Chronic Recurrent Multifocal Osteomyelitis (CRMO): Presentation, Pathogenesis, and Treatment

Curr Osteoporos Rep. 2017 Dec;15(6):542-554. doi: 10.1007/s11914-017-0405-9.

Abstract

Purpose of review: Chronic non-bacterial osteomyelitis (CNO) with its most severe form chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory bone disorder. We summarize the clinical presentation, diagnostic approaches, most recent advances in understanding the pathophysiology, and available treatment options and outcomes in CNO/CRMO.

Recent findings: Though the exact molecular pathophysiology of CNO/CRMO remains somewhat elusive, it appears likely that variable defects in the TLR4/MAPK/inflammasome signaling cascade result in an imbalance between pro- and anti-inflammatory cytokine expressions in monocytes from CNO/CRMO patients. In this context, we present previously unpublished data on cytokine and chemokine expression in monocytes and tissues. CNO/CRMO is an autoinflammatory bone disorder resulting from imbalanced cytokine expression from innate immune cells. Though the exact molecular pathophysiology remains unclear, variable molecular defects appear to result in inflammasome activation and pro-inflammatory cytokine expression in monocytes from CNO/CRMO patients. Recent advances suggest signaling pathways and single molecules as biomarkers for CNO/CRMO as well as future treatment targets.

Keywords: Biomarkers; Bone; CNO; CRMO; Chronic non-bacterial osteomyelitis; Chronic recurrent multifocal osteomyelitis; Cytokine; Inflammation; Treatment.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Bone Density Conservation Agents / therapeutic use
  • Chemokine CCL2 / immunology
  • Chemokine CCL4 / immunology
  • Chemokine CCL5 / immunology
  • Chemokines / immunology
  • Cytokines / immunology*
  • Diphosphonates / therapeutic use
  • Disease Models, Animal
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Inflammasomes / immunology*
  • Interleukin-12 / immunology
  • Interleukin-6 / immunology
  • Methotrexate / therapeutic use
  • Mice
  • Mitogen-Activated Protein Kinases / immunology*
  • Monocytes / immunology*
  • Osteomyelitis / diagnosis
  • Osteomyelitis / immunology*
  • Osteomyelitis / therapy
  • Receptors, Interleukin-2 / immunology
  • Signal Transduction
  • Sulfasalazine / therapeutic use
  • Toll-Like Receptor 4 / immunology*
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors

Substances

  • Adrenal Cortex Hormones
  • Anti-Inflammatory Agents, Non-Steroidal
  • Bone Density Conservation Agents
  • Chemokine CCL2
  • Chemokine CCL4
  • Chemokine CCL5
  • Chemokines
  • Cytokines
  • Diphosphonates
  • Immunosuppressive Agents
  • Inflammasomes
  • Interleukin-6
  • Receptors, Interleukin-2
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor-alpha
  • Interleukin-12
  • Sulfasalazine
  • Mitogen-Activated Protein Kinases
  • Methotrexate

Supplementary concepts

  • Chronic recurrent multifocal osteomyelitis