Salivary biomarkers for periodontal health and disease: A comprehensive review of diagnostics, prognostics and emerging applications: A literature review

Background: Periodontal disease is highly prevalent and typically diagnosed with clinical measures like pocket depth, attachment loss and bleeding; that capture past damage rather than current activity. Salivary biomarkers offer a non‑invasive alternative that could improve diagnosis, risk assessment and monitoring. The objective of this review is to summarize current evidence on salivary biomarkers in periodontal health and disease, evaluate their diagnostic and prognostic performance and discuss translational potential. Searches were conducted in PubMed/PMC, Scopus and Google Scholar for human studies that measured salivary biomarkers in gingivitis or periodontitis. Eligible papers were selected based on relevance and clarity of clinical and biomarker data, and information was grouped by biomarker category. Several biomarker families show promise. Pro‑inflammatory cytokines particularly IL‑1β, IL‑6 and IL‑17 consistently correlate with probing depth and bleeding. Matrix metalloproteinases, such as MMP‑8 and MMP‑9, reflect active collagen breakdown and often exhibit good sensitivity for distinguishing health from disease. The RANKL/OPG ratio is strongly associated with alveolar bone loss and disease severity. Oxidative‑stress markers (e.g., 8‑hydroxydeoxyguanosine, 4‑hydroxy‑2‑nonenal and advanced glycation end‑products) and S100 proteins (S100A8/A9) are emerging indicators of inflammatory burden, though results are inconsistent. Novel approaches including panels combining multiple proteins or microRNAs may enhance diagnostic accuracy but require further validation. Salivary biomarkers are promising for non‑invasive assessment of periodontal disease. Individual markers such as IL‑1β, MMP‑8 and the RANKL/OPG ratio stand out, yet heterogeneity in study designs, assays and populations limits comparability. Standardized sampling protocols, larger longitudinal studies and validation of multi‑marker panels are necessary before these assays can be integrated into routine periodontal care.