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)

Deterioration of bone health is a major concern during progression and treatment of patients with breast cancer, especially in postmenopausal women. Disease- and treatment-associated skeletal-related events include fractures, spinal compression, bone pain, and hypercalcemia of malignancy. Bisphosphonates, which inhibit osteoclastic bone resorption, are important new agents in the management of skeletal-related events, and their impact on breast cancer-related bone metastases and on bone loss during long-term estrogen deprivation therapies such as aromatase inhibitors is reviewed. Intravenous pamidronate has become the standard bisphosphonate to reduce or delay skeletal complications of advanced breast cancer bone metastases, but the more potent agent, zoledronic acid, appears to be at least as effective. Another agent, ibandronate, is also active but has not been investigated in comparison with the other intravenous bisphosphonates. Zoledronic acid is the most convenient to administer, requiring only a short infusion. The effects of bisphosphonates on bone health in women with early breast cancer are also being investigated. A single yearly infusion of zoledronic acid has been shown to significantly increase bone mineral density in osteoporotic postmenopausal women and to reduce biochemical markers of bone turnover. The possibility of such treatment-reversing aromatase inhibitor-associated bone loss during adjuvant therapy of breast cancer is being evaluated in a trial of letrozole, with zoledronic acid added initially or after the onset of bone loss or fracture.
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PMID:Optimizing bisphosphonate therapy in patients with breast cancer on endocrine therapy. 1571 98

Bone metastases commonly occur in the course of malignant tumor disease. For many years, attempts have been made to identify factors for the management of cancer-induced skeletal complications. Nowadays, synthetic antiresorptive agents are considered to be indispensable for the treatment of cancer-related skeletal events, such as bone metastasis. The most common of these drugs are the bisphosphonates, which represent one of the most significant advances over the last 10 years in the field of supportive care and cancer. They are used for the treatment of cancer-induced hypercalcemia, for the prevention and treatment of postmenopausal osteoporosis, for patients with bone metastases secondary to breast cancer and multiple myeloma. A third-generation bisphosphonate, zolendronate, has been shown to minimize the destructive consequences of bone metastases and to exert a profound effect on tumor-induced osteolysis and tumor growth in bone. Zoledronate is already used for the treatment of hypercalcemia of malignancy, multiple myeloma-related osteolytic events and for patients with documented bone metastases from solid tumors in conjunction with standard antineoplastic therapy. The structure-function activity of the three generations of bisphosphonates developed to date, the in vitro models used for studying their effects on osteoclasts and osteoblasts, as well as the results of clinical trials obtained by the third generation bisphosphonate, zoledronic acid, are presented.
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PMID:In vitro and in vivo antiresorptive effects of bisphosphonates in metastatic bone disease. 1579 91

Biophosphonates are analogues of pyrophosphate. The mechanism of action of bisphosphates is the inhibition of osteoclast activation (antiresorptive mechanism). The oral bioavailability of biophosphonates is only about 1-2%, and because of gastrointestinal side effects (mainly esophageal irritation), oral agents are less useful in oncology. Biophosphonates are used for the treatment of Paget s disease of bone, the prevention of osteoporosis, and in another clinical scenarios as the prevention of bone disease after organ transplantation. In clinical oncology biophosphonates are used for the treatment of hypercalcemia of malignancy, prevention and treatment of bone events related to bone metastases, and in the prevention of osteoporosis related to breast cancer. According to American Society of Clinical Oncology (ACO) guidelines, biophosphonates should be used in hypercalcemia of malignancy and bone events related to metastases of breast cancer and multiple myeloma.
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PMID:[Biphosphonates in oncology]. 1645 91

Ibandronate is an experimental intravenous bisphosphonate under study for the prevention or treatment of osteoporosis and skeletal complications of bone metastases, as well as hypercalcemia of malignancy. To review the data on this drug, PubMed/MEDLINE was searched for pertinent studies in English; data from January 1986-October 2005 were reviewed. In preclinical studies, ibandronate was an extremely potent bisphosphonate compared with its predecessors and was active in all animal models of human postmenopausal and corticosteroid-associated osteoporosis. Similar to other bisphosphonates, ibandronate exhibits antitumor activity and prevents or reduces bone metastases. Forty to fifty percent of the dose is bound to bone; renal clearance of unchanged drug accounts for 70% of total body clearance. Early clinical trials demonstrated efficacy and tolerability of intravenous ibandronate in the prevention or treatment of postmenopausal and corticosteroid-associated osteoporosis when administered once every 3 months. Intravenous ibandronate also reduces skeletal complications of bone metastases, including pain, although the cumulative dose used is much higher than that used in osteoporosis, as the drug is administered every 3-4 weeks. Single doses of intravenous ibandronate are probably also effective in the treatment of hypercalcemia of malignancy. The major tolerability issue with intravenous bisphosphonates is renal safety, thus the drugs generally require infusion (e.g., 0.25 hr for zoledronic acid, 2-24 hrs for pamidronate). However, intravenous ibandronate can be administered by bolus injection over a few minutes without an elevated risk of nephrotoxicity. The experimental intravenous dosage is 2 mg every 3 months for treatment or prevention of osteoporosis, and 2-6 mg every 3-4 weeks or in a single dose for treatment of bone metastases or hypercalcemia of malignancy, respectively. Ibandronate can be used in the presence of severe renal impairment with proper dosage adjustment. The drug will be an interesting addition to the available drugs for osteoporosis, bone metastases, and hypercalcemia of malignancy. Studies of intravenous ibandronate as an adjunctive treatment for cancers that tend to metastasize to bone are under way. Whether intravenous ibandronate will be a therapeutic advance is best answered by randomized, controlled trials. These are ongoing and should provide data with which to make better-informed choices concerning intravenous bisphosphonates.
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PMID:Ibandronate, an experimental intravenous bisphosphonate for osteoporosis, bone metastases, and hypercalcemia of malignancy. 1663 95

Approximately 70% of patients with advanced prostate cancer have bone metastases, which are associated with considerable skeletal morbidity, accompanied by severe bone pain that requires narcotics or palliative radiation therapy, pathological fractures, spinal cord compression and hypercalcemia of malignancy (HCM), which consequentiy lower the patient's quality of life. Bisphosphonates, potent inhibitors of osteoclast activity and survival, therefore inhibiting osteoclast-mediated bone absorption, transiently palliative bone pain and decrease analgesic usage in patients who have hormone-refractory prostate cancer (HRPC) with bone metastases. Recently, a randomized controlled trial showed that a third-generation bisphosphonate, zoledronic acid reduced bone pain and skeletal-related events (SREs). In this manuscript, we reviwed the efficacy of bisphosphonates in HRPC with bone metastases from several clinical studies and discuss treatment of advanced prostate cancer with bisphosphonates.
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PMID:[The effect of bisphosphonates on bone metastasis of hormone-refractory prostate cancer]. 1684 64

Bone metastases are a common occurrence in patients with breast cancer, lung cancer and prostate cancer. Bone metastases cause considerable morbidity including pain, impaired mobility, pathologic fracture, spinal cord or nerve root compression, bone marrow infiltration and hypercalcemia of malignancy. These complications result from the derangement of normal bone metabolism that arise from interactions between factors originating in tumor cells and others originating in the microenvironment of the bone. Fortunately, there is an increasing array of treatment options for the skeletal complications associated with bone metastases arising from breast, lung, and prostate cancer. The goals of treatment for such skeletal complications are to relieve pain and reduce the risk of fracture. Traditional therapies to treat skeletal malignancies include radiation, surgery, and chemotherapy. In recent years, bisphosphonates have become the treatment of choice because of their ability to reduce bone resorption, leading to decreases in hypercalcemia, new osteolytic lesions, and fractures, thereby ameliorating pain and improving quality of life.
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PMID:Managing bone complications of solid tumors. 1696 20

In recent years, a growing number of reports in the literature have linked osteonecrosis of the jaw bones with intravenously administered bisphosphonates prescribed for the treatment of hypercalcemia of malignancy due to bone lesions of multiple myeloma or bone metastases in patients with breast or prostate cancer. Furthermore, an association between chronic oral bisphosphonate use in patients with osteoporosis or Paget's disease, and bone necrosis in the mandible or maxilla has been demonstrated in numerous case reports and case series in the last couple of years. Therapeutically, osteonecrosis of the jaws seems to be difficult to treat surgically, often resulting in a recurring or even progressing lesion. In the present case report of a bisphosphonate-associated osteonecrosis of the maxilla in a patient with osteoporosis, the current literature will be discussed, and open research questions and potential problems for our daily dental practice routine will be addressed.
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PMID:[Biphosphonate-associated osteonecrosis of the maxilla. Case report and review of the literature]. 1707 15

Intervenous (IV) bisphosphonates are used for cancer patients with hypercalcemia of malignancy (HCM) and breast cancer bone metastases (BM). Recently, zoledronic acid, the most potent third generation bisphosphonate, has been approved for both HCM and BM of broad tumors. It showed 850-fold stronger activity than pamidronate in bone resorption assay, and clinical efficacy against multiple cancer bone lesion has been confirmed in randomized clinical trials. Zoledronic acid becomes one of the most used bisphosphonate for cancer patients in the world, and the results of clinical trials for cancer treatment-induced bone loss or postmenopausal osteoporosis are now updating.
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PMID:[Therapeutic agents for disorders of bone and calcium metabolism: Zoledronic acid]. 1721 Oct 90

A 60-year-old woman was diagnosed with esophageal small cell carcinoma in October 2004 and received chemotherapy. However, the tumor grew gradually and multiple bone metastases occurred. Anorexia, nausea, emesis, numbness in both hands, and disturbed consciousness developed at the end of January 2006, and the patient was admitted to Fukushima Medical University Hospital. Abdominal pain, marked hypercalcemia and hyperamylasemia were noted and the patient was diagnosed with severe acute pancreatitis. Because the level of blood parathyroid hormone-related protein was elevated, we considered that esophageal small cell carcinoma caused human hypercalcemia of malignancy and that metastatic bone tumors caused local osteolytic hypercalcemia, eventually leading to severe acute pancreatitis. This is an extremely rare case of esophageal small cell carcinoma associated with hypercalcemia causing severe acute pancreatitis.
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PMID:A case of esophageal small cell carcinoma associated with hypercalcemia causing severe acute pancreatitis. 1795 66

The skeleton is one of the most common sites of metastasis in patients with lung cancer. It has been reported that the incidence of bone metastases in lung cancer patients is approximately 30-40%, and the median survival time (MST) of patients with such metastases is 6-7 months. Metastatic bone disease leads to various complications or skeletal related events (SREs), including pain, pathologic fracture, vertebral deformity and collapse, spinal cord compression, and hypercalcemia of malignancy. These events often lead to rapid deterioration in quality of life (QOL). The fundamental treatment for bone metastasis from advanced lung cancer is disease control by systemic chemotherapy. So the prevention and treatment of bone metastases is mainly dependent on an effective treatment against lung cancer itself. As a direct treatment for bone metastases, radiation therapy, surgery and bisphosphonates are the main ways.
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PMID:[Bone metastases in lung cancer]. 1837 26


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