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Z Orthop Unfall 2019; 157(02): 154-163
DOI: 10.1055/a-0658-5922
Review/Übersicht
Georg Thieme Verlag KG Stuttgart · New York

Osteozyten

Dirigenten des Knochenstoffwechsels Article in several languages: English | deutsch
Markus Rupp
1   Klinik und Poliklinik für Unfall-, Hand- und Wiederherstellungschirurgie, Operative Notaufnahme, Universitätsklinikum Gießen und Marburg, Standort Gießen
2   Labor für Experimentelle Unfallchirurgie, Justus-Liebig-Universität Gießen
,
Felix Merboth
2   Labor für Experimentelle Unfallchirurgie, Justus-Liebig-Universität Gießen
,
Diaa Eldin Daghma
2   Labor für Experimentelle Unfallchirurgie, Justus-Liebig-Universität Gießen
,
Christoph Biehl
1   Klinik und Poliklinik für Unfall-, Hand- und Wiederherstellungschirurgie, Operative Notaufnahme, Universitätsklinikum Gießen und Marburg, Standort Gießen
2   Labor für Experimentelle Unfallchirurgie, Justus-Liebig-Universität Gießen
,
Thaqif El Khassawna
2   Labor für Experimentelle Unfallchirurgie, Justus-Liebig-Universität Gießen
,
Christian Heiß
1   Klinik und Poliklinik für Unfall-, Hand- und Wiederherstellungschirurgie, Operative Notaufnahme, Universitätsklinikum Gießen und Marburg, Standort Gießen
2   Labor für Experimentelle Unfallchirurgie, Justus-Liebig-Universität Gießen
› Author Affiliations
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Publication History

Publication Date:
26 October 2018 (online)

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Zusammenfassung

Lange Zeit galten Osteozyten als passive Zuschauer der Knochenhomöostase, dem Gleichgewicht zwischen Knochenaufbau durch Osteoblasten und Knochenabbau durch Osteoklasten. Das Dogma der ruhenden, im Knochen eingemauerten funktionslosen Zellen hat sich seit der Jahrtausendwende grundlegend gewandelt. Osteozyten stehen vielmehr im Mittelpunkt des Knochenstoffwechsels und können somit als dessen Dirigent angesehen werden. Auf Grundlage einer Literaturrecherche in PubMed und Google Scholar mit den einzeln oder in Kombination verwendeten Suchbegriffen „osteocyte“, „fracture healing“, „bone healing“, „bone remodeling“, „bone metabolism“, „sclerostin“, „RANKL/OPG“, „Wnt-signaling pathway“, „FGF-23“ wurde die Rolle der Osteozyten im Knochenstoffwechsel anhand von präklinischen und klinischen Studien sowie Übersichtsarbeiten erarbeitet. Einzelne Fallberichte wurden hierfür nicht verwandt. Im Rahmen der Literaturrecherche wurden nur Publikationen in englischer oder deutscher Sprache berücksichtigt. Die sich aus Osteoblasten entwickelnden Osteozyten sind funktionell die zentrale Schaltstelle im Knochenmetabolismus. Morphologisch bildet ein Netzwerk von Osteozyten, die 90 – 95% der Zellen im Knochen ausmachen und im Gegensatz zu Osteoblasten und Osteoklasten das Alter des Gesamtorganismus erreichen können, durch mit Nexus miteinander verbundenen Dendriten innerhalb des Knochens die optimale Grundlage für deren funktionelle Aufgaben. Neben der Aufgabe als Mechanosensor im Knochen wird die Osteoblastenfunktion über Sclerostin, die Osteoklastenfunktion über den RANK/RANKL/OPG-Signalweg gesteuert. Ferner wird die Mineralisierung des Knochens über die lokale Phosphatkonzentration, der systemische Phosphathaushalt in Interaktion mit der Niere über FGF23 hormonell gesteuert. Das Verständnis der Rolle der Osteozyten verspricht eine weitere Verbesserung möglicher Therapiealternativen. Hinsichtlich des Knochenstoffwechsels sind bereits Sclerostinantikörper und Denosumab, ein monoklonaler Antikörper, der als OPG-Agonist fungiert, eingeführt worden. Neben den in der Osteoporosetherapie bereits etablierten Therapieansätzen sind Antikörper gegen FGF23 oder dessen Rezeptoren in der präklinischen und klinischen Erprobung. Auch Bortezomib, ein Proteasomeninhibitor, der die Lebensfähigkeit von Osteozyten verbessert, ist zur Therapie des multiplen Myeloms im klinischen Einsatz. Das zunehmende Verständnis der osteozytären Funktion lässt darüber hinaus weitere Therapiemöglichkeiten erwarten – in Orthopädie und Unfallchirurgie sind dies insbesondere die ossäre Integration von Implantaten und die medikamentöse Beeinflussung der (gestörten) Frakturheilung.

Schlüsselwörter

Osteozyten - Sclerostin - Knochenstoffwechsel - RANKL/OPG - Osteoporose
 

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