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Pathobiology of Modic Changes

Overview
Journal Eur Spine J
Specialty Orthopedics
Date 2016 Feb 26
PMID 26914098
Citations 174
Authors
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Abstract

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.

Citing Articles

The Association of Modic Changes and Disc-Endplate-Bone Marrow Complex Classification in Patients With Cervical Degenerative Disc Disease.

Jagadish T, Murugan C, Ramachandran K, Thippeswamy P, Anand K S S, Kanna R Global Spine J. 2025; :21925682251320893.

PMID: 39953676 PMC: 11830159. DOI: 10.1177/21925682251320893.


Modic changes: From potential molecular mechanisms to future research directions (Review).

Zhu W, Yang Z, Zhou S, Zhang J, Xu Z, Xiong W Mol Med Rep. 2025; 31(4).

PMID: 39918002 PMC: 11836598. DOI: 10.3892/mmr.2025.13455.


GATA6 Facilitates Progression of Intervertebral Disc Degeneration by Regulating Ferroptosis via Targeting TLR2/AKR1C3.

Wang X, Wang B, Shi J, Chen Z, Wu Y, Liu J Int J Biol Sci. 2025; 21(3):1174-1186.

PMID: 39897029 PMC: 11781159. DOI: 10.7150/ijbs.102776.


Gut Microbiome and Metabolome Changes in Chronic Low Back Pain Patients With Vertebral Bone Marrow Lesions.

Li W, Tu J, Zheng J, Das A, Yan Q, Jiang X JOR Spine. 2025; 8(1):e70042.

PMID: 39877797 PMC: 11772216. DOI: 10.1002/jsp2.70042.


Intervertebral Disc Degeneration and Regeneration: New Molecular Mechanisms and Therapeutics: Obstacles and Potential Breakthrough Technologies.

Taylor W, Erwin W Cells. 2025; 13(24.

PMID: 39768194 PMC: 11674193. DOI: 10.3390/cells13242103.


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