Therapeutic Potential of Selective Phosphodiesterase Type III Inhibitor in Osteonecrosis Induced by Anti-Resorptive Therapies

• Grant number: 25/22134-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2026
• End date: December 31, 2026
• Field of knowledge: Health Sciences - Dentistry - Oral and Maxillofacial Surgery
• Principal Investigator: Leonardo Perez Faverani
• Grantee: Gabriela Kalinsqui Lopes
• Host Institution: Faculdade de Odontologia de Piracicaba (FOP). Universidade Estadual de Campinas (UNICAMP). Piracicaba , SP, Brazil

Abstract

Medication-Related Osteonecrosis of the Jaw (MRONJ) is associated with the use of antiresorptive agents such as bisphosphonates and denosumab, and involves mechanisms including inhibition of bone remodeling, reduced angiogenesis, and local infections. Treatment prioritizes conservative approaches, including the PENTOCO protocol (pentoxifylline and tocopherol), which improves bone perfusion and healing but may present adverse effects. As an alternative, cilostazol has shown promise due to its vasodilatory, anti-inflammatory, and pro-angiogenic properties, with potential to promote bone regeneration and aid in the treatment of MRONJ.The aim of this study is to evaluate the therapeutic potential of cilostazol as a pharmacological alternative in the conservative management of medication-related osteonecrosis of the jaw. In this in vivo study, 40 six-month-old Wistar rats weighing approximately 350 grams will be used, all undergoing bilateral ovariectomy. They will be randomly assigned to four experimental groups (n=10):* Control Group: will receive 0.9% saline solution (0.45 mL);* ZOL, ZOL+C50, and ZOL+C100 Groups: will receive zoledronic acid (100¿¿g/kg) every 3 days for 7 weeks.Rats in the ZOL+C50 and ZOL+C100 groups will undergo daily oral administration (gavage) of cilostazol at doses of 50 mg/kg/day and 100 mg/kg/day, respectively. This administration will begin after tooth extraction and continue until euthanasia. The mandibles will be resected, fragmented, and prepared for histological and histometric analyses, as well as clinical evaluations based on photographic records of the extraction sockets at the end of the experimental period.