PURPOSE: The aim of this study is to confirm the influence of a fixed orthodontic appliance on the difference in protein expression in the salivary proteomic profile of patients undergoing orthodontic therapy compared to the control group, using proteomic analysis techniques. MATERIALS AND PROCEDURES: The study was conducted on 18 subjects. All subjects were 13 years old and male, without any organic diseases or a record of antibiotic usage in the month prior to the study, who are undergoing fixed orthodontic therapy. The number of subjects in therapy was twelve (N = 12), including six control subjects (N = 6), but without orthodontic appliances with inclusion and exclusion criteria without risk to patients. Inclusive criteria for the participants' participation in the research are: age of 13 years, male gender and indication for fixed orthodontic therapy. The excluded criteria for the participation of respondents in the research are: existence of some of the systemic diseases that would further alter the affect result of the research, non-response to control examinations and sudden appearance of the disease during the research period. There was no risk for the subjects in this study. Since the salivary proteomic profile in that age group is variable, the first saliva sampling was performed 24 hours before placement and immediately prior to the placement of the fixed orthodontic appliance. Saliva was then taken again from all subjects from both groups 48 hours later, on the seventh day of therapy, and on the thirtieth day of therapy. The saliva collection procedure was based on three consecutive sputa directly into a Petri dish, after which the saliva was pipetted into Eppendorf tubes, previously marked with the subjects’ data. Immediately after the sample collection, the saliva was frozen at -20°C and transported on ice so the samples could be stored at -80°C. Finally, the method of sample analysis by mass spectrometry was performed. RESULTS: The most significant finding in the analysis of all results obtained from control and therapeutic groups in this study was found on the thirtieth day, and it is in support of and in accordance with the biology of bone remodeling after the application of fixed orthodontic therapies used for tooth displacement. From the analysis of isolated proteins obtained in this study, we can assume the potential role of individual molecules. A total of 198 proteins were identified in the saliva samples, which is in line with similar saliva studies. Proteins detected by mass spectrometry were classified on the basis of their functional characteristics, available in the UniProt database. During the initial and later phase of orthodontic therapy, we identified proteins involved in neurological processes, inflammation/stress, cytoskeleton, signal transduction/protein expression, and other processes. On the 30th day after the placement of the orthodontic appliance, the saliva proteome contained an additional group of proteins involved in bone remodeling. CONCLUSION: From the findings of the research, we can conclude that the appearance of confirmed molecules: BMP4, BMPER, IGFBP3 and FGF, which occurs during orthodontic tooth movement, almost identically coincides with the appearance of molecules in the process of bone regeneration that mimics the sequence of events during embryonic development. Of all the bone morphogenetic proteins, the above study identified the BMP4 molecule in saliva, which certainly occupies an important place in dental development and periodontal regeneration. The identification of the BMPER molecule in addition to the BMP4 molecule to which it clearly binds, confirms the coordinated activity of growth factors and their inhibitors, which are also confirmed at the proteomic level in the saliva sample as biological material. Furthermore, IGFBP3 in saliva has been confirmed and identified as a key molecule in bone metabolism. Finally, FGF identifications in the control and therapeutic groups indicate their presence in various forms, which could be related to their protective function, as well as their role in regeneration and bone remodeling. Considerig that this is the first identification of the BMP molecule (BMP4) in saliva, this result is extremely important from the aspect of biology of bone morphogenetic proteins, its presence in biological fluids and the development of new knowledge about how and where BMP4 reached the saliva (locally or systemically through the blood) and further, what is its real role in orthodontic therapy. To date, proteomic analysis has confirmed the identification of the BMP6 molecule from the blood and BMP1 (which is not a true BMP molecule, but a proteinase), wich to is crucial in the activation of BMP molecules and their antagonists.