STUDY OF THE EFFECT OF SYSTEMIC ANTIBIOTICOTHERAPIES ASSOCIATED OR NOT TO PENTOXYFILLINE AND TOCOPHEROL IN THE TREATMENT OF MEDICATION-RELATED OSTEONECROSIS OF THE JAWS

• Grant number: 22/16877-8
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: December 01, 2024
• End date: November 30, 2026
• Field of knowledge: Health Sciences - Dentistry - Oral and Maxillofacial Surgery
• Principal Investigator: Francisley Ávila Souza
• Grantee: Maísa Pereira da Silva
• Host Institution: Faculdade de Odontologia (FOA). Universidade Estadual Paulista (UNESP). Campus de Araçatuba. Araçatuba , SP, Brazil

Abstract

Oral infection and inflammation promote a critical role in the pathogenesis of drug- induced osteonecrosis of the jaw (OMIM). The risk of contamination of exposed bone tissue, as well as the imminent risk of odontogenic infection, is important. The control of biological sites, in order to avoid contamination, as well as maintaining a satisfactory microbiota for bone repair is something that is among the conducts for OMIM. The objective of this project will be to evaluate the treatment of drug-induced osteonecrosis of the jaws, through systemic application of antibiotic therapy (penicillin G, clindamycin, doxycycline), both associated or not with pentoxifylline and tocopherol (PENTO protocol). 192 Wistar rats will be used, which will be treated with 04 applications of 0.035 mg/kg of zoledronic acid (ZOL) via the caudal route with intervals of 15 days between applications and subsequently will have their lower right molars removed. After extraction, the animals will continue with treatment with ZOL in the same protocol until euthanasia. The animals will be divided into eight groups (n=8) according to the respiratory therapies: SAL (Saline solution - ZOL will not be applied) and will not be performed as therapies; ZOL (Zoledronate - Clot), will not be performedas therapies; AMOX (Amoxicillin), 265mg/kg of Amoxicillin per day for two weeks; CLI (Clindamycin), 75 mg/kg of Clindamycin per day for two weeks; DOX (Doxycycline), 35 mg/kg of Doxycycline per day for two weeks. All therapy protocols will be associated with Pentoxifylline and Tocopherol, with the administration of pentoxifylline 50 mg/kg/day IP and 80 mg/kg/day of ±-tocopherol orally via gavage. For in vivo analysis of mineralized sections, 64 animals will be used, which will receive calcein and alizarin and 28 days after extraction will be euthanized for evaluation: 1) clinical analysis 2) microtomographic analysis and 3) confocal laser microscopy 4) biomarkers of bone metabolism and redox state 5) Minimum Inhibitory Concentration (MIC). For in vivo analysis of demineralized sections, 128 animals will be used, which after 14 and 28 days of extraction data will be euthanized for evaluation: 1) histometric and histomorphometric analysis 2) immunohistochemistry through the expression of osteocalcin (OC) proteins, receptor activator of nuclear factor kappa B ligand (RANKL), tartrate-resistant acid phosphatase (TRAP) 3) molecular analysis (RT- PCR). The data obtained will be submitted to statistical analysis with a significance level of 5%.