Metastatic bone disease: pathogenesis and new strategies for treatment.

Bone is the third leading site of metastatic disease, after the lung and liver. Pain, pathological fractures, neurological deficits, and forced immobilization significantly decrease the quality of life of patients with bone metastasis. The development of metastasis, from the migration of malignant cells from the primary tumor to their proliferation at a distant site, involves a series of sequential steps: angiogenesis, matrix degradation, cell motility, cell attachment, and cellular proliferation. A better understanding of the pathogenesis of metastasis may be expected to lead to the development of new treatment modalities for bone metastasis. Currently, antiangiogenic agents, matrix metalloproteinase (MMP) inhibitors, and hyperthermia are some of the newer therapeutic modalities that seem to hold promise for the treatment of metastatic bone disease.