Is IL-1β Further Evidence for the Role of Propionibacterium acnes in Degenerative Disc Disease? Lessons From the Study of the Inflammatory Skin Condition Acne Vulgaris

The pathogenesis of degenerative disc disease is a complex and multifactorial process in which genetics, mechanical trauma, altered loading and nutrition present significant etiological factors. Infection of the intervertebral disc with the anaerobic bacterium Propionibacterium acnes is now also emerging as a potentially new etiological factor. This human commensal bacterium is well known for its long association with the inflammatory skin condition acne vulgaris. A key component of inflammatory responses to P. acnes in acne appears to be interleukin (IL)-1β. Similarly, in degenerative disc disease (DDD) there is compelling evidence for the fundamental roles of IL-1β in its pathology. We therefore propose that P. acnes involvement in DDD is biologically very plausible, and that IL-1β is the key inflammatory mechanism driving the host response to P. acnes infection. Since there is a solid theoretical basis for this phenomenon, we further propose that the relationship between P. acnes infection and DDD is causal

Propionibacterium acnes biofilm is present in intervertebral discs of patients undergoing microdiscectomy

Background In previous studies, Propionibacterium acnes was cultured from intervertebral disc tissue of similar to 25% of patients undergoing microdiscectomy, suggesting a possible link between chronic bacterial infection and disc degeneration. However, given the prominence of P. acnes as a skin commensal, such analyses often struggled to exclude the alternate possibility that these organisms represent perioperative microbiologic contamination. This investigation seeks to validate P. acnes prevalence in resected disc cultures, while providing microscopic evidence of P. acnes biofilm in the intervertebral discs. Methods Specimens from 368 patients undergoing microdiscectomy for disc herniation were divided into several fragments, one being homogenized, subjected to quantitative anaerobic culture, and assessed for bacterial growth, and a second fragment frozen for additional analyses. Colonies were identified by MALDI-TOF mass spectrometry and P. acnes phylotyping was conducted by multiplex PCR. For a sub-set of specimens, bacteria localization within the disc was assessed by microscopy using confocal laser scanning and FISH. Results Bacteria were cultured from 162 discs (44%), including 119 cases (32.3%) with P. acnes. In 89 cases, P. acnes was cultured exclusively;in 30 cases, it was isolated in combination with other bacteria (primarily coagulase-negative Staphylococcus spp.) Among positive specimens, the median P. acnes bacterial burden was 350 CFU/g (12 - similar to 20,000 CFU/g). Thirtyeight P. acnes isolates were subjected to molecular sub-typing, identifying 4 of 6 defined phylogroups: IA1, IB, IC, and II. Eight culture-positive specimens were evaluated by fluorescence microscopy and revealed P. acnes in situ. Notably, these bacteria demonstrated a biofilm distribution within the disc matrix. P. acnes bacteria were more prevalent in males than females (39% vs. 23%, p = 0.0013). Conclusions This study confirms that P. acnes is prevalent in herniated disc tissue. Moreover, it provides the first visual evidence of P. acnes biofilms within such specimens, consistent with infection rather than microbiologic contamination

Measurement of vertebral endplate bone marrow lesion (Modic change) composition with water-fat MRI and relationship to patient-reported outcome measures.

PurposeVertebral endplate bone marrow lesions ("Modic changes", MC) are associated with chronic low back pain (CLBP). Bone marrow composition in MC is poorly understood. The goals of this study were to: (1) measure bone marrow fat fraction (BMF) in CLBP patients with MC using water-fat MRI and (2) assess the relationship between BMF measurements and patient-reported clinical characteristics.MethodsIn this cross-sectional study, 42 CLBP patients (men, n = 21; age, 48 ± 12.4 years) and 18 asymptomatic controls (men, n = 10; 42.7 ± 12.8 years) underwent 3 T MRI between January 2016 and July 2018. Imaging consisted of T1- and T2-weighted sequences to evaluate MC and spoiled gradient-recalled echo sequence with asymmetric echoes and least-squares fitting to measure BMF. BMF was compared between vertebrae with and without MC using mixed effects models. The relationship between the BMF measurements and patient-reported disability scores was examined using regression.ResultsTwenty-seven subjects (26 CLBP, 1 control) had MC, and MC presence coincided with significantly altered BMF. In MC 1, BMF was lower than endplates without MC (absolute difference -22.3%; p < 0.001); in MC 2, BMF was higher (absolute difference 21.0%; p < 0.001). Absolute BMF differences between affected and unaffected marrow were larger in patients with greater disability (p = 0.029-0.032) and were not associated with pain (p = 0.49-0.83).ConclusionBMF is significantly altered in MC. Water-fat MRI enables BMF measurements that may eventually form the basis for quantitative assessments of MC severity and progression

Serum Biomarkers for Connective Tissue and Basement Membrane Remodeling are Associated with Vertebral Endplate Bone Marrow Lesions as Seen on MRI (Modic Changes)

Vertebral endplate bone marrow lesions, visualized on magnetic resonance imaging (MRI) as Modic changes (MC), are associated with chronic low back pain (cLBP). Since guidelines recommend against routine spinal MRI for cLBP in primary care, MC may be underdiagnosed. Serum biomarkers for MC would allow early diagnosis, inform clinical care decisions, and supplement treatment monitoring. We aimed to discover biomarkers in the blood serum that correlate with MC pathophysiological processes. For this single-site cross-sectional study, we recruited 54 subjects with 38 cLBP patients and 16 volunteers without a history of LBP. All subjects completed an Oswestry Disability Index (ODI) questionnaire and 10-cm Visual Analog Score (VAS) for LBP (VASback) and leg pain. Lumbar T1-weighted and fat-saturated T2-weighted MRI were acquired at 3T and used for MC classification in each endplate. Blood serum was collected on the day of MRI. Biomarkers related to disc resorption and bone marrow fibrosis were analyzed with enzyme-linked immune-absorbent assays. The concentration of biomarkers between no MC and any type of MC (AnyMC), MC1, and MC2 were compared. The Area Under the Curve (AUC) of the Receiver Operating Characteristics were calculated for each biomarker and for bivariable biomarker models. We found that biomarkers related to type III and type IV collagen degradation and formation tended to correlate with the presence of MC (p = 0.060-0.088). The bivariable model with the highest AUC was PRO-C3 + C4M and had a moderate diagnostic value for AnyMC in cLBP patients (AUC = 0.73, specificity = 78.9%, sensitivity = 73.7%). In conclusion, serum biomarkers related to the formation and degradation of type III and type IV collagen, which are key molecules in bone marrow fibrosis, correlated with MC presence. Bone marrow fibrosis may be an important pathophysiological process in MC that should be targeted in larger biomarker and treatment studies

Influence of patient‐specific factors when comparing multifidus fat infiltration between chronic low back pain patients and asymptomatic controls

Abstract Introduction Many studies have attempted to link multifidus (MF) fat infiltration with muscle quality and chronic low back pain (cLBP), but there is no consensus on these relationships. Methods In this cross‐sectional cohort study, 39 cLBP patients and 18 asymptomatic controls were included. The MF muscle was manually segmented at each lumbar disc level and fat fraction (FF) measurements were taken from the corresponding advanced imaging water‐fat images. We assessed the distribution patterns of MF fat from L1L2 to L5S1 and compared these patterns between groups. The sample was stratified by age, sex, body mass index (BMI), subject‐reported pain intensity (VAS), and subject‐reported low back pain disability (oswestry disability index, ODI). Results Older patients had significantly different MF FF distribution patterns compared to older controls (p < 0.0001). Male patients had 34.8% higher mean lumbar spine MF FF compared to male controls (p = 0.0006), significantly different MF FF distribution patterns (p = 0.028), 53.7% higher mean MF FF measurements at L2L3 (p = 0.037), and 50.6% higher mean MF FF measurements at L3L4 (p = 0.041). Low BMI patients had 29.7% higher mean lumbar spine MF FF compared to low BMI controls (p = 0.0077). High BMI patients only had 4% higher mean lumbar spine MF FF compared to high BMI controls (p = 0.7933). However, high BMI patients had significantly different MF FF distribution patterns compared to high BMI controls (p = 0.0324). Low VAS patients did not significantly differ from the control cohort for any of our outcomes of interest; however, high VAS patients had 24.3% higher mean lumbar spine MF FF values (p = 0.0011), significantly different MF FF distribution patterns (p < 0.0001), 34.7% higher mean MF FF at L2L3 (p = 0.040), and 34.6% higher mean MF FF at L3L4 (p = 0.040) compared to the control cohort. Similar trends were observed for ODI. Conclusions This study suggests that when the presence of paraspinal muscle fat infiltration is not characteristic of an individual's age, sex, and BMI, it may be associated with lower back pain

The Relationship Between Endplate Pathology and Patient-reported Symptoms for Chronic Low Back Pain Depends on Lumbar Paraspinal Muscle Quality.

Study designCross-sectional cohort study of chronic low back pain (CLBP) patients and matched controls.ObjectiveTo explore the interplay between vertebral endplate damage and adjacent paraspinal muscle (PSM) quality, and to test their association in a cohort of patients with CLBP and matched controls.Summary of background dataNonspecific CLBP is challenging to diagnose, in part, due to uncertainty regarding the source of pain. Delineating interactions among potential CLBP mechanisms may enhance diagnosis and treatment customization.MethodsWe collected advanced MRI imaging on 52 adult subjects, including 38 CLBP patients and 14 age- and sex-matched asymptomatic control subjects. Mean multifidus and erector spinae fat fraction (FF) was measured throughout the spine using an IDEAL MRI sequence. Presence of cartilage endplate (CEP) defects was determined at each disc level using UTE MRI. Logistic regression was used to test association of PSM FF, CEP defects, modic changes (MC), disc degeneration, and their interplay.ResultsWe observed that CEP defects were the strongest predictor of nonspecific CLBP (OR: 14.1, P &lt; 0.01) even after adjusting for MC and disc degeneration (OR: 26.1, P = 0.04). PSM quality did not independently distinguish patient and control groups, except for patients with high self-reported disability.At specifically L4L5, CEP damage was most prevalent and CEP damage was significantly associated with CLBP (OR: 3.7, 95% CI: 1.2-21.5, P = 0.03). CEP damage at L4L5 was predictive of CLBP when adjacent to PSMs with greater FF (MF, OR 14.7, P = 0.04; ES, OR: 17.3, P = 0.03), but not when PSM FF was lower and comparable to values in control, asymptomatic subjects.ConclusionThese results demonstrate the clinically important reciprocity between passive and dynamic spinal stabilizers, and support the notion that therapies targeting the PSMs may provide clinical benefit even in the presence of other spinal pathologies.Level of evidence4

Serum Biomarkers for Connective Tissue and Basement Membrane Remodeling are Associated with Vertebral Endplate Bone Marrow Lesions as Seen on MRI (Modic Changes).

Vertebral endplate bone marrow lesions, visualized on magnetic resonance imaging (MRI) as Modic changes (MC), are associated with chronic low back pain (cLBP). Since guidelines recommend against routine spinal MRI for cLBP in primary care, MC may be underdiagnosed. Serum biomarkers for MC would allow early diagnosis, inform clinical care decisions, and supplement treatment monitoring. We aimed to discover biomarkers in the blood serum that correlate with MC pathophysiological processes. For this single-site cross-sectional study, we recruited 54 subjects with 38 cLBP patients and 16 volunteers without a history of LBP. All subjects completed an Oswestry Disability Index (ODI) questionnaire and 10-cm Visual Analog Score (VAS) for LBP (VASback) and leg pain. Lumbar T1-weighted and fat-saturated T2-weighted MRI were acquired at 3T and used for MC classification in each endplate. Blood serum was collected on the day of MRI. Biomarkers related to disc resorption and bone marrow fibrosis were analyzed with enzyme-linked immune-absorbent assays. The concentration of biomarkers between no MC and any type of MC (AnyMC), MC1, and MC2 were compared. The Area Under the Curve (AUC) of the Receiver Operating Characteristics were calculated for each biomarker and for bivariable biomarker models. We found that biomarkers related to type III and type IV collagen degradation and formation tended to correlate with the presence of MC (p = 0.060-0.088). The bivariable model with the highest AUC was PRO-C3 + C4M and had a moderate diagnostic value for AnyMC in cLBP patients (AUC = 0.73, specificity = 78.9%, sensitivity = 73.7%). In conclusion, serum biomarkers related to the formation and degradation of type III and type IV collagen, which are key molecules in bone marrow fibrosis, correlated with MC presence. Bone marrow fibrosis may be an important pathophysiological process in MC that should be targeted in larger biomarker and treatment studies