Skeletal metastasis is a major complication of advanced breast cancer which results in bone fractures and considerable pain burden.Tumor cells arriving at bone metastatic sites disrupt the balance between bone resorbing osteoclasts and bone forming osteoblasts promoting the formation of osteolytic lesions.Osteoclasts recruited to the site of metastasis lead to the destruction of bone and formation of osteolytic lesions.Many of the effects of breast cancer cells on osteoclasts are attributed to indirect, osteoblast-mediated actions, such as the ability of PTHrP to promote expression by osteoblasts of a key osteoclastogenic factor, RANKL.However, there are still gaps in our understanding of the mechanisms underlying responsiveness of bone cells to cancer signals.