{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T22:44:13Z","timestamp":1786833853021,"version":"build-2736575974"},"reference-count":50,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2012,12,30]],"date-time":"2012-12-30T00:00:00Z","timestamp":1356825600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Periodontal Research"],"published-print":{"date-parts":[[2013,10]]},"abstract":"<jats:sec><jats:title>Background and Objective<\/jats:title><jats:p>Local host\u2010modulation therapy is an emerging approach to prevent disease progression in sites with moderate periodontitis. The combination of simvastatin and alendronate would be an intriguing host\u2010modulatory strategy because of the bone\u2010anabolic properties of simvastatin and the antiresorptive\/bone\u2010targeting characteristics of alendronate. The objective of this study was to evaluate the effects of local administration of a simvastatin\u2013alendronate\u2013\u03b2\u2010cyclodextrin (<jats:styled-content style=\"fixed-case\">SIM<\/jats:styled-content>\u2013<jats:styled-content style=\"fixed-case\">ALN<\/jats:styled-content>\u2013<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>) conjugate for preventing experimental periodontitis bone loss.<\/jats:p><\/jats:sec><jats:sec><jats:title>Material and Methods<\/jats:title><jats:p>Twenty\u2010four mature female Sprague\u2013Dawley rats were treated with three, 12\u00a0\u03bcL injections, administered one week apart, bilaterally into the palatal\/interproximal gingiva. The injections contained: (i) a conjugate of 0.5\u00a0mg of<jats:styled-content style=\"fixed-case\">SIM<\/jats:styled-content>and 3.75\u00a0mg of<jats:styled-content style=\"fixed-case\">ALN<\/jats:styled-content>\u2013<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>in H<jats:sub>2<\/jats:sub>O; (ii) H<jats:sub>2<\/jats:sub>O alone; or (iii) no treatment. One week later, the same sites were subjected to induction of experimental periodontitis by three injections (i.e. one injection administered every other day for five\u00a0d) of 0.01\u00a0mg of<jats:italic>Escherichia coli<\/jats:italic>endotoxin [lipopolysaccharide (<jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content>)] in phosphate\u2010buffered saline (<jats:styled-content style=\"fixed-case\">PBS<\/jats:styled-content>) or<jats:styled-content style=\"fixed-case\">PBS<\/jats:styled-content>alone. After an additional week, the rats were killed, the palates were harvested and interproximal bone volume and adjacent thickness were calculated using microcomputed tomography. Subsequently, specimens were decalcified, and interproximal histologic sections were stained with hematoxylin and eosin for evaluation of alveolar crest osteoclasts and surrounding inflammation. Values were compared among treatment groups using analysis of variance and the Kruskal\u2013Wallis test.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Interproximal bone volume was reduced by<jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content>injections (<jats:italic>p\u00a0<\/jats:italic>\u2264<jats:italic>\u00a0<\/jats:italic>0.04), yet when experimental periodontitis was preceded by treatment with<jats:styled-content style=\"fixed-case\">SIM<\/jats:styled-content>\u2013<jats:styled-content style=\"fixed-case\">ALN<\/jats:styled-content>\u2013<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>, more bone was preserved than after treatment with carrier alone (<jats:italic>p\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>0.007). While<jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content>caused a significant loss in bone thickness over the palatal roots (<jats:italic>p\u00a0<\/jats:italic>\u2264<jats:italic>\u00a0<\/jats:italic>0.04), the injection protocol (<jats:styled-content style=\"fixed-case\">PBS<\/jats:styled-content>) also caused a significant loss of palatal bone thickness (<jats:italic>p<\/jats:italic>\u00a0\u2264\u00a00.03). However, prophylactic<jats:styled-content style=\"fixed-case\">SIM<\/jats:styled-content>\u2013<jats:styled-content style=\"fixed-case\">ALN<\/jats:styled-content>\u2013<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>injections resulted in no further loss of bone thickness during experimental periodontitis.<jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content>injections gave histologic evidence of increased osteoclasts and subsulcular inflammation, both of which were reduced when preceded by treatment with<jats:styled-content style=\"fixed-case\">SIM<\/jats:styled-content>\u2013<jats:styled-content style=\"fixed-case\">ALN<\/jats:styled-content>\u2013<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>(<jats:italic>p\u00a0<\/jats:italic>\u2264<jats:italic>\u00a0<\/jats:italic>0.0002).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The primary conclusion of this study was that locally applied<jats:styled-content style=\"fixed-case\">SIM<\/jats:styled-content>\u2013<jats:styled-content style=\"fixed-case\">ALN<\/jats:styled-content>\u2013<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>has the potential to prevent episodes of periodontitis bone loss.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jre.12036","type":"journal-article","created":{"date-parts":[[2013,1,1]],"date-time":"2013-01-01T17:53:13Z","timestamp":1357062793000},"page":"541-548","source":"Crossref","is-referenced-by-count":32,"title":["Effects of local simvastatin\u2013alendronate conjugate in preventing periodontitis bone loss"],"prefix":"10.1111","volume":"48","author":[{"given":"U.","family":"Price","sequence":"first","affiliation":[{"name":"Department of Surgical Specialties University of Nebraska Medical Center, College of Dentistry Lincoln NE USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. \u2010O. T.","family":"Le","sequence":"additional","affiliation":[{"name":"Department of Surgical Specialties University of Nebraska Medical Center, College of Dentistry Lincoln NE USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. E.","family":"Powell","sequence":"additional","affiliation":[{"name":"Department of Growth and Development University of Nebraska Medical Center, College of Dentistry Lincoln NE USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. J.","family":"Schmid","sequence":"additional","affiliation":[{"name":"Research\/Administration University of Nebraska Medical Center College of Dentistry Lincoln NE USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. B.","family":"Marx","sequence":"additional","affiliation":[{"name":"Department of Statistics University of Nebraska Lincoln NE USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences University of Nebraska Medical Center College of Pharmacy Omaha NE USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences University of Nebraska Medical Center College of Pharmacy Omaha NE USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Narayana","sequence":"additional","affiliation":[{"name":"Department of Oral Biology University of Nebraska Medical Center, College of Dentistry Lincoln NE USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. 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