Rheumatoid arthritis is an autoimmune diseasecharacterized by chronic inflammationthat affects joints and cartilage. Bone complications such asRA-relatedosteoporosis are one of the most extra-articular manifestations. Many inflammatory mediators are released during RA disease pathophysiology; these mediators stimulate osteoclast genesis of bone by direct effects on RANKL and OPG. The study aimedto measure RANKL, OPG in RA patients treated with Etanercept only and other groups treated with Methotrexate onlyat baseline and after three months to evaluate bone state. An observational case-control prospective study was done on 30 RA patients who received MTX, 30 RA patients who received ETN, and 30 healthy,age-matched control groups. The level of RANKL and OPG was measured at baseline and after three months of therapy by immunoenzymatically assay (ELISA). The results were tabulated and statistically analyzed usingthe statistical package for social science. The result demonstrated that RANKL level had a positive correlation with age and disease duration in contrast to OPG level showed a negative correlation with age and duration of disease. In the patients group treated with MTX at baseline, the RANKL level was significantly higher (181.336±65.583) than post-therapy (166.097±69.229), while the OPG level at baseline significantly lower (594.398±133.238) than post therapy (614.499±150.879). In ETN treated patients, the level of RANKL in baseline was significantly higher than (231.247±73.134) RANKL level post-therapy (200.363±76.807), while OPG level in baseline waslower (463.263±96.392) than post therapy (503.608±107.692). The study demonstrated in baseline RANKL/OPG ratio significant higher (0.4340±0.234) than post therapy (0.3690±0.222). All RA patients had or were at high risk for osteoporosis.Both Etanarcept and methotrexate produce insignificant differences on OPG and RANKL levels, in the same time this biomarkers are not good indicators for bone state.