title: Pathobiology of Modic changes.
abstract: 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.
  
  
  
  Non-systematic literature review.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Orthopaedic Surgery, University of California San Francisco, 513 Parnassus Ave, S-1164, San Francisco, CA, 94143-0514, USA. dudli@panamerica.ch.
authors.forename: Stefan
authors.initials: S
authors.lastname: Dudli
authors.affiliation: Department of Orthopaedic Surgery, University of California San Francisco, 513 Parnassus Ave, S-1164, San Francisco, CA, 94143-0514, USA.
authors.forename: Aaron J
authors.initials: AJ
authors.lastname: Fields
authors.affiliation: Department of Orthopaedics and Traumatology, University of Hong Kong, Hong Kong, China.
authors.forename: Dino
authors.initials: D
authors.lastname: Samartzis
authors.affiliation: Department of Physical and Rehabilitation Medicine, Medical Research Center Oulu, Finnish Institute of Occupational Health, University of Oulu and Oulu University Hospital, Oulu, Finland.
authors.forename: Jaro
authors.initials: J
authors.lastname: Karppinen
authors.affiliation: Department of Orthopaedic Surgery, University of California San Francisco, 513 Parnassus Ave, S-1164, San Francisco, CA, 94143-0514, USA.
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Lotz
mesh_terms: D001853:Bone Marrow / Q000000981:diagnostic imaging / Q000473:pathology*; D006801:Humans; D007403:Intervertebral Disc / Q000000981:diagnostic imaging / Q000473:pathology*; D017116:Low Back Pain / Q000000981:diagnostic imaging / Q000209:etiology* / Q000473:pathology; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008954:Models, Biological
keywords: Bone marrow lesion; Endplate damage; Low back pain; Modic changes; Pathobiology