneration within the vertebrae. These were carried out for each of 6 discs (T12-S1) for all patients (ie 360 discs and 720 endplates). Results: There were trends of increasing disc narrowing, disc bulging and fatty degeneration with increasing age in these patients. 83% of patients had disc bulging, 53% had endplate irregularities and 44% had fatty degeneration. There was a significant correlation between patient weight and fatty degeneration. 7.5% of vertebrae (in 22% of patients) demonstrated Modic I changes whilst Modic II changes were seen in 14% of vertebrae (40% of patients). This is considerably higher than the incidence reported in asymptomatic individuals where Modic I changes were seen in 0.7% of vertebrae (3% of individuals) and Modic II changes in 1.9% of vertebrae (10% of individuals). Conclusion: There is a higher incidence of Modic I and II changes in disc herniation patients than in asymptomatic individuals

Background and purpose. Modic changes (MC) are a risk factor for development of chronic low back pain (CLBP). There is no agreement about the cause of inflammation in MC, but autoimmunity has been suggested. The aim of the study was to investigate whether treatment with lactic acid bacteria for 100 days was associated with change of disability and pain, via a change in the gut microbiota inducing a change in the immune system, in patients with CLBP and type 1 MC during one year follow-up. Methods. Eighty-nine patients with CLBP and type 1 MC were randomized to receive either one capsule Lactobacillus Rhamnosis GG or placebo capsules twice daily for 100 days. Results. Missing values at one year were 4% and 3% in the disability and pain variables, respectively. The predefined outcomes disability and back and leg pain only changed little during follow-up with no statistically significant differences between groups. At one year, back pain had decreased by 1.1 more on a 0–10 scale (95% CI 0.20- 1.97) in the experimental group than in the control group. There were no differences regarding other predefined outcomes, i.e. global effect or percentage with minimal disability at one year. Nine percent of the patients reported gastrointestinal side-effects without difference between groups. Conclusions. No differences were found between groups regarding the predefined outcomes. Overall, the study confirmed that CLBP with MC1 is a grave back pain disorder, with little tendency to improvement. During follow-up, disability of the whole cohort was reduced by just 17%. Conflicts of interest: No conflicts of interest. Sources of funding: The study has been supported by The Danish Rheumatism Association and Peter and Helga Kornings Fond

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. Methods. Presence of MC was evaluated in lumbar MR images and gut microbiome assessed using 16S sequencing in TwinsUK dataset (N=309). Cases were identified by the presence of MC of any type, while controls were those without MC. Amplicon sequence variants (ASVs) have been obtained for 16S sequences followed by relative abundance calculation and centred log-ratio transformation. Linear mixed-effects models were applied to test for association between the ASVs at different taxon levels and MC adjusting for technical covariates and demographics. Results. Nominally significant (p<0.05) associations with MC were obtained for 6 ASVs annotated to species level (min p = 0.0016 for Sanguibacteroides justesenii), 8 ASVs annotated to genus level (min p = 0.0091 for Syntrophomonas), and 2 ASVs annotated to family level (min p = 0.0099 for Syntrophomonadaceae). None of the associations were significant after correction for multiple testing. Also, no statistically significant difference in microbial diversity was found between MC cases and controls. Conclusions. The results of this pilot study provide limited evidence of association between MC and gut microbiome. Further studies including MC stratified by subtype are warranted as well as studies based on advanced metagenome sequencing rather than 16S approach. No conflicts of interest. The study was supported by Versus Arthritis grant # 21227

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. Methods. Presence of MC was evaluated in lumbar MR images in the Northern Finland Birth Cohort 1966 (NFBC1966, N=1182) and TwinsUK (N=647). Genome-wide association analyses were carried out in the cohorts separately using a linear regression model fitted to test for additive effects of SNPs and adjusting for age, sex, BMI, and either family relatedness via a kinship matrix (TwinsUK) or population stratification using principal components (NFBC1966). Meta-analysis of the two studies was carried out using the inverse-variance weighting approach. Results. A locus associated with MC reaching genome-wide significance (p<5e-8) was found on chromosome 9 with the lead SNP rs1934268 in intron 6 of the PTPRD gene. The SNP is located in the region of binding for a number of transcription factors which are involved in the development of the musculoskeletal system and spine cord. Conclusions. The first GWAS of MC has identified a likely functional intronic locus in PTPRD on chromosome 9 implicating musculoskeletal development. This work sheds light on the genesis of MC and paves the way for further studies on the shared genetic factors underlying the various features of spine degeneration. No conflicts of interest. Sources of Funding: The study was supported by EU FP7 project PainOMICs (grant agreement #602736), University of Oulu (grant #24000692), Oulu University Hospital (grant #24301140), and the European Regional Development Fund (grant # 539/2010 A31592). MBF, MK, and SS contributed equally to this study

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. Methods. Individuals from the TwinsUK spine study having longitudinal T2-weighted lumbar MRI scans at baseline (n=996) and a decade later (n=438) were included. LDD, vertebral endplate defect expressed as a total endplate (TEP) score and Modic change (MC) were assessed using standard techniques. Mixed-effects models were used to determine the association between spine pathology features adjusted for covariates. Endplate defect heritability was estimated using variance component analysis. Results. Significant association between endplate defect, LDD, MRI features of LDD and MC was observed. Endplate defect was independently associated with severe disabling LBP episodes. An association between LDD at baseline and MC at follow-up was shown at upper lumbar levels. TEP score was heritable with estimated additive genetic component A = 55.3% (95% CI 43.0–65.4). Conclusion. Endplate defect, LDD and MC are all independent risk factors for episodes of severe and disabling LBP. Longitudinal analysis showed LDD is followed by MC. Endplate defect has significant heritability. However, whether endplate defect triggers LDD or these pathological changes occur concurrently could not be determined conclusively. Conflicts of interest: none. Sources of Funding: This work was funded by the EU FP7 project Pain_Omics

Background. The rate of subsidence for lumbar fusion surgery is variable from 7- 89%. Subsidance can affect the outcome of surgery by compramising alignment, foraminal height and stability. Modic changes have been shown to affect the stiffness and strength of the vertebral end plate and shown to affect both fusion rates and clinical outcome. Ongoing laboratory investigations into the material properties of the degenerate lumbar spine show modic changes affect the end plate and trabecular bone mechanics. This study aims to bridge this basic science research into clinical practice. Methods. A retrospective analysis of all patients in two tertiary spinal centres who have undergone lumbar interbody fusion with the implantation of a ‘cage’ over the past 6 years were analysed by two independent spinal surgeons. Pre-operative MRI findings were correlated with post-operative interbody cage subsidence after 1 year. Results. A total of 108 Interbody cages were included. Comparison of demographics did not reveal and significant between group variations. Comparison made between those displaying no modic changes and those displaying any of the three modic change types revealed a significantly higher subsidence rate in those displaying modic changes (p=0.003). Subgroup analysis showed that Type 2 modic changes (n=27) had a significantly higher subsidence rate (p=0.002). Those displaying type 3 modic changes (n=7) did not have any incidents of subsidence. Conclusions. Type 2 modic changes are associated with a higher rate of Lumbar interbody cage subsidence in this study. Those displaying type 3 changes seem to be protected from interbody cage subsidence. No Conflict of Interest. Funding: Produced as part of a research grant from the Gwen Fish Trust and Action Arthritis