Alendronate therapy in experimental osteonecrosis induction: study in rats

• Grant number: 10/18647-2
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2011
• End date: February 28, 2013
• Field of knowledge: Health Sciences - Dentistry - Periodontology
• Principal Investigator: Elcio Marcantonio Junior
• Grantee: Elcio Marcantonio Junior
• Host Institution: Faculdade de Odontologia (FOAr). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Associated researchers: Cleopatra da Silva Planeta ; Fabio Cardoso Cruz ; Luis Carlos Spolidorio ; Nicolau Conte Neto

Abstract

Bisphosphonates (BPs) are relevant anti-reabsorption drugs, indicated to the treatment of bone loss induced by a sort of diseases. This class of drugs is usually well tolerated by the organism, however since 2003 they have been associated to a serious side effect named bisphosphonate induced osteonecrosis of the jaw (BRONJ) that have been generating a great concern due to the large number of clinical reports in the literature. Several theories have been proposed, however its etiology and pathogenesis still remain unclear. On the other hand, it's known that most of cases are triggered by an invasive dental procedure, such as tooth extractions or dental implants. The contemporaneous literature only offers limited histological data usually characterized by bone necrosis associated to an infectious process, showing the necessity of studies directed to the elucidation of this necrosis pathogenesis. The aim of this project is to evaluate a combination of risk factors to BRONJ development, such as long-term treatment with alendronate by parenteral route, surgical dental procedure and stress by an experimental model of osteonecrosis in rats. To this purpose, it will be performed two studies: the first one using long term high alendronate dosages associated to tooth extraction and the second one using long term therapeutically alendronate dosages associated to dental implants and stress. In the present research project it will be done biochemical analyses of bone metabolism markers and stress, histometric analyses of tooth socket and implants, immunohistochemistry to apoptosis and real time PCR to evaluate matrix metalloproteinases and bone proteins. (AU)