In the context of bone metastases, several proinflammatory cytokines (IL-1, IL-6, IL-11, TNF-α), chemokines (CCL2, CCL3, CCL15, CXCL8/IL-8), and additional factors such as parathyroid hormone-related protein (PTHrP) produced by stromal, immune, or tumor cells directly or indirectly stimulate osteoclastogenesis, thus accelerating the vicious cycle [61,66,76,77]. The gene discussed is PTHLH; the disease is neoplasm.