Pathogenese des Morbus Paget

Zusammenfassung

Der Morbus Paget des Knochens (Osteoitis deformans) ist gekennzeichnet durch einen fokal gesteigerten Knochenumbau mit initial vermehrter Resorption und reaktiv gesteigerter Neubildung von unzureichend strukturiertem Knochen. Die Erkrankung betrifft eine oder mehrere Stellen des gesamten Skeletts. Hinsichtlich der Pathogenese der Erkrankung kommt nach heutiger Kenntnis insbesondere genetischen Faktoren ein zentrale Rolle zu. Die bisher bei M. Paget und verwandten syndromalen Erkrankungen identifizierten Mutationen betreffen dabei unterschiedliche Gene (u. a. SQSTM-1/p62, VCP/p97, RANK, OPG),

die jedoch ganz überwiegend mit dem RANKRezeptor assoziierten NFκB-Signalweg in Verbindung gebracht werden können. Geografische Unterschiede und eine zeitliche Dynamik der Inzidenzraten deuten darüber hinaus auf einen relevanten Einfluss von Umwelfaktoren hin. Neben mechanischen und chemischen Noxen wird in diesem Kontext insbesondere die Bedeutung einer chronischen Infektion mit Paramyxoviren kontrovers diskutiert. Zusammenfassend ist nach heutigem Kenntnisstand davon auszugehen, dass bestimmte genetische Veränderungen mit Bedeutung für das Remodeling des Knochens die Suszeptibilität für die Erkrankung erhöhen, während äußere Einflussfaktoren als Trigger für die klinische Manifestation anzusehen sind.

Summary

Paget’s disease of bone (osteitis deformans) is characterized by a focal increase of bone remodeling, starting with exaggerated resorption and reactively increased formation of insufficiently structured bone. The disease affects one or more sites throughout the whole skeleton. Concerning pathogenesis of the disorder, current concepts favour a critical role of genetic factors. Mutations identified to date in Paget’s disease of bone and related disorders affect different genes (including SQSTM-1/p62, VCP/p97, RANK, OPG) which predominantly are associated with the NFκBPathway downstream the Receptor activator of NFκB (RANK). Geographical inhomogenities and temporal dynamics of incidence rates suggest a significant impact of environmental factors. Besides mechanical burden and noxious chemical substances, the relevance of chronic paramyxoviral infections is discussed controversially in this context. In summary current knowledge suggests that genetic alterations with relevance for bone remodeling increase susceptibility for the disease while environmental factors can be regarded as triggering factors for clinical manifestation.

Schlüsselwörter

Morbus Paget - Osteitis deformans - RANK/ RANKL/OPG

Keywords

Paget’s disease of bone - osteitis deformans - RANK/RANKL/OPG

• Literatur

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