IADR Abstract Archives
Chronic administration of zoledronate affects healing parameters in C57Bl/6 mice
Objectives: The aim of this study was to investigate the development of MRONJ-type lesions in C57Bl/6 adult male mice (IACUC n°00262-2019) at the late time point of socket healing, after continuous and cumulative administration of ZL in two different dosages
Methods: Mice were divided into 3 groups according to the treatment: intraperitoneal injection (IP) of saline solution (SS, control, n=3) or ZL at a concentration of 250ug / Kg (n=3) and 500ug/Kg (n=4), once a week, starting 4 weeks before extraction of the right upper incisor and continuing until the day 30 post-sugery. At the end of 30 days, bone samples were collected for histomorformetry (H&E), and immunohistochemistry for bone and inflammatory markers
Results: While the control group exhibit a dental socket filled with mature bone, the ZL-250 and ZL-500 groups presented a significant and gradual increase in the area density of inflammatory infiltrate dependent of each dosage. Bone matrix area density was significantly lower in ZL-250 and ZL-500 groups. Area density of COX2+ cells, an inflammatory parameter positively related to bone neoformation, was decreased in both ZL treated groups compared to the control. Area densities of fibroblasts, RANKL+ cells, and empty osteocyte lacunae were increased in ZL-250 and ZL-500 groups. Interestingly, the area density of detached osteoclasts, a typical characteristic of MRONJ lesions, was higher in the ZL250 group compared to the SS, while ZL500 group presented a lower density of attached osteoclasts compared to the others.
Conclusions: Chronic administration of both ZL dosages significantly affected inflammatory and healing parameters post tooth extraction in mice in C57BL/6, with increasing effects at the higher dosage.
Methods: Mice were divided into 3 groups according to the treatment: intraperitoneal injection (IP) of saline solution (SS, control, n=3) or ZL at a concentration of 250ug / Kg (n=3) and 500ug/Kg (n=4), once a week, starting 4 weeks before extraction of the right upper incisor and continuing until the day 30 post-sugery. At the end of 30 days, bone samples were collected for histomorformetry (H&E), and immunohistochemistry for bone and inflammatory markers
Results: While the control group exhibit a dental socket filled with mature bone, the ZL-250 and ZL-500 groups presented a significant and gradual increase in the area density of inflammatory infiltrate dependent of each dosage. Bone matrix area density was significantly lower in ZL-250 and ZL-500 groups. Area density of COX2+ cells, an inflammatory parameter positively related to bone neoformation, was decreased in both ZL treated groups compared to the control. Area densities of fibroblasts, RANKL+ cells, and empty osteocyte lacunae were increased in ZL-250 and ZL-500 groups. Interestingly, the area density of detached osteoclasts, a typical characteristic of MRONJ lesions, was higher in the ZL250 group compared to the SS, while ZL500 group presented a lower density of attached osteoclasts compared to the others.
Conclusions: Chronic administration of both ZL dosages significantly affected inflammatory and healing parameters post tooth extraction in mice in C57BL/6, with increasing effects at the higher dosage.