{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T09:09:14Z","timestamp":1789895354861,"version":"4.0.1"},"reference-count":40,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2008,8,1]],"date-time":"2008-08-01T00:00:00Z","timestamp":1217548800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Periodontology"],"published-print":{"date-parts":[[2008,8]]},"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> We recently demonstrated that a 2\u2010year subantimicrobial\u2010dose doxycycline (SDD) regimen (double\u2010masked, placebo\u2010controlled clinical trial) in postmenopausal (PM) women exhibiting mild systemic bone loss (osteopenia) and local bone loss (periodontitis) reduced the progression of periodontal attachment loss (intent\u2010to\u2010treat 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.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> GCF was collected from SDD\u2010 and placebo\u2010treated PM subjects (n = 64 each) at the baseline and 1\u2010 and 2\u2010year 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\u20101 collagen breakdown product\/bone resorption marker (a carboxyterminal telopeptide cross\u2010link fragment of type I collagen [ICTP]; radioimmunoassay), and interleukin\u20101\u03b2 (enzyme\u2010linked immunosorbent assay). Statistical analyses were performed using generalized estimating equations; primary analyses were intent\u2010to\u2010treat.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Collagenase activity was significantly reduced by SDD treatment relative to placebo based on intent\u2010to\u2010treat (<jats:italic>P<\/jats:italic> = 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 (<jats:italic>P<\/jats:italic> &lt;0.001). Matrix metalloproteinase (MMP)\u20108 accounted for \u223c80% of total collagenase in GCF, with much less MMP\u20101 and \u221213, and SDD reduced the odds of elevated MMP\u20108 by 60% compared to placebo (<jats:italic>P<\/jats:italic> = 0.006).<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> These observations support the therapeutic potential of long\u2010term 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.<\/jats:p>","DOI":"10.1902\/jop.2008.070623","type":"journal-article","created":{"date-parts":[[2008,8,1]],"date-time":"2008-08-01T12:56:43Z","timestamp":1217595403000},"page":"1409-1418","source":"Crossref","is-referenced-by-count":75,"title":["Subantimicrobial\u2010Dose Doxycycline Modulates Gingival Crevicular Fluid Biomarkers of Periodontitis in Postmenopausal Osteopenic Women"],"prefix":"10.1002","volume":"79","author":[{"given":"Lorne 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