Osteolytic and osteoblastic bone metastases: two extremes of the same spectrum?

Normal bone development and maintenance are sustained through a balanced communication between osteoclasts and osteoblasts. Invasion of the bone compartment by cancer cells causes an imbalance in their activities and results in predominantly bone lysing or bone forming phenotypes depending on the origin of the cancer. Tumor-induced bone lesions usually exhibit disturbances of both cell types. Thus, osteoclast activity is activated in a predominantly osteoblastic lesion and vice versa. These cancer-induced bone responses favor the survival and growth of cancer cells in their new environment. Therapies that can restore the balance may limit the growth of cancer cells in the bone. The recent development of agents that target the osteolytic components of bone metastasis, including bisphosphonates and denosumab, showed promising results in osteolytic bone diseases such as multiple myeloma but were less effective in improving the osteoblastic bone disease found in prostate cancer. Thus, while osteolytic components are present in both osteoblastic and osteolytic bone lesions, inhibition of the osteolytic component is not sufficient to alter the vicious cycle leading to tumors with an osteoblastic phenotype. These observations suggest that osteolytic and osteoblastic bone metastases are not the same and tumor-induced osteoblastic and osteolytic activity play different roles in supporting their growth and survival.