Evaluation of Local and Systemic Melatonin Administration on Bone Healing After Tooth Extraction in Bisphosphonate-Treated Rats

The purpose of our study was to investigate the effects of systemic and local application of melatonin after tooth extraction in bisphosphonate applied rats, on the healing of extraction socket histopathologically and immunohistochemically. Forty four Wistar albino rats were included in the study. Subjects were divided into 4 groups: Control (C), Bisphosphonate (BIF), Bisphosphonate + Local Melatonin (BIF + LM) and Bisphosphonate + Systemic Melatonin (BIF + SM). Zoledronic acid was applied intraperitoneally once a week from the beginning of the experiment to all the groups except control group. On the 28th day of the experiment lower left first molar tooth were extracted in all subjects. Local and systemic melatonin were applied immediately after tooth extraction. All subjects were sacrificed on the 56th day of the experiment. According to the results, epithelization in BIF + LM groups was significantly higher statistically than epithelization in BIF and BIF + SM groups. It was determined that, osteonecrosis values were significantly lower than BIF groups in C, BIF + LM and BIF + SM groups and lower than C group in BIF + LM and BIF + SM groups respectively. Inflamation values were found significantly lower in C, BIF + LM and BIF + SM groups than BIF group. When examined immunohistochemically, osteocalsin values were significantly higher than BIF groups in C, BIF + LM and BIF + SM groups and higher than BIF + SM and C groups in BIF + LM groups statistically. The levels of VEGF were determined to be significantly higher than BIF group in BIF + LM and BIF + SM groups statistically. In this rat model, melatonin was associated with reduced severity of bisphosphonate-related osteonecrosis of the jaw-like histopathological changes and higher angiogenic/osteogenic immunoreactivity, suggesting a potential therapeutic role in mitigating lesion severity. These findings do not establish prevention and require confirmation in further preclinical and clinical studies.