Osteoimmunologic and Immune-Aging Signatures in Postmenopausal Women with Periodontitis and Low Bone Mineral Density: A Cross-Sectional Study.

Background/Objective: Periodontitis and osteoporosis frequently co-occur after menopause, yet the immune-bone pathways linking oral and skeletal phenotypes remain incompletely defined. This study investigated whether periodontitis severity and low bone mineral density (BMD) in postmenopausal women are associated with convergent systemic inflammaging and immunosenescence phenotypes and with a salivary RANKL/OPG imbalance. Methods: In this cross-sectional study, 280 postmenopausal women were assigned to a 2 × 2 factorial design based on periodontal status (severe vs. no/mild) and BMD status (low vs. normal; DXA T-score). Full-mouth periodontal measurements (PD, CAL, BOP, plaque index, tooth count; stage/grade) were recorded. Salivary RANKL and OPG were quantified, and the RANKL/OPG ratio was calculated. Systemic inflammaging markers (hs-CRP, IL-6, TNF-α) and CMV IgG were assessed, and T-cell immune-aging phenotypes were profiled by flow cytometry (CD3, CD4, CD8, CD45RA, CCR7, CD28, CD57, KLRG1, PD-1, CD27). Results: Severe periodontitis and low BMD were each associated with higher salivary RANKL/OPG ratios and greater systemic inflammatory burden, with modest interaction effects. Immune-aging profiles showed higher proportions of late-differentiated CD8+ phenotypes, and CMV seropositivity was strongly associated with immunosenescence markers. Conclusions: In postmenopausal women, periodontal destruction and low BMD were aligned with osteoclastogenic and immune-aging signatures, consistent with oral-skeletal immune crosstalk. Findings should be interpreted as associative rather than causal, and longitudinal observational studies are warranted to clarify temporality.