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The 60 patients included in the study were randomly divided into two groups according to the intracanal dressing. After removing gutta-percha from the root canals, RANKL, OPG, TNF-\u03b1, PGE-2, and TGF-\u03b2 samples were obtained from the apical tissues using three paper cones and the selected dressing material was placed into the canals. In the second appointment, the dressing was removed, and the second samples were taken using the same method. Pre-treatment and post-treatment RANKL, OPG, TNF-\u03b1, PGE-2, and TGF-\u03b2 levels were determined using an enzyme-linked immunosorbent assay test. Data were analysed using <jats:italic>t<\/jats:italic>-test, the Mann\u2013Whitney <jats:italic>U<\/jats:italic> test, the Wilcoxon test, The Fisher\u2013Freeman\u2013Halton test, and Path analysis. No significant difference was found between the groups in terms of demographic variables (age, gender, tooth region, and smoking) (<jats:italic>p<\/jats:italic>\u2009&gt;\u20090.05). There was a statistically significant decrease in RANKL\/OPG, TNF-\u03b1, PGE-2, and TGF-\u03b2 levels before and after treatment in both groups (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). A significant difference was observed in the percentage change of RANKL\/OPG, TNF-\u03b1, and TGF-\u03b2 ratios between the groups (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). A statistically higher decrease in RANKL\/OPG, TNF-\u03b1, and TGF-\u03b2 levels was observed in the calcium hydroxide-based intracanal dressing group (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). No significant difference was observed between the groups in terms of PGE-2 percentage change (<jats:italic>p<\/jats:italic>\u2009&gt;\u20090.05). Tricalcium silicate-based intracanal dressing effectively reduced RANKL\/OPG, TNF-\u03b1, PGE-2, and TGF-\u03b2 levels in periapical lesions, but calcium hydroxide-based intracanal dressing resulted in a higher percentage reduction in RANKL\/OPG, TNF-\u03b1, and TGF-\u03b2 levels. The effects of both medicaments on PGE-2 levels were similar.<\/jats:p>\n          <jats:p>\n            <jats:bold>Trial registration<\/jats:bold> The study was registered in clinical trials database on 12 March 2024 (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/www.clinicaltrials.gov\" ext-link-type=\"uri\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>). Registration number: NCT06307678.<\/jats:p>","DOI":"10.1007\/s10266-025-01093-6","type":"journal-article","created":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T04:13:08Z","timestamp":1743394388000},"page":"1667-1677","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Effect of tricalcium silicate-based intracanal dressing on bone resorption and inflammatory mediators in periapical lesions: a randomized controlled clinical trial"],"prefix":"10.1007","volume":"113","clinical-trial-number":[{"clinical-trial-number":"nct06307678","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"O\u011fuzhan","family":"\u00dcnal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2647-7988","authenticated-orcid":false,"given":"Meltem","family":"S\u00fcmb\u00fcll\u00fc","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esra","family":"Lalo\u011flu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,28]]},"reference":[{"key":"1093_CR1","doi-asserted-by":"publisher","first-page":"712","DOI":"10.1111\/IEJ.13467","volume":"54","author":"CS Tib\u00farcio-Machado","year":"2021","unstructured":"Tib\u00farcio-Machado CS, Michelon C, Zanatta FB, et al. 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