Painful osseous metastases.

Up to 90% of patients with metastatic or advanced stage cancer will experience significant cancer-related pain. Approximately half or more of patients diagnosed with cancer may experience bone pain. It has been estimated that tumor metastases to the skeleton affect roughly 400,000 United States citizens annually. Carcinoma from breast, lung, and prostate cancers account for about 80% of secondary metastatic bone disease. Bone metastases may cause devastating clinical complications associated with dramatic reductions in quality of life, mobility, and independence as well as excruciating refractory pain. Associated complications from osseous metastases also present a substantial economic burden. Currently, there is still a significantly high number of patients suffering with unrelieved pain from osseous metastases. Treatments for painful osseous metastases may not only diminish pain, but may also improve quality of life and independence/mobility, and reduce skeletal morbidity, potential pathologic fractures, spinal cord compression, and other "skeletal-related events." Treatment strategies for painful osseous metastases include systemic analgesics, intrathecal analgesics, glucocorticoids, radiation (external beam radiation, radiopharmaceuticals), ablative techniques (radiofrequency ablation (RFA) and cryoablation), bisphosphonates, chemotherapeutic agents, inhibitors of RANK-RANKL interaction (e.g., denosumab), hormonal therapies, interventional techniques (e.g., kyphoplasty), and surgical approaches. Although the mechanisms underlying the development of bone metastases are not completely understood, there appears to be important bi-directional interactions between the tumor and the bone microenvironment. A greater understanding of the pathophysiology of painful osseous metastases may lead to better and more selective targeted analgesic therapy. Additionally, potential future therapeutic approaches to painful osseous metastases may revolutionize approaches to analgesia for this condition, leading to optimal outcomes with maximal pain relief and minimal adverse effects.