The effect of melatonin on prevention of bisphosphonate-related osteonecrosis of the jaw: an animal study in rats

Abstract

Objectives: Melatonin induces human stem cells, converts pre-osteoblasts to mature osteoblasts, and reduces the duration of this transition. However, melatonin itself prevents activation of osteoclasts. Here, we evaluate the role of melatonin in prevention of bisphosphonate-related osteonecrosis of the jaw. Materials and Methods: In this experimental-interventional study, 30 rats were evaluated in 3 groups. The first and second groups received saline and zoledronic acid, respectively, for 4 weeks and the third group received 4 weeks of zoledronic acid and 3 weeks of melatonin simultaneously. First-right-maxillary-molar extraction was performed for all animals, which were sacrificed after 4 weeks of recovery. The extraction sockets were examined histologically for the presence of osteonecrosis, number of osteoclasts and fibroblasts, severity of inflammation, and vascularization. Data were analyzed by chi-square, one-way ANOVA, Tukey, Kruskal-Wallis and Fisher's exact statistical tests (alpha=0.05). Results: Osteonecrosis was observed in 20, 90, and 70 of the first, second and third groups, respectively (P=0.008). The lowest number of osteoclasts and fibroblasts was seen in the third group. Conclusion: Melatonin may effectively prevent some undesirable side effects of bisphosphonates. However, further studies are required to confirm the results of this study.