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Background: To investigate changes in the levels and relative ratios of sclerostin, osteoprotegerin (OPG), and receptor activator of nuclear factor-κB ligand (RANKL) in the gingival crevicular fluid (GCF) of patients with periodontitis after non-surgical periodontal treatment., Methods: Fifty-four individuals (27 healthy controls and 27 patients with chronic periodontitis [CP]) were enrolled in the study. Periodontitis patients received non-surgical periodontal therapy. GCF sampling and clinical periodontal parameters were assessed before and 6 weeks after therapy. Sclerostin, OPG, and RANKL levels were measured by enzyme-linked immunosorbent assay, and their relative ratios were calculated., Results: Total amounts and concentrations of sclerostin were significantly higher in patients with CP than in healthy individuals (P <0.025) and decreased after treatment (P <0.05). The RANKL/OPG ratio was significantly lower in healthy individuals than in patients with periodontitis before and after treatment (P <0.025), but no significant difference was observed in patients with periodontitis after treatment (P >0.05). The sclerostin/OPG and sclerostin/RANKL ratios were significantly lower in healthy individuals than in patients with periodontitis before and after treatment (P <0.025) and decreased in patients with periodontitis after treatment (P <0.05)., Conclusions: The GCF sclerostin level may be more reliable than the RANKL/OPG ratio as a diagnostic and prognostic marker of periodontal disease and treatment outcome. Regulation of sclerostin levels may aid the development of new therapeutic strategies for the treatment of periodontal disease.