Evaluation the effects of melatonin combined vitamin D on zoledronic acid treated osteoblast in vitro

Bisphosphonates are widely used in osteoporosis, Paget's disease, Osteogenesis imperfecta and malign tumor therapies. Clinicians often experience jaw osteonecrosis cases due to use of bisphosphonates and other antiresoptive agents. Except bisphosphonates, denosumab, antiangiogenics and other antiresorptive drugs can cause this clinic situation called Medication Related Osteonecrosis of Jaw. Zoledronic acid inhibits osteoblast proliferation and activity, but in contrary melatonin and vitamin D enhance osteoblast's differentiation and proliferation. Additionally, melatonin is a powerful antioxidant. Vitamin D effects directly on bone tissue because of the vitamin D receptors on osteoblasts. Vitamin D also stimulates differentiation and mineralization in human and rat's osteoblasts. Melatonin which regulates circadian rhythm, is known for reducing bone loss. It is thought that melatonin makes these effects with upregulation of bone matrix proteins and otocoids. Low level laser therapy, squestrectomy, plasma rich fibrin and antibiotic drug lavage are some different therapy methods of MRONJ. There are lots of different options are trying to treat MRONJ, but there is no certain way yet and these researches take a wide place in the literature. In our study, we survey vitality and effect of melatonin and vitamin D's effects on different concentrations of zoledronic acid treated human-osteoblasts by MTT (Metil Tiazoldifenil Tetrazolyum) test method at 24 and 48th hour. We created 36 different group combination and compared gene expressions (RUNX-2, BMP-2 ve OSX(Osterix)) of the osteoblasts in these each groups with real time PCR (Polymerase Chain Reaction). And also ELISA tests (ALP, caspase-3 and IL-8) were done in these each group and the results compared.