Dataset Information

Prevalence, Patterns, and Genetic Association Analysis of Modic Vertebral Endplate Changes.

ABSTRACT: STUDY DESIGN:A prospective genetic association study. PURPOSE:The etiology of Modic changes (MCs) is unclear. Recently, the role of genetic factors in the etiology of MCs has been evaluated. However, studies with a larger patient subset are lacking, and candidate genes involved in other disc degeneration phenotypes have not been evaluated. We studied the prevalence of MCs and genetic association of 41 candidate genes in a large Indian cohort. OVERVIEW OF LITERATURE:MCs are vertebral endplate signal changes predominantly observed in the lumbar spine. A significant association between MCs and lumbar disc degeneration and nonspecific low back pain has been described, with the etiopathogenesis implicating various mechanical, infective, and biochemical factors. METHODS:We studied 809 patients using 1.5-T magnetic resonance imaging to determine the prevalence, patterns, distribution, and type of lumbar MCs. Genetic association analysis of 71 single nucleotide polymorphisms (SNPs) of 41 candidate genes was performed based on the presence or absence of MCs. SNPs were genotyped using the Sequenome platform, and an association test was performed using PLINK software. RESULTS:The mean age of the study population (n=809) was 36.7±10.8 years. Based on the presence of MCs, the cohort was divided into 702 controls and 107 cases (prevalence, 13%). MCs were more commonly present in the lower (149/251, 59.4%) than in the upper (102/251, 40.6%) endplates. L4-5 endplates were the most commonly affected levels (30.7%). Type 2 MCs were the most commonly observed pattern (n=206, 82%). The rs2228570 SNP of VDR (p=0.02) and rs17099008 SNP of MMP20 (p=0.03) were significantly associated with MCs. CONCLUSIONS:Genetic polymorphisms of SNPs of VDR and MMP20 were significantly associated with MCs. Understanding the etiopathogenetic mechanisms of MCs is important for planning preventive and therapeutic strategies.

SUBMITTER: Kanna RM

PROVIDER: S-EPMC5573854 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Prevalence, Patterns, and Genetic Association Analysis of Modic Vertebral Endplate Changes.

Kanna Rishi Mugesh RM Shanmuganathan Rajasekaran R Rajagopalan Veera Ranjani VR Natesan Senthil S Muthuraja Raveendran R Cheung Kenneth Man Chee KMC Chan Danny D Kao Patrick Yu Ping PYP Yee Anita A Shetty Ajoy Prasad AP

Asian spine journal 20170807 4

<h4>Study design</h4>A prospective genetic association study.<h4>Purpose</h4>The etiology of Modic changes (MCs) is unclear. Recently, the role of genetic factors in the etiology of MCs has been evaluated. However, studies with a larger patient subset are lacking, and candidate genes involved in other disc degeneration phenotypes have not been evaluated. We studied the prevalence of MCs and genetic association of 41 candidate genes in a large Indian cohort.<h4>Overview of literature</h4>MCs are ...[more]

PMID: 28874978

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Project description:BackgroundVertebral endplate signal changes (VESC) are more common among patients with low back pain (LBP) and/or sciatica than in people who are not seeking care for back pain. The distribution and characteristics of VESC have been described in people from clinical and non-clinical populations. However, while the clinical course of VESC has been studied in patients, the natural course in the general population has not been reported. The objectives of this prospective observational study were to describe: 1) the distribution and characteristics of VESC in the lumbar spine, 2) its association with disc degeneration, and 3) its natural course from 40 to 44 years of age.MethodsThree-hundred-and-forty-four individuals (161 men and 183 women) sampled from the Danish general population had MRI at the age of 40 and again at the age of 44. The following MRI findings were evaluated using standardised evaluation protocols: type, location, and size of VESC, disc signal, and disc height. Characteristics and distribution of VESC were analysed by frequency tables. The association between VESC and disc degeneration was analysed by logistic regression analysis. The change in type and size of VESC was analysed by cross-tabulations of variables obtained at age 40 and 44 and tested using McNemar's test of symmetry.ResultsTwo-thirds (67%) of VESC found in this study were located in the lower part of the spine (L4-S1). VESC located at disc levels L1-L3 were generally small and located only in the anterior part of the vertebra, whereas those located at disc levels L4-S1 were more likely to extend further into the vertebra and along the endplate. Moreover, the more the VESC extended into the vertebra, the more likely it was that the adjacent disc was degenerated. The prevalence of endplate levels with VESC increased significantly from 6% to 9% from age 40 to 44. Again, VESC that was only observed in the endplate was more likely to come and go over the four-year period compared with those which extended further into the vertebra, where it generally persisted.ConclusionThe prevalence of VESC increased significantly over the four-year period. Furthermore, the results from this study indicate that the distribution of VESC, its association with disc degeneration and its natural course, is dependent on the size of the signal changes.

Project description:BackgroundVertebral endplate signal intensity changes visualized by magnetic resonance imaging termed Modic changes (MC) are highly prevalent in low back pain patients. Interconvertibility between the three MC subtypes (MC1, MC2, MC3) suggests different pathological stages. Histologically, granulation tissue, fibrosis, and bone marrow edema are signs of inflammation in MC1 and MC2. However, different inflammatory infiltrates and amount of fatty marrow suggest distinct inflammatory processes in MC2.AimsThe aims of this study were to investigate (i) the degree of bony (BEP) and cartilage endplate (CEP) degeneration in MC2, (ii) to identify inflammatory MC2 pathomechanisms, and (iii) to show that these marrow changes correlate with severity of endplate degeneration.MethodsPairs of axial biopsies (n = 58) spanning the entire vertebral body including both CEPs were collected from human cadaveric vertebrae with MC2. From one biopsy, the bone marrow directly adjacent to the CEP was analyzed with mass spectrometry. Differentially expressed proteins (DEPs) between MC2 and control were identified and bioinformatic enrichment analysis was performed. The other biopsy was processed for paraffin histology and BEP/CEP degenerations were scored. Endplate scores were correlated with DEPs.ResultsEndplates from MC2 were significantly more degenerated. Proteomic analysis revealed an activated complement system, increased expression of extracellular matrix proteins, angiogenic, and neurogenic factors in MC2 marrow. Endplate scores correlated with upregulated complement and neurogenic proteins.DiscussionThe inflammatory pathomechanisms in MC2 comprises activation of the complement system. Concurrent inflammation, fibrosis, angiogenesis, and neurogenesis indicate that MC2 is a chronic inflammation. Correlation of endplate damage with complement and neurogenic proteins suggest that complement system activation and neoinnervation may be linked to endplate damage. The endplate-near marrow is the pathomechanistic site, because MC2 occur at locations with more endplate degeneration.ConclusionMC2 are fibroinflammatory changes with complement system involvement which occur adjacent to damaged endplates.

Project description:BackgroundAlthough deformation and fracture of the vertebral endplate have been implicated in spinal conditions such as vertebral fracture and disc degeneration, few biomechanical studies of this structure are available. The goal of this study was to quantify the mechanical behavior of the vertebral endplate.MethodsEight-five rectangular specimens were dissected from the superior and/or inferior central endplates of human lumbar spine segments L1 to L4. Micro-computed tomography (μCT) imaging, four-point-bend testing, and ashing were performed to quantify the apparent elastic modulus and yield stress (modulus and yield stress, respectively, of the porous vertebral endplate), tissue yield stress (yield stress of the tissue of the vertebral endplate, excluding pores), ultimate strain, fracture strain, bone volume fraction (BV/TV), bone mineral density (BMD), and various measures of tissue density and composition (tissue mineral density, ash fraction, and ash density). Regression was used to assess the dependence of mechanical properties on density and composition.ResultsWide variations in elastic and failure properties, and in density and tissue composition, were observed. BMD and BV/TV were good predictors of many of the apparent-level mechanical properties, including modulus, yield stress, and in the case of the inferior vertebral endplate, failure strains. Similar values of the mechanical properties were noted between superior and inferior vertebral endplates. In contrast to the dependence of apparent stiffness and strength on BMD and BV/TV, none of the mechanical properties depended on any of the tissue-level density measurements.ConclusionThe dependence of many of the mechanical properties of the vertebral endplate on BV/TV and BMD suggests possibilities for noninvasive assessment of how this region of the spine behaves during habitual and injurious loading. Further study of the nonmineral components of the endplate tissue is required to understand how the composition of this tissue may influence the overall mechanical behavior of the vertebral endplate.

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.

Dataset Information

Prevalence, Patterns, and Genetic Association Analysis of Modic Vertebral Endplate Changes.

Publications

Prevalence, Patterns, and Genetic Association Analysis of Modic Vertebral Endplate Changes.

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