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Effect of untreated and treated temporomandibular joint arthritis on mandibular volume development in growing rabbits

Einfluss einer Kiefergelenkarthritis und ihrer Therapie auf die Volumenentwicklung des Unterkiefers: eine Studie am wachsenden Kaninchen

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Abstract

Objectives

The goal of this work was to investigate the volume development of the mandible in growing rabbits with bilaterally induced temporomandibular joint (TMJ) arthritis that was either left untreated or treated with the tumor necrosis factor-alpha (TNF-α) antagonist etanercept.

Methods

A total of 18 New Zealand White rabbits aged 8 weeks were randomized to three groups of 6 animals each. Two of these groups were used as arthritis groups by sensitizing the 12 animals to ovalbumin (OA) at 10 weeks, followed by intraarticular OA injections to induce bilateral TMJ arthritis and repeating these injections every 3 weeks to maintain the inflammation. One of the two arthritis groups was treated by weekly subcutaneous etanercept injections, whereas the other group was left untreated. The remaining 6 animals served as controls. Maxillofacial CT scans were obtained at 3-week intervals (from week 10 of the rabbits’ lives to the end of the experiment at 22 weeks) to volumetrically track the development of the mandibles after segmentation.

Results

The mandibles did not grow at a continuous rate, but the rate of development was found to decrease in all groups over the course of the study (weeks 10–22). The most extensive volume increases were noted during weeks 10–13. Severe growth deficiencies, especially of the condylar processes, were observed in the arthritis group not receiving treatment. The arthritis group treated with etanercept showed better rates of growth without, however, reaching the normal range of the control group.

Conclusion

Antigen-induced TMJ arthritis was found to involve severe problems of growth similar to those in juvenile idiopathic arthritis. Etanercept can improve the volume development but does not reestablish an entirely normal rate of growth.

Zusammenfassung

Ziel

Ziel dieser Studie war es, die Volumenentwicklung des Unterkiefers beim wachsenden Kaninchen mit bilateraler Kiefergelenkarthritis zu untersuchen. Ferner sollte der therapeutische Effekt des TNF-α-Antagonisten Etanercept beurteilt werden.

Methodik

Achtzehn weiße, 8 Wochen alte New Zealand Kaninchen wurden randomisiert auf 3 Gruppen zu je 6 Tieren verteilt. Bei 12 Tieren erfolgte im Alter von 10 Wochen eine Sensibilisierung auf Ovalbumin (OA) und anschließend die Induktion einer beidseitigen Kiefergelenkarthritis durch intraartikuläre OA-Injektionen. Zur Aufrechterhaltung der Entzündung wurden die intraartikulären Injektionen alle 3 Wochen wiederholt. Bei 6 der 12 Tiere erfolgte eine Therapie mit wöchentlichen subkutanen Etanercept-Injektionen, und 6 weitere Tiere dienten als Kontrollgruppe ohne jeglichen Eingriff. Von allen Tieren wurden beginnend mit der 10. Woche alle 3 Wochen bis zum Versuchsende im Alter von 22 Wochen Computertomographien (CT) des Gesichtsschädels durchgeführt. Die Entwicklung des Unterkiefers wurde nach Segmentierung auf Basis der CT-Daten mittels Volumetrie 3-dimensional untersucht.

Ergebnisse

Die Unterkieferentwicklung war nicht stetig. Die Wachstumsgeschwindigkeit nahm von der 10. bis zur 22. Woche in allen Gruppen ab, die höchste wurde zwischen der 10. und der 13. Woche beobachtet. Die Arthritis verursachte schwere Wachstumsstörungen, vor allem bei den Gelenkfortsätzen. Die Etanercept-Gruppe zeigte eine bessere, jedoch nicht vollkommen normale Unterkieferentwicklung im Vergleich zur Kontrollgruppe.

Schlussfolgerung

Die antigeninduzierte Arthritis des Kiefergelenks erzeugt schwere Wachstumsstörungen, die denen bei der juvenilen idiopathischen Arthritis ähneln. Unter Therapie mit Etanercept kommt es zu einer Besserung, aber nicht zu einer vollständigen Normalisierung des Wachstums.

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Acknowledgment

This study was supported by the Research Fund of the German Orthodontic Society.

Danksagung

Diese Arbeit wurde durch den Forschungsfonds der Deutschen Gesellschaft für Kieferorthopädie unterstützt.

Compliance with ethical guidelines

Conflict of interest. T.M. Präger, S. Rafayelyan, H. Landau, N. Pischon, K. Minden, P.-G. Jost-Brinkmann, R. Müller-Hartwich, and A. Mußler state that there is no conflict of interest.

All national guidelines on the care and use of laboratory animals have been followed and the necessary approval was obtained from the relevant authorities.

Einhaltung ethischer Richtlinien

Interessenkonflikt. T.M. Präger, S. Rafayelyan, H. Landau, N. Pischon, K. Minden, P.-G. Jost-Brinkmann, R. Müller-Hartwich und A. Mußler geben an, dass kein Interessenkonflikt besteht.

Alle nationalen Richtlinien zur Haltung und zum Umgang mit Labortieren wurden eingehalten und die notwendigen Zustimmungen der zuständigen Behörden liegen vor.

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Authors and Affiliations

  1. Department of Orthodontics, Dentofacial Orthopedics and Pedodontics, Charité Center for Dental, Oral and Maxillofacial Medicine, Charité – Universitätsmedizin Berlin, Assmannshauser Str. 4–6, 14197, Berlin, Germany

    T.M. Präger, S. Rafayelyan, H. Landau, P.-G. Jost-Brinkmann & R. Müller-Hartwich

  2. Department of Periodontology and Synoptic Dentistry, Charité Center for Dental, Oral and Maxillofacial Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany

    N. Pischon

  3. German Rheumatism Research Centre Berlin (DRFZ), Berlin, Germany

    K. Minden

  4. Department of Radiology, Charité – Universitätsmedizin Berlin, Berlin, Germany

    A. Mußler

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  1. T.M. Präger
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  3. H. Landau
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Correspondence to T.M. Präger.

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Präger, T., Rafayelyan, S., Landau, H. et al. Effect of untreated and treated temporomandibular joint arthritis on mandibular volume development in growing rabbits. J Orofac Orthop 76, 265–274 (2015). https://doi.org/10.1007/s00056-015-0288-2

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