title: Development of mandibular osteoradionecrosis in rats: Importance of dental extraction.
abstract: OBJECTIVE
  To develop an animal model of mandibular osteoradionecrosis (ORN) using a high-energy radiation source (as used in human therapeutics) and to assess the role of tooth extraction on ORN development.
  Ten animals were irradiated with a single 35- or 50-Gy dose. Three weeks later, the second left mandibular molar was extracted from three animals in each group. Nine weeks after irradiation, the animals were euthanized, with an injection of contrast agent in the bloodstream to highlight vascularization. Mandibles were harvested and studied using micro-CT, histology, tartrate-resistant acid phosphatase activity and scanning electron microscopy.
  
  
  RESULTS
  This study demonstrates that a single 50-Gy dose associated with molar extraction is necessary for ORN development. In these conditions, absence of healing of the mucosa and bone, dental effects, fibrosis, an increase in osteoclast activity and a decrease in vascularization were observed. We also determined that molar extraction increases the impact of the cellular effects of radiation.
  
  
  CONCLUSIONS
  The mandibular ORN animal model was validated after 50-Gy irradiation and molar extraction. The results of this study therefore support an animal ORN model and tissue engineering strategies will now be developed to regenerate bone for patients with head and neck cancer.
authors.affiliation: Inserm U791 (Head: Prof. P. Weiss), LIOAD, Faculté de Chirurgie Dentaire, 1 Place Alexis Ricordeau, 44042 Nantes Cedex 1, France; Faculté de Chirurgie Dentaire (Head: Prof. Y. Amouriq), Université de Nantes, 1 Place Alexis Ricordeau, 44042 Nantes Cedex 1, France; IRCCyN, CNRS 6597, IVC (Head: Prof. Patrick Le Callet), Polytech'Nantes, rue Christian Pauc, 44306 Nantes Cedex 3, France; CHU Nantes, Pôle Hospitalo-Universitaire 4 OTONN (Head: Dr. G. Amador del Valle), 1 Place Alexis Ricordeau, 44093 Nantes Cedex 1, France; Service d'Odontologie Restauratrice et Chirurgicale (Head: Prof. Y. Amouriq), CHU de Nantes, PHU4OTONN, 1 Place Alexis Ricordeau, 44093 Nantes Cedex 1, France. Electronic address: pauline.blery@univ-nantes.fr.
authors.forename: Pauline
authors.initials: P
authors.lastname: Bléry
authors.affiliation: Inserm U791 (Head: Prof. P. Weiss), LIOAD, Faculté de Chirurgie Dentaire, 1 Place Alexis Ricordeau, 44042 Nantes Cedex 1, France; CHU Nantes, Pôle Hospitalo-Universitaire 4 OTONN (Head: Dr. G. Amador del Valle), 1 Place Alexis Ricordeau, 44093 Nantes Cedex 1, France; Service d'Oto-Rhino-Laryngologie et de Chirurgie Cervico-Faciale (Head: Prof. P. Bordure), CHU de Nantes, Pôle Hospitalo-Universiatire 4 OTONN, France.
authors.forename: Florent
authors.initials: F
authors.lastname: Espitalier
authors.affiliation: Inserm U791 (Head: Prof. P. Weiss), LIOAD, Faculté de Chirurgie Dentaire, 1 Place Alexis Ricordeau, 44042 Nantes Cedex 1, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Hays
authors.affiliation: Inserm U791 (Head: Prof. P. Weiss), LIOAD, Faculté de Chirurgie Dentaire, 1 Place Alexis Ricordeau, 44042 Nantes Cedex 1, France.
authors.forename: Eléonore
authors.initials: E
authors.lastname: Crauste
authors.affiliation: IRSN Institut de Radioprotection et de Sûreté Nucléaire, IRSN/PRP-HOM/SRBE/LR2I (Head: Dr. M. Benderitter), 31 avenue de la division Leclerc BP17, 92260 Fontenay aux Roses, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Demarquay
authors.affiliation: Inserm U791 (Head: Prof. P. Weiss), LIOAD, Faculté de Chirurgie Dentaire, 1 Place Alexis Ricordeau, 44042 Nantes Cedex 1, France; CHU Nantes, Pôle Hospitalo-Universitaire 4 OTONN (Head: Dr. G. Amador del Valle), 1 Place Alexis Ricordeau, 44093 Nantes Cedex 1, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Pilet
authors.affiliation: Inserm U791 (Head: Prof. P. Weiss), LIOAD, Faculté de Chirurgie Dentaire, 1 Place Alexis Ricordeau, 44042 Nantes Cedex 1, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Sourice
authors.affiliation: Inserm U791 (Head: Prof. P. Weiss), LIOAD, Faculté de Chirurgie Dentaire, 1 Place Alexis Ricordeau, 44042 Nantes Cedex 1, France; CHU Nantes, Pôle Hospitalo-Universitaire 4 OTONN (Head: Dr. G. Amador del Valle), 1 Place Alexis Ricordeau, 44093 Nantes Cedex 1, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Guicheux
authors.affiliation: Inserm U791 (Head: Prof. P. Weiss), LIOAD, Faculté de Chirurgie Dentaire, 1 Place Alexis Ricordeau, 44042 Nantes Cedex 1, France; CHU Nantes, Pôle Hospitalo-Universitaire 4 OTONN (Head: Dr. G. Amador del Valle), 1 Place Alexis Ricordeau, 44093 Nantes Cedex 1, France; Service d'Oto-Rhino-Laryngologie et de Chirurgie Cervico-Faciale (Head: Prof. P. Bordure), CHU de Nantes, Pôle Hospitalo-Universiatire 4 OTONN, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Malard
authors.affiliation: IRSN Institut de Radioprotection et de Sûreté Nucléaire, IRSN/PRP-HOM/SRBE/LR2I (Head: Dr. M. Benderitter), 31 avenue de la division Leclerc BP17, 92260 Fontenay aux Roses, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Benderitter
authors.affiliation: Inserm U791 (Head: Prof. P. Weiss), LIOAD, Faculté de Chirurgie Dentaire, 1 Place Alexis Ricordeau, 44042 Nantes Cedex 1, France; Faculté de Chirurgie Dentaire (Head: Prof. Y. Amouriq), Université de Nantes, 1 Place Alexis Ricordeau, 44042 Nantes Cedex 1, France; CHU Nantes, Pôle Hospitalo-Universitaire 4 OTONN (Head: Dr. G. Amador del Valle), 1 Place Alexis Ricordeau, 44093 Nantes Cedex 1, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Weiss
authors.affiliation: IRSN Institut de Radioprotection et de Sûreté Nucléaire, IRSN/PRP-HOM/SRBE/LR2I (Head: Dr. M. Benderitter), 31 avenue de la division Leclerc BP17, 92260 Fontenay aux Roses, France.
authors.forename: Noëlle
authors.initials: N
authors.lastname: Mathieu
mesh_terms: D000818:Animals; D007091:Image Processing, Computer-Assisted; D008334:Mandible / Q000098:blood supply / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology; D008855:Microscopy, Electron, Scanning; D010025:Osteoradionecrosis / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology; D011829:Radiation Dosage; D011833:Radiation Injuries, Experimental / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology; D017207:Rats, Sprague-Dawley; D014081:Tooth Extraction; D014945:Wound Healing / Q000502:physiology / Q000528:radiation effects; D055114:X-Ray Microtomography
keywords: Animal model; Irradiation; Mandibular; Micro-CT; Osteoradionecrosis; Tooth extraction