{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T12:02:05Z","timestamp":1789387325249,"version":"build-2803163510"},"reference-count":0,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2001,8,1]],"date-time":"2001-08-01T00:00:00Z","timestamp":996624000000},"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":[[2001,8]]},"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Chemically modified non\u2010antimicrobial tetracyclines (CMTs) have been shown to inhibit pathologically elevated collagenase (and other matrix metalloproteinase, MMP) activity and bone resorption in vivo and in vitro.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> In the current study, suboptimal doses of CMT\u20108 (a non\u2010antimicrobial chemically modified doxycycline) and a bisphosphonate (clodronate, an anti\u2010bone resorption compound) were administered daily, either as a single agent or as a combination therapy, to rats with experimental periodontitis induced by repeated injection of bacterial endotoxin (LPS) into the gingiva. At the end of the l\u2010week protocol, the gingival tissues were dissected, extracted, and the extracts analyzed for MMPs (collagenases and gelatinases) and for elastase, and the defleshed jaws were morphometrically analyzed for alveolar bone loss.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> LPS injection significantly (<jats:italic>P<\/jats:italic> &lt;0.00l) increased alveolar bone loss and increased collagenase (MMP\u20108), gelatinase (MMP\u20109), and elastase activities. Treatment of the LPS\u2010injected rats with suboptimal CMT\u20108 alone or suboptimal clodronate alone produced slight reductions in the tissue\u2010destructive proteinases and no significant reductions in alveolar bone loss. However, a combination of suboptimal CMT\u20108 and clodronate \u201cnormalized\u201d the pathologically elevated levels of MMPs, elastase, and alveolar bone loss, indicating synergistic inhibition of tissue breakdown in this animal model of periodontitis.<\/jats:p><jats:p><jats:bold>Conclusions:<\/jats:bold> Combination of a CMT and a bisphosphonate may be a useful treatment to optimally suppress periodontal destruction and tooth loss and in other tissue\u2010destructive inflammatory diseases such as arthritis. <jats:italic>J Periodontol 2001;72:1069\u20101077.<\/jats:italic><\/jats:p>","DOI":"10.1902\/jop.2001.72.8.1069","type":"journal-article","created":{"date-parts":[[2005,2,2]],"date-time":"2005-02-02T07:00:21Z","timestamp":1107327621000},"page":"1069-1077","source":"Crossref","is-referenced-by-count":51,"title":["A Combination of a Chemically Modified Doxycycline and a Bisphosphonate Synergistically Inhibits Endotoxin\u2010Induced Periodontal Breakdown in Rats"],"prefix":"10.1002","volume":"72","author":[{"given":"Analeyda","family":"Llavaneras","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nungavaram S.","family":"Ramamurthy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pia","family":"Heikkil\u00e4","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olli","family":"Teronen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuula","family":"Salo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry R.","family":"Rifkin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria E.","family":"Ryan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorne M.","family":"Golub","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timo","family":"Sorsa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2001,8]]},"container-title":["Journal of Periodontology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/aap.onlinelibrary.wiley.com\/doi\/pdf\/10.1902\/jop.2001.72.8.1069","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T13:38:40Z","timestamp":1760881120000},"score":1,"resource":{"primary":{"URL":"https:\/\/aap.onlinelibrary.wiley.com\/doi\/10.1902\/jop.2001.72.8.1069"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,8]]},"references-count":0,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2001,8]]}},"alternative-id":["10.1902\/jop.2001.72.8.1069"],"URL":"https:\/\/doi.org\/10.1902\/jop.2001.72.8.1069","archive":["Portico"],"relation":{},"ISSN":["0022-3492","1943-3670"],"issn-type":[{"value":"0022-3492","type":"print"},{"value":"1943-3670","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,8]]}}}