Multiple cells in bone tumors secrete RANKL, including myeloma and stromal cells in multiple myeloma (MM) and tumor stromal cells in giant cell tumor of bone (GCTB), while osteoclast-like multinucleated giant cells in GCTB express RANK, allowing denosumab to alter the tumor microenvironment during treatment. This evidence concerns the gene TNFSF11 and bone giant cell tumor.