ORAL FLUID BIOMARKERS IN THE DIAGNOSIS OF PERIODONTAL INFLAMMATION IN ADOLESCENTS AND YOUNG ADULTS: A CRITICAL REVIEW OF THE EVIDENCE BASE AND A CONCEPTUAL FRAMEWORK FOR CLINICAL-LABORATORY SCREENING

Abstract

Introduction. Periodontal inflammatory diseases are prevalent in adolescents and young adults: gingivitis is diagnosed in up to 70–80% of adolescents, while early-onset periodontitis affects 4–11%. There is a need for non-invasive early detection strategies based on biological markers. Saliva, gingival crevicular fluid (GCF), and oral rinse offer accessible biological matrices for biomarker-based screening, yet evidence for this age group remains limited and heterogeneous. Aim. To critically analyze current evidence on salivary and GCF biomarkers of periodontal inflammation in adolescents and young adults, evaluate their diagnostic value and limitations, and propose a conceptual framework for clinical-laboratory screening based on literature analysis. Materials and methods. A narrative review with elements of structured critical analysis was conducted. Literature search was performed in PubMed/MEDLINE, Scopus, Web of Science and Google Scholar covering 2000–2024, with priority given to systematic reviews, metaanalyses and clinical studies evaluating biomarkers in saliva, GCF or oral rinse with established association with periodontal clinical parameters. Ten biomarker groups were assessed: tissue destruction markers, pro- and anti-inflammatory cytokines, neutrophil markers, antimicrobial proteins, oxidative stress and antioxidant markers, bone remodeling markers, and phosphatase enzymes. Evidence was rated by pathogenetic rationale, analytical and clinical validity, reproducibility, availability of cut-off values, and applicability in adolescents. Results. Thirty-nine sources covering 10 biomarker groups were analyzed. aMMP-8, measurable in saliva and oral rinse by non-invasive point-of-care (chair-side) testing, is the most evidence-based marker of active collagenolytic process that may precede clinically detectable tissue destruction. No single biomarker demonstrated sufficient specificity for stand-alone use in adolescents. Pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, IL-8) are sensitive but non-specific; their diagnostic value increases in combination with aMMP-8 and as IL-1β/IL-10 ratio. Neutrophil markers (calprotectin/S100A8-A9, MPO, elastase) reflect early innate immune activation but require age-specific validation. Antioxidant enzymes (catalase, SOD, GPx, TAC) and RANKL/OPG have auxiliary value and are subject to physiological variability in adolescents. Phosphatase enzymes – alkaline phosphatase (ALP) and acid phosphatase/tartrate-resistant acid phosphatase (ACP/TRAP) – show diagnostic potential but are confounded by skeletal growth and orthodontic tooth movement in adolescents. Conclusions. No single biomarker can serve as an independent diagnostic criterion for periodontal inflammation in adolescents. A multi-biomarker approach addressing five pathogenetic axes – collagenolytic destruction of periodontal connective tissue (aMMP-8), proinflammatory activation (IL-1β/IL-6), regulatory balance (IL-1β/IL-10), neutrophil response (calprotectin or MPO) and oxidative component (catalase or TAC) – appears most rational. Based on literature analysis, a three-level conceptual screening framework is proposed that accounts for age-specific characteristics of adolescents and prioritizes non-invasive biological sampling. Clinical validation of this framework in prospective studies is required.