Validity of Osteoprotegerin and Receptor Activator of NF-κB Ligand for the Detection of Bone Metastasis in Breast Cancer

Osteoprotegerin (OPG) is a robust antiresorptive molecule that acts as a decoy receptor for the receptor activator of nuclear factor κB ligand (RANKL), the mediator of osteoclastogenesis. This study was designed to explore the possible role of serum OPG and RANKL in detecting bone metastasis in breast cancer and its interaction with clinicopathologic parameters. Serum levels of RANKL and OPG were estimated in 44 metastatic and 36 nonmetastatic breast cancer patients using ELISA kits. Serum OPG levels were significantly reduced in patients with bone metastasis and correlated negatively with the number of bone lesions and CA 15-3 levels. At concentrations ≤82 pg/ml, OPG showed a high specificity in identifying the presence of bone metastasis (92%), albeit with low sensitivity (59%), which improved after the exclusion of diabetics and patients treated with aromatase inhibitors (AI). Serum RANKL levels were significantly higher in the presence of bone metastasis and hypercalcemia. At concentrations >12.5 pg/ml, RANKL had an associated sensitivity of 86%, albeit with low specificity (53%), in detecting bone metastasis. The RANKL/OPG ratio significantly increased in the presence of bone metastasis with appropriate sensitivity and specificity (73% and 72%, respectively) at a cutoff of ≥0.14 for the detection of bone metastasis. Serum OPG and RANKL/OPG ratios are promising biomarkers for detecting bone metastasis in breast cancer patients.