Seltene autoinflammatorische Knochenerkrankungen

Zusammenfassung

Autoinflammatorische Knochenerkrankungen sind gekennzeichnet durch eine entzündliche zelluläre Infiltration des Knochens, Osteoklastenaktivierung, Osteolyse und gesteigertes Knochenremodelling infolge einer aberranten Aktivierung des angeborenen Immunsystems. Der Knochenabbau infolge chronischer Osteomyelitis zeigt die enge Verknüpfung zwischen Immun- und Skelett system. Die Identifizierung von definierten molekularen Defekten bei verschiedenen Erkrankungen konnte bereits zu einem besseren Verständnis der komplexen Interaktion zwischen Knochen und Immunsystem beitragen. Die sporadisch auftretende chronische nichtinfektiöse Osteomyelitis stellt die am häufigsten vorkommende Erkrankung dar. Zu den seltenen monogenetischen autoinflammatorischen Erkrankungen zählen: IL-1- Rezeptorantagonist-Mangel, Majeed-Syndrom und Cherubism. Weitere der sogenannten Inflammasom- und auch Stoffwechsel-erkrankungen aufgrund von Enzymdefekten (Hypophosphatasie, hypertrophe Osteoarthropathie) beeinhalten eine signifikante inflammatorisch bedingte Knochenpathologie. Im folgenden Artikel werden diese seltenen Erkrankungen von den molekularen Pathologien bis hin zur klinischen Präsentation diskutiert. Ein besseres Verständnis der pathophysiologischen Grundlagen von autoinflammatorischen Knochenerkrankungen könnte zur Entwicklung weiterer gezielter Therapieansätze beitragen, wovon letztlich auch Patienten mit häufiger vorkommenden Knochenerkrankungen profitieren.

Summary

Autoinflammatory bone disorders are characterized by infiltration of the bone marrow by cells of the (innate?) immune system (chronic osteomyelitis), increased osteoclast activity, osteolysis and accelerated bone remodeling and are caused by an aberrant activation of the innate immune system. Bone resorption due to chronic inflammation highlights the interaction between the immune and the skeletal system. The most common disease subtype is sporadic chronic non-bacterial osteomyelitis (CNO). Several monogenetic and often multisystemic diseases with non-infectious, autoinflammatory bone involvement have been described. In this article we discuss the following osteopathies from their pathophysiology to the clinical phenotype and treatment options: murine CNO, Majeed syndrome, cherubism, hypophosphatasia and primary hypertrophic osteoarthropathy. Some monogenic inflammasomopathies may also present with bone involvement. The analysis of autoinflammatory bone diseases and of CNO mouse models as well as the identification of distinct inflammatory pathways offer still informative insights in the complex interplay between the immune and the skeletal system. Targeting of molecular defects in rare monogenic autoinflammatory disorders may also help to develop new specific treatment strategies for more common diseases with bone inflammation and inflammation-induced bone resorption.

Schlüsselwörter

Seltene Erkrankungen - Inflammation - Genetik - chronische nichtinfektiöse Osteomyelitis

Keywords

Rare diseases - inflammation - genetics - chronic non-bacterial osteomyelitis

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