{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T23:32:29Z","timestamp":1776468749182,"version":"3.51.2"},"reference-count":29,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T00:00:00Z","timestamp":1736899200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82102221"],"award-info":[{"award-number":["82102221"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["aap.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Periodontology"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Previous research has indicated a potential connection between smoking and tooth loss, but it remains unclear how the metabolites of nicotine, cotinine (COT) and trans\u20103\u2032\u2010hydroxycotinine (HC), and the nicotine metabolite ratio (NMR) affect the occurrence and progress of tooth loss. In this study, we aimed to investigate the relationship between tooth loss and smoking metabolites, then verify how the systemic immunoinflammatory index (SII) or monocyte to high\u2010density lipoprotein cholesterol ratio (MHR) levels mediate this process.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The cross\u2010sectional study data were collected from the National Health and Nutrition Examination Survey (NHANES). After screening and comparing the baseline data, regression models were utilized to evaluate the relationship between serum COT\u00a0+\u00a0HC level and tooth loss, as well as COT\u00a0+\u00a0HC and SII\/MHR and tooth loss. Furthermore, bootstrapping was applied to test the mediation effect of SII and MHR in the association between COT\u00a0+\u00a0HC and tooth loss.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 9036 subjects were included in the study, with 2795 individuals in the COT\/HC\u2212 group and 6241 in the COT\/HC+ group. In the models with covariates adjusted, COT\u00a0+\u00a0HC level was found to be positively correlated with tooth loss (Model 3: odds ratio [OR]\u00a0=\u00a01.001, 95% CI\u00a0=\u00a01.001\u20131.001), especially in the fourth quartile (Q4) of COT\u00a0+\u00a0HC level (Model 3: OR\u00a0=\u00a02.647, 95% CI\u00a0=\u00a02.645\u20132.649) as compared to Q1. Furthermore, NMR was found to be negatively associated with tooth loss after adjustments (Model 3: OR\u00a0=\u00a00.803, 95% CI\u00a0=\u00a00.802\u20130.803). For mediation analysis, COT\u00a0+\u00a0HC level was significantly correlated with SII score, and SII was proved to be positively associated with tooth loss; meanwhile, COT\u00a0+\u00a0HC level was significantly correlated with MHR, and MHR was positively associated with tooth loss. SII and MHR played a partial mediating role in the association between COT\u00a0+\u00a0HC and tooth loss, and the indirect effect was 0.0001 (SII; 95% CI\u00a0=\u00a00.0000\u20130.0002) and 0.0002 (MHR; 95% CI\u00a0=\u00a00.0001\u20130.0004), respectively. The mediating effect of both SII and MHR was 0.0003 (95% CI\u00a0=\u00a00.0001\u20130.0004).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study revealed that the level of nicotine metabolites (COT\u00a0+\u00a0HC) was a risk factor, while higher NMR was a protective factor for tooth loss, and further demonstrated the partial mediating role of SII and MHR in the association between COT\u00a0+\u00a0HC and tooth loss.<\/jats:p><\/jats:sec><jats:sec><jats:title>Plain Language Summary<\/jats:title><jats:p>Prior studies have suggested a possible link between smoking and tooth loss, but how certain nicotine byproducts and their ratios impact tooth loss is unclear. This research aimed to explore how these smoking metabolites influence tooth loss. Data from national health surveys were used for a cross\u2010sectional study to assess the connection between cotinine levels in the blood and tooth loss, as well as to understand if immune and cholesterol markers mediate the link between smoking metabolites and tooth loss. The results showed a positive relationship between cotinine levels and tooth loss. The immune and cholesterol markers were found to partially mediate the relationship between smoking metabolites and tooth loss. Higher levels of nicotine byproducts were linked to an increased risk of tooth loss.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jper.24-0249","type":"journal-article","created":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T09:16:59Z","timestamp":1736932619000},"page":"807-816","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Cotinine, trans\u20103\u2032\u2010hydroxycotinine, and nicotine metabolite ratio indicate association between smoking and tooth loss"],"prefix":"10.1002","volume":"96","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2909-3397","authenticated-orcid":false,"given":"Yuwei","family":"Zhang","sequence":"first","affiliation":[{"name":"Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research College of Stomatology Xi'an Jiaotong University  Xi'an Shaanxi China"},{"name":"Clinical Research Center of Shaanxi Province for Dental and Maxillofacial Diseases  Xi'an Shaanxi 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