{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T10:21:44Z","timestamp":1781605304143,"version":"3.54.5"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T00:00:00Z","timestamp":1749686400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Vice Chancellor for Research Affairs of Shiraz University of Medical Sciences","award":["23017"],"award-info":[{"award-number":["23017"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>White spot lesions (WSLs) are frequently encountered after orthodontic treatment. Natural remineralization is often limited, necessitating supplementary treatments.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>This study evaluated the remineralizing effects of 10% xylitol varnish, 5% fluoride varnish, and placebo on WSLs after orthodontic treatment.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Materials and Methods<\/jats:title>\n                  <jats:p>This single-center, randomized, placebo-controlled, triple-blind clinical trial enrolled 84 patients (n\u2005=\u200528\/group) aged 14\u201225 years, who had developed WSLs after completing orthodontic treatment. The participants were randomly assigned to 5% fluoride varnish, 10% xylitol varnish, or placebo varnish groups. Randomization was performed using computer-generated block randomization. Participants, the clinician applying the varnishes and outcome assessors were all blinded to group allocation. Varnishes were applied every three months after debonding, and enamel mineralization was assessed using DIAGNOdent and visual scoring at baseline (T0), 6 months (T1), and 12 months (T2). Statistical analysis included the Kruskal-Wallis test, GEE modeling, and chi-squared test for WSL frequency (p\u2005&amp;lt;\u20050.05).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Eighty-one participants were included in the intention-to-treat (ITT) and 76 in the per-protocol analyses. Significant improvements in mineral content were observed in all the groups after six (p\u2005=\u20050.007) and 12 months (p\u2005&amp;lt;\u20050.001). At T2, the fluoride group demonstrated a greater increase in enamel mineralization compared to the xylitol group (p=\u20050.045 in ITT, p\u2005=\u20050.063 in per-protocol). Visual assessment revealed significantly fewer WSLs in the fluoride group (12.1%) compared to the placebo group (25.1%) at T2 (OR\u2005=\u20050.41, 95% CI: 0.24\u20130.69, p\u2005=\u20050.001). No significant difference in WSL reduction was noted between the xylitol and placebo groups.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Both fluoride and xylitol varnishes improved enamel mineralization, with fluoride showing superior long-term efficacy in reducing WSLs. These findings support using fluoride varnish after orthodontic treatment to prevent and manage WSLs.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Harms<\/jats:title>\n                  <jats:p>No harm was observed during this study.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Trial Registration<\/jats:title>\n                  <jats:p>This trial was registered and approved by the Iranian Registry of Clinical Trials under the registration code IRCT20180913041032N2.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Funding<\/jats:title>\n                  <jats:p>This study was funded by Shiraz University of Medical Sciences.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ejo\/cjaf047","type":"journal-article","created":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T07:03:26Z","timestamp":1749711806000},"source":"Crossref","is-referenced-by-count":1,"title":["Effectiveness of fluoride and xylitol varnishes in treating post-orthodontic white spot lesions: a randomized clinical trial"],"prefix":"10.1093","volume":"47","author":[{"given":"Hooman","family":"Zarif Najafi","sequence":"first","affiliation":[{"name":"Orthodontic Research Center, School of Dentistry, Shiraz University of Medical Sciences , Mehr Avenue, Ghasrodasht Street, Shiraz, 71956 - 15878 ,","place":["Iran"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7013-6048","authenticated-orcid":false,"given":"Mojgan","family":"Shavakhi","sequence":"additional","affiliation":[{"name":"Dental Research Center, Department of Orthodontics, Dental Research Institute, School of Dentistry, Isfahan University of Medical Sciences , Hezar Jerib Street, Isfahan 81746-73461 ,","place":["Iran"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,6,12]]},"reference":[{"key":"2025061203032209200_CIT0001","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1016\/j.ajodo.2015.07.039","article-title":"Caries prevention during orthodontic treatment: In-vivo assessment of high-fluoride varnish to prevent white spot lesions","volume":"149","author":"Perrini","year":"2016","journal-title":"Am J Orthod Dentofacial Orthop"},{"key":"2025061203032209200_CIT0002","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/0889-5406(88)90453-2","article-title":"Orthodontic appliances and enamel demineralization: part 1. Lesion development","volume":"94","author":"\u00d8gaard","year":"1988","journal-title":"Am J Orthod Dentofacial Orthop"},{"key":"2025061203032209200_CIT0003","doi-asserted-by":"publisher","first-page":"1343","DOI":"10.1007\/s00784-013-1073-5","article-title":"Fluoride releasing and enamel demineralization around orthodontic brackets by fluoride-releasing composite containing nanoparticles","volume":"18","author":"Melo","year":"2014","journal-title":"Clin Oral Investig"},{"key":"2025061203032209200_CIT0004","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/0889-5406(88)90360-5","article-title":"Orthodontic appliances and enamel demineralization Part 2. Prevention and treatment of lesions","volume":"94","author":"\u00d8gaard","year":"1988","journal-title":"Am J Orthod Dentofacial Orthop"},{"key":"2025061203032209200_CIT0005","doi-asserted-by":"publisher","first-page":"1187","DOI":"10.1177\/0022034510376046","article-title":"New approaches to enhanced remineralization of tooth enamel","volume":"89","author":"Cochrane","year":"2010","journal-title":"J Dent Res"},{"key":"2025061203032209200_CIT0006","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1016\/j.adaj.2018.05.010","article-title":"Enamel remineralization therapies for treating postorthodontic white-spot lesions: a systematic review","volume":"149","author":"Fernandez-Ferrer","year":"2018","journal-title":"J Am Dent Assoc"},{"key":"2025061203032209200_CIT0007","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1093\/ejo\/cjw023","article-title":"Management of post-orthodontic white spot lesions: an updated systematic review","volume":"39","author":"Sonesson","year":"2017","journal-title":"Eur J Orthod"},{"key":"2025061203032209200_CIT0008","doi-asserted-by":"publisher","first-page":"4153","DOI":"10.1007\/s00784-020-03610-z","article-title":"Effectiveness of remineralizing agents in the prevention and reversal of orthodontically induced white spot lesions: a systematic review and network meta-analysis","volume":"24","author":"Hu","year":"2020","journal-title":"Clin Oral Investig"},{"key":"2025061203032209200_CIT0009","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1186\/s40510-016-0138-9","article-title":"Effects of various remineralizing agents on the outcome of post-orthodontic white spot lesions (WSLs): a clinical trial","volume":"17","author":"Singh","year":"2016","journal-title":"Prog Orthod"},{"key":"2025061203032209200_CIT0010","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1093\/ejo\/cjw061","article-title":"Changes in white spot lesions following post-orthodontic weekly application of 1.25 per cent fluoride gel over 6 months\u2014a randomized placebo-controlled clinical trial. Part II: clinical data evaluation","volume":"39","author":"Bock","year":"2017","journal-title":"Eur J Orthod"},{"key":"2025061203032209200_CIT0011","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.ajodo.2012.09.007","article-title":"Effectiveness of MI Paste Plus and PreviDent fluoride varnish for treatment of white spot lesions: a randomized controlled trial","volume":"143","author":"Huang","year":"2013","journal-title":"Am J Orthod Dentofacial Orthop"},{"key":"2025061203032209200_CIT0012","doi-asserted-by":"publisher","first-page":"810","DOI":"10.1016\/j.ajodo.2015.12.010","article-title":"Comparative assessment of fluoride varnish and fluoride film for remineralization of postorthodontic white spot lesions in adolescents and adults over a 6-month period: a single-center, randomized controlled clinical trial","volume":"149","author":"He","year":"2016","journal-title":"Am J Orthod Dentofacial Orthop"},{"key":"2025061203032209200_CIT0013","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1007\/s00784-011-0520-4","article-title":"Randomized controlled trial on fluoride varnish application for treatment of white spot lesion after fixed orthodontic treatment","volume":"16","author":"Du","year":"2012","journal-title":"Clin Oral Investig"},{"key":"2025061203032209200_CIT0014","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1093\/ejo\/cjw065","article-title":"Interventions for orthodontically induced white spot lesions: a systematic review and meta-analysis","volume":"39","author":"H\u00f6chli","year":"2017","journal-title":"Eur J Orthod"},{"key":"2025061203032209200_CIT0015","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1016\/j.tox.2007.10.026","article-title":"Involvement of both mitochondrial-and death receptor-dependent apoptotic pathways regulated by Bcl-2 family in sodium fluoride-induced apoptosis of the human gingival fibroblasts","volume":"243","author":"Lee","year":"2008","journal-title":"Toxicology"},{"key":"2025061203032209200_CIT0016","doi-asserted-by":"publisher","first-page":"305","DOI":"10.3109\/15376516.2012.657259","article-title":"Effects of NaF on the expression of intracellular Ca2+ fluxes and apoptosis and the antagonism of taurine in murine neuron","volume":"22","author":"Haojun","year":"2012","journal-title":"Toxicol Mech Methods"},{"key":"2025061203032209200_CIT0017","first-page":"22","article-title":"Fluoride: safety issues","volume":"72","author":"Li","year":"1993","journal-title":"J Indiana Dent Assoc."},{"key":"2025061203032209200_CIT0018","doi-asserted-by":"publisher","first-page":"1922","DOI":"10.1002\/adma.200702377","article-title":"Biodegradable xylitol-based polymers","volume":"20","author":"Bruggeman","year":"2008","journal-title":"Adv Mater"},{"key":"2025061203032209200_CIT0019","doi-asserted-by":"publisher","first-page":"290","DOI":"10.3390\/nu2030290","article-title":"Streptococcus mutans, caries and simulation models","volume":"2","author":"Forssten","year":"2010","journal-title":"Nutrients."},{"key":"2025061203032209200_CIT0020","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1159\/000261011","article-title":"Effect of xylitol and sorbitol on polysaccharide production by and adhesive properties of Streptococcus mutans","volume":"21","author":"S\u00f6derling","year":"1987","journal-title":"Caries Res"},{"key":"2025061203032209200_CIT0021","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1177\/0895937409335642","article-title":"Xylitol, mutans streptococci, and dental plaque","volume":"21","author":"S\u00f6derling","year":"2009","journal-title":"Adv Dent Res"},{"key":"2025061203032209200_CIT0022","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1007\/s00284-009-9496-6","article-title":"Xylitol and erythritol decrease adherence of polysaccharide-producing oral streptococci","volume":"60","author":"S\u00f6derling","year":"2010","journal-title":"Curr Microbiol"},{"key":"2025061203032209200_CIT0023","doi-asserted-by":"publisher","first-page":"4","DOI":"10.21767\/2471-299X.1000041","article-title":"Xylitol and fluoride provide an alternative preventive therapy in antibiotic resistance crisis","volume":"02","author":"Palchaudhuri","year":"2016","journal-title":"Med Clin Rev."},{"key":"2025061203032209200_CIT0024","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1159\/000260780","article-title":"Influence of xylitol on demineralization of enamel","volume":"18","author":"Arends","year":"1984","journal-title":"Caries Res"},{"key":"2025061203032209200_CIT0025","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1093\/jmicro\/52.5.471","article-title":"Remineralization effects of xylitol on demineralized enamel","volume":"52","author":"Miake","year":"2003","journal-title":"J Electron Microsc (Tokyo)"},{"key":"2025061203032209200_CIT0026","first-page":"31","article-title":"Remineralizing potential, antiplaque and antigingivitis effects of xylitol and sorbitol sweetened chewing gum","volume":"14","author":"Steinberg","year":"1992","journal-title":"Clin Prev Dent"},{"key":"2025061203032209200_CIT0027","first-page":"93","article-title":"Stabilisation of rampant caries: polyol gums and arrest of dentine caries in two long-term cohort studies in young subjects","volume":"45","author":"M\u00e4kinen","year":"1995","journal-title":"Int Dent J"},{"key":"2025061203032209200_CIT0028","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1590\/s1678-77572012000200004","article-title":"Xylitol concentrations in artificial saliva after application of different xylitol dental varnishes","volume":"20","author":"Pereira","year":"2012","journal-title":"J Appl Oral Sci"},{"key":"2025061203032209200_CIT0029","first-page":"505","article-title":"The combined effect of xylitol and fluoride in varnish on bovine teeth surface microhardness","volume":"45","author":"Vongsavan","year":"2014","journal-title":"Southeast Asian J Trop Med Public Health"},{"key":"2025061203032209200_CIT0030","doi-asserted-by":"publisher","first-page":"1495","DOI":"10.1016\/j.jdent.2014.08.009","article-title":"Effect of xylitol varnishes on remineralization of artificial enamel caries lesions in vitro","volume":"42","author":"Cardoso","year":"2014","journal-title":"J Dent"},{"key":"2025061203032209200_CIT0031","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.jdent.2016.03.011","article-title":"Effect of xylitol varnishes on remineralization of artificial enamel caries lesions in situ","volume":"50","author":"Cardoso","year":"2016","journal-title":"J Dent"},{"key":"2025061203032209200_CIT0032","doi-asserted-by":"publisher","first-page":"105873","DOI":"10.1016\/j.archoralbio.2023.105873","article-title":"Xylitol associated or not with fluoride: Is the action the same on de-and remineralization","volume":"159","author":"Carvalho","year":"2024","journal-title":"Arch Oral Biol"},{"key":"2025061203032209200_CIT0033","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1093\/ejo\/cjab049","article-title":"Evaluation of the preventive effect of two concentrations of xylitol varnish versus fluoride varnish on enamel demineralization around orthodontic brackets: a randomized controlled trial","volume":"44","author":"Zarif Najafi","year":"2022","journal-title":"Eur J Orthod"},{"key":"2025061203032209200_CIT0034","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1177\/1740774510391683","article-title":"Comparison of dynamic block randomization and minimization in randomized trials: a simulation study","volume":"8","author":"Xiao","year":"2011","journal-title":"Clin Trials"},{"key":"2025061203032209200_CIT0035","first-page":"249","article-title":"In vitro study of laser diode 655\u00a0nm diagnosis of occlusal caries","volume":"69","author":"Costa","year":"2002","journal-title":"ASDC J Dent Child"},{"key":"2025061203032209200_CIT0036","first-page":"287","article-title":"Clinical evaluation of diagnodent in detection of occlusal caries in children","volume":"30","author":"Olmez","year":"2006","journal-title":"J Clin Pediatr Dent"},{"key":"2025061203032209200_CIT0037","doi-asserted-by":"publisher","first-page":"227","DOI":"10.4103\/0970-4388.57658","article-title":"Comparison of validity of DIAGNOdent with conventional methods for detection of occlusal caries in primary molars using the histological gold standard: an in vivo study","volume":"27","author":"Goel","year":"2009","journal-title":"J Indian Soc Pedod Prev Dent"},{"key":"2025061203032209200_CIT0038","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1007\/s10103-012-1111-6","article-title":"Evaluation of a new fluorescence-based device in the detection of incipient occlusal caries lesions","volume":"28","author":"Achilleos","year":"2013","journal-title":"Lasers Med Sci"},{"key":"2025061203032209200_CIT0039","doi-asserted-by":"publisher","first-page":"cjad070","DOI":"10.1093\/ejo\/cjad070","article-title":"White spot lesions after fixed appliance treatment\u2014Can we expect spontaneous long-term (\u2265 15 years) improvement","volume":"46","author":"Bock","year":"2024","journal-title":"Eur J Orthod"},{"key":"2025061203032209200_CIT0040","doi-asserted-by":"publisher","first-page":"527","DOI":"10.17219\/dmp\/140964","article-title":"Systematic review of preventive and treatment measures regarding orthodontically induced white spot lesions","volume":"60","author":"Yazarloo","year":"2023","journal-title":"Dent Med Probl"},{"key":"2025061203032209200_CIT0041","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1159\/000540375","article-title":"Effectiveness of fluoride varnishes for white spot lesion prevention and remineralization during orthodontic treatment: a randomized controlled trial","volume":"58","author":"Moraes","year":"2024","journal-title":"Caries Res"},{"key":"2025061203032209200_CIT0042","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1007\/s00784-025-06172-0","article-title":"A 12-months randomized clinical trial comparing fluoride-based remineralising protocols on post-orthodontic initial caries lesions","volume":"29","author":"Wan Hassan","year":"2025","journal-title":"Clin Oral Investig"},{"key":"2025061203032209200_CIT0043","doi-asserted-by":"publisher","first-page":"e70062","DOI":"10.1002\/cre2.70062","article-title":"Effect of xylitol and fluoride varnish on biofilm and saliva in orthodontic patients: a triple-blind randomized clinical trial","volume":"11","author":"Babanouri","year":"2025","journal-title":"Clin Exp Dent Res"},{"key":"2025061203032209200_CIT0044","doi-asserted-by":"publisher","first-page":"3421","DOI":"10.1007\/s00784-021-03930-8","article-title":"Prevention of non-cavitated lesions with fluoride and xylitol varnishes during orthodontic treatment: a randomized clinical trial","volume":"25","author":"Silva","year":"2021","journal-title":"Clin Oral Investig"},{"key":"2025061203032209200_CIT0045","doi-asserted-by":"publisher","first-page":"51","DOI":"10.35629\/5252-03025164","article-title":"Review on role of Xylitol in the re-mineralization of dental caries","volume":"3","author":"Bisla","year":"2021","journal-title":"Int J Dent Med Sci Res"},{"key":"2025061203032209200_CIT0046","first-page":"49","article-title":"Mechanisms of action of fluoride in dental caries","volume":"22","author":"Khan","year":"2002","journal-title":"Pak Oral Dent J"}],"container-title":["European Journal of Orthodontics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ejo\/article-pdf\/47\/4\/cjaf047\/63474162\/cjaf047.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ejo\/article-pdf\/47\/4\/cjaf047\/63474162\/cjaf047.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T07:03:28Z","timestamp":1749711808000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ejo\/article\/doi\/10.1093\/ejo\/cjaf047\/8160715"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,12]]},"references-count":46,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,6,12]]}},"URL":"https:\/\/doi.org\/10.1093\/ejo\/cjaf047","relation":{},"ISSN":["0141-5387","1460-2210"],"issn-type":[{"value":"0141-5387","type":"print"},{"value":"1460-2210","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,8]]},"published":{"date-parts":[[2025,6,12]]},"article-number":"cjaf047"}}