Receptor Activator of Nuclear Transcription Factor Nf-b (Rank), Its Ligand (Rankl) and Natural Inhibitor Osteoprotegerin (Opg) in Blood Serum of Primary Bone Tumor Patients: Association With Clinicopathological Features and Inflammatory Cytokines Levels

Abstract

Abstract. RANK/RANKL/OPG system (the key regulator of bone homeostasis) component levels were measured in blood serum of 199 patients with primary bone tumors and tumor-like lesions: 121 with bone sarcomas (53 osteosarcoma, 46 chondrosarcoma, 12 chordoma, 8 Ewing sarcoma), 32 with borderline giant cell bone tumor (GCBT), 46 with benign bone neoplasms; 131 persons comprised the control group. OPG, sRANKL, sRANK, IL-6, 8, 16 serum levels were measured by standard ELISA kits. Giant-cell bone tumor (GCBT) manifesting high osteoclastogenic and osteolytic activities was characterized by high serum content of all three components studied and the highest sRANKL/OPG ratio. The group of patients with various benign bone tumors and tumor-like lesions displayed similar to GCBT, but lower indices. Malignant bone tumor patients could be divided into 2 subgroups with opposite characteristics: osteosarcoma and Ewing sarcoma patients demonstrated low sRANK and high sRANKL levels, while chondrosarcoma and chordoma patients, on the contrary -high sRANK and low sRANKL levels. The highest IL-6 levels were revealed in GCBT patients, while serum IL-8 and IL-16 did not differ between groups. Thus, disturbances in osteolysis activators and inhibitors balance in blood serum of primary bone tumor patients were revealed. Their extent depended on neoplasm character (malignant, borderline, or benign) and histological structure of malignant sarcomas. Most prominent changes were found in GCBT characterized by active bone destruction and an accepted target of anti-RANKL antibody denosumab treatment. Hence, the proteins studied can be regarded as promising serologic markers and therapeutic targets in this rare disease.