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

**Authors:** Irina-Georgeta Sufaru, Maria-Alexandra Martu, Maria-Georgeta Laza, Sorina Mihaela Solomon, Ionut Luchian, Liliana Pasarin, Diana Tatarciuc, Ioana Martu

PMC · DOI: 10.3390/diagnostics16050708 · Diagnostics · 2026-02-27

## TL;DR

This study explores how gum disease and low bone density in postmenopausal women are linked through immune and aging-related changes.

## Contribution

The study identifies immune-aging and inflammaging signatures associated with periodontitis and low bone density in postmenopausal women.

## Key findings

- Severe periodontitis and low BMD were each associated with higher salivary RANKL/OPG ratios and greater systemic inflammation.
- Immune-aging profiles showed increased late-differentiated CD8+ T cells and CMV seropositivity linked to immunosenescence markers.
- Findings suggest oral-skeletal immune crosstalk but are associative, not causal.

## Abstract

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.

## Linked entities

- **Proteins:** TNFSF11 (TNF superfamily member 11), BTF3P11 (basic transcription factor 3 pseudogene 11), IL6 (interleukin 6), TNF (tumor necrosis factor), cd.3 (Cd.3 conserved hypothetical protein), CD4 (CD4 molecule), CD8A (CD8 subunit alpha), CCR7 (C-C motif chemokine receptor 7), CD28 (CD28 molecule), B3GAT1 (beta-1,3-glucuronyltransferase 1), KLRG1 (killer cell lectin like receptor G1), PDCD1 (programmed cell death 1), CD27 (CD27 molecule)
- **Diseases:** periodontitis (MONDO:0005076), osteoporosis (MONDO:0005298)

## Full-text entities

- **Genes:** TNFSF11 (TNF superfamily member 11) [NCBI Gene 8600] {aka CD254, ODF, OPGL, OPTB2, RANKL, TNLG6B}, PDCD1 (programmed cell death 1) [NCBI Gene 5133] {aka ADMIO4, AIMTBS, CD279, PD-1, PD1, SLEB2}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, CCR7 (C-C motif chemokine receptor 7) [NCBI Gene 1236] {aka BLR2, CC-CKR-7, CCR-7, CD197, CDw197, CMKBR7}, BTF3P11 (basic transcription factor 3 pseudogene 11) [NCBI Gene 690] {aka BRF3L1, BTF3L1, HUMBTFB, OCIF, OPG, TNFRSF11B}, B3GAT1 (beta-1,3-glucuronyltransferase 1) [NCBI Gene 27087] {aka CD57, GLCATP, GLCUATP, HNK1, LEU7, NK-1}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, PTPRC (protein tyrosine phosphatase receptor type C) [NCBI Gene 5788] {aka B220, CD45, CD45R, GP180, IMD105, L-CA}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, CD28 (CD28 molecule) [NCBI Gene 940] {aka IMD123, Tp44}, KLRG1 (killer cell lectin like receptor G1) [NCBI Gene 10219] {aka 2F1, CLEC15A, MAFA, MAFA-2F1, MAFA-L, MAFA-LIKE}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, CD27 (CD27 molecule) [NCBI Gene 939] {aka S152, S152. LPFS2, T14, TNFRSF7, Tp55}
- **Diseases:** inflammatory (MESH:D007249), Periodontitis (MESH:D010518), osteoporosis (MESH:D010024), CMV (MESH:D003586)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12984706/full.md

## References

54 references — full list in the complete paper: https://tomesphere.com/paper/PMC12984706/full.md

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Source: https://tomesphere.com/paper/PMC12984706