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01.05.2013 | Original Article

Oral mucosa produces cytokines and factors influencing osteoclast activity and endothelial cell proliferation, in patients with osteonecrosis of jaw after treatment with zoledronic acid

verfasst von: Marco Mozzati, Germana Martinasso, Marina Maggiora, Matteo Scoletta, Marta Zambelli, Stefano Carossa, Manuela Oraldi, Giuliana Muzio, Rosa Angela Canuto

Erschienen in: Clinical Oral Investigations | Ausgabe 4/2013

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Abstract

Objectives

The intravenous injection of bisphosphonates, currently used as treatment for osteoporosis, bone Paget’s disease, multiple myeloma, or bone metastases, can cause jaw bone necrosis especially in consequence of trauma. The present research aimed to clarify the mechanisms underlying bone necrosis, exploring involvement of the oral mucosa “in vivo.”

Patients and methods

Specimens of oral mucosa were removed from bisphosphonate-treated patients with or without jaw bone necrosis. In mucosa specimens, expression was evaluated of: cytokines involved in the inflammatory process, factors involved in osteoclast activity, i.e., receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin, a factor involved in cell proliferation, namely hydroxymethylglutaryl coenzyme A reductase, and a factor involved in angiogenesis, namely vascular endothelial growth factor (VEGF).

Results

Interleukin (IL)-6 and the RANK/osteoprotegerin ratio were significantly elevated in mucosa from patients with versus without jaw necrosis, whereas hydroxymethylglutaryl coenzyme A reductase and VEGF were significantly decreased.

Conclusions

Our results suggest that mucosa, stimulated by bisphosphonate released from the bone, can contribute to the development of jaw necrosis, reducing VEGF, and producing IL-6 in consequence of hydroxymethylglutaryl coenzyme A reductase reduction. In turn, IL-6 stimulates osteoclast activity, as shown by the increased RANKL/osteoprotegerin ratio.

Clinical relevance

The results of this study suggest the importance of evaluating during bisphosphonate treatment the production of IL-6, RANKL, osteoprotegerin, and VEGF, in order to monitor the jaw osteonecrosis onset. To avoid repeated mucosa excisions, the determination of these factors could be carried out in crevicular fluid.

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Titel: Oral mucosa produces cytokines and factors influencing osteoclast activity and endothelial cell proliferation, in patients with osteonecrosis of jaw after treatment with zoledronic acid
verfasst von: Marco Mozzati
Germana Martinasso
Marina Maggiora
Matteo Scoletta
Marta Zambelli
Stefano Carossa
Manuela Oraldi
Giuliana Muzio
Rosa Angela Canuto
Publikationsdatum: 01.05.2013
Verlag: Springer-Verlag
Erschienen in: Clinical Oral Investigations / Ausgabe 4/2013
Print ISSN: 1432-6981
Elektronische ISSN: 1436-3771
DOI: https://doi.org/10.1007/s00784-012-0800-7

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Oral mucosa produces cytokines and factors influencing osteoclast activity and endothelial cell proliferation, in patients with osteonecrosis of jaw after treatment with zoledronic acid