Removal of matrix-bound zoledronate prevents post-extraction osteonecrosis of the jaw by rescuing osteoclast function
| Autor: | Mohammed Elsalanty, Charles E. McKenna, Gary M. Whitford, Pheba Abraham, Mohamed E. Awad, David H. Pashley, Zoya B. Kurago, Ranya Elsayed, Balasudha Baladhandayutham |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Histology
Physiology Endocrinology Diabetes and Metabolism medicine.medical_treatment Osteoclasts Pharmacology Matrix (biology) Zoledronic Acid Article Bone and Bones Mass Spectrometry Rats Sprague-Dawley 03 medical and health sciences Mice 0302 clinical medicine Osteoclast medicine Animals Humans Chelation Amino Acids Dental alveolus Edetic Acid Cell Proliferation Chelating Agents Diphosphonates Chemistry Cell Differentiation 030206 dentistry X-Ray Microtomography Bisphosphonate medicine.disease Molar In vitro Resorption Rats medicine.anatomical_structure RAW 264.7 Cells Jaw 030220 oncology & carcinogenesis Tooth Extraction Bisphosphonate-Associated Osteonecrosis of the Jaw Calcium Osteonecrosis of the jaw |
| Popis: | Unlike other antiresorptive medications, bisphosphonate molecules accumulate in the bone matrix. Previous studies of side-effects of anti-resorptive treatment focused mainly on systemic effects. We hypothesize that matrix-bound bisphosphonate molecules contribute to the pathogenesis of bisphosphonate-related osteonecrosis of the jaw (BRONJ). In this study, we examined the effect of matrix-bound bisphosphonates on osteoclast differentiation in vitro using TRAP staining and resorption assay, with and without pretreatment with EDTA. We also tested the effect of zoledronate chelation on the healing of post-extraction defect in rats. Our results confirmed that bisphosphonates bind to, and can be chelated from, mineralized matrix in vitro in a dose-dependent manner. Matrix-bound bisphosphonates impaired the differentiation of osteoclasts, evidenced by TRAP activity and resorption assay. Zoledronate-treated rats that underwent bilateral dental extraction with unilateral EDTA treatment showed significant improvement in mucosal healing and micro-CT analysis on the chelated sides. The results suggest that matrix-bound bisphosphonates are accessible to osteoclasts and chelating agents and contribute to the pathogenesis of BRONJ. The use of topical chelating agents is a promising strategy for the prevention of BRONJ following dental procedures in bisphosphonate-treated patients. |
| Databáze: | OpenAIRE |
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