The bacteria-positive proportion in the disc tissue samples from surgery: a systematic review and meta-analysis.

PURPOSE: The role of bacteria, especially Propionibacterium acnes (P. acnes), in human intervertebral disc diseases has raised attention in recent years. However, limited sample size of these studies and diverse bacteria-positive proportion made this topic still controversial. We aimed to review related articles and summarize the bacteria-positive proportion in these studies. METHODS: We searched the PubMed, Cochrane Library, Embase for related literature from January 2001 to May 2018, and the reference articles were also searched. The random effects or fixed effects meta-analysis was used to pool the overall positive proportion or odds ratio of these studies. RESULTS: We found 16 relevant articles and 2084 cases of the bacteria culture from surgery. Within the 16 included studies, 12 studies' results supported the infection in the discs. The pooled bacterial infection rate was 25.3%. The pooled P. acnes infection rate was 15.5%. The overall pooled P. acnes proportion in bacteria-positive discs was 56.4%. We also found that the presence of bacteria may contribute to the development of Modic change with the odds ratio as 1.27 (95% CI: 0.44-3.64), but this result is not significant due to heterogeneity, so further study is needed. CONCLUSION: The existence of bacteria in the intervertebral discs was proved by many studies. However, the variety in sample collecting and culture methods is still obvious and the positive rate also fluctuated within the studies. Standardized and reliable methods should be taken to promote the study in the future. These slides can be retrieved under Electronic Supplementary Material.

Low virulence bacterial infections in cervical intervertebral discs: a prospective case series.

STUDY DESIGN: A prospective cross-sectional case series study. OBJECTIVE: To investigate the prevalence of low virulence disc infection and its associations with characteristics of patients or discs in the cervical spine. BACKGROUND: Low virulence bacterial infections could be a possible cause of intervertebral disc degeneration and/or back pain. Controversies are continuing over whether these bacteria, predominantly Propionibacterium acnes (P. acnes), represent infection or contamination. However, the current studies mainly focus on the lumbar spine, with very limited data on the cervical spine. METHODS: Thirty-two patients (20 men and 12 women) who underwent anterior cervical fusion for degenerative cervical spondylosis or traumatic cervical cord injury were enrolled. Radiological assessments included X-ray, CT, and MRI of the cervical spine. Endplate Modic changes, intervertebral range of motion, and disc herniation type were evaluated. Disc and muscle tissues were collected under strict sterile conditions. Samples were enriched in tryptone soy broth and subcultured under anaerobic conditions, followed by identification of the resulting colonies by the PCR method. RESULTS: Sixty-six intervertebral discs were excised from thirty-two patients. Positive disc cultures were noted in eight patients (25%) and in nine discs (13.6%). The muscle biopsy (control) cultures were negative in 28 patients and positive in 4 patients (12.5%); three of whom had a negative disc culture. Seven discs (10.6%) were positive for coagulase-negative Staphylococci (CNS) and two discs were positive for P. acnes (3.0%). A younger patient age and the extrusion or sequestration type of disc herniation, which represented a complete annulus fibrous failure, were associated with positive disc culture. CONCLUSIONS: Our data show that CNS is more prevalent than P. acnes in degenerative cervical discs. The infection route in cervical discs may be predominantly through an annulus fissure. Correlation between these infections and clinical symptoms is uncertain; therefore, their clinical significance needs to be investigated in the future. These slides can be retrieved under Electronic Supplementary Material.

Latent infection of low-virulence anaerobic bacteria in degenerated lumbar intervertebral discs.

BACKGROUND: The existence of latent low-virulence anaerobic bacteria in degenerated intervertebral discs (IVDs) remains controversial. In this study, the prevalence of low-virulence anaerobic bacteria in degenerated IVDs was examined, and the correlation between bacterial infection and clinical symptoms was analysed. METHODS: Eighty patients with disc herniation who underwent discectomy were included in this study. Under a stringent protocol to ensure sterile conditions, 80 disc samples were intraoperatively retrieved and subjected to microbiological culture. Meanwhile, tissue samples from the surrounding muscle and ligaments were harvested and cultured as contamination markers. The severity of IVD degeneration and the prevalence of Modic changes (MCs) were assessed according to preoperative MRI analysis. RESULTS: Of the 80 cultured discs, 54 were sterile, and 26 showed the presence of bacteria: Propionibacterium acnes (21 cases) and coagulase-negative staphylococci (5 cases). MRI revealed that the presence of bacteria was significantly associated with MCs (P<0.001). However, there was no significant association between bacterial infection and the severity of IVD degeneration (P = 0.162). CONCLUSIONS: Our findings further validated the presence of low-virulence anaerobic bacteria in degenerated IVDs, and P. acnes was the most frequent bacterium. In addition, the latent infection of bacteria in IVDs was associated with Modic changes. Therefore, low-virulence anaerobic bacteria may play a crucial role in the pathophysiology of MCs and lumbar disc herniation.

ISSLS PRIZE IN CLINICAL SCIENCE 2017: Is infection the possible initiator of disc disease? An insight from proteomic analysis.

STUDY DESIGN: Proteomic and 16S rDNA analysis of disc tissues obtained in vivo. OBJECTIVE: To address the controversy of infection as an aetiology for disc disorders through protein profiling. There is raging controversy over the presence of bacteria in human lumbar discs in vivo, and if they represent contamination or infection. Proteomics can provide valuable insight by identifying proteins signifying bacterial presence and, also host defence response proteins (HDRPs), which will confirm infection. METHODS: 22 discs (15-disc herniations (DH), 5-degenerate (DD), 2-normal in MRI (NM) were harvested intraoperatively and immediately snap frozen. Samples were pooled into three groups and proteins extracted were analysed with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Post identification, data analysis was performed using Uniprotdb, Pantherdb, Proteome discoverer and STRING network. Authentication for bacterial presence was performed by PCR amplification of 16S rDNA. RESULTS: LC-MS/MS analysis using Orbitrap showed 1103 proteins in DH group, compared to 394 in NM and 564 in DD. 73 bacterial specific proteins were identified (56 specific for Propionibacterium acnes; 17 for Staphylococcus epidermidis). In addition, 67 infection-specific HDRPs, unique or upregulated, such as Defensin, Lysozyme, Dermcidin, Cathepsin-G, Prolactin-Induced Protein, and Phospholipase-A2, were identified confirming presence of infection. Species-specific primers for P. acnes exhibited amplicons at 946 bp (16S rDNA) and 515 bp (Lipase) confirming presence of P. acnes in both NM discs, 11 of 15 DH discs, and all five DD discs. Bioinformatic search for protein-protein interactions (STRING) documented 169 proteins with close interactions (protein clustering co-efficient 0.7) between host response and degenerative proteins implying that infection may initiate degradation through Ubiquitin C. CONCLUSION: Our study demonstrates bacterial specific proteins and host defence proteins to infection which strengthen the hypothesis of infection as a possible initiator of disc disease. These results can lead to a paradigm shift in our understanding and management of disc disorders.

Ribosomal PCR assay of excised intervertebral discs from patients undergoing single-level primary lumbar microdiscectomy.

PURPOSE: To determine the presence of infectious microorganisms in the herniated discs of immunocompetent patients, using methodology that we hoped would be of higher sensitivity and specificity than has been reported in the past. Recent studies have demonstrated a significant rate of positive cultures for low virulent organisms in excised HNP samples (range 19-53%). These studies have served as the theoretical basis for a pilot trial, and then, a well done prospective randomized trial that demonstrated that systemic treatment with antibiotics may yield lasting improvements in a subset of patients with axial back pain. Whether the reported positive cultures in discectomy specimens represent true positives is as yet not proven, and critically important if underlying the basis of therapeutic approaches for chronic low back pain. METHODS: This consecutive case series from a single academic center included 44 patients with radiculopathy and MRI findings of lumbar HNP. Patients elected for lumbar microdiscectomy after failure of conservative management. All patients received primary surgery at a single spinal level in the absence of immune compromise. Excised disc material was analyzed with a real-time PCR assay targeting the 16S ribosomal RNA gene followed by amplicon sequencing. No concurrent cultures were performed. Inclusion criteria were as follows: sensory or motor symptoms in a single lumbar nerve distribution; positive physical examination findings including positive straight leg raise test, distributional weakness, and/or a diminished deep tendon reflexes; and magnetic resonance imaging of the lumbar spine positive for HNP in a distribution correlating with the radicular complaint. RESULTS: The PCR assay for the 16S rRNA sequence was negative in all 44 patients (100%). 95% CI 0-8%. CONCLUSIONS: Based on the data presented here, there does not appear to be a significant underlying rate of bacterial disc infection in immunocompetent patients presenting with radiculopathy from disc herniation.

The distribution of infection with Propionibacterium acnes is equal in patients with cervical and lumbar disc herniation.

BACKGROUND: Cervical and back pains are important clinical problems affecting human populations globally. It is suggested that Propionibacterium acnes (P. acnes) is associated with disc herniation. The aim of this study is to evaluate the distribution of P. acnes infection in the cervical and lumbar disc material obtained from patients with disc herniation. METHODS AND MATERIAL: A total of 145 patients with mean age of 45.21 ± 11.24 years who underwent micro-discectomy in cervical and lumbar regions were enrolled into the study. The samples were excited during the operation and then cultured in the anaerobic incubations. The cultured P. acnes were detected by 16S rRNA-based polymerase chain reaction. RESULTS: In this study, 145 patients including 25 cases with cervical and 120 cases with lumbar disc herniation were enrolled to the study. There was no significant difference in the age of male and female patients (p = 0.123). P. acnes infection was detected in nine patients (36%) with cervical disc herniation and 46 patients (38.3%) with lumbar disc herniation and no significant differences were reported in P. acnes presence according to the disc regions (p = 0.508.). Moreover, there was a significant difference in the presence of P. acnes infection according to the level of lumbar disc herniation (p = 0.028). CONCLUSION: According to the results, the presence of P. acnes is equal in patients with cervical and lumbar disc herniation. There was a significant difference in the distribution of P. acnes infection according to level of lumbar disc herniation. LEVEL OF EVIDENCE: II.

Modic changes in the adjacent vertebrae due to disc material infection with Propionibacterium acnes in patients with lumbar disc herniation.

INTRODUCTION: Modic changes (MCs) in vertebral bones are induced by two mechanisms of mechanical factors and infection. As Propionibacterium acnes (P. acnes) have been reported to be associated with LBP. The aim of this study is to evaluate the MCs in patients with disc herniation and positive for P. acnes. METHODS AND MATERIAL: A total of 120 patients with disc herniation surgery were enrolled into the study. The samples were excised during discectomy and then cultured in both anaerobic and aerobic incubations. Gram staining was employed for investigation of all colonies. The cultured P. acnes were detected by 16S rRNA-based polymerase chain reaction (PCR). MCs of baseline MRI were evaluated. RESULTS: In this study, 120 subjects (69 male and 51 female) with mean age of 43.15 ± 12.62 years were investigated. Sixty disc samples and eight muscle samples were positive for microorganisms. Moreover, 16S rDNA gene was identified in 46 (38.3%) disc samples. Moreover, 36/46 patients with P. acnes in their sample had MCs. CONCLUSION: According to the results and presence of 36/46 MCs in patients with lumbar disc herniation, positive for P. acnes suggests that P. acnes can lead to edema on the vertebrae endplates near to infected area.

What Is the Role of the Bacterium Propionibacterium acnes in Type 1 Modic Changes? A Review of the Literature.

This review presents a summary of the pathology and epidemiology of Modic changes and the possible role of Propionibacterium acnes. This information is followed by a synthesis of the most recent clinical research involved in culturing the discs of patients with degenerative disc disease for the presence of bacteria. We also discuss a randomized controlled trial that investigates the effects of antibiotics on patients with chronic low back pain and type 1 Modic changes. We conclude with a brief discussion of the difficulties involved in this research and the significance of the findings.

Relationship between annular tear and presence of Propionibacterium acnes in lumbar intervertebral disc.

PURPOSE: Propionibacterium acnes (P. acnes) in the intervertebral disc may result in low back pain. The purpose of this study was to determine how P. acnes accesses the disc. METHODS: Patients with low back pain and/or sciatica were examined using X-ray and MRI before surgery. The intervertebral disc space height was measured on X-ray image. Disc and muscle samples were obtained from 46 patients undergoing discectomy at the lumbar spine. The tear of annulus was inspected before discectomy. In the disc and muscle tissue cultures, 16S rDNA gene specific for P. acnes was examined using PCR. RESULTS: The discs from 11 (23.9 %) patients were identified as 16S rDNA positive, in which two patients also had 16S rDNA in their muscles. 16S rDNA gene was significantly more likely to appear in the discs with annular tear than those without tear (P < 0.05). The disc space height was significantly decreased when the disc contained P. acnes. CONCLUSION: P. acnes is significantly more likely to be present in herniated discs with an annular tear than in herniated discs without such a tear. Since in the vast majority of these cases, no P. acnes was found in control muscle samples, a true infection with P. acnes is far more likely than a contamination.

Lumbar discitis caused by Clostridium perfringens.

We report here a rare case of chronic lumbar discitis caused by Clostridium perfringens in an elderly patient that was treated with a combination of ß-lactams and clindamycin. Molecular analysis performed on the strain revealed an unusual toxin gene pattern.

Does the gut microbiome influence disc health and disease? The interplay between dysbiosis, pathobionts, and disc inflammation: a pilot study.

BACKGROUND CONTEXT: Gut microbiome alterations resulting in inflammatory responses have been implicated in many distant effects on different organs. However, its influence on disc health is still not fully investigated. PURPOSE: Our objective was to document the gut biome in healthy volunteers and patients with disc degeneration and to understand the role of gut dysbiosis on human disc health. STUDY DESIGN: Experimental case-control study. PATIENT SAMPLE: We included 40 patients with disc degeneration (DG) and 20 healthy volunteers (HV). HV comprised of age groups 30 to 60 years with no known record of back pain and no clinical comorbidities, with normal MRI. Diseased group (DG) were patients in the same age group undergoing surgery for disc disease (disc herniation-25; discogenic stenosis-15) and without instability (with Modic-20; and non-Modic-20). OUTCOME MEASURES: N/A. METHODS: We analyzed 16S V3-V4 rDNA gut metagenome from 20 healthy volunteers (HV) and compared the top signature genera from 40 patients with disc degeneration (DG) across Modic and non-Modic groups. Norgen Stool DNA Kit was used for DNA extraction from ∼200 mg of each faecal sample collected using the Norgen Stool Collection Kit.16S V3-V4 rDNA amplicons were generated with universal bacterial primers 341F and 806R and amplified with Q5 High-Fidelity DNA Polymerase. Libraries were sequenced with 250×2 PE to an average of 0.1 million raw reads per sample (Illumina Novaseq 6000). Demultiplexed raw data was assessed with FastQC, and adapter trimmed reads >Q30 reads were processed in the QIME2 pipeline. Serum C-reactive protein (CRP) was measured by the immunoturbimetry method and Fatty acid-binding protein 5 (FABP5) was measured in albumin-globulin-depleted plasma through global proteome analysis. RESULTS: We observed significant gut dysbiosis between HV and DG and also between the Modic and non-Modic groups. In the Modic group, commensals Bifidobacterium and Ruminococcus were significantly depleted, while pathobionts Streptococcus, Prevotella, and Butryvibrio were enriched. Firmicutes/Bacteroidetes ratio was decreased in DG (Modic-0.62, non-Modic-0.43) compared to HV (0.70). Bacteria-producing beneficial short-chain fatty acids were also depleted in DG. Elevated serum CRP and increased FABP5 were observed in DG. CONCLUSION: The study revealed gut dysbiosis, an altered Firmicutes/Bacteroidetes ratio, reduced SCFA-producing bacteria, and increased systemic and local inflammation in association with disc disease, especially in Modic changes. The findings have considerable importance for our understanding and prevention of disc degeneration.

Bacterial identification in herniated intervertebral discs: a prospective cohort study.

BACKGROUND CONTEXT: Reports of Cutibacterium acnes isolated in cultures of intervertebral disc samples suggest it as possibly responsible for inflammatory conditions causing Modic changes on spinal magnetic resonance imaging (MRI). PURPOSE: Our objective was to investigate the prevalence of C. acnes in samples of intervertebral disc of patients with lumbar disc herniation; to investigate prognostic factors and the relationship of Modic changes with infection 1 year after microdiscectomy. STUDY DESIGN: Prospective cohort study. PATIENT SAMPLE: In this single-center study, patients consecutively operated on for disc herniation had samples of the disc, multifidus muscle and ligamentum flavum (as an indication of contamination) extracted for culture. OUTCOME MEASURES: Age, sex, alcohol and tobacco consumption, body mass index; function, pain, and Modic chances in MRI before surgery and MRI 1 year later; rate of disc, muscle and ligament infection (primary outcome); diabetes and corticoid use (confoundings). METHODS: The protruded disc, muscle and ligament samples were sent for culture analysis in up to 30 minutes. A subsample of 17 patients underwent next-generation sequencing (NGS) molecular analysis too. We performed descriptive analysis and comparison of groups of patients with and without infection or contamination using Student's t, Mann-Whitney, chi-square, or Fisher's exact tests as appropriate, and pre- and postsurgical comparisons with the Wilcoxon test. RESULTS: From January 2018 to September 2019, 112 patients underwent open lumbar microdiscectomy, 67 (59.8%) men. Cultures showed 7 (6.3%) positive cases in the disc (2 with C. acnes), 3 (2.7%) in the ligament, and 12 (10, 7%) in muscle. No evidence of a difference in Modic alterations pre- or postoperatively was found between patients with and without positive culture 1 year after surgery. No association was found between culture positivity and functional or pain differences either. NGS results were all negative for C. acnes. CONCLUSIONS: We identified infective bacterial presence in the herniated disc in less than 2% of patients with disc herniation. C. acnes was not identified in any disc microbiome analysis. No significant association was observed between positivity for tissue infection and any clinical prognostic factor.

Does nuclear tissue infected with bacteria following disc herniations lead to Modic changes in the adjacent vertebrae?

PURPOSE: To investigate the prevalence of infected herniated nucleus material in lumbar disc herniations and to determine if patients with an anaerobic infected disc are more likely to develop Modic change (MC) (bone oedema) in the adjacent vertebrae after the disc herniation. MCs (bone oedema) in vertebrae are observed in 6 % of the general population and in 35-40 % of people with low back pain. These changes are strongly associated with low back pain. There are probably a mechanical cause and an infective cause that causes MC. Several studies on nuclear tissue from herniated discs have demonstrated the presence of low virulent anaerobic microorganisms, predominantly Propionibacterium acnes, in 7-53 % of patients. At the time of a herniation these low virulent anaerobic bacteria may enter the disc and give rise to an insidious infection. Local inflammation in the adjacent bone may be a secondary effect due to cytokine and propionic acid production. METHODS: Patients undergoing primary surgery at a single spinal level for lumbar disc herniation with an MRI-confirmed lumbar disc herniation, where the annular fibres were penetrated by visible nuclear tissue, had the nucleus material removed. Stringent antiseptic sterile protocols were followed. RESULTS: Sixty-one patients were included, mean age 46.4 years (SD 9.7), 27 % female. All patients were immunocompetent. No patient had received a previous epidural steroid injection or undergone previous back surgery. In total, microbiological cultures were positive in 28 (46 %) patients. Anaerobic cultures were positive in 26 (43 %) patients, and of these 4 (7 %) had dual microbial infections, containing both one aerobic and one anaerobic culture. No tissue specimens had more than two types of bacteria identified. Two (3 %) cultures only had aerobic bacteria isolated. In the discs with a nucleus with anaerobic bacteria, 80 % developed new MC in the vertebrae adjacent to the previous disc herniation. In contrast, none of those with aerobic bacteria and only 44 % of patients with negative cultures developed new MC. The association between an anaerobic culture and new MCs is highly statistically significant (P = 0.0038), with an odds ratio of 5.60 (95 % CI 1.51-21.95). CONCLUSION: These findings support the theory that the occurrence of MCs Type 1 in the vertebrae adjacent to a previously herniated disc may be due to oedema surrounding an infected disc. The discs infected with anaerobic bacteria were more likely (P < 0.0038) to develop MCs in the adjacent vertebrae than those in which no bacteria were found or those in which aerobic bacteria were found.

Antibiotic treatment in patients with chronic low back pain and vertebral bone edema (Modic type 1 changes): a double-blind randomized clinical controlled trial of efficacy.

PURPOSE: Modic type 1 changes/bone edema in the vertebrae are present in 6 % of the general population and 35-40 % of the low back pain population. It is strongly associated with low back pain. The aim was to test the efficacy of antibiotic treatment in patients with chronic low back pain (>6 months) and Modic type 1 changes (bone edema). METHODS: The study was a double-blind RCT with 162 patients whose only known illness was chronic LBP of greater than 6 months duration occurring after a previous disc herniation and who also had bone edema demonstrated as Modic type 1 changes in the vertebrae adjacent to the previous herniation. Patients were randomized to either 100 days of antibiotic treatment (Bioclavid) or placebo and were blindly evaluated at baseline, end of treatment and at 1-year follow-up. OUTCOME MEASURES: Primary outcome, disease-specific disability, lumbar pain. Secondary outcome leg pain, number of hours with pain last 4 weeks, global perceived health, EQ-5D thermometer, days with sick leave, bothersomeness, constant pain, magnetic resonance image (MRI). RESULTS: 144 of the 162 original patients were evaluated at 1-year follow-up. The two groups were similar at baseline. The antibiotic group improved highly statistically significantly on all outcome measures and improvement continued from 100 days follow-up until 1-year follow-up. At baseline, 100 days follow-up, 1-year follow-up the disease-specific disability-RMDQ changed: antibiotic 15, 11, 5.7; placebo 15, 14, 14. Leg pain: antibiotics 5.3, 3.0, 1.4; placebo 4.0, 4.3, 4.3. Lumbar pain: antibiotics 6.7, 5.0, 3.7; placebo 6.3, 6.3, 6.3. For the outcome measures, where a clinically important effect size was defined, improvements exceeded the thresholds, and a trend towards a dose-response relationship with double dose antibiotics being more efficacious. CONCLUSIONS: The antibiotic protocol in this study was significantly more effective for this group of patients (CLBP associated with Modic I) than placebo in all the primary and secondary outcomes.

Brucellar discitis as a cause of lumbar disc herniation: a case report.

Brucellosis is an infectious disease spread by consumption of non-pasteurized milk products or through contact with infected animals. Spinal involvement is one of the most important complications and the lumbar area is the most frequently affected site. Among the neurological consequences, nerve root compression can be a result of epidural abscess, granuloma or discitis secondary to vertebral body involvement. In this case report we present a 50-year-old male patient with brucellar discitis without spondylitis which caused lumbar disc herniation. We want to emphasize that discitis should also be considered in differential diagnosis of nerve root compression in suspected cases.

PEEK cage cervical ventral fusion in spondylodiscitis.

PURPOSE: Cervical spondylodiscitis is a quite rare finding regarding the number and the common location of spinal abscesses in the lumbar region. While in thoracic and lumbar discitis, single-step surgery with neural decompression, disc space evacuation, and subsequent fusion is well known, there is no such report in cervical discitis. Here the authors present their experience with ventral polyetherketone (PEEK) cage fusion in cervical spondylodiscitis in a single-step procedure. METHODS: Between January 2006 and November 2008, five patients (three men, two woman; ages 71, 77, 58, 66 and 66 years) suffering from cervical spondylodiscitis and epidural abscess underwent disc evacuation, myelon decompression and subsequent ventral fusion using an empty PEEK cage disc replacement in one single setting. All five patients presented with significant neurological symptoms like cervicobrachialgia, tetraparesis and disturbance of the urinary incontinence. In all five patients, disc evacuation, myelon decompression and cervical fusion using a PEEK cage disc replacement in a single-stage surgery were performed. All wounds were closed primarily. Postoperatively, all patients received a specific antibiotic therapy for at least 6 weeks. RESULTS: This treatment strategy was successful in all patients with respect to clinical signs, laboratory parameters and radiological findings. All patients improved neurologically. Follow-up revealed a stable osteosynthesis without signs of instability. One cage was explanted despite neurological improvement and normal infectious parameters at another surgical department. No complications were observed. CONCLUSIONS: In all, abscess drainage and ventral fusion with PEEK-cage disc replacement in one single setting was proven to be a successful treatment option in cervical discitis and spinal epidural abscess.

Cutibacterium acnes in Spine Pathology: Pathophysiology, Diagnosis, and Management.

Cutibacterium acnes, long thought to be skin flora of pathological insignificance, has seen a surge in interest for its role in spine pathology. C acnes has been identified as a pathogen in native spine infection and osteomyelitis, which has implications in the management compared with more commonly recognized pathogens. In addition, It has also been recognized as a pathogen in postoperative and implant-associated infections. Some evidence exists pointing to C acnes as an unrecognized source of otherwise aseptic pseudarthrosis. Recently, it is hypothesized that low virulent organisms, in particular C acnes, may play a role in degenerative disk disease and the development of Modic end plate changes found in MRI. To this end, controversial implications exist in terms of the use of antibiotics to treat certain patients in the setting of degenerative disk disease. C acnes continues to remain an expanding area of interest in spine pathology, with important implications for the treating spine surgeon.

Modic changes, possible causes and relation to low back pain.

UNLABELLED: In patients with low back pain (LBP) it is only possible to diagnose a small proportion, (approximately 20%), on a patho-anatomical basis. Therefore, the identification of relevant LBP subgroups, preferably on a patho-anatomical basis, is strongly needed. Signal changes on MRI in the vertebral body marrow adjacent to the end plates also known as Modic changes (MC) are common in patients with LBP (18-58%) and is strongly associated with LBP. In asymptomatic persons the prevalence is 12-13%. MC are divided into three different types. Type 1 consists of fibro vascular tissue, type 2 is yellow fat, and type 3 is sclerotic bone. The temporal evolution of MC is uncertain, but the time span is years. Subchondral bone marrow signal changes associated with pain can be observed in different specific infectious, degenerative and immunological diseases such as osseous infections, osteoarthritis, ankylosing spondylitis and spondylarthritis. In the vertebrae, MC is seen in relation to vertebral fractures, spondylodiscitis, disc herniation, severe disc degeneration, injections with chymopapain, and acute Schmorl's impressions. The aim of this paper is to propose two possible pathogenetic mechanisms causing Modic changes. These are: A mechanical cause: Degeneration of the disc causes loss of soft nuclear material, reduced disc height and hydrostatic pressure, which increases the shear forces on the endplates and micro fractures may occur. The observed MC could represent oedema secondary to the fracture and subsequent inflammation, or a result of an inflammatory process from a toxic stimulus from the nucleus pulposus that seeps through the fractures. A bacterial cause: Following a tear in the outer fibres of the annulus e.g. disc herniation, new capilarisation and inflammation develop around the extruded nuclear material. Through this tissue it is possible for anaerobic bacteria to enter the anaerobic disc and in this environment cause a slowly developing low virulent infection. The MC could be the visible signs of the inflammation and oedema surrounding this infection, because the anaerobic bacteria cannot thrive in the highly aerobic environment of the MC type 1. PERSPECTIVES: One or both of the described mechanisms can - if proven - be of significant importance for this specific subgroup of patients with LBP. Hence, it would be possible to give a more precise and relevant diagnosis to 20-50% of patients with LBP and enable in the development of efficient treatments which might be antibiotics, special rehabilitation programmes, rest, stabilizing exercise, or surgical fixation, depending on the underlying cause for the MC.