Low back pain-related healthcare utilization following intraosseous basivertebral nerve radiofrequency ablation: a pooled analysis from three prospective clinical trials.

BACKGROUND: The effectiveness and safety of intraosseous basivertebral nerve ablation (BVNA) for treating vertebrogenic pain is established, but low back pain-related healthcare utilization (LBPr-HU) following BVNA continues to be defined. METHODS: LBPr-HU data were pooled from 3 prospective studies. LBPr-HU categories of interest included non-invasive conservative care, opioid utilization, lumbosacral spinal injection (LSI), lumbosacral radiofrequency ablation (LRFA), and lumbosacral spinal surgery. Pre- and post-BVNA LBPr-HU were compared at both 1- and 5-years using McNemar's test for proportions and paired t-tests for means. RESULTS: Two hundred forty-seven patients received BVNA and had 1-year follow-up; 205 had long-term follow-up (mean of 5.3 ± 1.33 years). Twenty-seven percent fewer participants initiated conservative care in the year post-BVNA compared to the year preceding BVNA (P < .001; 95% CI 19.8-34.5). Of 77/247 participants taking opioids at baseline, 40.3% and 61.7% fewer were taking them at one-year and 5.3 ± 1.33 years post-BVNA, respectively (P < .001). Of participants receiving LSIs in the year preceding BVNA, 81.2% fewer received LSI(s) in the year post-BVNA (P < .001; 95% CI 70.7-90.7); a 76.4% reduction in LSIs was maintained through a mean of 5.3 ± 1.33 years post-BVNA. LRFA rates were 1.6% at 1-year post-BVNA and 8.3% at 5.3 ± 1.33 years post-BVNA. Lumbar fusion surgery was 0.8% at 1-year post-BVNA and 6.5% at 5.3 ± 1.33 years post-BVNA. CONCLUSIONS: In this aggregate analysis of patients with vertebrogenic pain, utilization of conservative care, opioids, LSIs, and LRFA were substantially reduced through 5 years post-BVNA compared to baseline. Lumbar fusion rates were less than half the published value at 5 years in similar populations.

Prevalence, risk factors, natural history, and prognostic significance of Modic changes in the cervical spine: a comprehensive systematic review and meta-analysis of 12,754 participants.

OBJECTIVE: Modic changes (MCs) in the cervical spine are common, but remain an under-researched phenomenon, particularly regarding their prevalence, natural history, risk factors, and implications for surgical outcomes. This systematic review and meta-analysis endeavors to elucidate the multifactorial dimensions and clinical significance of cervical MCs. METHODS: Following PRISMA guidelines, a comprehensive systematic search was performed using Medline (via PubMed), EMBASE, Scopus, and Web of Science databases from their dates of inceptions to September 4, 2023. All identified articles were meticulously screened based on their relevance to our investigative criteria. Bias was assessed using quality assessments tools, including Quality in Prognosis Studies (QUIPS) and Newcastle-Ottawa Scale (NOS). Diverse datasets encompassing MCs prevalence, demographic influences, risk factors, cervical sagittal parameters, and surgical outcomes were extracted. Meta-analysis using both random and common effects model was used to synthesis the metadata. RESULTS: From a total of 867 studies, 38 met inclusion criteria and underwent full-text assessment. The overall prevalence of cervical MCs was 26.0% (95% CI: 19.0%, 34.0%), with a predominance of type 2 MCs (15% ; 95% CI: 0.10%, 0.23%). There was no significant difference between MCs and non-MCs in terms of neck pain (OR:3.09; 95% CI: 0.81, 11.88) and radicular pain (OR: 1.44; 95% CI: 0.64, 3.25). The results indicated a significantly higher mean age in the MC group (MD: 1.69 years; 95% CI: 0.29 years, 3.08 years). Additionally, smokers had 1.21 times the odds (95% CI: 1.01, 1.45) of a higher risk of developing MCs compared to non-smokers. While most cervical sagittal parameters remained unaffected, the presence of MCs indicated no substantial variation in pain intensity. However, a significant finding was the lower Japanese Orthopaedic Association (JOA) scores observed in MC patients at the 3-month (MD: -0.34, 95% CI: -0.62, -0.07) and 6-month (MD: -0.40, 95% CI: -0.80, 0.00) postoperative periods, indicating a prolonged recovery phase. CONCLUSION: This study found a predominant of type 2 MCs in the cervical spine. However, there was no significant mean difference between MCs and non-MC groups regarding neck pain and radicular pain. The results underscore the necessity for expansive, longitudinal research to elucidate the complexity of cervical MCs, particularly in surgical and postoperative contexts.

Novel Modic grading scoring system and its clinical validation: a preliminary investigation.

PURPOSE: To propose a novel Modic grading scoring system and explore the relationship between the Modic grading score and disc degeneration, disc herniation, disc height, and clinical symptom scores. METHOD: In total, 194 patients were included in the study. The new Modic grading scoring system included four indicators: invaded vertebral height, invaded endplate length, endplate morphology, and grade of endplate defects. The severity of Modic changes was visually quantified by numerical scores, and the kappa value was used to verify the interobserver and intraobserver reliability. Spearman correlation analysis was used to explore the relationship between the Modic grading score and intervertebral disc degeneration, disc herniation, disc height, and clinical symptom scores. RESULTS: The interobserver and intraobserver reliability showed substantial to almost perfect agreement in the new Modic grading scoring system. The Modic grading score was positively correlated with intervertebral disc degeneration (r = 0.757, p < 0.001) and negatively correlated with the intervertebral disc height index (r = - 0.231, p < 0.001). There was no significant correlation between the Modic grading scoring system and disc herniation (r = 0.369, p = 0.249). Additionally, there was no significant correlation between the Modic grading score and the Japanese Orthopaedic Association score (r = - 0.349, p = 0.25), Oswestry Disability Index score (r = 0.246, p = 0.11), or visual analogue scale score (r = 0.315, p = 0.35). CONCLUSION: The new Modic grading scoring system had good interobserver and intraobserver reliability. The Modic grading score was positively correlated with intervertebral disc degeneration and negatively correlated with the intervertebral disc height.

Association of modic changes and postoperative surgical site infection after posterior lumbar spinal fusion.

PURPOSE: Postoperative surgical site infection is one of the most serious complications following spine surgery. Previous studies have reported Modic changes (MC) represent a subclinical infection. This study aims to investigate the relation between Modic changes and surgical site infection after posterior lumbar fusion surgery. METHODS: We retrospectively reviewed the records of 424 patients who received posterior lumbar fusion. Preoperative clinical and radiological parameters were recorded. Primary outcome was the rate of postoperative surgical site infection. Covariates included age, body mass index (BMI), sex, hypertension, diabetes mellitus, chronic heart failure, Pfirrmann classification, fused levels, and operation duration. The presence of Modic changes was used as an exposition variable, and adjusted for other risk factors in multivariate analyses. RESULTS: Of the 424 patients, 30 (7%) developed an acute surgical site infection. Infection had no relation to age, sex, BMI, and comorbidities. There were 212 (50%) patients with MC, and 23 (10.8%) had a surgical site infection, compared to 212 (50%) patients without MC in which there were 7 (3.3%) surgical site infections. MC was associated with surgical site infection in univariate analysis (odds ratio [OR] = 3.56, 95% confidence interval [CI]: 1.49-8.50, p = 0.004) and multivariate logistic regression analysis (OR = 3.05, 95% CI: 1.26-7.37, p = 0.013). There was statistically significant between specific type (p = 0.035) and grade of MCs (p = 0.0187) and SSI. CONCLUSIONS: MCs may be a potential risk factor for SSI following posterior lumbar spinal intervertebral fusion. Type I and grade C MCs showed a higher infection rate compared with other MC types and grades.

The area ratio of Modic changes has predictive value for postoperative surgical site infection in lumbar spine surgery: a retrospective study.

BACKGROUND: Increasing evidence suggests an association between Modic changes (MC) and subclinical infection and inflammatory reactions. However, the relationship between preoperative MC and surgical site infection (SSI) has not been fully explored. This study aims to investigate the correlation between MC and SSI. METHODS: A retrospective analysis was conducted on patients (n = 646) who underwent single-level lumbar spine surgery for lower back pain in our hospital between 2018 and 2023. According to the Centers for Disease Control and Prevention (CDC) criteria, the patients were divided into an SSI group (n = 40) and a Non-SSI group (n = 606). Univariate analysis was performed to determine the statistical differences in variables between the two groups, and the variables with significant differences were included in a multivariable logistic regression analysis to identify independent risk factors for SSI. Receiver operating characteristic (ROC) curve analysis was performed on the independent risk factors. RESULTS: The SSI group and the Non-SSI group exhibited significant differences in diabetes prevalence, MC prevalence, Total endplate score (TEPS) and area ratio of MC (P < 0.05). Age, gender, American Society of Anesthesiologists(ASA)score, hypertension, coronary heart disease (CHD), chronic obstructive pulmonary disease (COPD), MC classification, and the location of MC in the endplate showed no significant differences (P > 0.05). Multivariate binary logistic regression analysis was performed on the variables with significant differences, and the results indicated a significant correlation between TEPS (P = 0.009) and the area ratio of MC changes (P = 0.001) with SSI. ROC curve analysis was performed on the TEPS and area ratio of MC changes, and the results showed that the diagnostic value of TEPS (AUC: 0.641; CI: 0.522-0.759) is lower than the area ratio of MC (AUC: 0.722; CI: 0.621-0.824), and the combined diagnosis did not significantly improve the diagnostic value (AUC: 0.747; CI: 0.653-0.842). The area ratio of MC had moderate diagnostic value for SSI (AUC: 0.722; CI: 0.621-0.824), with a cut-off value of 24.62% determined by the Youden index (sensitivity: 69.2%; specificity: 73.1%), and for every 1% increase in the area ratio of MC changes, the risk of SSI in MC patients increased by 10.3% (OR = 1.103; CI: 1.044-1.167). CONCLUSION: The area ratio MC and the TEPS are independent risk factors for SSI after lumbar spine surgery. The predictive value of the area ratio of MC is greater than TEPS, and when the two are combined, the predictive value is not significantly improved. When the rate of MC exceeds 24.62%, caution should be exercised regarding the occurrence of SSI.

Vertebral bone quality score was associated with paraspinal muscles fat infiltration, but not modic classification in patients with chronic low back pain: a prospective cross-sectional study.

BACKGROUND: The lumbar vertebra and paraspinal muscles play an important role in maintaining the stability of the lumbar spine. Therefore, the aim of this study was to investigate the relationship between paraspinal muscles fat infiltration and vertebral body related changes [vertebral bone quality (VBQ) score and Modic changes (MCs)] in patients with chronic low back pain (CLBP). METHODS: Patients with CLBP were prospectively collected in four hospitals and all patients underwent 3.0T magnetic resonance scanning. Basic clinical information was collected, including age, sex, course of disease (COD), and body mass index (BMI). MCs were divided into 3 types based on their signal intensity on T1 and T2-weighted imaging. VBQ was obtained by midsagittal T1-weighted imaging (T1WI) and calculated using the formula: SIL1-4/SICSF. The Proton density fat fraction (PDFF) values and cross-sectional area (CSA) of paraspinal muscles were measured on the fat fraction map from the iterative decomposition of water and fat with the echo asymmetry and least-squares estimation quantitation (IDEAL-IQ) sequences and in/out phase images at the central level of the L4/5 and L5/S1 discs. RESULTS: This study included 476 patients with CLBP, including 189 males and 287 females. 69% had no Modic changes and 31% had Modic changes. There was no difference in CSA and PDFF for multifidus(MF) and erector spinae (ES) at both levels between Modic type I and type II, all P values>0.05. Spearman correlation analysis showed that VBQ was weakly negatively correlated with paraspinal muscles CSA (all r values < 0.3 and all p values < 0.05), moderately positive correlation with PDFF of MF at L4/5 level (r values = 0.304, p values<0.001) and weakly positively correlated with PDFF of other muscles (all r values<0.3 and all p values<0.001). Multivariate linear regression analysis showed that age (ß = 0.141, p < 0.001), gender (ß = 4.285, p < 0.001) and VBQ (ß = 1.310, p = 0.001) were related to the total PDFF of muscles. For MCs, binary logistic regression showed that the odds ratio values of age, BMI and COD were 1.092, 1.082 and 1.004, respectively (all p values ＜ 0.05). CONCLUSIONS: PDFF of paraspinal muscles was not associated with Modic classification. In addition to age and gender, PDFF of paraspinal muscles is also affected by VBQ. Age and BMI are considered risk factors for the MCs in CLBP patients.

Fatty infiltration of the erector spinae at the upper lumbar spine could be a landmark for low back pain.

PURPOSE: Intervertebral disc degeneration (IVDD), Modic changes, and fatty infiltration in the paraspinal muscles are possible causes of low back pain (LBP). Multifidus has been the most commonly blamed paraspinal muscle in the etiology of LBP. However, it contributes to 20% of the extensor moment on the lumbar spine. In the present study, we aimed to identify whether patients with LBP and asymptomatic subjects differed in terms of intervertebral discs, end-plates, and fatty infiltration in their paraspinal muscles. METHODS: Consecutive women and men, who visited the spine outpatient clinics with chronic LBP and had lumbar spine MRI for their LBP without leg pain were included. Asymptomatic subjects without LBP/leg pain for the last year were recruited. Modic changes, IVDD, and fatty infiltration in the paraspinal muscles were evaluated on lumbar spine magnetic resonance imagings of the patients with LBP and age-, gender- and BMI-matched asymptomatic controls. RESULTS: Low back pain was closely associated with fatty infiltration in the paraspinal muscles at all lumbar levels whereas it had association with severe IVDD and Modic changes at lower lumbar levels. Multifidus at the lower lumbar levels was the fattiest paraspinal muscle in both asymptomatic subjects and patients with LBP. Patients with LBP had severe fatty infiltration in the erector spinae at the upper lumbar levels. CONCLUSION: Severe IVDD and Modic changes were more common at lower lumbar levels in patients with LBP. Both asymptomatic subjects and those with LBP had fatty multifidus at lower lumbar levels, whereas those with LBP had fatty infiltration in the erector spinae at upper lumbar levels. We suggest that fatty infiltration could have started in the multifidus. The erector spinae had greater contribution to the lumbar extension compared to the multifidus. Thus, LBP could develop when the quality of the erector spinae at the upper lumbar levels impairs due to fatty infiltration.

Longitudinal changes of serum cytokines in patients with chronic low back pain and Modic changes.

OBJECTIVES: To explore serum cytokine levels over time in patients with chronic low back pain (cLBP) and Modic changes (MCs), difference in change between treatment groups in the Antibiotics in Modic Changes (AIM) study and associations between change in cytokines and low back pain. METHODS: Serum concentrations of 39 cytokines were measured at baseline and 1 year from 73 participants in the AIM study; 30 randomized to placebo, 43 to Amoxicillin. Low back pain intensity was measured by numeric rating scale. Change in cytokine levels over time were assessed by paired t-tests. Difference in change in cytokine levels between treatment groups and associations between changes in LBP and cytokine levels were assessed by linear regression models. Networks of cytokine changes in each treatment groups were explored by Pearson's correlations. RESULTS: Five cytokines changed from baseline to 1 year, (mean change, log transformed values with CI) C-X-C motif chemokine ligand (CXCL) 10 (IP-10) (0.11 (0.01-0.20)), CXCL13 (0.61 (0.00-0.12)), C-C motif chemokine ligand (CCL)26 (0.05 (0.01-0.1)), granulocyte macrophage-colony stimulating factor (GM-CSF) (-0.12 (-0.23 to 0.00)) and CXCL11 (0.12 (0.03-0.22)). Treatment group only influenced change in CCL21 (ß 0.07 (0.01-0.12)), and IL-6 (ß -0.17 (-0.30 to -0.03)). Change in CXCL13 (ß 2.43 (0.49-4.38)), CCL27 (ß 3.07 (0.46-5.69)), IL-8 (ß 1.83 (0.08-3.58)) and CCL19 (ß 3.10 (0.86-5.43)) were associated with change in LBP. The correlation networks of cytokine changes demonstrate small differences between treatment groups. CONCLUSIONS: Cytokine levels are relatively stable over time in our sample, with little difference between treatment groups. Some cytokines may be associated with LBP intensity. The differences between the correlation networks suggest that long-term Amoxicillin-treatment may have longstanding effects to be further explored.

Association between Modic changes and intervertebral vacuum phenomenon severity in patients undergoing percutaneous cement discoplasty.

BACKGROUND: Modic changes and intervertebral vacuum phenomenon (IVP) are considered spinal degenerative changes. The correlation between Modic and IVP has not been analyzed in the literature. PURPOSE: To analyze the correlation between IVP severity, Modic changes, and subchondral sclerosis across the lumbar spine in patients with lumbar degeneration. MATERIAL AND METHODS: This is a retrospective study analyzing patients who underwent percutaneous cement discoplasty at a single institution between 2015 and 2020. Preoperative magnetic resonance imaging and computed tomography scans were analyzed to make the measurements. Modic type and grade as well as severity of IVP were preoperatively measured. The association between Modic type, grade, subchondral sclerosis, and the presence of IVP was analyzed. RESULTS: In total, 110 patients (mean age = 77.03 ± 7.1 years) were finally included in the study. Per level correlation analysis showed a significant positive association between IVP and Modic type, IVP and Modic grade, and IVP and subchondral sclerosis. Moreover, subchondral sclerosis was significantly associated with Modic type and grade. CONCLUSION: Our study showed a significant positive correlation among Modic changes, IVP, and subchondral sclerosis throughout the lumbar spine. Our findings support the theory that endplate degeneration parameters are associated with the presence and severity of IVP.

Are serum thyroid hormone, parathormone, calcium, and vitamin D levels associated with lumbar spine degeneration? A cross-sectional observational clinical study.

PURPOSE: Low back pain (LBP) impairs the quality of life and rises healthcare costs. The association of spine degeneration and LBP with metabolic disorders have been reported, previously. However, metabolic processes related with spine degeneration remained unclear. We aimed to analyze whether serum thyroid hormones, parathormone, calcium, and vitamin D levels were associated with lumbar intervertebral disc degeneration (IVDD), Modic changes, and fatty infiltration in the paraspinal muscles. METHODS: We cross-sectionally analyzed a retrospective database. Patients who visited internal medicine outpatient clinics with suspect of endocrine disorders and chronic LBP were searched. Patients with biochemistry results within 1 week before lumbar spine magnetic resonance imaging (MRI) were included. Age- and gender-matched cohorts were made-up and analyzed. RESULTS: Patients with higher serum free thyroxine levels were more likely to have severe IVDD. They were also more likely to have fattier multifidus and erector spinae at upper lumbar levels, less fatty psoas and less Modic changes at lower lumbar levels. Higher PTH levels were observed in patients with severe IVDD at L4-L5 level. Patients with lower serum vitamin D and calcium levels had more Modic changes and fattier paraspinal muscles at upper lumbar levels. CONCLUSION: Serum hormone, vitamin D, and calcium levels were associated with not only IVDD and Modic changes but also with fatty infiltration in the paraspinal muscles, mainly at upper lumbar levels in patients with symptomatic backache presenting to a tertiary care center. Complex inflammatory, metabolic, and mechanical factors present in the backstage of spine degeneration.

Asymmetric distribution of Modic changes in patients with lumbar disc herniation.

PURPOSE: This study aims to report a new distribution pattern of Modic changes (MCs) in patients with lumbar disc herniation (LDH) and investigate the prevalence, correlative factors and clinical outcomes of asymmetric Modic changes (AMCs). METHODS: The study population consisted of 289 Chinese Han patients who were diagnosed with LDH and single-segment MCs from January 2017 to December 2019. Demographic, clinical and imagological information was collected. Lumbar MRI was performed to assess MCs and intervertebral discs. The visual analogue score (VAS) and Oswestry disability index (ODI) were evaluated in patients undergoing surgery preoperatively and at the final follow-up. Correlative factors contributing to AMCs were analysed by multivariate logistic regression. RESULTS: The study population included 197 patients with AMCs and 92 patients with symmetric Modic changes (SMCs). The incidence of leg pain (P < 0.001) and surgical treatment (P = 0.027) in the AMC group was higher than that in the SMC group. The VAS of low back pain was lower (P = 0.048), and the VAS of leg pain was higher (P = 0.036) in the AMC group than in the SMC group preoperatively. Multivariate logistic regression analysis revealed that leg pain (OR = 2.169, 95% CI = 1.218 ~ 3.864) and asymmetric LDH (OR = 7.342, 95% CI = 4.170 ~ 12.926) were independently associated with AMCs. The receiver operating characteristic curve showed an AUC of 0.765 (P < 0.001). CONCLUSION: AMCs were a more common phenomenon than SMCs in this study. The asymmetric and symmetric distribution of MCs was closely related to LDH position. AMCs were related to leg pain and higher pain levels. Surgery can achieve satisfactory clinical improvement for asymmetric and symmetric MCs.

Raftlin and 8-iso-prostaglandin F2α levels and gene network analysis in patients with Modic changes.

PURPOSE: Oxidative stress in the vertebral endplates of patients with low back pain and Modic changes (MCs) (types I, II, and III) endplate changes on magnetic resonance imaging. 8-iso-prostaglandin F2α (8-iso-PGF2α) has been proposed as new indicator of oxidative stress. Raftlin, as an inflammatory biomarker, has been previously reported in inflammatory diseases. Oxidative stress plays an important role in various human diseases. This study was aimed to assess Raftlin and 8-iso-PGF2α levels in patients with MCs. METHODS: Patients with MCI, II, and III (n = 45) and age- and sex matched controls subjects (n = 45) were enrolled in this study. 8-iso-PGF2α and Raftlin levels in the serum samples of both groups were measured with enzyme-linked immunosorbent assay. RESULTS: In our study results, raftlin levels changed in parallel with prostaglandin levels (p < 0.05). Raftlin levels changed in parallel with prostaglandin levels (p < 0.05). The levels of 8-iso-PGF2α and Raftlin levels showed increase in patients with MCs and the control group (p < 0.05). In addition, a significant positive correlation was found between MC-I, MC-II, MC-III and Raftlin (r = 0.756, 0.733, 0.701 p < 0.001, respectively). A significant positive correlation was found between ISO (Respectively; r = 0.782, 0.712, 0.716 p < 0.001). In our evaluation between Raftlin and Iso, a significant positive relationship was determined. (r = 0.731, p < 0.001). CONCLUSION: Our findings indicated that oxidative stress in patients with MC-I may be aggravated and it may cause an inflammation formation of the lesion areas in these patients. Also, the increased 8-iso-PGF2α and Raftlin levels in patients with MC-II and MC-III may be an adaptive response to against oxidative stress.

Do Modic changes contribute to lumbar instability or other way around? A retrospective study based on their types, extents, and affected lumbar segments.

BACKGROUND: Which types of Modic changes (MCs) and whether or how specific factors associated to MCs work on lumbar instability have yet to be well understood. The purpose of this study was to investigate the influences of the types of MCs, the extent of MCs lesion involvement, and different lumbar levels involved by MCs on lumbar instability. METHODS: This retrospective study included 263 adult subjects with MCs who underwent lumbar X-ray examinations in the neutral, flexion, and extension positions. All patients who met our inclusion criteria were examined with 1.5 Tesla magnetic resonance units. Two experienced authors with more than three-year clinical experience independently evaluated and measured the subjects' radiographic images. The subgroup analysis was performed to detect the differences in subjects' baseline characteristics and lumbar segmental motions among three types of MCs, the extent of MCs lesion involvement and different lumbar levels involved by MCs. RESULTS: There was a statistical difference in body mass index (BMI) between different involvement extent of MCs (p < 0.01), indicating that the subjects with high BMI are more likely to develop severe MCs. The subjects with Modic type 1 change (MC1) had a significant increase in lumbar angular motion than those with Modic type 2 change (MC2) and Modic type 3 change (MC3) (p < 0.01) and compared with MC3, a significant increase in lumbar translation motion was detected in subjects with MC1 and MC2 (p < 0.01). While, angular motion decreased, translation motion increased significantly as the extent of MCs lesion involvement aggravated (p < 0.01). However, there were no statistical differences in lumbar angular and translation motions between different lumbar levels involved by MCs (p > 0.05). CONCLUSIONS: Higher BMI might be a risk factor for the development of severe MCs. MC1 and MC2 significantly contribute to lumbar instability. The extents of MCs lesion involvement are strongly associated with lumbar instability. However, different lumbar levels involved by MCs have little effect on lumbar stability.

Influence of endplate avulsion and Modic changes on the inflammation profile of herniated discs: a proteomic and bioinformatic approach.

PURPOSE: The aim of this observational radiographic and proteomic study is to explore the influence of both Modic change (MC) and endplate avulsion (EPA) on the inflammation profile of herniated discs using a proteomic and bioinformatics approach. METHODS: Fifteen nucleus pulposus (NP) harvested from surgery underwent LC-MS/MC analysis, the proteome was subsequently scanned for inflammatory pathways using a bioinformatics approach. All proteins that were identified in inflammatory pathways and Gene Ontology and present in > 7 samples were integrated in a multiple regression analysis with MC and EPA as predictors. Significant proteins were imputed in an interaction and pathway analysis. RESULTS: Compared to annulus fibrosus tear (AFT), six proteins were significantly altered in EPA: catalase, Fibrinogen beta chain, protein disulfide-isomerase, pigment epithelium-derived factor, osteoprotegerin and lower expression of antithrombin-III, all of which corresponded to an upregulation of pathways involved in coagulation and detoxification of reactive oxygen species (ROS). Moreover, the presence of MC resulted in a significant alteration of nine proteins compared to patients without MC. Patients with MC showed a significantly higher expression of clusterin and lumican, and lower expression of catalase, complement factor B, Fibrinogen beta chain, protein disulfide-isomerase, periostin, Alpha-1-antitrypsin and pigment epithelium-derived factor. Together these altered protein expressions resulted in a downregulation of pathways involved in detoxification of ROS, complement system and immune system. Results were verified by Immunohistochemistry with CD68 cell counts. CONCLUSION: Both EPA and MC status significantly influence disc inflammation. The beneficial inflammatory signature of EPA illustrates that endplate pathology does not necessarily have to worsen the outcome, but the pathological inflammatory state is dependent on the presence of MC.

Are Modic changes 'Primary infective endplatitis'?-insights from multimodal imaging of non-specific low back pain patients and development of a radiological 'Endplate infection probability score'.

PURPOSE: To probe the pathophysiological basis of Modic change (MC) by multimodal imaging rather than by MRI alone. METHODS: Nineteen radiological signs found in mild infections and traumatic endplate fractures were identified by MRI and CT, and by elimination, three signs unique to infection and trauma were distilled. By ranking the Z score, radiological 'Endplate Infection Probability Score' (EIPS) was developed. The score's ability to differentiate infection and traumatic endplate changes (EPC) was validated in a fresh set of 15 patients each, with documented infection and trauma. The EIPS, ESR, CRP, and Numeric Pain Rating Scale (NRS) were then compared between 115 patients with and 80 patients without MC. RESULTS: The EIPS had a confidence of 66.4%, 83% and, 100% for scores of 4, 5 and, 6, respectively, for end plate changes suggesting infection. The mean EIPS was 4.85 ± 1.94 in patients with Modic changes compared to - 0.66 ± 0.49 in patients without Modic changes (p < 0.001). Seventy-eight (67.64%) patients with MC had a score of 6, indicating high infection possibility. There was a difference in the NRS (p < 0.01), ESR (p = 0.05), CRP (p < 0.01), and type of pain (p < 0.01) between patients with and without MC. CONCLUSION: Multimodal imaging showed many radiological signs not easily seen in MRI alone and thus missed in Modic classification. There were distinct radiological differences between EPCs of trauma and infection which allowed the development of an EIPS. The scores showed that 67.64% of our study patients with Modic changes had EPCs resembling infection rather than trauma suggesting the possibility of an infective aetiology and allowing us to propose an alternate theory of 'Primary Endplatitis'.

MRI grading of spinal stenosis is not associated with the severity of low back pain in patients with lumbar spinal stenosis.

BACKGROUND: Although lumbar spinal stenosis (LSS) often coexists with other degenerative conditions, few studies have fully assessed possible contributing factors for low back pain (LBP) in patients with LSS. The purpose of this study was to identify factors associated with the severity of LBP in patients with LSS. METHODS: The patients with neurogenic claudication caused by LSS, which was confirmed by magnetic resonance imaging (MRI) were included in this cross-sectional study. Data included ratings of LBP, buttock and leg pain, and numbness on a numerical rating scale (NRS), 36-item Short-Form Survey (SF-36) scores, muscle mass measured by bioelectrical impedance analysis, and radiographic measurements including lumbopelvic alignment and slippage. The severity of LSS, endplate defects, Modic endplate changes, intervertebral disc degeneration, and facet joint osteoarthritis were evaluated on MRI. Spearman correlation and multivariate linear regression analyses were used to examine the factors associated with the severity of LBP (NRS score). RESULTS: A total of 293 patients (135 male and 158 female, average age 72.6 years) were analyzed. LBP was moderately correlated with buttock and leg pain, and buttock and leg numbness. Significant but weak correlations were observed between LBP and body mass index, appendicular and trunk muscle mass, all domains of SF-36, pelvic tilt, total number of endplate defects and Modic endplate changes, and summary score of disc degeneration grading, but not severity or number of spinal stenoses. In the multivariate regression analysis, age, female sex, trunk muscle mass, diabetes, NRS buttock and leg pain, NRS buttock and leg numbness, SF-36 vitality, pelvic tilt, and total number of endplate defects were associated with the severity of LBP. CONCLUSIONS: Trunk muscle mass, lumbopelvic alignment, and endplate defects, but not severity of stenosis are partly associated with severity of LBP, but buttock and leg pain and buttock and leg numbness have strongest relationships with LBP in patients with LSS.

A new radiological index for the assessment of higher body fat status and lumbar spine degeneration.

OBJECTIVE: Obesity has been proposed as a risk factor for low back pain (LBP) and intervertebral disc degeneration (IVDD). Even though body mass index (BMI) is used as a parameter for obesity, it could not represent percentage and distribution of the body fat. Subcutaneous fat tissue thickness (SFTT) was proposed as one of the magnetic resonance imaging (MRI) parameters to evaluate the percentage of the body fat. In this study, we aimed to find out whether SFTT at lower back correlated with LBP and spine degeneration. MATERIALS AND METHODS: We retrospectively reviewed a database of the patients with LBP. Concomitantly, asymptomatic control subjects were retrieved. Patients and control subjects were evaluated in terms of IVDD and Modic changes at all lumbar levels on MRI. SFTT was measured both on MRI and computed tomography (CT) scans, where applicable. RESULTS: SFTT at the lumbar spine had moderate-to-strong correlations with BMI. SFTT at L1-L2 level was significantly associated with severe IVDD at L5-S1 level, and Modic changes at L4-L5 and L5-S1 levels. BMI had no significant association with severe IVDD and Modic changes at lumbar spine. BMI and mean SFTT of all lumbar levels had ORs of 0.735 (95% CI: 0.631-0.857, p < 0.001) and 1.389 (95% CI: 1.266-1.524, p < 0.001) in predicting symptomatic subjects with LBP. CONCLUSION: SFTT at upper lumbar levels could predict severe IVDD and Modic changes better than BMI, specifically in men. SFTT was better than BMI in predicting a symptomatic patient with LBP.

Traumatic vertebra and endplate fractures promote adjacent disc degeneration: evidence from a clinical MR follow-up study.

OBJECTIVES: The integrity of endplate is important for maintaining the health of adjacent disc and trabeculae. Yet, pathological impacts of traumatic vertebra and endplate fractures were less studied using clinical approaches. This study aims to investigate their effects on the development of adjacent disc degeneration, segmental kyphosis, Modic changes (MCs), and high-intensity zones (HIZs). MATERIALS AND METHODS: Magnetic resonance (MR) images of patients with acute traumatic vertebral compression fractures (T11-L5) were studied. On MR images, endplate fractures were evaluated as present or absent. Disc signal, height, bulging area, sagittal Cobb angle, MCs, and HIZs were measured on baseline and follow-up MR images to study the changes of the disc in relation to vertebra fractures and endplate fractures. RESULTS: Ninety-seven patients were followed up for 15.4 ± 14.0 months. There were 123 fractured vertebrae, including 79 (64.2%) with endplate fractures and 44 (35.8%) without. Both the adjacent and control discs decreased in signal and height over time (p < 0.001), and the disc adjacent to vertebral fractures had greater signal and height loss than the control disc (p < 0.05). In the presence of endplate fractures, the adjacent discs had greater signal decrease in follow-up (p < 0.05), as compared to those without endplate fractures. Sagittal Cobb angle significantly increased in segments with endplate fractures (p < 0.05). Vertebra fractures were associated with new occurrence of MCs in the fractured vertebra (p < 0.001) but not HIZs in the adjacent disc. CONCLUSIONS: Traumatic vertebral fractures were associated with accelerated adjacent disc degeneration, which appears to be further promoted by concomitant endplate fractures. Endplate fractures were associated with progression of segmental kyphosis.

Modic changes and its association with other MRI phenotypes in east Anatolian low back pain patients.

OBJECTIVE: Modic changes (MCs) are known to be associated with low back pain (LBP). Literature contains conflicting reports about the prevalence of MCs and other spinal phenotypes among different populations with LBP patients. We aimed to evaluate the prevalence of MCs in the lumbar spine and associated features in Eastern Anatolian chronic LBP patients. METHODS: The study sample comprised of 786 consecutive patients [(490 female, 296 male), (mean age 39.7; range 20-78)] with a history of low back pain for at least 3 months. Data about MCs involvement, Schmorl's nodes (SN), disc degeneration (DD), disc displacement, disc height and osteophytes were obtained via MRI. Patients' demographic characteristics, Oswestry disability index (ODI) and visual analog scale (VAS) scores were assessed using a questionnaire. RESULTS: MCs were present in 67.2% (528/786) of the patients. Of all evaluated lumbar-level changes, 86 (6.2%) were Type I, 991 (76.8%) were Type II, 11 (0.8%) were Type III, 47 (6.5%) were Type II/III, 89 (8.5%) were Type I/II, and 29 (1.2%) were Type I/II/III MCs. MCs were significantly associated with severe DD (p < 0.001), disc displacement (p < 0.001), SN (p < 0.001), and osteophytes (p < 0.001). In the multivariate regression analysis, BMI (for both ODI and VAS) and age (only for ODI) were the only independent predictors of clinical severity. CONCLUSIONS: The present study is the largest cross-sectional study of adult members of the Eastern Anatolian population with chronic LBP. Modic changes were detected in 67.2% of patients with chronic LBP and the prevalence of other phenotypic features differed significantly between MCs and non-MCs disc levels. Nevertheless, the results of the current study do not support a causal relationship of MCs or any MRI changes with clinical symptom severity.

Frequency and characteristics of bacterial and viral low-grade infections of the intervertebral discs: a prospective, observational study.

STUDY DESIGN: Monocentric, prospective, observational study. OBJECTIVE: The clinical relevance of bacterial colonization of intervertebral discs is controversial. This study aimed to determine a possible relationship between bacterial and viral colonization and low-grade infection of the discs. METHODS: We investigated 447 disc samples from 392 patients. Microbiological culture was used to examine the samples for bacterial growth, polymerase chain reaction (PCR) was used for detection of herpes simplex virus types 1 and 2 (HSV-1, HSV-2) and Cytomegalovirus (CMV), and histopathological analysis was used to detect signs of inflammation. The results were compared between subgroups organized according to gender, age, location of the samples, surgical approach, preoperative C-reactive protein (CRP), preoperative and 6 months postoperative Oswestry Disability Index (ODI) and Neck Disability Index (NDI), and Modic changes (MC) of the corresponding endplates. Also, we assessed the occurrence of postoperative infections within 6 months. RESULTS: Microbiological culture was positive in 38.78% of the analyzed intervertebral discs. Altogether, 180 bacteria were isolated. Coagulase-negative staphylococci (CONS) (23.41%) and Cutibacterium acnes (18.05%) were the most frequently detected microorganisms. None of HSV-1, HSV-2, or CMV were detected. Male patients (p = 0.00036) and cervical segments (p = 0.00001) showed higher rates of positive culture results. Ventral surgical approaches ( p < 0.001) and Type 2 MC (p = 0.0127) were significantly associated with a positive microbiological result ( p< 0.001). Neither pre- nor postoperative ODI and NDI are associated with positive culture results. In 4 (1.02%) patients, postoperative spondylodiscitis occurred. CONCLUSIONS: With 447 segments from 392 patients, we present one of the largest studies to date. While disc degeneration caused by HSV-1, HSV-2, and CMV seems unlikely, we found positive microbiological culture results in 38.78% of all discs. The role of local skin flora and sample contamination should be the focus of further investigations. LEVEL OF EVIDENCE: III. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov (ID: NCT04712487, https://www. CLINICALTRIALS: gov/ct2/show/study/NCT04712487 ).