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Clinical Oral Investigations

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01-12-2018 | Original Article

Bone mineralization and vascularization in bisphosphonate-related osteonecrosis of the jaw: an experimental study in the rat

Authors: Jean-Daniel Kün-Darbois, Hélène Libouban, Guillaume Mabilleau, Florence Pascaretti-Grizon, Daniel Chappard

Published in: Clinical Oral Investigations | Issue 9/2018

Abstract

Objectives

Pathogenesis of bisphosphonate-related osteonecrosis of the jaws (BRONJ) is not fully explained. An antiangiogenic effect of bisphosphonates (BPs) or an altered bone quality have been advocated. The aims of the present study were to analyze alveolar mandibular vascularization and bone quality in rats with BRONJ.

Materials and methods

Thirty-eight Sprague-Dawley rats were randomized into two groups: zoledronic acid (ZA), n = 27, and control (CTRL) n = 11. The ZA group received a weekly IV injection of ZA (100 μg/kg) during 10 weeks. The CTRL group received saline. After 6 weeks, extraction of the right mandibular molars was performed. Rats were sacrificed after 14 weeks. Microtomography characterized bone lesions and vascularization after injection of a radio-opaque material. Raman microspectroscopy evaluated bone mineralization.

Results

Fifty-five percent of ZA rats presented bone exposure and signs of BRONJ. None sign was found at the left hemimandible in the ZA group and in the CTRL group. Vascular density appeared significantly increased in the right hemimandibles of the CTRL group compared to the left hemimandibles. Vascularization was reduced in the ZA group. A significantly increased of the mineral-to-amide ratio was found in the alveolar bone of ZA rats by Raman microspectroscopy.

Conclusions

In a rat model of BRONJ, microtomography evidenced osteonecrosis in BRONJ. Raman spectroscopy showed an increased mineralization. Vascularization after tooth extraction was impaired by ZA.

Clinical relevance

Prolonged BP administration caused an increase in the mineralization and a quantitative reduction of the vascularization in the alveolar bone; both factors might be involved concomitantly in the BRONJ pathophysiology.

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Title: Bone mineralization and vascularization in bisphosphonate-related osteonecrosis of the jaw: an experimental study in the rat
Authors: Jean-Daniel Kün-Darbois
Hélène Libouban
Guillaume Mabilleau
Florence Pascaretti-Grizon
Daniel Chappard
Publication date: 01-12-2018
Publisher: Springer Berlin Heidelberg
Published in: Clinical Oral Investigations / Issue 9/2018
Print ISSN: 1432-6981
Electronic ISSN: 1436-3771
DOI: https://doi.org/10.1007/s00784-018-2385-2

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Bone mineralization and vascularization in bisphosphonate-related osteonecrosis of the jaw: an experimental study in the rat

Abstract

Objectives

Materials and methods

Results

Conclusions

Clinical relevance

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Objectives

Materials and methods

Results

Conclusions

Clinical relevance

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