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Evaluation of the osseointegration of implants placed in reparational alveolar bone of rats treated with zoledronic acid

Grant number: 21/03851-8
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): September 01, 2022
Effective date (End): August 31, 2024
Field of knowledge:Health Sciences - Dentistry - Oral and Maxillofacial Surgery
Principal Investigator:Francisley Ávila Souza
Grantee:Laís Kawamata de Jesus
Host Institution: Faculdade de Odontologia (FOA). Universidade Estadual Paulista (UNESP). Campus de Araçatuba. Araçatuba , SP, Brazil


Bisphosphonates (BPs) are anti-resorptive drugs that affect bone remodeling and are commonly prescribed for treatments of bone or oncological disorders, however, the dose and prolonged use can lead to the development of Medication-Related Osteonecrosis of the Jaw (MRONJ). The aim of this project will be to evaluate the osseointegration of implants placedin reparational alveolar bone after local preventive therapies during treatment with zoledronic acid. For this purpose, 144 male Wistar rats will be treated with 04 applications of 0.035 mg/kg of zoledronic acid (ZOE) through the caudal vein with 15 days intervals between applications and subsequently have their right lower molars removed. After extraction, animals will continue with treatment with ZOE in the same protocol, as well as after implant placement until euthanasia. The animals will be divided into six groups (n = 8) according to the treatment of the dental socket: GS (Sham - will not be applied ZOE, tooth socket filled with blood clot), GZ (blood clot only), GB (B-tricalcium phosphate), GBD (B-tricalcium phosphate + 10% doxycycline), GBDP (B-tricalcium phosphate + 10% doxycycline + antimicrobial photodynamic therapy) and GDP (10% doxycycline + antimicrobial photodynamic therapy). After 28 days of extractions, each animal will receive an implant (2.2x4mm) in the region of the reparational socket of the lower left first molar, totaling 144 implants. All animals will be sacrificed 28 days after implant placement. For the 48 animals belonging to the mineralized sections methodology, the analyzes will be performed in microtomography, laser confocal microscopy and histometry (alizarin red and Stevenel blue). The 48 animals belonging to the biomechanical analysis and topographic characterization after the removal of the implants, will be anesthetized and in vivo the removal torque will be measured, followed by the topographic characterization of the surface of the removed implants, by means of scanning electron microscopy, coupled to the X-ray dispersive energy spectrometry system (SEM-EDX) for qualitative/quantitative analysis of tissue neoformed bone with the measurement of the elements calcium (Ca), phosphorus (P) and oxygen (O). For the 48 animals belonging to the methodology of demineralized sections, a qualitative and immunohistochemical histological analysis will be performed by means of the expression of the proteins osteocalcin (OC), osteopontin (OP), nuclear factor kappa B receptor activating receptor (RANKL), tartrate-resistant acid phosphatase (TRAP). All values obtained will be tabulated and submitted to statistical analysis, considering p<0.05. (AU)

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