Denosumab, a fully-human monoclonal antibody that binds RANKL and neutralises its function, has demonstrated efficacy in reducing SREs in three phase 3 trials, including in patients with bone metastases associated with breast cancer, prostate cancer and other solid tumours or multiple myeloma [19,20,21,22], illustrating the part that the RANKL pathway plays in metastatic bone disease (Table 1). The gene discussed is TNFSF11; the disease is breast carcinoma.