OBJECTIVES: To establish osteonecrosis of the jaws in rats treated with different doses of zoledronic acid (ZA). METHODS: Male Wistar rats (n=6-7) received three consecutive weekly intravenous ZA infusions at doses of 0.04, 0.20 or 1.00mg/kg ZA or saline (control). Four weeks after the last administration, the animals were submitted to simple extraction of the lower left first molar. An additional dose of ZA was administered seven days later, and the animals were sacrificed 28 days after exodontia. Weight was measured and blood was collected weekly for analysis. The jaw was radiographically and microscopically examined along with the liver, spleen, kidney and stomach. RESULTS: All ZA doses showed a higher radiolucent area than the control (p<0.0001), but the dose of 0.04mg/kg did not show BRONJ. Doses of 0.20 and 1.00mg/kg ZA showed histological evidence of bone necrosis (p=0.0004). Anaemia (p<0.0001, r(2)=0.8073) and leucocytosis (p<0.0001, r(2)=0.9699) are seen with an increase of lymphocytes (p<0.0001, r(2)=0.6431) and neutrophils and monocytes (p=0.0218, r(2)=0.8724) in all the animals treated with an increasing dose of ZA. Haemorrhage and ectasia were observed in the spleen (p=0.0004) and stomach (p=0.0168) in a dose-dependent manner, and the animals treated with ZA showed a lower rate of weight gain (p<0.0001). CONCLUSIONS: We designed a bisphosphonate-related osteonecrosis of the jaw model that reproduces radiographic and histological parameters and mimics clinical alterations such as leucocytosis, anaemia and idiosyncratic inflammatory post infusion reactions.
OBJECTIVES: To establish osteonecrosis of the jaws in rats treated with different doses of zoledronic acid (ZA). METHODS: Male Wistar rats (n=6-7) received three consecutive weekly intravenous ZA infusions at doses of 0.04, 0.20 or 1.00mg/kg ZA or saline (control). Four weeks after the last administration, the animals were submitted to simple extraction of the lower left first molar. An additional dose of ZA was administered seven days later, and the animals were sacrificed 28 days after exodontia. Weight was measured and blood was collected weekly for analysis. The jaw was radiographically and microscopically examined along with the liver, spleen, kidney and stomach. RESULTS: All ZA doses showed a higher radiolucent area than the control (p<0.0001), but the dose of 0.04mg/kg did not show BRONJ. Doses of 0.20 and 1.00mg/kg ZA showed histological evidence of bone necrosis (p=0.0004). Anaemia (p<0.0001, r(2)=0.8073) and leucocytosis (p<0.0001, r(2)=0.9699) are seen with an increase of lymphocytes (p<0.0001, r(2)=0.6431) and neutrophils and monocytes (p=0.0218, r(2)=0.8724) in all the animals treated with an increasing dose of ZA. Haemorrhage and ectasia were observed in the spleen (p=0.0004) and stomach (p=0.0168) in a dose-dependent manner, and the animals treated with ZA showed a lower rate of weight gain (p<0.0001). CONCLUSIONS: We designed a bisphosphonate-related osteonecrosis of the jaw model that reproduces radiographic and histological parameters and mimics clinical alterations such as leucocytosis, anaemia and idiosyncratic inflammatory post infusion reactions.
Authors: Fátima Regina Nunes de Sousa; Vanessa Costa de Sousa Ferreira; Conceição da Silva Martins; Hugo Victor Dantas; Frederico Barbosa de Sousa; Virgínia Cláudia Carneiro Girão-Carmona; Paula Goes; Gerly Anne de Castro Brito; Renata Ferreira de Carvalho Leitão Journal: Sci Rep Date: 2021-04-07 Impact factor: 4.379
Authors: Vanessa Vasconcelos Cunha; Paulo Goberlânio de Barros Silva; José Vitor Mota Lemos; Joyce Ohana Lima Martins; Milena Oliveira Freitas; Rafael Linard Avelar Journal: Acta Cir Bras Date: 2020-11-30 Impact factor: 1.388
Authors: Maria Imaculada de Queiroz Rodrigues; Joyce Ohana de Lima Martins; Paulo Goberlânio de Barros Silva; Antônio Ernando Carlos Ferreira Júnior; Maria Elisa Quezado Lima Verde; Fabrício Bitú Sousa; Mário Rogério Lima Mota; Ana Paula Negreiros Nunes Alves Journal: J Oral Maxillofac Surg Date: 2020-08-15 Impact factor: 1.895