Dual-Biomarker Oral-Rinse Testing for aMMP-8 and Calprotectin: A Potential Adjunctive Tool for Risk Stratification...

Periodontitis is a chronic, biofilm-induced inflammatory disease characterized by episodic connective tissue destruction and is epidemiologically associated with cardiometabolic conditions, notably type 2 diabetes (T2D) and cardiovascular disease (CVD). Conventional clinical signs do not reliably distinguish quiescent from actively progressing disease, which delays intervention and interdisciplinary referral. Chair-side point-of-care testing (POCT) of oral fluids offers a pragmatic, non-invasive adjunct for real-time assessment of disease activity, not only in dental but also in medical settings. This narrative review, reported in line with the Scale for the Assessment of Narrative Review Articles (SANRA), examines the clinical rationale and current evidence for oral-rinse POCT targeting active matrix metalloproteinase-8 (aMMP-8) and calprotectin. Oral-rinse aMMP-8 reflects disease-active collagenolysis and shows the more robust single-marker performance for periodontitis, whereas oral-fluid calprotectin, a neutrophil-derived S100A8/A9 protein, behaves as a predominantly local inflammatory signal and lacks validated oral-fluid reference ranges. Combining the two markers may add information beyond either alone when used in tandem as a complementary pair, but the supporting data are heterogeneous, largely exploratory, and hypothesis-generating. Dual-biomarker oral-rinse POCT is therefore best framed as a risk-stratification and referral aid rather than a stand-alone diagnostic, with combined interpretation potentially supported by AI technologies. Standardized pre-analytics, transparent threshold reporting, oral-fluid calprotectin reference values, and prospective multicenter validation are required before broad implementation.