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October - December 2006: 
Volume 19, Issue 4

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Bone Metastases in Lung Cancer: The role of bisphosphonates
Abstract
Bone metastases and associated skeletal complications are common in patients with lung cancer. It is estimated that approximately 30- 40% of those patients will develop bone metastases, principally osteolytic lesions, with considerable skeletal morbidity including bone pain, pathologic fracture, spinal cord compression, nerve root compression, bone marrow infiltration, and hypercalcemia of malignancy. These complications result from excessive bone metabolism, particulary excessive bone resorption, and consequent derangement of bone structure. Treatment of bone metastases and their complications classically include radiotherapy and/or radionuclides administration, surgery to bone and analgesic therapy. In recent years newer nitrogen-containing bisphosphonates have proven to be an efficient and well-tolerated treatment for preventing skeletal complications associated with bone metastases in several malignant diseases including lung cancer. Bisphosphonates inhibit bone resorption by increasing apoptosis of osteoclasts by the inhibition of signaling- proteins essential for cell function and survival. In addition, they may have a direct antitumor action. Newer bisphosphonates are administered intravenοusly every 3-4 weeks with varying infusion duration. Oral medications have low bioavailability and are also associated with increased incidence of gastrointestinal side effects. Common side effects of bisphosphonate treatment include bone pain, fatigue, nausea and vomiting, headache, fever, influenza-like syndrome, anemia and renal toxicity. Although clinical benefit of bisphosphonates is less clear in lung cancer patients with bone metastases whο have poorer prognosis, often less than 6 months, several studies have shown a reduction of risk for developing a Skeletal Related Event (SRE) (with the exception of spinal cord compression), longer median time to first SRE and sustained palliation of bone pain, but no effect on survival. In summary, bisphosphonates may have an important role in the current treatment of metastatic bone disease in lung cancer patients. Further therapeutic implications, such as antitumor effect and prevention of bone metastases, are also under study. Pneumon 2006; 19(4):324-338.