TNFRSF11B and neoplasm: Additional insights from neuroendocrine neoplasms in general suggest that bone metastases arise from a “vicious cycle,” in which tumor cells stimulate osteoclast activation primarily through RANKL overexpression and suppression of osteoprotegerin, leading to excessive bone resorption, release of growth factors from the bone matrix, and further tumor proliferation within a hypoxic, acidic, and calcium-rich microenvironment (49).