Paula Barba-Recreo1, Jose Luis Del Castillo Pardo de Vera2, Mariano García-Arranz3, Laura Yébenes4, Miguel Burgueño2. 1. Department of Oral and Maxillofacial Surgery (Head of the Department: Miguel Burgueño), University Hospital La Paz, Madrid, Spain. Electronic address: p.barba.recreo@gmail.com. 2. Department of Oral and Maxillofacial Surgery (Head of the Department: Miguel Burgueño), University Hospital La Paz, Madrid, Spain. 3. Cell Therapy Laboratory (Head of the Department: Prof. Damián García Olmo), Unidad de Invesigación, IdIPAZ, University Hospital La Paz, Madrid, Spain. 4. Department of Pathology, University Hospital La Paz, Madrid, Spain.
Abstract
INTRODUCTION: Bisphosphonate-related osteonecrosis of the jaws (BRONJ) is a pathologic condition of increasing frequency, with a poorly understood pathophysiology and which can be difficult to manage. The aim of this study was to find a reproducible experimental model that directly relates chronic bisphosphonate administration with the development of osteonecrosis with or without tooth extraction, with no other drug involved. MATERIAL AND METHODS: Twenty male Wistar rats were divided into 4 groups (n = 5/group). Animals were injected over 9 weeks with zoledronic acid (0.1 mg/kg). In groups 1 and 2 three times a week intraperitoneally, and in group 3 once a week intravenously. A control group (group 4) received intraperitoneal injections of saline solution three times a week. After 8 weeks of treatment, 3 right upper jaw molars were extracted in groups 1, 3 and 4 and all rats were sacrificed 1 week later. The maxillae were histologically analyzed for presence of osteonecrosis foci, number of osteoclasts, vascularity, bone resorption status and presence of abscess. Radiographic examination was performed with a plain radiograph of each hemi-head. RESULTS: We found that group 1 (dental extractions and highest cumulative dose of zoledronic acid) had the highest incidence of osteonecrosis (80%), absence of bone resorption (100%) and lowest number of osteoclasts (mean 7.9/field at 40×). Zoledronic acid-treated groups showed variable degrees of osteosclerosis and trabecular disorganization on X-ray study. CONCLUSIONS: We offer a new animal model of BRONJ after zoledronic acid administration and dental extractions, achieving bone changes similar or superior to previous studies, highlighting the dental extraction as an important trigger factor.
INTRODUCTION:Bisphosphonate-related osteonecrosis of the jaws (BRONJ) is a pathologic condition of increasing frequency, with a poorly understood pathophysiology and which can be difficult to manage. The aim of this study was to find a reproducible experimental model that directly relates chronic bisphosphonate administration with the development of osteonecrosis with or without tooth extraction, with no other drug involved. MATERIAL AND METHODS: Twenty male Wistar rats were divided into 4 groups (n = 5/group). Animals were injected over 9 weeks with zoledronic acid (0.1 mg/kg). In groups 1 and 2 three times a week intraperitoneally, and in group 3 once a week intravenously. A control group (group 4) received intraperitoneal injections of saline solution three times a week. After 8 weeks of treatment, 3 right upper jaw molars were extracted in groups 1, 3 and 4 and all rats were sacrificed 1 week later. The maxillae were histologically analyzed for presence of osteonecrosis foci, number of osteoclasts, vascularity, bone resorption status and presence of abscess. Radiographic examination was performed with a plain radiograph of each hemi-head. RESULTS: We found that group 1 (dental extractions and highest cumulative dose of zoledronic acid) had the highest incidence of osteonecrosis (80%), absence of bone resorption (100%) and lowest number of osteoclasts (mean 7.9/field at 40×). Zoledronic acid-treated groups showed variable degrees of osteosclerosis and trabecular disorganization on X-ray study. CONCLUSIONS: We offer a new animal model of BRONJ after zoledronic acid administration and dental extractions, achieving bone changes similar or superior to previous studies, highlighting the dental extraction as an important trigger factor.
Authors: Akrivoula Soundia; Danny Hadaya; Navid Esfandi; Rafael Scaf de Molon; Olga Bezouglaia; Sarah M Dry; Flavia Q Pirih; Tara Aghaloo; Sotirios Tetradis Journal: Bone Date: 2016-06-18 Impact factor: 4.398
Authors: Giovanni Mergoni; Paolo Vescovi; Roberto Sala; Elisabetta Merigo; Pietro Passerini; Roberta Maestri; Domenico Corradi; Paolo Govoni; Samir Nammour; Massimiliano G Bianchi Journal: Support Care Cancer Date: 2015-07-21 Impact factor: 3.603