Biology of bone metastases.

BACKGROUND: Bone metastases cause morbidity and mortality in multiple malignancies. In addition to portending a dire prognosis, bone metastases cause bone pain, fractures, hypercalcemia, spinal cord compression, and other nerve compression syndromes. Improved understanding of the mechanisms that predispose tumor metastases to bone is needed to improve patients' therapeutic options, maintain their quality of life, and improve their survival. METHODS: This review discusses selected preclinical and clinical data regarding bone metastasis development and cytokine/molecular interactions predisposing to bone metastases formation. Potential interventions for reducing bone metastases are also described. RESULTS: Biologic mechanisms resulting in metastases of tumor cells to bone are being studied. Among these are the RANKL pathway, osteoclast activation via cytokines (produced by tumor cell and cells in the bone microenvironment), interactions with transient and stromal cells in the bone microenvironment, and molecules such as PTHrP and endothelin-1. These molecules offer important opportunities for targeted interventions to decrease bone metastases-associated morbidity. CONCLUSIONS: Knowledge of the pathophysiology of bone and cancer is developing rapidly. Relationships among cancer cells, bone-derived cells, and cytokines provide opportunities for the development of new interventions. Therapy targeting osteoclast/osteoblast interactions has proven benefit for patients with bone metastases.