Effects of Topical Therapy with Metronidazole and Ozonized Oil Delivered in a Mucoadhesive Paste for the Treatment of Medication-Related Osteonecrosis of the Jaw

• Grant number: 25/18832-0
• Support Opportunities: Scholarships in Brazil - Master
• Start date: January 01, 2026
• End date: February 28, 2027
• Field of knowledge: Health Sciences - Dentistry - Dental Clinics
• Principal Investigator: Ana Paula Farnezi Bassi
• Grantee: Douglas Sadrac de Biagi Ferreira
• Host Institution: Faculdade de Odontologia (FOA). Universidade Estadual Paulista (UNESP). Campus de Araçatuba. Araçatuba , SP, Brazil

Abstract

Medication-related osteonecrosis of the jaws (MRONJ) is a severe complication mainly associated with the use of bisphosphonates and denosumab, whose multifactorial ethiopathogenesis hinders prevention and treatment. In the absence of established therapies, topical alternatives with antimicrobial, anti-inflammatory, and reparative properties have been investigated. Despite the reported antimicrobial and reparative effects of ozonized oils, their topical use is limited by low retention in oral sites. Thus, mucoadhesive formulations emerge as a promising approach to prolong local release and enhance their effects. Moreover, the association with antimicrobial and anesthetic agents, such as metronidazole (MTZ) and lidocaine (LDC), may broaden therapeutic efficacy in the infected and painful environment of MRONJ. This project aims to evaluate the effects of a mucoadhesive paste containing ozonized grape seed oil (25%; 2000 mEq O¿/kg), with or without the addition of MTZ (10%) and LDC (2%), in an experimental model of MRONJ in Wistar rats treated with zoledronic acid. Clinical, microtomographic (micro-CT), histological, and immunohistochemical parameters related to inflammation, angiogenesis, and bone remodeling will be analyzed. It is expected that the proposed combination will favor tissue repair and represent a promising translational strategy for the management of MRONJ.