Effects of Subcutaneous Administration of Glucocorticoids by Pellets on a Mouse Model of Ligature-Induced Periodontal Disease

<b>Background/Objective:</b> Glucocorticoids (GC) have anti-inflammatory effects, but long-term use can suppress bone formation and cause osteoporosis. The impact of inflammatory environments, such as periodontitis, on alveolar bone metabolism remains insufficiently understood. <b>Methods:</b> We used wild-type (C57BL/6J, <i>n</i> = 47) mice to compare glucocorticoid (GC) effects with and without sustained-release GC pellets. Mice were divided into GC-administered (2 weeks: <i>n</i> = 8; 4 weeks: <i>n</i> = 8; 8 weeks: <i>n</i> = 7) and non-GC-administered groups (2 weeks: <i>n</i> = 8; 4 weeks: <i>n</i> = 8; 8 weeks: <i>n</i> = 8). A ligature wire was placed around the left first molar of all mice to induce periodontal disease, while the right first molar served as a control. Femur and alveolar bone changes were assessed at 2, 4, and 8 weeks using μCT, HE staining, tartrate-resistant acid phosphatase (TRAP) staining, and immunohistochemistry (TNF-α). Anonymized evaluators performed histological analyses, and statistical analyses. One-way ANOVA with the Tukey post hoc test and <i>t</i> tests. <b>Results:</b> GC administration significantly reduced femoral bone mass at 2, 4, and 8 weeks. In mice without ligature, GC administration did not significantly affect alveolar bone mass or osteoblast number at 2 or 4 weeks, but a reduction was noted at 8 weeks post-treatment. No significant differences in osteoclast numbers or TNF-α levels were observed after GC administration. In a periodontal disease mouse model, GC administration led to greater bone loss, fewer osteoblasts, and increased osteoclasts and TNF-α levels. <b>Conclusions:</b> GC use in periodontal disease risks abnormal bone metabolism and progressive alveolar bone resorption.