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Site Specific Effects of Zoledronic Acid during Tibial and Mandibular Fracture Repair

Numerous factors can affect skeletal regeneration, including the extent of bone injury, mechanical loading, inflammation and exogenous molecules. Bisphosphonates are anticatabolic agents that have been widely used to treat a variety of metabolic bone diseases. Zoledronate (ZA), a nitrogen-containing...

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Autores principales: Yu, Yan Yiu, Lieu, Shirley, Hu, Diane, Miclau, Theodore, Colnot, Céline
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3281002/
https://www.ncbi.nlm.nih.gov/pubmed/22359627
http://dx.doi.org/10.1371/journal.pone.0031771
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author Yu, Yan Yiu
Lieu, Shirley
Hu, Diane
Miclau, Theodore
Colnot, Céline
author_facet Yu, Yan Yiu
Lieu, Shirley
Hu, Diane
Miclau, Theodore
Colnot, Céline
author_sort Yu, Yan Yiu
collection PubMed
description Numerous factors can affect skeletal regeneration, including the extent of bone injury, mechanical loading, inflammation and exogenous molecules. Bisphosphonates are anticatabolic agents that have been widely used to treat a variety of metabolic bone diseases. Zoledronate (ZA), a nitrogen-containing bisphosphonate (N-BP), is the most potent bisphosphonate among the clinically approved bisphosphonates. Cases of bisphosphonate-induced osteonecrosis of the jaw have been reported in patients receiving long term N-BP treatment. Yet, osteonecrosis does not occur in long bones. The aim of this study was to compare the effects of zoledronate on long bone and cranial bone regeneration using a previously established model of non-stabilized tibial fractures and a new model of mandibular fracture repair. Contrary to tibial fractures, which heal mainly through endochondral ossification, mandibular fractures healed via endochondral and intramembranous ossification with a lesser degree of endochondral ossification compared to tibial fractures. In the tibia, ZA reduced callus and cartilage formation during the early stages of repair. In parallel, we found a delay in cartilage hypertrophy and a decrease in angiogenesis during the soft callus phase of repair. During later stages of repair, ZA delayed callus, cartilage and bone remodeling. In the mandible, ZA delayed callus, cartilage and bone remodeling in correlation with a decrease in osteoclast number during the soft and hard callus phases of repair. These results reveal a more profound impact of ZA on cartilage and bone remodeling in the mandible compared to the tibia. This may predispose mandible bone to adverse effects of ZA in disease conditions. These results also imply that therapeutic effects of ZA may need to be optimized using time and dose-specific treatments in cranial versus long bones.
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spelling pubmed-32810022012-02-22 Site Specific Effects of Zoledronic Acid during Tibial and Mandibular Fracture Repair Yu, Yan Yiu Lieu, Shirley Hu, Diane Miclau, Theodore Colnot, Céline PLoS One Research Article Numerous factors can affect skeletal regeneration, including the extent of bone injury, mechanical loading, inflammation and exogenous molecules. Bisphosphonates are anticatabolic agents that have been widely used to treat a variety of metabolic bone diseases. Zoledronate (ZA), a nitrogen-containing bisphosphonate (N-BP), is the most potent bisphosphonate among the clinically approved bisphosphonates. Cases of bisphosphonate-induced osteonecrosis of the jaw have been reported in patients receiving long term N-BP treatment. Yet, osteonecrosis does not occur in long bones. The aim of this study was to compare the effects of zoledronate on long bone and cranial bone regeneration using a previously established model of non-stabilized tibial fractures and a new model of mandibular fracture repair. Contrary to tibial fractures, which heal mainly through endochondral ossification, mandibular fractures healed via endochondral and intramembranous ossification with a lesser degree of endochondral ossification compared to tibial fractures. In the tibia, ZA reduced callus and cartilage formation during the early stages of repair. In parallel, we found a delay in cartilage hypertrophy and a decrease in angiogenesis during the soft callus phase of repair. During later stages of repair, ZA delayed callus, cartilage and bone remodeling. In the mandible, ZA delayed callus, cartilage and bone remodeling in correlation with a decrease in osteoclast number during the soft and hard callus phases of repair. These results reveal a more profound impact of ZA on cartilage and bone remodeling in the mandible compared to the tibia. This may predispose mandible bone to adverse effects of ZA in disease conditions. These results also imply that therapeutic effects of ZA may need to be optimized using time and dose-specific treatments in cranial versus long bones. Public Library of Science 2012-02-16 /pmc/articles/PMC3281002/ /pubmed/22359627 http://dx.doi.org/10.1371/journal.pone.0031771 Text en Yu et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Yu, Yan Yiu
Lieu, Shirley
Hu, Diane
Miclau, Theodore
Colnot, Céline
Site Specific Effects of Zoledronic Acid during Tibial and Mandibular Fracture Repair
title Site Specific Effects of Zoledronic Acid during Tibial and Mandibular Fracture Repair
title_full Site Specific Effects of Zoledronic Acid during Tibial and Mandibular Fracture Repair
title_fullStr Site Specific Effects of Zoledronic Acid during Tibial and Mandibular Fracture Repair
title_full_unstemmed Site Specific Effects of Zoledronic Acid during Tibial and Mandibular Fracture Repair
title_short Site Specific Effects of Zoledronic Acid during Tibial and Mandibular Fracture Repair
title_sort site specific effects of zoledronic acid during tibial and mandibular fracture repair
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3281002/
https://www.ncbi.nlm.nih.gov/pubmed/22359627
http://dx.doi.org/10.1371/journal.pone.0031771
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