Dataset Information

ISSLS PRIZE IN BASIC SCIENCE 2017: Intervertebral disc/bone marrow cross-talk with Modic changes.

ABSTRACT: STUDY DESIGN:Cross-sectional cohort analysis of patients with Modic Changes (MC). OBJECTIVE:Our goal was to characterize the molecular and cellular features of MC bone marrow and adjacent discs. We hypothesized that MC associate with biologic cross-talk between discs and bone marrow, the presence of which may have both diagnostic and therapeutic implications. BACKGROUND DATA:MC are vertebral bone marrow lesions that can be a diagnostic indicator for discogenic low back pain. Yet, the pathobiology of MC is largely unknown. METHODS:Patients with Modic type 1 or 2 changes (MC1, MC2) undergoing at least 2-level lumbar interbody fusion with one surgical level having MC and one without MC (control level). Two discs (MC, control) and two bone marrow aspirates (MC, control) were collected per patient. Marrow cellularity was analyzed using flow cytometry. Myelopoietic differentiation potential of bone marrow cells was quantified to gauge marrow function, as was the relative gene expression profiles of the marrow and disc cells. Disc/bone marrow cross-talk was assessed by comparing MC disc/bone marrow features relative to unaffected levels. RESULTS:Thirteen MC1 and eleven MC2 patients were included. We observed pro-osteoclastic changes in MC2 discs, an inflammatory dysmyelopoiesis with fibrogenic changes in MC1 and MC2 marrow, and up-regulation of neurotrophic receptors in MC1 and MC2 bone marrow and discs. CONCLUSION:Our data reveal a fibrogenic and pro-inflammatory cross-talk between MC bone marrow and adjacent discs. This provides insight into the pain generator at MC levels and informs novel therapeutic targets for treatment of MC-associated LBP.

SUBMITTER: Dudli S

PROVIDER: S-EPMC5409869 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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ISSLS PRIZE IN BASIC SCIENCE 2017: Intervertebral disc/bone marrow cross-talk with Modic changes.

Dudli Stefan S Sing David C DC Hu Serena S SS Berven Sigurd H SH Burch Shane S Deviren Vedat V Cheng Ivan I Tay Bobby K B BKB Alamin Todd F TF Ith Ma Agnes Martinez MAM Pietras Eric M EM Lotz Jeffrey C JC

European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society 20170131 5

<h4>Study design</h4>Cross-sectional cohort analysis of patients with Modic Changes (MC).<h4>Objective</h4>Our goal was to characterize the molecular and cellular features of MC bone marrow and adjacent discs. We hypothesized that MC associate with biologic cross-talk between discs and bone marrow, the presence of which may have both diagnostic and therapeutic implications.<h4>Background data</h4>MC are vertebral bone marrow lesions that can be a diagnostic indicator for discogenic low back pain ...[more]

PMID: 28138783

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Project description:PurposeDegenerative spondylolisthesis (DS) in the setting of symptomatic lumbar spinal stenosis is commonly treated with spinal fusion in addition to decompression with laminectomy. However, recent studies have shown similar clinical outcomes after decompression alone, suggesting that a subset of DS patients may not require spinal fusion. Identification of dynamic instability could prove useful for predicting which patients are at higher risk of post-laminectomy destabilization necessitating fusion. The goal of this study was to determine if static clinical radiographs adequately characterize dynamic instability in patients with lumbar degenerative spondylolisthesis (DS) and to compare the rotational and translational kinematics in vivo during continuous dynamic flexion activity in DS versus asymptomatic age-matched controls.MethodsSeven patients with symptomatic single level lumbar DS (6 M, 1 F; 66 ± 5.0 years) and seven age-matched asymptomatic controls (5 M, 2 F age 63.9 ± 6.4 years) underwent biplane radiographic imaging during continuous torso flexion. A volumetric model-based tracking system was used to track each vertebra in the radiographic images using subject-specific 3D bone models from high-resolution computed tomography (CT). In vivo continuous dynamic sagittal rotation (flexion/extension) and AP translation (slip) were calculated and compared to clinical measures of intervertebral flexion/extension and AP translation obtained from standard lateral flexion/extension radiographs.ResultsStatic clinical radiographs underestimate the degree of AP translation seen on dynamic in vivo imaging (1.0 vs 3.1 mm; p = 0.03). DS patients demonstrated three primary motion patterns compared to a single kinematic pattern in asymptomatic controls when analyzing continuous dynamic in vivo imaging. 3/7 (42%) of patients with DS demonstrated aberrant mid-range motion.ConclusionContinuous in vivo dynamic imaging in DS reveals a spectrum of aberrant motion with significantly greater kinematic heterogeneity than previously realized that is not readily seen on current clinical imaging.Level of evidenceLevel V data These slides can be retrieved under Electronic Supplementary Material.

Project description:Study designA longitudinal cohort study.ObjectiveTo define a set of objective biomechanical metrics that are representative of adult spinal deformity (ASD) post-surgical outcomes and that may forecast post-surgical mechanical complications. Current outcomes for ASD surgical planning and post-surgical assessment are limited to static radiographic alignment and patient-reported questionnaires. Little is known about the compensatory biomechanical strategies for stabilizing sagittal balance during functional movements in ASD patients.MethodsWe collected in-clinic motion data from 15 ASD patients and 10 controls during an unassisted sit-to-stand (STS) functional maneuver. Joint motions were measured using noninvasive 3D depth mapping sensor technology. Mathematical methods were used to attain high-fidelity joint-position tracking for biomechanical modeling. This approach provided reliable measurements for biomechanical behaviors at the spine, hip, and knee. These included peak sagittal vertical axis (SVA) over the course of the STS, as well as forces and muscular moments at various joints. We compared changes in dynamic sagittal balance (DSB) metrics between pre- and post-surgery and then separately compared pre- and post-surgical data to controls.ResultsStandard radiographic and patient-reported outcomes significantly improved following realignment surgery. From the DSB biomechanical metrics, peak SVA and biomechanical loads and muscular forces on the lower lumbar spine significantly reduced following surgery (- 19 to - 30%, all p < 0.05). In addition, as SVA improved, hip moments decreased (- 28 to - 65%, all p < 0.05) and knee moments increased (+ 7 to + 28%, p < 0.05), indicating changes in lower limb compensatory strategies. After surgery, DSB data approached values from the controls, with some post-surgical metrics becoming statistically equivalent to controls.ConclusionsLongitudinal changes in DSB following successful multi-level spinal realignment indicate reduced forces on the lower lumbar spine along with altered lower limb dynamics matching that of controls. Inadequate improvement in DSB may indicate increased risk of post-surgical mechanical failure. These slides can be retrieved under Electronic Supplementary Material.

Project description:Background contextEndplate (EP) injury plays critical roles in painful IVD degeneration since Modic changes (MCs) are highly associated with pain. Models of EP microfracture that progress to painful conditions are needed to better understand pathophysiological mechanisms and screen therapeutics.PurposeEstablish in vivo rat lumbar EP microfracture model and assess crosstalk between IVD, vertebra and spinal cord.Study design/settingIn vivo rat EP microfracture injury model with characterization of IVD degeneration, vertebral remodeling, spinal cord substance P (SubP), and pain-related behaviors.MethodsEP-injury was induced in 5 month-old male Sprague-Dawley rats L4-5 and L5-6 IVDs by puncturing through the cephalad vertebral body and EP into the NP of the IVDs followed by intradiscal injections of TNFα (n=7) or PBS (n=6), compared with Sham (surgery without EP-injury, n=6). The EP-injury model was assessed for IVD height, histological degeneration, pain-like behaviors (hindpaw von Frey and forepaw grip test), lumbar spine MRI and μCT, and spinal cord SubP.ResultsSurgically-induced EP microfracture with PBS and TNFα injection induced IVD degeneration with decreased IVD height and MRI T2 signal, vertebral remodeling, and secondary damage to cartilage EP adjacent to the injury. Both EP injury groups showed MC-like changes around defects with hypointensity on T1-weighted and hyperintensity on T2-weighted MRI, suggestive of MC type 1. EP injuries caused significantly decreased paw withdrawal threshold, reduced axial grip, and increased spinal cord SubP, suggesting axial spinal discomfort and mechanical hypersensitivity and with spinal cord sensitization.ConclusionsSurgically-induced EP microfracture can cause crosstalk between IVD, vertebra, and spinal cord with chronic pain-like conditions.Clinical significanceThis rat EP microfracture model was validated to induce broad spinal degenerative changes that may be useful to improve understanding of MC-like changes and for therapeutic screening.

Project description:IntroductionThe emerging field of the disc microbiome challenges traditional views of disc sterility, which opens new avenues for novel clinical insights. However, the lack of methodological consensus in disc microbiome studies introduces discrepancies. The aims of this study were to (1) compare the disc microbiome of non-Modic (nonMC), Modic type 1 change (MC1), and MC2 discs to findings from prior disc microbiome studies, and (2) investigate if discrepancies to prior studies can be explained with bioinformatic variations.MethodsSequencing of 16S rRNA in 70 discs (24 nonMC, 25 MC1, and 21 MC2) for microbiome profiling. The experimental setup included buffer contamination controls and was performed under aseptic conditions. Methodology and results were contrasted with previous disc microbiome studies. Critical bioinformatic steps that were different in our best-practice approach and previous disc microbiome studies (taxonomic lineage assignment, prevalence cut-off) were varied and their effect on results were compared.ResultsThere was limited overlap of results with a previous study on MC disc microbiome. No bacterial genera were shared using the same bioinformatic parameters. Taxonomic lineage assignment using "amplicon sequencing variants" was more sensitive and detected 48 genera compared to 22 with "operational taxonomic units" (previous study). Increasing filter cut-off from 4% to 50% (previous study) reduced genera from 48 to 4 genera. Despite these differences, both studies observed dysbiosis with an increased abundance of gram-negative bacteria in MC discs as well as a lower beta-diversity. Cutibacterium was persistently detected in all groups independent of the bioinformatic approach, emphasizing its prevalence.ConclusionThere is dysbiosis in MC discs. Bioinformatic parameters impact results yet cannot explain the different findings from this and a previous study. Therefore, discrepancies are likely caused by different sample preparations or true biologic differences. Harmonized protocols are required to advance understanding of the disc microbiome and its clinical implications.

Project description:Lumbar intervertebral disc herniation, as a leading cause of low back pain, productivity loss, and disability, is a common musculoskeletal disorder that results in significant socioeconomic burdens. Despite extensive clinical and basic scientific research efforts, herniation etiopathogenesis, particularly its initiation and progression, is not well understood. Understanding herniation etiopathogenesis is essential for developing effective preventive measures and therapeutic interventions. Thus, this review seeks to provide a thorough overview of the advances in herniation-oriented research, with a discussion on ongoing challenges and potential future directions for clinical, translational, and basic scientific investigations to facilitate innovative interdisciplinary research aimed at understanding herniation etiopathogenesis. Specifically, risk factors for herniation are identified and summarized, including familial predisposition, obesity, diabetes mellitus, smoking tobacco, selected cardiovascular diseases, disc degeneration, and occupational risks. Basic scientific experimental and computational research that aims to understand the link between excessive mechanical load, catabolic tissue remodeling due to inflammation or insufficient nutrient supply, and herniation, are also reviewed. Potential future directions to address the current challenges in herniation-oriented research are explored by combining known progressive development in existing research techniques with ongoing technological advances. More research on the relationship between occupational risk factors and herniation, as well as the relationship between degeneration and herniation, is needed to develop preventive measures for working-age individuals. Notably, researchers should explore using or modifying existing degeneration animal models to study herniation etiopathogenesis, as such models may allow for a better understanding of how to prevent mild-to-moderately degenerated discs from herniating.

Dataset Information

ISSLS PRIZE IN BASIC SCIENCE 2017: Intervertebral disc/bone marrow cross-talk with Modic changes.

Publications

ISSLS PRIZE IN BASIC SCIENCE 2017: Intervertebral disc/bone marrow cross-talk with Modic changes.

Similar Datasets

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