Correlation between gene expression and MRI STIR signals in patients with chronic low back pain and Modic changes indicates immune involvement.
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ABSTRACT:
SUBMITTER: Vigeland MD
PROVIDER: S-EPMC8741947 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveTo evaluate potential MRI-defined effect modifiers of amoxicillin treatment in patients with chronic low back pain and type 1 or 2 Modic changes (MCs) at the level of a previous lumbar disc herniation (index level).MethodsIn a prospective trial (AIM), 180 patients (25-64 years; mean age 45; 105 women) were randomised to receive amoxicillin or placebo for 3 months. Primary outcome was the Roland-Morris Disability Questionnaire (RMDQ) score (0-24 scale) at 1 year. Mean RMDQ score difference between the groups at 1 year defined the treatment effect; 4 RMDQ points defined the minimal clinically important effect. Predefined baseline MRI features of MCs at the index level(s) were investigated as potential effect modifiers. The predefined primary hypothesis was a better effect of amoxicillin when short tau inversion recovery (STIR) shows more MC-related high signal. To evaluate this hypothesis, we pre-constructed a composite variable with three categories (STIR1/2/3). STIR3 implied MC-related STIR signal increases with volume ≥ 25% and height > 50% of vertebral body and maximum intensity increase ≥ 25% and presence on both sides of the disc. As pre-planned, interaction with treatment was analysed using ANCOVA in the per protocol population (n = 155).ResultsThe STIR3 composite group (n = 41) and STIR signal volume ≥ 25% alone (n = 45) modified the treatment effect of amoxicillin. As hypothesised, STIR3 patients reported the largest effect (- 5.1 RMDQ points; 95% CI - 8.2 to - 1.9; p for interaction = 0.008).ConclusionsPredefined subgroups with abundant MC-related index-level oedema on STIR modified the effect of amoxicillin. This finding needs replication and further support.Key points• In the primary analysis of the AIM trial, the effect of amoxicillin in patients with chronic low back pain and type 1 or 2 MCs did not reach the predefined cut-off for clinical importance. • In the present MRI subgroup analysis of AIM, predefined subgroups with abundant MC-related oedema on STIR reported an effect of amoxicillin. • This finding requires replication and further support.
| S-EPMC8128743 | biostudies-literature
Project description:BackgroundThe HIF-1α/Notch signaling pathway regulates cell proliferation, apoptosis, and metabolism in the intervertebral discs (IVDs) and is implicated in disc degeneration. The nucleus pulposus (NP) is an important structure adjacent to the IVDs. However, the role of the HIF-1α/Notch signaling pathway in NP cells obtained from patients with different Modic changes (MCs) remains unclear. The purpose of the present study was to investigate the role of HIF-1α and components of the Notch pathway in the NP obtained from patients with various MCs.MethodsA total of 85 NP tissue samples were collected from patients undergoing diskectomy for the treatment of low back pain. The NP tissues were divided into four groups based on the adjacent endplate degeneration, namely, MC I, II, III, and negative MC groups. The expression of HIF-1α and Notch-related components was measured and compared.ResultsThe expression of HIF-1α, Notch1, and Notch2 was gradually increased in the MC I and MC II groups compared with that in the negative MC group. HIF-1α and Notch-related components were rarely detected in the MC III group.ConclusionsThe expression of HIF-1α/Notch increased in the NP cells of patients with MC I and MC II. HIF-1α and Notch-related components are potential biomarkers and the HIF-1α/Notch signaling pathway may serve as a promising therapeutic target for disc degeneration in patients with MCs.
| S-EPMC7390108 | biostudies-literature
Project description:Modic changes (MC) have been linked with low back pain (LBP) and worse outcomes from some treatments. No studies have investigated the impact that MCs may have on patient outcomes from lumbar facet injections. Therefore, the purpose of this study is to investigate whether the presence of Modic changes is related to 'improvement' in patients undergoing imaging-guided lumbar facet injection therapy.Outcomes from 226 patients with MRI scans within 3 months of their imaging-guided lumbar facet injections were investigated to determine whether MCs are related to 'improvement' post injection. At 1 day, 1 week and 1 month post injection the Patients Global Impression of Change scale answers were collected by postal questionnaire. This was the primary outcome measure. The numerical rating scale for pain data was collected prior to treatment and at the same post injection time points. The MRI scans were independently evaluated by two examiners for the presence/absence of Modic changes and the type of Modic change if present. Kappa statistics were used for reliability of diagnosis analysis. Chi-squared test and logistic regression analysis tested MCs with 'improvement'.Intra- and inter-examiner reliability for the diagnosis of MCs was Kappa?=?0.77 and 0.74. Intra- and inter-examiner reliability for categorizing MCs was K?=?0.77 and K?=?0.78. At 1 month post injection 45.2 % of patients without MCs reported clinically relevant 'improvement' compared to 34.2 % of patients with MC I and 32.1 % of patients with MC II. However, this did not reach statistical significance. Logistic regression found that Modic changes were not predictive of 'improvement'.There was a tendency for patients without MCs to have better outcomes but this did not reach statistical significance. The reliability of diagnosing MCs was substantial.
| S-EPMC4558765 | biostudies-other
Project description:Modic changes (MC) are associated with low back pain (LBP), but effective treatments are lacking. The aim of this randomized, placebo-controlled, double-blinded trial was to evaluate the efficacy of zoledronic acid (ZA) for chronic LBP among patients with MC in magnetic resonance imaging (MRI).Inclusion criteria were LBP lasting ?3 months, with an intensity of ?6 on a 10-cm VAS or an Oswestry Disability Index (ODI) of ?30%, and MC in MRI. Patients were randomized into single intravenous infusion of ZA 5 mg (n = 20), or placebo (n = 20) groups. The primary outcome was LBP intensity, secondary outcomes leg pain intensity, ODI, health-related quality of life (RAND-36), lumbar flexibility, sick leaves and use of pain medication. The treatment differences at one month and one year were analysed using ANCOVA with adjustment for the baseline score.The mean difference (MD) between the groups in the primary outcome, intensity of LBP, was 1.4 (95% confidence intervals (CI) 0.01 to 2.9) in favour of ZA at one month. We observed no significant between-group difference in the intensity of LBP at one year (MD 0.7; 95% CI -1.0 to 2.4) or in secondary outcomes at any time point except that 20% of patients in the ZA group used non-steroidal anti-inflammatory drugs at one year compared to 60% in the placebo group (P = 0.022). Acute phase reactions (fever, flu-like symptoms, arthralgia) emerged in 95% of the patients in the ZA group, compared to 35% in the placebo group.ZA was effective in reducing the intensity of LBP in the short term and in reducing the use of NSAIDs within the time span of one year among patients with chronic LBP and MC confirmed in MRI. Although the results seem encouraging, larger studies are required to analyse the effectiveness and safety of ZA for patients with MC.ClinicalTrial.gov identifier NCT01330238.
| S-EPMC3996022 | biostudies-literature
Project description:BackgroundPrevious systematic reviews have reported positive associations between Modic changes (MCs) and low back pain (LBP), but due to their narrow scope and new primary studies, there is a need for a comprehensive systematic review. Our objectives were to investigate if MCs are associated with non-specific LBP and/or activity limitation and if such associations are modified by other factors.MethodsA protocol for this review was registered at PROSPERO prior to commencing the work (PROSPERO record: CRD42015017350). The MEDLINE, CINAHL and EMBASE databases were searched for relevant studies from first record to June 15th 2016. Prospective or retrospective cross-sectional cohort studies and case-control studies including people of all ages from general, working and clinical study populations were eligible for inclusion. Risk of bias assessment and data extraction for associations and potential modifiers were completed independently by pairs of reviewers. Meta-analysis was performed for homogeneous studies and presented as odds ratios (OR) with 95% CI.ResultsIn all, 5210 citations were identified and 31 studies were included. One study had low risk of bias. Fifteen studies (48%) reported statistically significant positive associations between MCs and LBP and one study found a statistically significant negative association. Meta-analysis performed for studies using concordant pain with provocative discography as the clinical outcome resulted in an OR of 4.01 (1.52-10.61). One of seven studies reported a statistically significant positive association between MCs and activity limitation. Lumbar disc level and disc degeneration were found to modify the association between MCs and LBP.ConclusionsThe results from this comprehensive systematic review indicate that the associations between MCs and LBP-related outcomes are inconsistent. The high risk of bias and the heterogeneity in terms of study samples, clinical outcomes and prevalence estimates of MCs and LBP may explain these findings. It is likely that new studies with low risk of bias will affect the direction and strength of these associations.
| S-EPMC6070210 | biostudies-literature
Project description:BackgroundModic changes (MC) are associated with low back pain (LBP). In this study, we compared changes in size and type of MC, after a single intravenous infusion of 5 mg zoledronic acid (ZA) or placebo, among chronic LBP patients with MC on magnetic resonance imaging (MRI), and evaluated whether the MRI changes correlate with symptoms.MethodsAll patients (N = 19 in ZA, 20 in placebo) had MRI at baseline (0.23-1.5 T) and at one year (1.5-3 T). We evaluated the level, type and volume of all the MC. The MC were classified into M1 (M1 (100%)), predominating M1 (M1/2 (65:35%)) or predominating M2 (M1/2 (35:65%)), and M2 (M2 (100%)). The first two were considered M1-dominant, and the latter two M2-dominant. Volumes of M1 and M2 were calculated separately for the primary MC, which was assumed to cause the symptoms, and the other MC. We analysed the one-year treatment differences in M1 and M2 volumes using analysis of covariance with adjustments for age, sex, body mass index, and smoking. The correlations between the MRI changes and the changes in LBP symptoms were analysed using Pearson correlations.ResultsIn the ZA group, 84.2% of patients had M1-dominant primary MC at baseline, compared to 50% in the placebo group (p = 0.041). The primary MC in the ZA group converted more likely to M2-dominant (42.1% ZA, 15% placebo; p = 0.0119). The other MC (15 ZA, 8 placebo) were on average 42% smaller and remained largely M2-dominant. The M1 volume of the primary MC decreased in the ZA group, but increased in the placebo group (-0.83 cm3 vs 0.91 cm3; p = 0.21). The adjusted treatment difference for M1 volume was -1.9 cm3 (95% CI -5.0 to 1.2; p = 0.22) and for M2 volume 0.23 cm3 (p = 0.86). In the MC that remained M1-dominant, volume change correlated positively with increased symptoms in the placebo group, whereas the correlations were negative and weak in the ZA group.ConclusionsZoledronic acid tended to speed up the conversion of M1-dominant into M2-dominant MC and decrease the volume of M1-dominant MC, although statistical significance was not demonstrated.Trial registrationThe registration number in ClinicalTrials.gov is NCT01330238 and the date of registration February 11, 2011.
| S-EPMC5481864 | biostudies-literature
Project description:BACKGROUND: Clinical experience suggests that many patients with Modic changes have relatively severe and persistent low back pain (LBP), which typically appears to be resistant to treatment. Exercise therapy is the recommended treatment for chronic LBP, however, due to their underlying pathology, Modic changes might be a diagnostic subgroup that does not benefit from exercise. The objective of this study was to compare the current state-of-the art treatment approach (exercise and staying active) with a new approach (load reduction and daily rest) for people with Modic changes using a randomized controlled trial design. METHODS: Participants were patients from an outpatient clinic with persistent LBP and Modic changes. They were allocated using minimization to either rest therapy for 10 weeks with a recommendation to rest for two hours daily and the option of using a flexible lumbar belt or exercise therapy once a week for 10 weeks. Follow-up was at 10 weeks after recruitment and 52 weeks after intervention and the clinical outcome measures were pain, disability, general health and global assessment, supplemented by weekly information on low back problems and sick leave measured by short text message (SMS) tracking. RESULTS: In total, 100 patients were included in the study. Data on 87 patients at 10 weeks and 96 patients at one-year follow-up were available and were used in the intention-to-treat analysis. No statistically significant differences were found between the two intervention groups on any outcome. CONCLUSIONS: No differences were found between the two treatment approaches, 'rest and reduced load' and 'exercise and staying active', in patients with persistent LBP and Modic changes. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00454792.
| S-EPMC3348080 | biostudies-literature
Project description:BackgroundNo previous clinical trials have investigated MRI findings as effect modifiers for conservative treatment of low back pain. This hypothesis-setting study investigated if MRI findings modified response to rest compared with exercise in patients with chronic low back pain and Modic changes.MethodsThis study is a secondary analysis of a randomised controlled trial comparing rest with exercise. Patients were recruited from a specialised outpatient spine clinic and included in a clinical trial if they had chronic low back pain and an MRI showing Modic changes. All patients received conservative treatment while participating in the trial. Five baseline MRI findings were investigated as effect modifiers: Modic changes Type 1 (any size), large Modic changes (any type), large Modic changes Type 1, severe disc degeneration and large disc herniation. The outcome measure was change in low back pain intensity measured on a 0-10 point numerical rating scale at 14-month follow-up (n = 96). An interaction ≥ 1.0 point (0-10 scale) between treatment group and MRI findings in linear regression was considered clinically important.ResultsThe interactions for Modic Type 1, with large Modic changes or with large Modic changes Type 1 were all potentially important in size (-0.99 (95 % CI -3.28 to 1.29), -1.49 (-3.73 to 0.75), -1.49 (-3.57 to 0.58), respectively) but the direction of the effect was the opposite to what we had hypothesized-that people with these findings would benefit more from rest than from exercise. The interactions for severe disc degeneration (0.74 (-1.40 to 2.88)) and large disc herniation (-0.92 (3.15 to 1.31)) were less than the 1.0-point threshold for clinical importance. As expected, because of the lack of statistical power, no interaction term for any of the MRI findings was statistically significant.ConclusionsThree of the five MRI predictors showed potentially important effect modification, although the direction of the effect was surprising and confidence intervals were wide so very cautious interpretation is required. Further studies with adequate power are warranted to study these and additional MRI findings as potential effect modifiers for common interventions.
| S-EPMC4566202 | biostudies-literature
Project description:BackgroundLimited reliability data exist for evaluation of spinal edema changes on magnetic resonance imaging (MRI) with short tau inversion recovery (STIR) sequences.PurposeTo assess the inter-observer reliability for evaluation of STIR signal increase related to Modic changes (MCs) on MRI of the lumbar spine.Material and methodsWe prospectively included 120 patients imaged to confirm their eligibility for the AIM (Antibiotics In Modic changes) trial. Three experienced radiologists independently evaluated MCs on T1-/T2-weighted fast spin-echo images and subsequently MC-related STIR signal increases. Inter-observer reliability was analyzed at four endplates (L4-S1) by calculating kappa values and means of differences with 95% limits of agreement.ResultsOverall agreement (mean Fleiss' kappa for all endplates and observers) was very good for presence of STIR signal increase (0.86), and moderate for its categorized height (0.51), anteroposterior extent (0.48), and volume (0.56). For height of region with STIR signal increase measured in % points of vertebral body height, the largest mean of differences was 6.9 and widest range for limits of agreement was ±22.3 for all endplates combined. The corresponding numbers were 11.2 ± 34.5 for anteroposterior extent of the STIR signal increase measured in % points of anteroposterior endplate diameter and 0.9 ± 7.6 for its maximum measured intensity on a % point scale (0% = normal vertebral marrow intensity, 100% = cerebrospinal fluid intensity).ConclusionInter-observer reliability was very good for the presence and intensity of MC-related STIR signal increases, and moderate for their size.
| S-EPMC6990614 | biostudies-literature
Project description:Long-term antibiotics are prescribed for a variety of medical conditions, recently including low back pain with Modic changes. The molecular impact of such treatment is unknown. We conducted longitudinal transcriptome and epigenome analyses in patients (n = 100) receiving amoxicillin treatment or placebo for 100 days in the Antibiotics in Modic Changes (AIM) study. Gene expression and DNA methylation were investigated at a genome-wide level at screening, after 100 days of treatment, and at one-year follow-up. We identified intra-individual longitudinal changes in gene expression and DNA methylation in patients receiving amoxicillin, while few changes were observed in patients receiving placebo. After 100 days of amoxicillin treatment, 28 genes were significantly differentially expressed, including the downregulation of 19 immunoglobulin genes. At one-year follow-up, the expression levels were still not completely restored. The significant changes in DNA methylation (n = 4548 CpGs) were mainly increased methylation levels between 100 days and one-year follow-up. Hence, the effects on gene expression occurred predominantly during treatment, while the effects on DNA methylation occurred after treatment. In conclusion, unrecognized side effects of long-term amoxicillin treatment were revealed, as alterations were observed in both gene expression and DNA methylation that lasted long after the end of treatment.
| S-EPMC10376514 | biostudies-literature