Medication-related osteonecrosis of the jaw. Introduction of a new modified experimental model.
OBJECTIVE
To evaluate a modified experimental model for medication-related osteonecrosis of the jaw (MRONJ) through the upper right central incisor extraction followed by intravenous bisphosphonate administration.


METHODS
Forty five rats underwent the upper right central incisor tooth extraction were divided in 2 groups: Group I - experimental group, 30 rats received an intravenous administration protocol of zoledronic acid 35μg/kg into the tail vein every two weeks, totalizing four administrations, during eight weeks of administration, previously the extraction, and Group II - control group, 15 rats didn't received any medication before extraction. The groups were subdivided in postoperative periods: 14/28/42 days. Clinical analysis and microtomography were performed to verify the presence of osteonecrosis. In addition, descritive histological analysis of hematoxylin-eosin stained sections was performed to evaluate the presence of osteonecrosis or necrotic foci.


RESULTS
Twelve (40%) rats, from experimental group, showed clinical signs of MRONJ (p=0.005), however, all samples showed imaginologic findings like osteolysis and loss of integrity of the cellular walls (p≤0.001). Microscopic evaluation revealed osteonecrosis areas with microbial colonies and inflammatory infiltrate (p≤0.001). In the control group, all animals presented the chronology of a normal wound healing.


CONCLUSIONS
The presence of medication-related osteonecrosis of the jaw after maxillary central incisor extraction in rats. This new experimental model may be considered an option for the study of MRONJ.
DDS, MSc student, Department of Oral Surgery, Universidade Sagrado Coração (USC), Bauru-SP, Brazil. Design of the study, technical procedures, MicroCt evaluation, manuscript writing., Department of Oral Surgery, Universidade Sagrado Coração, Bauru SP , Brazil.
Cláudia
C
Curra
DDS, MSc, PhD, Assistant Professor, Department of Oral Surgery, USC, and Postdoc-student, Department of Oral Surgery, Bauru Dental School, Universidade de São Paulo (USP), Bauru-SP, Brazil. Design of the study, technical procedures, interpretation of data, MicroCt evaluation, microscopic evaluation, manuscript writing. , Universidade de São Paulo, Department of Oral Surgery, Bauru Dental School, Universidade de São Paulo, Bauru SP , Brazil.
Camila Lopes
CL
Cardoso
DDS, MSc, PhD, Assistant Professor, Department of Oral Surgery, Bauru Dental School, USP, Bauru-SP, Brazil. Design of the study, interpretation of data, manuscript writing. , Universidade de São Paulo, Department of Oral Surgery, Bauru Dental School, USP, Bauru SP , Brazil.
Osny
O
Ferreira
DDS, MSc, PhD, Assistant Professor, Department of Oral Surgery, USC, Bauru-SP, Brazil. Design of the study, interpretation of data, manuscript writing. , Department of Oral Surgery, USC, Bauru SP , Brazil.
Marcos Martins
MM
Curi
DDS, MSc, PhD, Assistant Professor, Universidade Estadual Paulista (UNESP), Araçatuba-SP, Brazil. Design of the study, interpretation of data, microscopic evaluation, manuscript writing. , Universidade Estadual Paulista, Universidade Estadual Paulista, Araçatuba SP , Brazil.
Mariza Akemi
MA
Matsumoto
DDS, MSc, PhD, Postdoc-student, Department of Endodontics, Bauru Dental School, USP, Bauru-SP, Brazil. Interpretation of data, MicroCt evaluation, manuscript writing. , Universidade de São Paulo, Department of Endodontics, Bauru Dental School, USP, Bauru SP , Brazil.
Bruno Cavalini
BC
Cavenago
DDS, MSc, PhD, Assistant Professor, Department of Oral Surgery, USC, Bauru-SP, Brazil. Design of the study, interpretation of data, manuscript writing. , Department of Oral Surgery, USC, Bauru SP , Brazil.
Pâmela Letícia Dos
PL
Santos
DDS, MSc, PhD, Assistant Professor, Department of Implantology, Bauru Dental School, USP, Bauru-SP, Brazil. Interpretation of data, statistical analysis, manuscript writing. , Universidade de São Paulo, Department of Implantology, Bauru Dental School, USP, Bauru SP , Brazil.
Joel Ferreira
JF
Santiago
D061605:Administration, Intravenous / Q000379:methods; D016301:Alveolar Bone Loss / Q000000981:diagnostic imaging; D000818:Animals; D059266:Bisphosphonate-Associated Osteonecrosis of the Jaw / Q000000981:diagnostic imaging / Q000473:pathology*; D004164:Diphosphonates / Q000008:administration & dosage* / Q000009:adverse effects; D007093:Imidazoles / Q000008:administration & dosage* / Q000009:adverse effects; D007180:Incisor / Q000601:surgery; D008297:Male; D008439:Maxillary Diseases / Q000000981:diagnostic imaging; D023421:Models, Animal; D010000:Osteitis / Q000473:pathology; D010014:Osteolysis / Q000139:chemically induced / Q000000981:diagnostic imaging; D017208:Rats, Wistar; D014081:Tooth Extraction / Q000009:adverse effects / Q000379:methods; D055114:X-Ray Microtomography / Q000295:instrumentation; D000077211:Zoledronic Acid
D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid