FIGURE 2.

The vicious cycle in osteolytic bone metastases. A vicious cycle develops when tumour cells in bone secrete parathyroid hormone–related protein (pthrp) and multiple other cytokines and growth factors that stimulate osteoblasts to produce rankl(receptor activator of nuclear factor κB ligand). In turn, ranklbinds to rank on the surfaces of osteoclast precursors, stimulating their differentiation and activation. The osteoclasts resorb bone, which releases a variety of cytokines and growth factors that complete the cycle by stimulating tumour cells to secrete additional pthrpand other factors. Adapted from Roodman 2004¹⁷. opg= osteoprotegerin; bmp= bone morphogenic proteins; tgf-β = transforming growth factor β; igf= insulin-like growth factor; fgf= fibroblast growth factor; vegf= vascular endothelial growth factor; et1 = endothelin 1; pdgf= platelet-derived growth factor.