Endplate changes following discectomy: natural history and associations between imaging and clinical data

Weiner, Bradley K.; Vilendecic, Milorad; Ledić, Darko; Eustacchio, Sandro; Varga, Péter; Gorenšek, Matevž; Fernandez-Moure, Joseph; Hipp, John A.

doi:10.1007/s00586-014-3734-8

Cited by 37 publications

(29 citation statements)

References 31 publications

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“…MC are associated with endplate damage, which causes a hydraulic coupling of the disc and the bone marrow 12,13,15,16 . Here, we also show that there is a pro-inflammatory and fibrogenic coupling of the disc and the marrow in MC, which is likely the consequence of biologic communication between the two compartments.…”

Section: Discussionmentioning

confidence: 99%

“…In the bone marrow, many different cells express TrkB and TrkC 35 which can be due to both a change in cellularity and in transcription activity. Given the association of MC with endplate damage 3,12,13 , the strong expression of TrkA, TrkB, and TrkC by osteoblasts and stromal cells in the callus during fracture healing is noteworthy 36–39 . They generally have an osteogenic and angiogenic effect, but also pro-osteoclastic effects for TrkB have been reported 36,37,39,40 .…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2017

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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 upregulation 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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

et al. 2017

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“…MC associate with endplate damage that can increase the efflux of cytokines into the bone marrow. This is because endplate damage disrupts the tightly controlled metabolite transport between the disc and the bone marrow and leads to a hydraulic coupling . In the bone marrow, pro‐inflammatory cytokines promote fibrotic changes and skew the hematopoietic elements toward the myeloid lineage, which results in an over‐production of granulocytes, monocytes/macrophages, erythrocytes, and megakaryocytes .…”

Section: Discussionmentioning

confidence: 99%

“…How P. acnes seeds into the disc and could cause MC1 is unknown, but it is assumed that P. acnes enters the blood stream during innocuous events such as tooth brushing, or through haematogenous spread from a distant septic location . When disc immunoisolation is violated by disc herniation or endplate damage (both of which associate with MC1), it is suspected that blood borne P. acnes may invade the disc and proliferate . Yet, the potential for P. acnes to survive and proliferate within the disc, and trigger reactive bone marrow changes in adjacent vertebra has not been demonstrated.…”

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confidence: 99%

Propionibacterium acnes infected intervertebral discs cause vertebral bone marrow lesions consistent with Modic changes

Dudli

Liebenberg

Magnitsky

et al. 2016

Journal Orthopaedic Research

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Modic type I change (MC1) are vertebral bone marrow lesions adjacent to degenerated discs that are specific for discogenic low back pain. The etiopathogenesis is unknown, but occult discitis, in particular with Propionibacteria acnes (P. acnes), has been suggested as a possible etiology. If true, antibiotic therapy should be considered for patients with MC1. However, this hypothesis is controversial. While some studies report up to 40% infection rate in herniated discs, others fail to detect infected discs and attribute reports of positive cultures to contamination during sampling procedure. Irrespective of the clinical controversy, whether it is biologically plausible for P. acnes to cause MC1 has never been investigated. Therefore, the objective of this study was to test if P. acnes can proliferate within discs and cause reactive changes in the adjacent bone marrow. P. acnes was aseptically isolated from a symptomatic human L4/5 disc with MC1 and injected into rat tail discs. We demonstrate proliferation of P. acnes and up-regulation of IL-1 and IL-6 within three days of inoculation. At day-7, disc degeneration was apparent along with fibrotic endplate erosion. TNF-a immunoreactivity was enhanced within the effected endplates along with cellular infiltrates. The bone marrow appeared normal. At day-14, endplates and trabecular bone close to the disc were almost completely resorbed and fibrotic tissue extended into the bone marrow. T-cells and TNF-a immunoreactivity were identified at the disc/marrow junction. On MRI, bone marrow showed MC1-like changes. In conclusion, P. acnes proliferate within the disc, induce degeneration, and cause MC1-like changes in the adjacent bone marrow. ß

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“…Endplate defects co-locate with MC and are predictive for future MC [3, 38]. Yet, because endplate damage promotes DD [38–41], evidences linking endplate damage to MC independently of DD are unavailable. Similar to endplate damage, disc herniation predisposes to DD and MC [18, 19].…”

Section: Etiopathogenesis Of Modic Changesmentioning

confidence: 99%

Pathobiology of Modic changes

et al. 2016

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Purpose Low back pain (LBP) is the most disabling condition worldwide. Although LBP relates to different spinal pathologies, vertebral bone marrow lesions visualized as Modic changes on MRI have a high specificity for discogenic LBP. This review summarizes the pathobiology of Modic changes and suggests a disease model. Methods Non-systematic literature review. Results Chemical and mechanical stimulation of nociceptors adjacent to damaged endplates are likely a source of pain. Modic changes are adjacent to a degenerated intervertebral disc and have three generally interconvertible types suggesting that the different Modic change types represent different stages of the same pathological process, which is characterized by inflammation, high bone turnover, and fibrosis. A disease model is suggested where disc/ endplate damage and the persistence of an inflammatory stimulus (i.e., occult discitis or autoimmune response against disc material) create predisposing conditions. The risk to develop Modic changes likely depends on the inflammatory potential of the disc and the capacity of the bone marrow to respond to it. Bone marrow lesions in osteoarthritic knee joints share many characteristics with Modic changes adjacent to degenerated discs and suggest that damage-associated molecular patterns and marrow fat metabolism are important pathogenetic factors. There is no consensus on the ideal therapy. Non-surgical treatment approaches including intradiscal steroid injections, anti-TNF-α antibody, antibiotics, and bisphosphonates have some demonstrated efficacy in mostly non-replicated clinical studies in reducing Modic changes in the short term, but with unknown long-term benefits. New diagnostic tools and animal models are required to improve painful Modic change identification and classification, and to clarify the pathogenesis. Conclusion Modic changes are likely to be more than just a coincidental imaging finding in LBP patients and rather represent an underlying pathology that should be a target for therapy.

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Endplate changes following discectomy: natural history and associations between imaging and clinical data

Cited by 37 publications

References 31 publications

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

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

Propionibacterium acnes infected intervertebral discs cause vertebral bone marrow lesions consistent with Modic changes

Pathobiology of Modic changes

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