Association of gingival crevicular fluid biomarkers during periodontal maintenance with subsequent progressive periodontitis

Richard A Reinhardt, Julie A. Stoner, Lorne M. Golub, Hsi Ming Lee, Pirkka V. Nummikoski, Timo Sorsa, Jeffrey B Payne

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Background: The analysis of biomarkers in gingival crevicular fluid (GCF) may be helpful in forecasting patient vulnerability to future attachment loss. The purpose of this study is to correlate GCF biomarkers of inflammation and bone resorption with subsequent periodontal attachment and bone loss in a longitudinal trial of a matrix metalloproteinase (MMP) inhibitor. Methods:GCF was collected fromtwo periodontal pockets(mean ± SD: 5.1 ± 1.0mm) at baseline and annually in postmenopausal females withmoderate to advanced periodontitis undergoing periodontal maintenance every 3 to 4 months during a 2-year double-masked, placebo-controlled, randomized clinical trial of subantimicrobial dose doxycycline (SDD; 20 mg two times a day). Subjects were randomized to SDD (n = 64) or a placebo (n = 64). GCF was analyzed for the inflammation markers interleukin (IL)-1β (using enzymelinked immunosorbent assay), total collagenase activity (using hydrolysis of a synthetic octapeptide), and MMP-8 (using a Western blot) and the boneresorptionmarker carboxyterminal telopeptide cross-link fragment of type I collagen (ICTP) (using a radioimmunoassay). Generalized estimating equations were used to associate these biomarkers, categorized into tertiles, with subsequent clinical attachment (using an automated disk probe) or interproximal bone loss (using radiography). Odds ratio (OR) values compared highest to lowest tertile groups. Results: Increases in GCF IL-1β and MMP-8 during the first year of periodontal maintenance were associated with increased odds of subsequent (year 2) periodontal attachment loss (OR = 1.67; P = 0.01 and OR = 1.50; P = 0.02, respectively) driven by the placebo group. Elevated baseline ICTP was also associated with increased odds of 1- and 2-year loss of alveolar bone density (OR = 1.98; P = 0.0001) in the placebo group, not the SDD group, and a loss of bone height (OR = 1.38; P = 0.06), again driven by the placebo group. Conclusion: These data support the hypothesis that elevated GCF biomarkers of inflammation and bone resorption from a small number of moderate/deep sites have the potential to identify patients who are vulnerable to progressive periodontitis, and SDD may modify that risk.

Original languageEnglish (US)
Pages (from-to)251-259
Number of pages9
JournalJournal of periodontology
Volume81
Issue number2
DOIs
StatePublished - Feb 1 2010

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Gingival Crevicular Fluid
Periodontitis
Biomarkers
Maintenance
Odds Ratio
Placebos
Periodontal Attachment Loss
Matrix Metalloproteinase 8
Bone Resorption
Inflammation
Interleukin-1
Periodontal Pocket
Alveolar Bone Loss
Bone and Bones
Immunosorbents
Matrix Metalloproteinase Inhibitors
Doxycycline
Collagenases
Collagen Type I
Radiography

Keywords

  • Doxycycline
  • Gingival crevicular fluid
  • Interleukin-1
  • Matrix metalloproteinase-8
  • Periodontitis
  • Type I collagen

ASJC Scopus subject areas

  • Periodontics

Cite this

Association of gingival crevicular fluid biomarkers during periodontal maintenance with subsequent progressive periodontitis. / Reinhardt, Richard A; Stoner, Julie A.; Golub, Lorne M.; Lee, Hsi Ming; Nummikoski, Pirkka V.; Sorsa, Timo; Payne, Jeffrey B.

In: Journal of periodontology, Vol. 81, No. 2, 01.02.2010, p. 251-259.

Research output: Contribution to journalArticle

Reinhardt, Richard A ; Stoner, Julie A. ; Golub, Lorne M. ; Lee, Hsi Ming ; Nummikoski, Pirkka V. ; Sorsa, Timo ; Payne, Jeffrey B. / Association of gingival crevicular fluid biomarkers during periodontal maintenance with subsequent progressive periodontitis. In: Journal of periodontology. 2010 ; Vol. 81, No. 2. pp. 251-259.
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abstract = "Background: The analysis of biomarkers in gingival crevicular fluid (GCF) may be helpful in forecasting patient vulnerability to future attachment loss. The purpose of this study is to correlate GCF biomarkers of inflammation and bone resorption with subsequent periodontal attachment and bone loss in a longitudinal trial of a matrix metalloproteinase (MMP) inhibitor. Methods:GCF was collected fromtwo periodontal pockets(mean ± SD: 5.1 ± 1.0mm) at baseline and annually in postmenopausal females withmoderate to advanced periodontitis undergoing periodontal maintenance every 3 to 4 months during a 2-year double-masked, placebo-controlled, randomized clinical trial of subantimicrobial dose doxycycline (SDD; 20 mg two times a day). Subjects were randomized to SDD (n = 64) or a placebo (n = 64). GCF was analyzed for the inflammation markers interleukin (IL)-1β (using enzymelinked immunosorbent assay), total collagenase activity (using hydrolysis of a synthetic octapeptide), and MMP-8 (using a Western blot) and the boneresorptionmarker carboxyterminal telopeptide cross-link fragment of type I collagen (ICTP) (using a radioimmunoassay). Generalized estimating equations were used to associate these biomarkers, categorized into tertiles, with subsequent clinical attachment (using an automated disk probe) or interproximal bone loss (using radiography). Odds ratio (OR) values compared highest to lowest tertile groups. Results: Increases in GCF IL-1β and MMP-8 during the first year of periodontal maintenance were associated with increased odds of subsequent (year 2) periodontal attachment loss (OR = 1.67; P = 0.01 and OR = 1.50; P = 0.02, respectively) driven by the placebo group. Elevated baseline ICTP was also associated with increased odds of 1- and 2-year loss of alveolar bone density (OR = 1.98; P = 0.0001) in the placebo group, not the SDD group, and a loss of bone height (OR = 1.38; P = 0.06), again driven by the placebo group. Conclusion: These data support the hypothesis that elevated GCF biomarkers of inflammation and bone resorption from a small number of moderate/deep sites have the potential to identify patients who are vulnerable to progressive periodontitis, and SDD may modify that risk.",
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