BACKGROUND AND OBJECTIVES: The receptor activator of NF-kappaB ligand-osteoprotegerin (RANKL-OPG) bi-molecular system is the "bottle-neck" regulator of osteoclastogenesis and bone resorption, both in physiological and pathological conditions. This review aims to elaborate the current knowledge on RANKL and OPG in periodontal disease, and to evaluate their diagnostic and prognostic potential as biomarkers of the disease. MATERIALS AND METHODS: To pursue this aim, electronic and manual searches were performed for identifying clinical and in vivo studies on RANKL and OPG in gingival tissue, gingival crevicular fluid, saliva and blood. Smoking and diabetes mellitus were also considered for their potential effects. RESULTS: Papers fulfilling the inclusion criteria demonstrate that RANKL is up-regulated, whereas OPG is down-regulated in periodontitis, compared to periodontal health, resulting in an increased RANKL/OPG ratio. This ratio is further up-regulated in smokers and diabetics, and is not affected by conventional periodontal treatment. CONCLUSIONS: The increased RANKL/OPG ratio may serve as a biomarker that denotes the occurrence of periodontitis, but may not necessarily predict on-going disease activity. Its steadily elevated levels post treatment may indicate that the molecular mechanisms of bone resorption are still active, holding an imminent risk for relapse of the disease. Additional adjunct treatment modalities that would "switch-off" the RANKL/OPG ratio may therefore be required.
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