Subantimicrobial-dose doxycycline modulates gingival crevicular fluid biomarkers of periodontitis in postmenopausal osteopenic women

Lorne M. Golub, Ming Lee Hsi, Julie A. Stoner, Timo Sorsa, Richard A Reinhardt, Mark S. Wolff, Maria E. Ryan, Pirkka V. Nummikoski, Jeffrey B Payne

Research output: Contribution to journalArticle

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Abstract

Background: We recently demonstrated that a 2-year subantimicrobial-dose doxycycline (SDD) regimen (double-masked, placebo-controlled clinical trial) in postmenopausal (PM) women exhibiting mild systemic bone loss (osteopenia) and localboneloss (periodontitis) reduced the progression of periodontal attachment loss (intent-to-treat analysis) and the severity of gingival inflammation and alveolar bone loss (subgroups) without producing antibiotic side effects. We now describe SDD effects on biomarkers of collagen degradation and bone resorption in the gingival crevicular fluid (GCF) of the same vulnerable subjects. Methods: GCF was collected from SDD- and placebo-treated PM subjects (n = 64 each) at the baseline and 1- and 2-year appointments; the volume was determined; and the samples were analyzed for collagenase activity (using a synthetic peptide as substrate), relative levels of three genetically distinct collagenases (Western blot), a type-1 collagen breakdown product/bone resorption marker (a carboxyterminal telopeptide cross-link fragment of type I collagen [ICTP]; radioimmunoassay), and interleukin-1β (enzyme-linked immunosorbent assay). Statistical analyses were performed using generalized estimating equations; primary analyses were intent-to-treat. Results: Collagenase activity was significantly reduced by SDD treatment relative to placebo based on intent-to-treat (P = 0.01). ICTP showed a similar pattern of change during SDD treatment, and GCF collagenase activity and ICTP were positively correlated at all time periods (P <0.001). Matrix metalloproteinase (MMP)-8 accounted for ;80% of total collagenase in GCF, with much less MMP-1 and -13, and SDD reduced the odds of elevated MMP-8 by 60% compared to placebo (P = 0.006). Conclusion: These observations support the therapeutic potential of long-term SDD therapy to reduce periodontal collagen breakdown and alveolar bone resorption in PM women; effects on serum biomarkers of systemic bone loss in these subjects are being analyzed.

Original languageEnglish (US)
Pages (from-to)1409-1418
Number of pages10
JournalJournal of periodontology
Volume79
Issue number8
DOIs
StatePublished - Aug 1 2008

Fingerprint

Gingival Crevicular Fluid
Doxycycline
Periodontitis
Collagenases
Biomarkers
Bone Resorption
Placebos
Matrix Metalloproteinase 8
Alveolar Bone Loss
Collagen Type I
Periodontal Attachment Loss
Collagen
Matrix Metalloproteinase 13
Bone and Bones
Matrix Metalloproteinase 1
Metabolic Bone Diseases
Controlled Clinical Trials
Therapeutics
Interleukin-1
Radioimmunoassay

Keywords

  • Clinical trial
  • Collagenases gingival crevicular fluid
  • Osteopenia
  • Periodontitis
  • Postmenopause

ASJC Scopus subject areas

  • Periodontics

Cite this

Subantimicrobial-dose doxycycline modulates gingival crevicular fluid biomarkers of periodontitis in postmenopausal osteopenic women. / Golub, Lorne M.; Hsi, Ming Lee; Stoner, Julie A.; Sorsa, Timo; Reinhardt, Richard A; Wolff, Mark S.; Ryan, Maria E.; Nummikoski, Pirkka V.; Payne, Jeffrey B.

In: Journal of periodontology, Vol. 79, No. 8, 01.08.2008, p. 1409-1418.

Research output: Contribution to journalArticle

Golub, Lorne M. ; Hsi, Ming Lee ; Stoner, Julie A. ; Sorsa, Timo ; Reinhardt, Richard A ; Wolff, Mark S. ; Ryan, Maria E. ; Nummikoski, Pirkka V. ; Payne, Jeffrey B. / Subantimicrobial-dose doxycycline modulates gingival crevicular fluid biomarkers of periodontitis in postmenopausal osteopenic women. In: Journal of periodontology. 2008 ; Vol. 79, No. 8. pp. 1409-1418.
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abstract = "Background: We recently demonstrated that a 2-year subantimicrobial-dose doxycycline (SDD) regimen (double-masked, placebo-controlled clinical trial) in postmenopausal (PM) women exhibiting mild systemic bone loss (osteopenia) and localboneloss (periodontitis) reduced the progression of periodontal attachment loss (intent-to-treat analysis) and the severity of gingival inflammation and alveolar bone loss (subgroups) without producing antibiotic side effects. We now describe SDD effects on biomarkers of collagen degradation and bone resorption in the gingival crevicular fluid (GCF) of the same vulnerable subjects. Methods: GCF was collected from SDD- and placebo-treated PM subjects (n = 64 each) at the baseline and 1- and 2-year appointments; the volume was determined; and the samples were analyzed for collagenase activity (using a synthetic peptide as substrate), relative levels of three genetically distinct collagenases (Western blot), a type-1 collagen breakdown product/bone resorption marker (a carboxyterminal telopeptide cross-link fragment of type I collagen [ICTP]; radioimmunoassay), and interleukin-1β (enzyme-linked immunosorbent assay). Statistical analyses were performed using generalized estimating equations; primary analyses were intent-to-treat. Results: Collagenase activity was significantly reduced by SDD treatment relative to placebo based on intent-to-treat (P = 0.01). ICTP showed a similar pattern of change during SDD treatment, and GCF collagenase activity and ICTP were positively correlated at all time periods (P <0.001). Matrix metalloproteinase (MMP)-8 accounted for ;80{\%} of total collagenase in GCF, with much less MMP-1 and -13, and SDD reduced the odds of elevated MMP-8 by 60{\%} compared to placebo (P = 0.006). Conclusion: These observations support the therapeutic potential of long-term SDD therapy to reduce periodontal collagen breakdown and alveolar bone resorption in PM women; effects on serum biomarkers of systemic bone loss in these subjects are being analyzed.",
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AU - Sorsa, Timo

AU - Reinhardt, Richard A

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AU - Ryan, Maria E.

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