Bone metastases- Pharmacological treatment

Bone is a common site for tumor metastases from multiple cancer types including breast cancer, prostate cancer, lung cancer and multiple myeloma. The resulting bone lesions weaken the structural integrity of the bone, leading to an increased risk of skeletal complications (skeletal related events- SREs) such as hypercalcemia, spinal cord compression, surgery or radiotherapy to bone, pain or pathological fractures. From randomized trials in advanced breast cancer it can be seen that one of these major skeletal events occur on average every three to four months (Theriault RL, 1999. Hortobagyi GN,1996). SREs are a major cause of morbidity; they can dramatically reduce patient’s quality of life and are also associated with increased mortality (Coleman RE, 2001). In particular in breast cancer the experience of a pathological fracture increases the risk of death by 32% (Saad F, 2007). In many patients metastatic bone disease is a chronic condition with an increasing range of specific treatments to slow the progression of disease. The survival from the time of diagnosis varies among different tumor types, in particular for breast or prostate cancer it is measurable in years. In contrast the median survival time from the diagnosis of advanced lung cancer is measured in months (Coleman RE, 2006). Currently, three main modalities exist for the treatment of metastatic bone disease: medical treatment, radiation therapy and surgery. These treatments are combined, depending on the severity of bone destruction and the life expectancy of the patient. The intensity of treatment should be tailored to the patient's prognosis and life expectancy (De Vita VT, 2005). Medical therapy include chemotherapy, hormone therapy, immune therapy, target therapy and bisphosphonates. Patients with metastatic bone disease should be considered for therapy that effectively inhibits bone resorption. With the development of more potent agents in recent years, bisphosphonate therapy is the treatment of choice for skeletal complications of cancer because of its ability to reduce bone resorption, leading to less hypercalcemia, fewer new osteolytic lesions and reduced incidence of fracture (Fleish H, 2002). Newer nitrogen-containing bisphosphonates, such as zoledronic acid, pamidronate and ibandronate, have a unique mechanism of action and greater clinical activity than first generation bisphosphonates, such as etidronate and clodronate. Bisphosphonates, mostly compared with placebo, have been proven to reduce and delay the occurrence of skeletal events and control bone pain (Coleman RE, 2004) in many solid tumors (e.g. breast, prostate, lung, multiple myeloma).