J Korean Assoc Oral Maxillofac Surg.  2020 Aug;46(4):266-274. 10.5125/jkaoms.2020.46.4.266.

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

  • 1Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Isfahan (Khorasgan) Branch, Islamic Azad University, Isfahan, Iran
  • 2Department of Oral Pathology, Faculty of Dentistry,Isfahan (Khorasgan) Branch, Islamic Azad University, Isfahan, Iran
  • 3Department of Oral and Maxillofacial Radiology, School of Dentistry, Isfahan University of Medical Science, Isfahan, Iran


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. Firstright-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 ana-lyzed by chi-square, one-way ANOVA, Tukey, Kruskal–Wallis and Fisher’s exact statistical tests (α=0.05).
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.
Melatonin may effectively prevent some undesirable side effects of bisphosphonates. However, further studies are required to confirm the results of this study.


Bisphosphonate-related osteonecrosis of the jaw; Diphosphonates; Melatonin
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