title: Chronic Nonbacterial Osteomyelitis: Pathophysiological Concepts and Current Treatment Strategies.
abstract: Chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory bone disorder, covering a clinical spectrum with asymptomatic inflammation of single bones at the one end, and chronic recurrent multifocal osteomyelitis (CRMO) at the other end. The exact molecular pathophysiology of CNO remains largely unknown. Provided familial clusters and the association with inflammatory disorders of the skin and intestine suggest a genetic predisposition. Recently, profound dysregulation of cytokine responses was demonstrated in CRMO. Failure to produce antiinflammatory cytokines interleukin (IL)-10 and IL-19 contributes to activation of inflammasomes and subsequent IL-1β release. In IL-10-deficient and in CNO-prone chronic multifocal osteomyelitis mice, IL-1β was linked to bone inflammation. Further, alterations to the gut microbiome were suggested in contributing to IL-1β release from innate immune cells in mice, offering an interesting target in the search for molecular mechanisms in CNO. Here, we summarize clinical presentation and treatment options in CNO/CRMO, current pathophysiological concepts, available mouse models, and promising future scientific directions.
authors: From the Pediatric Rheumatology and Immunology, Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden; Department of Pediatrics, University of Würzburg, Würzburg; Children's Hospital, Vivantes Klinikum-Friedrichshain, Berlin, Germany.|S.R. Hofmann, MD, PhD, Pediatric Rheumatology and Immunology, Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden; A. Schnabel, MD, Pediatric Rheumatology and Immunology, Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden; A. Rösen-Wolff, MD, PhD, Pediatric Rheumatology and Immunology, Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden; H. Morbach, MD, PhD, Department of Pediatrics, University of Würzburg; H.J. Girschick, MD, PhD, Children's Hospital, Vivantes Klinikum-Friedrichshain; C.M. Hedrich, MD, PhD, Pediatric Rheumatology and Immunology, Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden.
authors: Sigrun R
authors: SR
authors: Hofmann
authors: From the Pediatric Rheumatology and Immunology, Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden; Department of Pediatrics, University of Würzburg, Würzburg; Children's Hospital, Vivantes Klinikum-Friedrichshain, Berlin, Germany.|S.R. Hofmann, MD, PhD, Pediatric Rheumatology and Immunology, Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden; A. Schnabel, MD, Pediatric Rheumatology and Immunology, Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden; A. Rösen-Wolff, MD, PhD, Pediatric Rheumatology and Immunology, Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden; H. Morbach, MD, PhD, Department of Pediatrics, University of Würzburg; H.J. Girschick, MD, PhD, Children's Hospital, Vivantes Klinikum-Friedrichshain; C.M. Hedrich, MD, PhD, Pediatric Rheumatology and Immunology, Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden.
authors: Anja
authors: A
authors: Schnabel
authors: From the Pediatric Rheumatology and Immunology, Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden; Department of Pediatrics, University of Würzburg, Würzburg; Children's Hospital, Vivantes Klinikum-Friedrichshain, Berlin, Germany.|S.R. Hofmann, MD, PhD, Pediatric Rheumatology and Immunology, Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden; A. Schnabel, MD, Pediatric Rheumatology and Immunology, Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden; A. Rösen-Wolff, MD, PhD, Pediatric Rheumatology and Immunology, Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden; H. Morbach, MD, PhD, Department of Pediatrics, University of Würzburg; H.J. Girschick, MD, PhD, Children's Hospital, Vivantes Klinikum-Friedrichshain; C.M. Hedrich, MD, PhD, Pediatric Rheumatology and Immunology, Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden.
authors: Angela
authors: A
authors: Rösen-Wolff
authors: From the Pediatric Rheumatology and Immunology, Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden; Department of Pediatrics, University of Würzburg, Würzburg; Children's Hospital, Vivantes Klinikum-Friedrichshain, Berlin, Germany.|S.R. Hofmann, MD, PhD, Pediatric Rheumatology and Immunology, Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden; A. Schnabel, MD, Pediatric Rheumatology and Immunology, Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden; A. Rösen-Wolff, MD, PhD, Pediatric Rheumatology and Immunology, Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden; H. Morbach, MD, PhD, Department of Pediatrics, University of Würzburg; H.J. Girschick, MD, PhD, Children's Hospital, Vivantes Klinikum-Friedrichshain; C.M. Hedrich, MD, PhD, Pediatric Rheumatology and Immunology, Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden.
authors: Henner
authors: H
authors: Morbach
authors: From the Pediatric Rheumatology and Immunology, Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden; Department of Pediatrics, University of Würzburg, Würzburg; Children's Hospital, Vivantes Klinikum-Friedrichshain, Berlin, Germany.|S.R. Hofmann, MD, PhD, Pediatric Rheumatology and Immunology, Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden; A. Schnabel, MD, Pediatric Rheumatology and Immunology, Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden; A. Rösen-Wolff, MD, PhD, Pediatric Rheumatology and Immunology, Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden; H. Morbach, MD, PhD, Department of Pediatrics, University of Würzburg; H.J. Girschick, MD, PhD, Children's Hospital, Vivantes Klinikum-Friedrichshain; C.M. Hedrich, MD, PhD, Pediatric Rheumatology and Immunology, Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden.
authors: Hermann J
authors: HJ
authors: Girschick
authors: From the Pediatric Rheumatology and Immunology, Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden; Department of Pediatrics, University of Würzburg, Würzburg; Children's Hospital, Vivantes Klinikum-Friedrichshain, Berlin, Germany. Christian.hedrich@uniklinikum-dresden.de.|S.R. Hofmann, MD, PhD, Pediatric Rheumatology and Immunology, Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden; A. Schnabel, MD, Pediatric Rheumatology and Immunology, Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden; A. Rösen-Wolff, MD, PhD, Pediatric Rheumatology and Immunology, Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden; H. Morbach, MD, PhD, Department of Pediatrics, University of Würzburg; H.J. Girschick, MD, PhD, Children's Hospital, Vivantes Klinikum-Friedrichshain; C.M. Hedrich, MD, PhD, Pediatric Rheumatology and Immunology, Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden. Christian.hedrich@uniklinikum-dresden.de.
authors: Christian M
authors: CM
authors: Hedrich
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D051379:Mice; D010019:Osteomyelitis / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism
chemical_list: D016207:Cytokines; D053583:Interleukin-1beta; D016753:Interleukin-10
keywords: CHRONIC NONBACTERIAL OSTEOMYELITIS; CHRONIC RECURRENT MULTIFOCAL OSTEOMYELITIS; CYTOKINE; INFLAMMATION; TREATMENT