In the “osteolytic vicious cycle”, tumour cells produce factors (i.e., IL-6, TNF-α, IL-1β) that stimulate differentiation of osteoclast precursors into mature osteoclasts directly, or indirectly, such as PTHrP, that acts by increasing osteoblastic RANKL production, eventually stimulating osteoclast formation [73]. The gene discussed is PTHLH; the disease is neoplasm.