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

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Yadegari Afshin, Aminzadeh Atousa, Seyyedkhamesi Samad, Aminian Maedeh,
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 ( Yadegari Afshin ) - Islamic Azad University Faculty of Dentistry Department of Oral and Maxillofacial Surgery
 ( Aminzadeh Atousa ) - Islamic Azad University Faculty of Dentistry Department of Oral Pathology
 ( Seyyedkhamesi Samad ) - Islamic Azad University Faculty of Dentistry Department of Oral and Maxillofacial Surgery
 ( Aminian Maedeh ) - Isfahan University of Medical Sciences School of Dentistry Department of Radiology

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 ana-lyzed by chi-square, one-way ANOVA, Tukey, Kruskal?Wallis and Fisher¡¯s exact statistical tests (¥á=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 os-teoclasts 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.

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Bisphosphonate-related osteonecrosis of the jaw; Diphosphonates; Melatonin

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