Pathobiology of Modic changes

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.

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

“…While the pathobiology behind MC-associated pain is unknown 4 , it is speculated to result from increased numbers of PGP-9.5 nerve fibers and TNF-α positive cells observed in damaged vertebral endplates adjacent to MC regions 9,10 . Since endplate damage is associated with MC, it is assumed to be a critical prerequisite for MC development 3,11–13 . Endplate damage increases communication between the bone marrow and the disc 14,15 because it allows hydraulic disc/vertebra coupling and increased convective flow induced by cyclic spinal loading 14–16 .…”

Contribution of the Endplates to Disc Degeneration

“…For example, in a cohort of low back pain patients, Kerttula et al noted 96% of MC1 were associated with adjacent endplate damage [106]. Although the precise etiology remains unclear, bone marrow lesions are believed to result from inflammatory constituents that diffuse from the adjacent discs [107, 108], which may be promoted at sites of endplate damage. Endplate damage compromises the immune privilege of the healthy disc, and allows comingling of disc material and the quiescent bone marrow.…”

Leaping the hurdles in developing regenerative treatments for the intervertebral disc from preclinical to clinical

“…Another major concern regarding MRI analysis is that there is a need for validation of regenerative process, since quantitative MRI has specifically been validated for IVD degeneration, but not for regeneration, which does not necessarily follow an identical reverse process. To this end, the recently identified correlation between IVD degeneration, modic changes and back pain indicates that in animal models too these entities need to be explored and properly characterized to fully cover the whole spectrum of spine pathology related to IVD degeneration. Lastly, long‐term animal studies are lacking, but must be performed to demonstrate long‐term safety and efficacy in clinically relevant animal models and detect pathological features that only develop after a long time period, such as tumorgenicity, before treatments are translated to human clinical trials.…”