Pathophysiology of bone metastases from solid malignancies

Bone metastases are common complications of many cancers. Among the mechanisms that set the scene for the development of bone metastases, several are shared by all forms of metastatic dissemination (pre-metastatic niche formation and chemotactic attraction of malignant cells, which invade the host tissue) and others are specific of bone tissue (homing of malignant cells to bone marrow niches and acquisition of an osteomimetic cell phenotype). After a latency period that can last several years, the malignant cells can proliferate into tumors that alter the normal bone remodeling process by inducing dysregulation of osteoblast and osteoclast function. These metastases may be lytic, characterized by major bone destruction; sclerotic, with excess bone formation; or mixed. Osteolysis occurs when the tumor cells stimulate osteoclast activity and inhibit osteoblast activity, whereas the opposite effects lead to bone sclerosis. Moreover, the mineralized bone matrix plays a major role in the formation of bone metastases, as its degradation releases growth factors and calcium that exert mitogenic effects on tumor cells. Thus, bone metastases are the site of a vicious circle in which mechanisms involved in bone resorption/formation promote tumor growth and vice versa.