Background: Osteopontin (OPN), a glycosylated phosphoprotein, is a bone matrix component produced by osteoblasts, osteoclasts, and macrophages as a multifunctional cytokine. OPN anchors osteoclasts to the bone surface, and its absence leads to impaired bone resorption. The aim of the present study was to assess the relation between clinical parameters and concentrations of OPN within gingival crevicular fluid (GCF) from inflamed gingiva and periodontitis sites and, subsequently, after the treatment of periodontitis sites. Methods: A total of 45 subjects were divided into the following three groups based on modified gingival index (MGI) and Ramfjord periodontal disease index (PDI) scores: healthy (group I), gingivitis (group II), and chronic periodontitis (group III). A fourth group consisted of 15 subjects from group III, 6 to 8 weeks after treatment (i.e. scaling and root planing [SRP]). GCF samples collected from each patient were quantified for OPN using the enzymatic immunometric assay. Further, the correlation between OPN levels in situ with clinical parameters was analyzed in all groups and before and after treatment in periodontitis patients. Results: The highest mean OPN concentration in GCF (14.347 µg/ml) was observed in group III, and the lowest mean OPN concentration in GCF (2.522 µg/ml) was observed in group I. Its levels in group III decreased to 8.419 µg/ml after treatment (group IV). Further, GCF OPN levels in all the groups showed a statistically significant positive correlation with clinical attachment loss (P<0.05). Conclusions: OPN levels increase in GCF from healthy to periodontitis states, and periodontal treatment results in the reduction of OPN levels. The data indicate that OPN may play a key role in, and could be considered a biomarker of, periodontal disease progression. [ABSTRACT FROM AUTHOR]