Medication Related Osteonecrosis of the Jaw: Melatonin functions and effects

Bisphosphonates (BPs) are drugs frequently prescribed in therapy of various pathological conditions affecting bones but they may have adverse effects, the most important one is represented by osteonecrosis of the jaws (Bisphosphonates related osteonecrosis of jaws, BRONJ) detected and described by Marx, since 2003, as a painful and nonhealing bone exposure. Despite many researches its exact aetiology, pathogenesis and adequate treatment protocol remain controversial. In the last decade other drugs have been related to this serious disease, now grouped into two categories: BPs and non-BPs (considering other antiresorptive or antiangiogenic medications); and now we describe this pathological condition with acronimus MRONJ (Medication Related Osteonecrosis of the Jaw). According to American Association of Oral and Maxillofacial Surgeons (AAOMS), MRONJ presents with exposed necrotic bone in maxillofacial region for more than 8 weeks, in patients without history of radiation therapy to the orofacial region, which are currently taking (or were) antiresorptive or antiangiogenic agents. MRONJ usually is induced by local trauma, such as tooth extraction or other invasive dental procedures; the risk of developing MRONJ increases proportionally to the dosage and duration of medication intake and it is greater in combination with chemotherapy. Since osteonecrosis seems related mostly to antiangiogenic effect of these drugs we want to evaluate the outcome of pharmacological doses of Melatonin in patient with MRONJ. Melatonin has an important role in angiogenesis increasing VEGF expression. Besides Melatonin has an important anti-inflammatory effect acting as an antioxidant by directly neutralising ROS. More over Melatonin interferes with bone resorption process by down regulation of the Receptor Activator of Nuclear Factor k-B Ligand ((RANKL)-mediated Osteoclast formation and Activation; in addition Melatonin promotes Osteoblast differentiation and stimulates the formation of collagen type I and new mineralised matrix.