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01-02-2021 | Bisphosphonate | Original Article

Bisphosphonate-related osteonecrosis induced change in alveolar bone architecture in rats with participation of Wnt signaling

Authors: Vanessa Costa de Sousa Ferreira, Amanda Pimentel Lopes, Nicholas Militão Alves, Fatima Regina Nunes Sousa, Karuza Maria Alves Pereira, Delane Viana Gondim, Vírginia Claúdia Carneiro Girão, Renata Ferreira Carvalho Leitão, Paula Goes

Published in: Clinical Oral Investigations | Issue 2/2021

Abstract

Objective

This work aimed to study the role of inflammation in medication-related osteonecrosis of the jaw (MRONJ) in rats with focus on Wnt signaling.

Methods

A total of 36 female Wistar rats (12 weeks ± 200 g) were divided into 2 groups (n = 6) in 3 experiments: saline (SAL) and zoledronic acid (ZOL). For MRONJ induction, rats received 0.1 mg/kg of ZOL (ip) 3×/week for 9 weeks. Animals from the SAL group received 0.1 mg/kg of 0.9% SAL, ip 3×/week for 9 weeks. On the 8th week, 3 left upper molars were extracted, and on the 11th week, they were euthanized. Maxillae were evaluated by macroscopic and histopathological analyses; scanning electron microscopy (SEM); immunohistochemistry for DKK-1, Wnt 10b, and caspase-3; and Raman spectrometry. Gingiva was also collected for TNF-α e IL-1β quantification.

Results

Bone necrosis was confirmed by healing impairment, reduced number of viable osteocytes, increased caspase-3 immunoexpression, and increased number of empty lacunae (p < 0.05). ZOL enhanced inflammation and increased gingival levels of IL-1β and TNF-α (p < 0.05). Irregular indentations were seen on bone after ZOL administration. Bone necrosis was marked by reduced amount of total and type I collagen. ZOL reduced the mineral/matrix ratio and increased carbonate/phosphate ratio. It was observed a significant reduction on Wnt10b and beta-catenin immunolabeling in the bone tissue of ZOL group.

Conclusion

In summary, MRONJ model caused bone necrosis due to intense inflammation. Wnt signaling seems to play an important role in this process.

Clinical relevance

New therapeutic strategies focusing on Wnt pathway can provide an interesting approach for future treatments.

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Title: Bisphosphonate-related osteonecrosis induced change in alveolar bone architecture in rats with participation of Wnt signaling
Authors: Vanessa Costa de Sousa Ferreira
Amanda Pimentel Lopes
Nicholas Militão Alves
Fatima Regina Nunes Sousa
Karuza Maria Alves Pereira
Delane Viana Gondim
Vírginia Claúdia Carneiro Girão
Renata Ferreira Carvalho Leitão
Paula Goes
Publication date: 01-02-2021
Publisher: Springer Berlin Heidelberg
Keywords: Bisphosphonate
Osteonecrosis
Zoledronic Acid
Published in: Clinical Oral Investigations / Issue 2/2021
Print ISSN: 1432-6981
Electronic ISSN: 1436-3771
DOI: https://doi.org/10.1007/s00784-020-03551-7

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Bisphosphonate-related osteonecrosis induced change in alveolar bone architecture in rats with participation of Wnt signaling

Abstract

Objective

Methods

Results

Conclusion

Clinical relevance

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Objective

Methods

Results

Conclusion

Clinical relevance

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