{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T21:36:20Z","timestamp":1788212180774,"version":"build-2803163510"},"reference-count":52,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T00:00:00Z","timestamp":1742947200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Periodontal Research"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>Poor accuracy of diagnostic and prognostic tools prevents the prediction of peri\u2010implant disease stability or progression. We analyzed metabolites from peri\u2010implant crevicular fluid (PICF) samples from healthy and diseased implants to identify those diagnostic of health and peri\u2010implant disease and predictive of peri\u2010implant bone loss over time.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Clinical, radiographic examinations and PICF samples were collected from 59 healthy implants, 33 implants with peri\u2010implantitis, and 38 implants with peri\u2010implant mucositis in 71 subjects. A subset of implants was evaluated at 6, 12, 18, and 24\u2009months. Over time, all initially healthy implants remained stable (Group B, <jats:italic>N<\/jats:italic>\u2009=\u200928), whereas 6 initially diseased implants continued to lose bone and 8 did not (Group C). PICF metabolites were measured using proton\u2010nuclear magnetic resonance (1H\u2010NMR) 2\u2010dimensional Total Correlation Spectroscopy. PCA and PLS\u2010DA tested the cross\u2010sectional clustering and importance of each metabolite, while the AUC summarized the accuracy of predicting radiographic bone changes \u2265\u20091\u2009mm at 6\u2010month intervals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>At baseline, the Cadaverine\/Lysine and Putrescine\/Lysine signatures diagnosed peri\u2010implantitis (AUC\u2009=\u20090.76 and 0.70; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.000) with good accuracy, while alpha\u2010ketoglutarate diagnosed implant health (AUC\u2009=\u20090.706; <jats:italic>p<\/jats:italic>\u2009=\u20090.002). Combining metabolites increased diagnostic accuracy (AUC<jats:sub>Cadaverine\/Lysine+Methionine<\/jats:sub>\u2009=\u20090.81; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01). Proline and 1\u20103\u2010diaminopropane predicted future bone loss (AUC<jats:sub>Proline<\/jats:sub>\u2009=\u20090.917 and AUC<jats:sub>1\u20103\u2010diaminopropane<\/jats:sub>\u2009=\u20090.854). ANOVA <jats:italic>post hoc<\/jats:italic> analysis established that biotin and propionate levels were higher in Group C compared to Groups A and B (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001; AUC<jats:sub>biotin<\/jats:sub>\u2009=\u20090.889; AUC<jats:sub>propionate<\/jats:sub>\u2009=\u20090.87). Valine levels were higher in Groups A and C compared to Group B (<jats:italic>p<\/jats:italic>\u2009=\u20090.002; AUC\u2009=\u20090.841).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p><jats:sup>1<\/jats:sup>H\u2010NMR 2\u2010dimensional spectroscopy identified PICF metabolites diagnostic of peri\u2010implantitis with high accuracy. Despite the small number of affected implants, metabolite signatures that predict future bone loss in peri\u2010implantitis appear to be different from those diagnostic of peri\u2010implantitis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jre.13400","type":"journal-article","created":{"date-parts":[[2025,3,29]],"date-time":"2025-03-29T17:31:16Z","timestamp":1743269476000},"page":"775-787","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Accuracy of Metabolomics in Peri\u2010Implant Crevicular Fluid for Diagnosis and Prognosis of Peri\u2010Implantitis"],"prefix":"10.1111","volume":"60","author":[{"given":"Hatem","family":"Alassy","sequence":"first","affiliation":[{"name":"Division of Basic Sciences, Department of Diagnostic and Biological Sciences, School of Dentistry University of Minnesota  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elias","family":"Kersten","sequence":"additional","affiliation":[{"name":"Division of Basic Sciences, Department of Diagnostic and Biological Sciences, School of Dentistry University of Minnesota  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janelle","family":"Hamilton","sequence":"additional","affiliation":[{"name":"Division of Basic Sciences, Department of Diagnostic and Biological Sciences, School of Dentistry University of Minnesota  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Botorous","sequence":"additional","affiliation":[{"name":"Division of Basic Sciences, Department of Diagnostic and Biological Sciences, School of Dentistry University of Minnesota  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0920-649X","authenticated-orcid":false,"given":"Angelomaria","family":"Iuorio","sequence":"additional","affiliation":[{"name":"Private Practice  Aversa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd","family":"Rappe","sequence":"additional","affiliation":[{"name":"Minnesota NMR Center (MNMR) University of Minnesota  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5922-3709","authenticated-orcid":false,"given":"Massimo","family":"Costalonga","sequence":"additional","affiliation":[{"name":"Division of Basic Sciences, Department of Diagnostic and Biological Sciences, School of Dentistry University of Minnesota  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,26]]},"reference":[{"issue":"1","key":"e_1_2_14_2_1","first-page":"S304","article-title":"Peri\u2010Implant Health, Peri\u2010Implant Mucositis, and Peri\u2010Implantitis: Case Definitions and Diagnostic Considerations","volume":"89","author":"Renvert S.","year":"2018","journal-title":"Journal of Periodontology"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.12334"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0757.2010.00348.x"},{"issue":"1","key":"e_1_2_14_5_1","first-page":"S257","article-title":"Peri\u2010Implant Mucositis","volume":"89","author":"Heitz\u2010Mayfield L. 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