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Abstract After the liver and lung, bone is the third most common site of metastases. Eighty percent of all bone metastases are secondary to breast, prostate, and lung carcinomas. Cancer cells metastasize to bone almost exclusively via hematogenous spread, although this may also result via direct extension of tumor. Bone metastases are generally classified into two types. Osteoblastic metastases are characterized by the deposition of new bone via increased osteoblastic activity, whereas osteolytic metastases are characterized by the destruction of normal bone via increased osteoclastic activity. Metastatic lesions can contain both components Bone metastases are a significant cause of morbidity and can lead to bone pain, immobility, hypercalcemia, pathological fractures, nerve root damage, and spinal cord compression. When bone metastases are suspected, imaging is needed to confirm the suspicion and determine the location and extent of involvement. Typically, the first test is a bone scan, which is a good whole-body screening test, followed by plain films to further characterize any lesions found on the bone scan. CT scan and MRI can be helpful in areas that remain in question or in cases where metastases were not detected, but suspicion is high. The goals of therapy are to relieve pain, improve function, and maintain skeletal integrity. Treatment should be individualized, and consideration should be given to the overall Summary 193 prognosis of a patient because long-term survivors are more at risk for late toxicities and require longer lasting relief. Current management of skeletal metastasis includes pain management/analgesia, systemic therapy (bone modifying agents, chemotherapy, hormone therapy), radiation therapy (externalbeam radiation therapy, radiopharmaceuticals), and surgery. Optimal treatment of skeletal metastasis is complex, and a multidisciplinary approach is often needed. Analgesic medication is the first-line therapy for pain management and is often administered with a stepwise approach. Surgery may be indicated when there is a fracture (or high risk of fracture) of the long bones or hips, as well as spinal cord or nerve compression. Post surgical radiation is also indicated to prevent further tumor growth. New, less invasive, surgical techniques are being investigated, including kyphoplasty and vertebroplasty. Both techniques involve injection of a bone cement into the collapsed vertebral bodies. In kyphoplasty, a balloon is inflated prior to adding the cement to recreate the normal height of the vertebrae. Both are outpatient procedures with few complications that are effective in providing pain relief. Radiation therapy is indicated for the treatment of spinal cord compression, treatment of bones at risk for pathologic fracture and palliation of pain caused by bone lesions. The American Society for Radiation Oncology Guidelines for palliative radiotherapy in bone metastases state that a single dose of radiation (8Gy) is as effective in providing pain relief as fractionated courses. Fractionated courses have lower retreatment Summary 194 rates (8% versus 20%), however, the single treatment is more convenient for the patient and retreatment is usually feasible when needed. Treatment of spinal cord compression typically requires a longer course of 10 fractions. Radioisotopes are a viable treatment option for multifocal bone metastases, and are typically used in prostate and breast cancer cases with osteoblastic lesions. Strontium-89 and samarium-153 are the isotopes currently used. These are effective in providing pain relief in 80% of patients, with 10% becoming pain free, with relief lasting 3-6 months. Both isotopes are myelosuppressive and are contraindicated in patients with leukocyte counts below 2400/mm3 and/or platelet counts below 60,000/mm3. Chemotherapy must be held typically for 6 weeks after treatment. Bisphosphonates decrease bone loss by inhibiting osteoclast activity. Pamidronate and zoledronic acid, are more potent osteoclast inhibitors than their first generation counterparts. These agents are effective in reducing the frequency of skeletal-related events in patients with bone metastases and in decreasing pain related to bone lesions in both multiple myeloma and solid tumors. Studies have shown zoledronic acid to be a more potent inhibitor and it may be given in a shorter infusion than pamidronate. Denosumab is a monoclonal antibody that inhibits RANKL, which in turn inhibits osteoclast activity. In clinical trials, denosumab significantly prolonged the time to a skeletal event in patients with bone metastases from breast and prostate cancer, Summary 195 when compared to zoledronic acid. In another study, early results show the median time to a skeletal event was significantly longer with denosumab in other malignancies, including myeloma, renal cell and lung cancers. The goals of chemotherapy and hormone therapy in patients with bone metastases are to control the tumor’s growth, thus potentially reducing the risk of associated bony complications. Even though the pain response is the most important end point for patients with metastatic bone disease receiving palliative care, the use of radiological or nuclear medicine imaging response criteria may allow an objective evaluation of the therapeutic outcome. Monitoring markers of bone turnover may be useful in assessing the extent of bone disease in patients with solid tumors metastatic to bone |