What Level of Inflammation Leads to Structural Damage in the Sacroiliac Joints? A Four-Year Magnetic Resonance Imaging Follow-Up Study of Low Back Pain Patients.

OBJECTIVE: Sacroiliac (SI) joint bone marrow edema (BME) is considered to be pivotal in the detection of early spondyloarthritis. However, the link between BME and development of spondyloarthritis-related bone remodeling remains unclear. This study was undertaken to investigate the evolution of BME and structural lesions in the SI joints over time. METHODS: Baseline and 4-year follow-up magnetic resonance imaging scans were conducted in 604 patients ages 18-40 years who were referred with low back pain to an outpatient spine clinic. Eight SI joint regions were scored for BME and categorized as absent, limited (<25% of subcortical bone region), intermediate (25-50%), or extensive (>50%). Structural lesions including erosions and fat lesions were scored as absent or present. RESULTS: SI joint BME was seen at either time point (baseline or at 4 years) in 41% of participants but was persistent at both time points in only 16% of participants. Structural SI joint lesions developed according to the extent of BME at baseline: limited, intermediate, and extensive BME (as compared to absent BME) were independently associated with erosion at follow-up with odds ratios (ORs) of 3, 5, and 46, respectively, and with fat lesions (ORs 3, 7, and 33, respectively). In regions with limited and intermediate BME at baseline, 60% and 50% had resolved by follow-up, respectively, while only 2% and 7% had evolved into extensive BME by follow-up. CONCLUSION: While extensive SI joint BME was a strong independent predictor of development of structural lesions, limited and intermediate BME were mostly transient and only rarely evolved into extensive BME or structural lesions. These findings enhance our understanding of the natural development of SI joint lesions and indicate different progression patterns for limited/intermediate versus extensive BME, possibly due to different etiologies.

Is pseudarthrosis after spinal instrumentation caused by a chronic infection?

HYPOTHESIS: To assess whether a chronic bacterial infection is present in a subset of patients with pseudarthrosis after instrumented spinal fusion. METHODS: This was a prospective diagnostic study including adult patients with previous instrumented spinal fusion. Patients underwent revision surgery for either pseudarthrosis or other causes (e.g. implant removal, curve progression or junctional kyphosis) (control group). Five separate biopsies were randomly collected, intraoperatively, from the pseudarthrosis site and cultivated under both aerobic (5 days) and anaerobic (14 days) conditions. If cultivation was positive in at least 2/5 tissue samples, the biopsy was sectioned and stained using peptide nucleic acid fluorescence in situ hybridization (PNA-FISH). Confocal laser scanning microscopy was used to examine the sections and visualize bacterial aggregates. RESULTS: The study included 32 pseudarthrosis and 32 control patients. Cultivation yielded bacteria in at least 1/5 biopsies in 52% of patients with no difference between the groups (p = 1.0). Bacteria of the same species was found in at least 2/5 samples in seven pseudarthrosis patients and four controls (p = 0.509). Propionibacterium acnes was found in 8 of these 11 samples. Microscopy demonstrated tissue-embedded bacterial aggregates in two of these patients but with no inflammatory cells indicating an active infection. The presence of bacteria was not associated with the number of previous spinal procedures or the pre-revision fusion length (p ≥ 0.503). CONCLUSIONS: Pseudarthrosis after instrumented spinal surgery was not significantly associated with the presence of bacteria at the pseudarthrosis site. Positive cultivation results are common after spinal instrumentation, but our results indicate that they rarely represent an organized infection. These slides can be retrieved under Electronic Supplementary Material.

Associations Between Spondyloarthritis Features and Magnetic Resonance Imaging Findings: A Cross-Sectional Analysis of 1,020 Patients With Persistent Low Back Pain.

OBJECTIVE: The Assessment of SpondyloArthritis international Society (ASAS) has previously published criteria for spondyloarthritis (SpA). In the Spines of Southern Denmark cohort, which included patients with persistent low back pain and an unknown proportion of patients with SpA, our objectives were 1) to estimate the prevalence of magnetic resonance imaging (MRI) findings and clinical features included in the ASAS criteria for SpA and 2) to explore the associations between MRI findings and clinical features. METHODS: We included patients ages 18-40 years with persistent low back pain who had been referred to the Spine Centre of Southern Denmark. We collected information on clinical features (including HLA-B27 and high-sensitivity C-reactive protein) and MRI findings in the spine and sacroiliac (SI) joints. RESULTS: Of 1,020 included patients, 537 (53%) had at least 1 of the clinical features included in the ASAS criteria for SpA. Three clinical features were common-inflammatory back pain according to the ASAS criteria, a good response to nonsteroidal antiinflammatory drugs (NSAIDs), and family history of SpA. The prevalence of these features ranged from 15% to 17%. Sacroiliitis on MRI according to the ASAS definition was present in 217 patients (21%). Of those 217 patients, 91 (42%) had the minimum amount of bone marrow edema required according to the ASAS definition (a low bone marrow edema score). The presence of HLA-B27, peripheral arthritis, a good response to NSAIDs, and preceding infection were independently positively associated with MRI findings in the SI joints (odds ratios [ORs] of 1.9-9.0). The remaining 8 clinical features were not positively associated with MRI findings. Importantly, only age was independently associated with low bone marrow edema score at the SI joints (OR of 1.1 per year). CONCLUSION: In this population, 53% had at least 1 clinical feature included in the ASAS criteria for SpA, and 21% had sacroiliitis according to the ASAS definition; furthermore, the associations between the clinical and imaging domains were inconsistent. The results indicate a need for further investigation of the importance of these findings in SpA, including investigation of the minimum requirements for defining sacroiliitis on MRI.

[Mechanism of low-back pain with focus on Modic changes]. / Mekanismer bag rygsygdomme medfokus på Modicforandringer.

Low-back pain (LBP) pathology and pain have previously been connected with physical strain. The coping was therefore characterized by ''be careful!'' messages. In the 1990s it was shown that these physical loads virtually did not mean anything regarding disc degeneration, although loads may create LBP episodes. Genetic aspects and the demonstration in 2006 that Modic changes (MC) generally correlated with LBP changed our perception, especially because antibiotics seemed to be effective in MC. Moreover, the role of cytokines is becoming increasingly clear. The following years will be very exciting.

SpineData - a Danish clinical registry of people with chronic back pain.

BACKGROUND: Large-scale clinical registries are increasingly recognized as important resources for quality assurance and research to inform clinical decision-making and health policy. We established a clinical registry (SpineData) in a conservative care setting where more than 10,000 new cases of spinal pain are assessed each year. This paper describes the SpineData registry, summarizes the characteristics of its clinical population and data, and signals the availability of these data as a resource for collaborative research projects. METHODS: The SpineData registry is an Internet-based system that captures patient data electronically at the point of clinical contact. The setting is the government-funded Medical Department of the Spine Centre of Southern Denmark, Hospital Lillebaelt, where patients receive a multidisciplinary assessment of their chronic spinal pain. RESULTS: Started in 2011, the database by early 2015 contained information on more than 36,300 baseline episodes of patient care, plus the available 6-month and 12-month follow-up data for these episodes. The baseline questionnaire completion rate has been 93%; 79% of people were presenting with low back pain as their main complaint, 6% with mid-back pain, and 15% with neck pain. Collectively, across the body regions and measurement time points, there are approximately 1,980 patient-related variables in the database across a broad range of biopsychosocial factors. To date, 36 research projects have used data from the SpineData registry, including collaborations with researchers from Denmark, Australia, the United Kingdom, and Brazil. CONCLUSION: We described the aims, development, structure, and content of the SpineData registry, and what is known about any attrition bias and cluster effects in the data. For epidemiology research, these data can be linked, at an individual patient level, to the Danish population-based registries and the national spinal surgery registry. SpineData also has potential for the conduct of cohort multiple randomized controlled trials. Collaborations with other researchers are welcome.

Patient preferences for treatment of low back pain-a discrete choice experiment.

BACKGROUND: Back pain imposes a substantial economic and social burden, and treatment decisions are distorted by conflicting evidence. Thus, it is important to include patient preferences in decision making and policy making. OBJECTIVE: To contribute to the understanding of patient preferences in relation to the choice of treatment for low back pain. METHODS: A discrete choice experiment was conducted with consecutive patients referred to a regional spine center. The respondents (n = 348) were invited to respond to a choice of two hypothetical treatment options and an opt-out option. The treatment attributes included the treatment modality, the risk of relapse, the reduction in pain, and the expected increase in the ability to perform activities of daily living. In addition, the wait time to achieve the treatment effect was used as a payment vehicle. Mixed logit models were created to perform analysis. Subgroup analysis, dividing respondents into sociodemographic and disease-related categories, further explored the willingness to wait. RESULTS: Respondents assigned positive utilities to positive treatment outcomes and disutility to higher risks and longer waits for effects of treatment and to surgical interventions. The model captured significant heterogeneity within the sample for the outcomes of pain reduction and the ability to pursue activities of daily living and for the treatment modality. The subgroup analysis revealed differences in the willingness to wait, especially with regard to treatment modality, the level of pain experienced at the time of data collection, and the respondents' preferences for surgery. CONCLUSIONS: The majority of the respondents prefer nonsurgical interventions, but patients are willing to wait for more ideal outcomes and preferred interventions. The results show that health care professionals have a very important task in communicating clearly about the expected results of treatment and the basis of their treatment decisions, as patients' preferences are highly individual.

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.

The predictive and external validity of the STarT Back Tool in Danish primary care.

PURPOSE: The STarT Back Tool (SBT) was recently translated into Danish and its concurrent validity described. This study tested the predictive validity of the Danish SBT. METHODS: Danish primary care patients (n = 344) were compared to a UK cohort. SBT subgroup validity for predicting high activity limitation at 3 months' follow-up was assessed using descriptive proportions, relative risks, AUC and odds ratios. RESULTS: The SBT had a statistically similar predictive ability in Danish primary care as in UK primary care. Unadjusted relative risks for poor clinical outcome on activity limitation in the Danish cohort were 2.4 (1.7-3.4) for the medium-risk subgroup and 2.8 (1.8-3.8) for the high-risk subgroup versus 3.1 (2.5-3.9) and 4.5 (3.6-5.6) for the UK cohort. Adjusting for confounders appeared to explain the lower predictive ability of the Danish high-risk group. CONCLUSIONS: The Danish SBT distinguished between low- and medium-risk subgroups with a similar predictive ability of the UK SBT. That distinction is useful information for informing patients about their expected prognosis and may help guiding clinicians' choice of treatment. However, cross-cultural differences in the SBT psychosocial subscale may reduce the predictive ability of the high-risk subgroup in Danish primary care.

The efficacy of systematic active conservative treatment for patients with severe sciatica: a single-blind, randomized, clinical, controlled trial.

STUDY DESIGN: Prospective single-blind, randomized, clinical, controlled trial. OBJECTIVE: To evaluate the efficacy of active conservative treatment and to compare 2 active conservative treatment programs for patients with severe sciatica. SUMMARY OF BACKGROUND DATA: Reviews have demonstrated little or no efficacy for passive conservative treatment modalities in patients suffering from sciatica. The results for surgery are conflicting. Cohort studies have shown excellent results for active treatment modalities in patients with sciatica. METHODS: One hundred eighty-one consecutive patients with radicular pain below the knee were examined at the baseline, at 8 weeks, and at 1 year after the treatment. Participants were randomized into 2 groups: (1) symptom-guided exercises + information + advice to stay active and (2) sham exercises + information + advice to stay active. Symptom-guided exercises consisted of a variety of back-related exercises given in accordance with a written algorithm in which symptoms or response to exercises determined the exercises given (http://www.sygehuslillebaelt.dk/wm345075, click exercises). Sham exercises were optional, designed to increase general blood circulation, and had no targeted effect on the back. The information was comprehensive and included anatomy, pathogenesis, and how discs heal without surgery. The advice included encouragement to stay as active as possible but to reduce activity if leg pain increased. The use of medication was optional, but only paracetamol and nonsteroidal anti-inflammatory drugs were recommended. RESULTS: A mean of 4.8 treatment sessions were provided. All patients experienced statistically significant and clinically important improvements in global assessment, functional status, pain, vocational status, and clinical findings. The symptom-guided exercise group improved significantly more than the sham exercise group in most outcomes. CONCLUSION: Active conservative treatment was effective for patients who had symptoms and clinical findings that would normally qualify them for surgery. Although participating patients had greater faith in the sham exercises before treatment, the symptom-guided exercises were superior for most outcomes.

Predictors of new vertebral endplate signal (Modic) changes in the general population.

Vertebral endplate signal changes (VESC), also known as Modic changes, have been reported to be associated with low back pain (LBP). However, little is known about predisposing factors for the development of new VESC. The aim of this study was to investigate the predictive value of lifestyle factors and disc-related magnetic resonance imaging (MRI) findings in relation to the development of new VESC. This prospective observational study included 344 people from the Danish general population who had an MRI and completed LBP questionnaires at the age of 40 and again at 44 years. Potential predictors of new VESC were female gender, disc-related MRI findings (disc degeneration, disc bulges, disc herniation, and other endplate changes) and lifestyle factors [high physical work or leisure activity, high body mass index (BMI), and heavy smoking]. Bivariate and multivariate logistic regressions were used to identify predictors of new VESC. New VESC at the age of 44 appeared in 67 of the 344. The majority (84%) of these new signal changes were type 1 VESC and almost half (45%) were only in the endplate and did not extend into the vertebral body. In the multivariate analysis, lumbar disc levels with disc degeneration, bulges or herniations at 40 were the only predictors of new VESC at age 44. Therefore, the development of new VESC at the age of 44 appears to be based on the status and dynamics of the disc, rather than being the result of gender or lifestyle factors such as smoking and physical load.

Self-reported hard physical work combined with heavy smoking or overweight may result in so-called Modic changes.

BACKGROUND: Recently, the MRI finding of "Modic changes" has been identified as pathologic spinal condition that probably reflects a vertebral inflammatory process (VIP), which coincides with spinal pain in most. We hypothesized that heavy smoking in combination with macro- or repeated microtrauma could lead to VIP. The objectives were to investigate if combinations of self-reported heavy smoking, hard physical work, and overweight would be more strongly linked with VIP than with other spinal conditions, such as degenerated discs and non-specific low back pain (LBP). METHODS: Secondary analysis was made of a data base pertaining to a population-based cross-sectional study. A population-generated cohort of 412 40-yr old Danes provided questionnaire information on smoking, weight, height, type of work, and LBP. MRI was used to determine the presence/absence of disc degeneration and of VIP. Associations were tested between three explanatory variables (type of work, smoking, and body mass index) and four outcome variables (LBP in the past year, more persistent LBP in the past year, disc degeneration, and VIP). Associations with these four outcome variables were studied for each single explanatory variable and for combinations of two at a time, and, finally, in a multivariable analysis including all three explanatory variables. RESULTS: There were no significant associations between the single explanatory variables and the two pain variables or with disc degeneration. However, VIP was found in 15% of non-smokers vs. 26% of heavy smokers. Similarly, VIP was noted in 11% of those in sedentary jobs vs. 31% of those with hard physical work. Further, the prevalence of VIP in those, who neither smoked heavily nor had a hard physical job was 13%, 25% in those who either smoked heavily or had a hard physical job, and 41% in those who both smoked heavily and worked hard. The odds ratio was 4.9 (1.6-13.0) for those who were both heavy smokers and had a hard physical job as compared to those who were classified as "neither". Similar but weaker findings were noted for the combination of overweight and hard physical work but not for the combination of smoking and overweight. CONCLUSION: Hard physical work in combination with either heavy smoking or overweight is strongly associated with VIP. If this finding can be reproduced in other studies, it may have consequences in relation to both primary and secondary prevention of LBP, because blue collar workers, who are most likely to experience the consequences of LBP, also are those who are most likely to smoke.

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.

Modic changes following lumbar disc herniation.

Only a small proportion (20%) of patients with LBP can be diagnosed based on a patho-anatomical entity. Therefore, the identification of relevant subgroups, preferably on a patoanatomical basis, is strongly needed. Modic changes have been described by several authors as being closely linked with LBP. The aims of this study were to describe the prevalence of Modic changes, their development as well as their association to LBP, previous disc contour, and surgery in patients with previous severe sciatica. This is a longitudinal cohort study where the patients were recruited from an RCT comparing two active conservative treatments, the 181 patients, who at baseline had radicular pain in or below the knee; all underwent a physical examination and MRI. MRI's, pain history and physical examination of 166 patients were obtained at follow-up 14 months later. The prevalence of Modic changes type 1 increased from 9% at baseline to 29% at follow-up. At that time, a strong association between Modic changes and non-specific LBP was noted. Apparently, Modic changes type 1 was more strongly associated with non-specific lumbar pain than Modic changes type 2. The development of new Modic changes was closely related to the level of a previous disc herniation. 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.

Generalized deep-tissue hyperalgesia in patients with chronic low-back pain.

Some chronic painful conditions including e.g. fibromyalgia, whiplash associated disorders, endometriosis, and irritable bowel syndrome are associated with generalized musculoskeletal hyperalgesia. The aim of the present study was to determine whether generalized deep-tissue hyperalgesia could be demonstrated in a group of patients with chronic low-back pain with intervertebral disc herniation. Twelve patients with MRI confirmed lumbar intervertebral disc herniation and 12 age and sex matched controls were included. Subjects were exposed to quantitative nociceptive stimuli to the infraspinatus and anterior tibialis muscles. Mechanical pressure (thresholds and supra-threshold) and injection of hypertonic saline (pain intensity, duration, distribution) were used. Pain intensity to experimental stimuli was assessed on a visual analogue scale (VAS). Patients demonstrated significantly higher pain intensity (VAS), duration, and larger areas of pain referral following saline injection in both infraspinatus and tibialis anterior. The patients rated significantly higher pain intensity to supra-threshold mechanical pressure stimulation in both muscles. In patients, the pressure pain-threshold was lower in the anterior tibialis muscle compared to controls. In conclusion, generalized deep-tissue hyperalgesia was demonstrated in chronic low-back pain patients with radiating pain and MRI confirmed intervertebral disc herniation, suggesting that this central sensitization should also be addressed in the pain management regimes.

Intensive dynamic back exercises for chronic low back pain: a clinical trial.

The effect of intensive dynamic back extensor exercises for patients with chronic low back pain was investigated in a controlled clinical trial in which chronic low back pain patients underwent a 3-month intensive training program with a total of 30 sessions. The 105 patients were divided into 3 groups: a treatment group, an alternative group which underwent 1/5 of the treatment group's exercise program per session, and an alternative group in which treatment consisted of thermotherapy, massage and mild exercise. Regardless of whether the treatment outcome is assessed qualitatively or quantitatively, a statistically significant, favorable difference was found between the results for the treatment group and for the alternative groups at conclusion and at the 3-month follow-up. It appeared from the quantitative assessment that patients in the treatment group who completed the training program at least once a week for the entire 1-year follow-up period were the only patients with a significantly better back status after 1 year compared to the time of inclusion. Irrespective of sex, age, duration and degree of severity of back trouble, or of pre-existing sciatica or pathological findings upon X-ray of the spine, patients obtained a favorable result from the training program. The therapy was found to be without risk, but patients with clinical signs of current lumbar nerve root compression or radiological signs of spondylolysis or halisteresis of the spine were excluded from the study.