However, as tumor cells populate the bone marrow microenvironment, they deregulate the normal bone remodeling cycle, pushing the balance towards osteoclast-mediated bone resorption, thereby facilitating further cancer cell invasion of the bone tissue, a model that is termed the “vicious cycle.” 1,59,75 Osteolytic tumor (eg, those that promote bone destruction) cells increase osteoclast activity through secretion of proinflammatory cytokines such as IL-1β, IL-6, and TNF, and chemokines such as chemokine C-C motif ligand 2 (CCL2), which act directly on osteoclasts. Here, TNF is linked to neoplasm.