Bone remodeling biomarkers of periodontal disease in saliva

Brandon D. Frodge, Jeffrey L. Ebersole, Richard J. Kryscio, Mark V. Thomas, Craig S. Miller

Research output: Contribution to journalArticlepeer-review

92 Scopus citations


Background: Tumor necrosis factor-alpha (TNF-α), C-telopeptide pyridinoline cross-links of type I collagen (ICTP), and receptor activator of nuclear factor-kappa B ligand (RANKL) have been associated with bone remodeling and periodontal tissue destruction. This study evaluated the level of these biomarkers in saliva with respect to periodontal disease status. Methods: Levels of TNF-α in unstimulated whole saliva of 74 adults (35 subjects with moderate to severe periodontal disease and 39 healthy controls) and salivary levels of RANKL and ICTP of a subset of 21 subjects and 21 matched controls were examined using enzyme immunosorbent assays in a case-control clinical study. Results: Salivary levels of TNF-α were detected in all subjects, whereas levels of ICTP and RANKL were detected in only a minority of subjects. Mean salivary levels of TNF-α were significantly higher in individuals with periodontal disease (mean: 4.33 pg/ml) than in controls (mean: 2.03 pg/ml; P = 0.02), with a maximum level (27.96 pg/ml) observed in periodontitis. Subjects with salivary TNF-α levels above a threshold of 5.75 pg/ml (i.e., two standard deviations above the mean of the controls) had significantly more sites with bleeding on probing, probing depths ≥4 mm, and attachment loss ≥2 mm (P≤0.01). Conclusion: Salivary levels of TNF-α were elevated in patients who had clinical indicators of periodontitis, suggesting that this biomarker may serve in a panel of salivary biomarkers that could facilitate the screening, diagnosis, and management of periodontal disease.

Original languageEnglish
Pages (from-to)1913-1919
Number of pages7
JournalJournal of Periodontology
Issue number10
StatePublished - Oct 2008


  • C-telopeptide pyridinoline
  • Periodontal diseases
  • Receptor activator of nuclear factor-kappa B ligand
  • Tumor necrosis factor-alpha

ASJC Scopus subject areas

  • Periodontics


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