Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0153690 (bone metastases)
 6,382 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bisphosphonates have become well established in the treatment of patients with metastatic bone disease, although the optimal use of these agents has not been defined clearly. Randomized, controlled trials have demonstrated that treatment with intravenous pamidronate can significantly reduce the rate of skeletal-related events in patients with bone metastases from myeloma or advanced breast carcinoma. To date, there are few data from controlled, randomized studies to support the use of bisphosphonates in patients with bone metastases from malignancies other than breast carcinoma and myeloma. The optimal duration of treatment is unknown. Recent data have demonstrated that prolonged treatment is tolerated well, with no obvious toxicity. Generally, treatment is continued irrespective of the development of skeletal-related events and until there is a substantial decline in performance status. The widespread use of bisphosphonates will have major financial implications. Retrospective studies have suggested that the cost-effectiveness ratio is high for patients with advanced breast carcinoma. These ratios may be improved by targeting therapy to patients at high risk of developing complications from skeletal metastatic disease. Among patients with skeletal metastases from breast carcinoma, a recent retrospective analysis demonstrated that patients with disease confined to the skeleton were at greater risk of pathologic fractures compared with patients who had additional extraosseous disease. It is interesting to note that approximately two-thirds of patients with advanced breast carcinoma in the randomized trials of intravenous pamidronate had disease confined to the skeleton. The use of markers of bone turnover to identify patients who are most likely to benefit from bisphosphonate therapy or to identify patients who will respond to such therapy is the subject of further investigation. There are conflicting data on the use of bisphosphonates as an adjuvant therapy. Currently, such treatment should occur only as part of a clinical trial. Bisphosphonates can be used to prevent bone loss as a result of therapy for malignant disease, e.g., premature menopause in patients with early breast carcinoma.
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PMID:Bisphosphonate therapy for patients with breast carcinoma. 1254 86

Breast cancer and bone health are closely linked. Early menopause induced by gonadotropin-releasing hormone analogues or chemotherapy as well as aromatase inhibitors reduce oestrogen levels, thereby causing cancer treatment-induced bone loss (CTIBL). Furthermore, bone metastases are commonly found in advanced disease. Current treatment options for bone lesions comprise systemic anti-tumour therapy, irradiation, surgery and bisphosphonates. The main mechanism of osteolysis, osteoclast activation, is induced by the RANK ligand and suppressed by osteoprotegerin (OPG). A human antibody targeting the RANK ligand, denosumab, had superior activity compared to OPG and was therefore further developed in the clinical setting. This article reviews clinical data on denosumab. Data were obtained by searching the Medline database and abstracts from the ASCO annual meeting, ASCO breast meeting, ECCO, ESMO, and the San Antonio Breast Cancer Symposium. Clinical trials have demonstrated that denosumab reduces markers of bone turnover, and suggest equal efficacy to bisphosphonates in reducing the rate of skeletal-related events. While overall fewer side effects were observed, a numerically increased rate of osteonecrosis of the jaw was reported. Denosumab was well tolerated, and clinical activity was similar to bisphosphonates in metastatic disease. Trials of denosumab in the prevention of CTIBL are ongoing.
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PMID:Breast Cancer: Rank Ligand Inhibition. 2177 14