Endplate Defect Is Heritable, Associated With Low Back Pain and Triggers Intervertebral Disc Degeneration

Munir, Sabrina; Freidin, Maxim B.; Rade, Marinko; Määttä, Juhani; Livshits, Gregory; Williams, Frances

doi:10.1097/brs.0000000000002721

Cited by 62 publications

(54 citation statements)

References 20 publications

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“…Kentaro et al demonstrated an association between endplate defect and FJ degeneration in rheumatoid arthritis [24]. Our data add knowledge for the relationship between endplate defect and FJ-originated lower back pain.…”

Section: Discussionsupporting

confidence: 74%

Relationship between Endplate Defects, Modic Change, Disc Degeneration, and Facet Joint Degeneration in Patients with Low Back Pain

Yuan

Ding

et al. 2019

BioMed Research International

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Purpose. The endplate defects (EDs), Modic changes (MCs), disc degeneration (DD), facet orientation (FO), and facet tropism (FT) were demonstrated to be related to the low back pain (LBP). The aim of this study was to investigate possible correlations between them. Methods. 75 patients were reviewed to evaluate the degenerative change in vertebral bodies (EDs and MCs), intervertebral discs (DD), and facet joint degeneration (FO and FT). All patients were categorized into four groups based on the grade of EDs. Clinical outcomes were evaluated with the visual analog scale (VAS) and Oswestry disability index (ODI) before and after surgery. Results. There was no difference between the four groups in baseline characteristics except for gender and weight. FT is positively correlated with FO. The same rule exists between EDs, the size of MCs II, FO (left) and FO (right), and VAS and ODI. The grade of EDs is positively correlated with the grade of DD. L4-L5 can bear more load than other levels; thus, the grade of EDs is higher than that of other lumbar levels. The preoperative LBP was relieved in all groups in varying degrees. The change of pain and dysfunction is inversely proportional to the grade of EDs in the general trend. Conclusion. The relationship between weight, gender, and disc degeneration provided a mechanism by which increasing weight can predispose to DD. Different grades of EDs had different effects on patients with LBP. There was a significant correlation between EDs, MCs II, DD, FT, and FO.

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Section: Discussionsupporting

confidence: 74%

Relationship between Endplate Defects, Modic Change, Disc Degeneration, and Facet Joint Degeneration in Patients with Low Back Pain

Yuan

Ding

et al. 2019

BioMed Research International

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“…Animal studies have largely overlooked the contribution of genetic background on disc aging phenotypes (Gorth, Shapiro, & Risbud, 2019; Novais et al, 2019; Tessier, Tran, Ottone, & Novais, 2019). This is important since previous studies with twins’ cohorts have reported a strong correlation between familiar aggregation and disc degeneration (Battié, 2009; Munir et al, 2018). Along with the higher grades of disc degeneration seen in SM/J at 6M, they differed the most in terms of gene expression compared to BL6 and LG/J.…”

Section: Discussionmentioning

confidence: 96%

Comparison of inbred mouse strains shows diverse phenotypic outcomes of intervertebral disc aging

et al. 2020

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Intervertebral disc degeneration presents a wide spectrum of clinically degenerative disc phenotypes; however, the contribution of genetic background to the degenerative outcomes has not been established. We characterized the spinal phenotype of 3 mouse strains with varying cartilage‐regenerative potential at 6 and 23 months: C57BL/6, LG/J and SM/J. All strains showed different aging phenotypes. Importantly, LG/J mice showed an increased prevalence of dystrophic disc calcification in caudal discs with aging. Quantitative‐histological analyses of LG/J and SM/J caudal discs evidenced accelerated degeneration compared to BL6, with cellular disorganization and cell loss together with fibrosis of the NP, respectively. Along with the higher grades of disc degeneration, SM/J, at 6M, also differed the most in terms of NP gene expression compared to other strains. Moreover, although we found common DEGs between BL6 and LG/J aging, most of them were divergent between the strains. Noteworthy, the common DEGs altered in both LG/J and BL6 aging were associated with inflammatory processes, response to stress, cell differentiation, cell metabolism and cell division. Results suggested that disc calcification in LG/J resulted from a dystrophic calcification process likely aggravated by cell death, matrix remodelling, changes in calcium/phosphate homeostasis and cell transformation. Lastly, we report 7 distinct phenotypes of human disc degeneration based on transcriptomic profiles, that presented similar pathways and DEGs found in aging mouse strains. Together, our results suggest that disc aging and degeneration depends on the genetic background and involves changes in various molecular pathways, which might help to explain the diverse phenotypes seen during disc disease.

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“…A recently published longitudinal twin-cohort study of 438 individuals reported that endplate defects, lumbar disc degeneration and MCs all are independent risk factors for episodes of severe and disabling LBP. Longitudinal analysis showed that MCs followed disc degeneration [8]. Endplate defect has a significant heritability of 55% [8] and clinically, MC are often associated with LBP at all times of the day and nightly pain and morning pain/stiffness are common complaints [9,10].…”

Section: Definition Pathoanatomy and Symptomatologymentioning

confidence: 99%

New Insights Link Low-Virulent Disc Infections to the Etiology of Severe Disc Degeneration and Modic Changes

Manniche

O’Neill

2019

Future Sci. OA

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Within the last 5 years, international research collaborations including those of several research groups skilled in microbiology, immunology and pathophysiology, have identified a low-virulent intradiscal infection with the ability to provoke gradual and progressive disc degeneration, end-plate disruption, Modic changes and persistent clinical lower-back pain. Certain strains of the Propionibacterium acne bacterium seem able to invade, colonize and develop a protective biofilm inside the disc. The interaction of P. acne , disc tissues and mononuclear cells of the bone marrow are shown to trigger a relevant immunological response and an ensuing destructive inflammation of the disc and adjacent vertebrae. This process presents on MRI as Modic changes. Recent proof-of-concept data provide compelling evidence for this bacterial disc infection hypothesis.

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Endplate Defect Is Heritable, Associated With Low Back Pain and Triggers Intervertebral Disc Degeneration

Abstract: 2.

Cited by 62 publications

References 20 publications

Relationship between Endplate Defects, Modic Change, Disc Degeneration, and Facet Joint Degeneration in Patients with Low Back Pain

Relationship between Endplate Defects, Modic Change, Disc Degeneration, and Facet Joint Degeneration in Patients with Low Back Pain

Comparison of inbred mouse strains shows diverse phenotypic outcomes of intervertebral disc aging

New Insights Link Low-Virulent Disc Infections to the Etiology of Severe Disc Degeneration and Modic Changes

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