Pathogenesis of bone metastasis

Bone metastases are more frequently seen as a complication of cancer than primary bone tumors. For example, it can be seen in as many as 70% of advanced stage breast and prostate cancer cases. Metastatic bone disease is generally categorized as osteoblastic, and osteolytic disease. However most of the cancer types demonstrate a wide spectrum between these two extremes. Paracrine interaction between parathyroid hormone–related protein (PTHrP) which increases the rate of bone osteolysis, and transforming growth factor-β (TGF-β) plays a role in osteolytic metastasis. Increased local bone PTHrP concentration increases expression of receptor activator of nuclear factor kappa-B ligand (RANKL) with resultant activation of osteoclastogenesis. Endothelin – 1 (ET-1), and dickkopf homolog -1 (DKK-1) produced by tumor involve in osteoblastic metastasis. DKK-1 is the central regulator of osteoblastic activity, and osteoblastic bone metastasis. For the elaboration of treatment strategies against frequently seen complication, that is, bone metastases, targets involving in pathogenesis of these complications should be taken into consideration.