This study is one of the first to jointly assess the levels of IL-1β, IL-17A, RANK-L and OPG in the saliva and relate them to the current classification of periodontal diseases [8], applying the severity and complexity (stage) as well as the risk of progression (grade) criteria to enable the identification of a biomarker or combined biomarkers that could discriminate different periodontitis statuses, facilitate an early non-clinical diagnosis, and allow for detection using a highly specific and sensitive multiplex assay. Here, TNFSF11 is linked to periodontitis.