BACKGROUND Initial research indicated that higher concentration of osteoprotegerin (OPG) is associated with healthy periodontium (protective) and its concentration decreases as the periodontal disease progresses. However, till date, there are no studies to investigate the levels of OPG in gingival crevicular fluid (GCF) after the treatment of periodontitis. Hence, the present study was carried out to assess its concentration in GCF to find out their association if any, and to explore its possible use as a 'novel bone marker' of the host modulation of periodontal disease. MATERIALS AND METHODS Sixty-four subjects were divided into 4 groups (16 each), based on clinical attachment loss (CAL) and radiological parameters (bone loss); healthy (group I), gingivitis (group II), slight periodontitis (group III), and moderate-to-severe periodontitis (group IV). Moderate-to-severe periodontitis subjects, after nonsurgical periodontal treatment, (SRP) constituted group V. GCF samples were collected to estimate the levels of OPG using enzyme-linked immunosorbent assay (ELISA). The Kruskal-Wallis, Man-Whitney U test, and Wilcoxon signed-rank tests were carried out to compare OPG levels among groups. The Spearman rank correlation test was used to correlate OPG levels between the study groups and the clinical parameters; P < 0.05 was considered significant. RESULTS The highest mean OPG concentration in GCF was obtained for group I (162.47 ± 51.171 pg/ μL) and the least for group IV (10.92 ± 1.913 pg/μL), suggesting a negative correlation between OPG concentration and CAL. OPG concentrations in GCF after the treatment of group IV increased from 10.92 ± 1.913 pg/μL to 15.63 ± 4.679 pg/μL. CONCLUSION OPG concentration in GCF was inversely proportional to CAL and not an active progression factor for periodontal disease. Further, after the treatment of moderate-to-severe periodontitis subjects (group IV), OPG concentrations increased. Hence, it can be concluded that OPG could be considered as a 'novel bone marker' the host modulation of periodontal disease.