Obesity influences the development of bisphosphonate-induced osteonecrosis in Wistar rats

Abstract

Medication-related osteonecrosis of the jaw (MRONJ) is characterized by bone exposure for more than eight weeks in patients who have used or been treated with antiresorptive or antiangiogenic drugs, without a history of radiation therapy or metastatic diseases in the jaws. Obesity is associated with changes in periodontal tissues and oral microbiota that are linked to bone alterations. This study aimed to analyze the influence of obesity on the development of bisphosphonate-induced osteonecrosis. The experiment randomly and simply divided 24 male Wistar rats (Rattus norvegicus) into four groups: healthy, with osteonecrosis, obese, and obese with osteonecrosis (n=6 per group). Osteonecrosis was induced through weekly intraperitoneal injection for eight weeks at a dose of 250 µg/kg of zoledronic acid in a 4 mg/5 mL solution, combined with trauma (exodontia). Obesity was induced through a high glycaemic index diet. Each group was qualitatively and quantitatively evaluated regarding the development of models and pathological anatomy of the lesions. The results were expressed in mean percentage and standard deviation and statistically analyzed using one-way analysis of variance (ANOVA) followed by Tukey's post-hoc test, with a significance level of 5% (p<0.05) to establish differences found between the groups. Animals in the osteonecrosis group and the obese with osteonecrosis group presented larger necrosis areas (averages: 172.83±18,19 µm² and 290.33±15,77 µm², respectively) (p<0,0001). Bone sequestration, hepatic steatosis, and increased adipocyte size were observed in the obese group (average: 97.75±1.91 µm²) and in the obese with osteonecrosis group (average: 98.41±1.56 µm²), indicating greater tissue damage in these groups (p<0,0001). All parameters analyzed (through histological, morphometric, and murinometric analyses) increased for the obese and obese with osteonecrosis groups, suggesting a possible influence of obesity on the results. However, further studies are needed to confirm the role of obesity in the possible exacerbation of osteonecrosis and understand the underlying mechanisms.

Osteonecrosis; Diphosphonates; Obesity; Mandible; Rats, Wistar