Bone is a common site for metastasis in breast cancer; approximately 75% of women with advanced breast cancer will develop bone metastases. Bone metastases associated with breast cancer are predominately osteolytic. OPG overexpression by breast cancer cells enhances osseous tumor growth. OPG promote tumor cell survival and protect them from TRAIL induced apoptosis. The present study aimed to assess the relevance of OPG to other prognostic factors in breast cancer patients with and without bone metastases.The study was conducted on eighty females who were divided into four groups: group I (n=20) healthy females as a control group, group II (n=20) non-metastatic breast cancer patients, group III a (n=20) breast cancer patients with bone metastases not receiving Bisphosphonates treatment and group III b (n=20) breast cancer patients with bone metastases and were receiving Bisphosphonates treatment. All participants were subjected to a thorough clinical assessment, and estimation of blood levels of fasting glucose, ALT, AST, alkaline phosphatase, urea, creatinine, bilirubin, and OPG. The serum levels of OPG showed a significant increase in breast cancer patients (with and without bone metastasis) compared to the control group. Also, a significant increase in OPG level was found in breast cancer patients with bone metastasis with Bisphosphonates treatment compared to those without Bisphosphonates treatment. Also, a significantly positive correlation was found between OPG and each of tumor size and lymph node involvement. This means that OPG may be used as a prognostic marker in breast cancer patients.