Objective: This study aimed to investigate the bisphosphonate and denosumab effects in medication-related osteonecrosis of the jaws (MRONJ) caused by periodontal disease with analyses of serum biomarkers and histopathology. Materials and Methods: Forty Copenhagen rats were used in the study. A ligature wire was wrapped around the first molars to induce periodontal disease. The rats were divided into a zoledronic acid group (ZG) (n=12), a denosumab group (DG) (n=12), a saline group (SG) (n=10), and a control group (CG) (n=6). Prostate cancer was induced by injections for ZG, DG, and SG following the ligature application, and injections were repeated on the 14th and 21st days. While periodontal disease was evaluated clinically with gingival edema, swelling and redness, serum osteocalcin, osteopontin, parathormone and receptor activator of nuclear factor-kappa B ligand (RANKL) levels were evaluated using the LUMINEX technique. The Mann-Whitney U test was used for the comparison of parameters between groups (p<0.05). Results: The osteocalcin levels were increased in CG, RANKL levels were decreased in DG, osteopontin levels were increased in ZG, and parathormone levels were increased in both ZG and CG. Conclusion: Since the long-term use of bisphosphonates can cause osteonecrosis in the jaw bones, it should not be overlooked that this can also be caused by chronic inflammatory conditions such as periodontal disease.