Because PTHrP and other cytokines converge on the RANKL pathway once tumor load increases, the effect of sympathetic activation on RANKL expression by host bone marrow osteoblasts is likely to be most relevant to the early phases of bone colonization by metastatic cancer cells and to the initial steps of the osteolytic cycle of bone destruction induced by metastatic cancer cells, when bone tumor burden is still low. This evidence concerns the gene PTHLH and metastatic malignant neoplasm.