RANK, RANKL and OPG Expression in Breast Cancer – Influence on Osseous Metastasis

In women, malignant breast tumours are among the most common malignant diseases in Europe. In advanced breast cancer, the risk of bone metastasis increases to 65–75 %. The discovery of the physiological bone metabolism parameters RANK (receptor activator of nuclear factor-κB), RANKL (receptor activator of nuclear factor-κB ligand) and OPG (osteoprotegerin) as well as their pathophysiological involvement in bone-related diseases is the subject of new therapeutic strategies. The formation of osteolytic bone metastasis requires increased osteoclast activity. Activation of osteoclasts by excessive direct RANKL or reduced OPG expression of osseous metastatic tumour cells remains to be elucidated. More than 50 % of primary breast cancer cells express OPG and RANK, while RANKL could be detected only in 14–60 %. Increased OPG concentrations in the serum of patients with bone metastases have been shown in several studies, whereas the RANKL results are described in an opposite manner. The use of OPG as a biomarker for the detection of osteolytic bone metastases is not consistent and needs to be proved in further studies. Increased RANKL activity was found in diseases characterised by excessive bone loss and formed the basis of new therapeutic options. In several studies, a human monoclonal antibody to RANKL (denosumab) was investigated for the treatment of bone diseases. Denosumab is a promising therapeutic option due to its bone-protective effects.