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Query: UMLS:C0020437 (hypercalcemia)
 10,293 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the UK an aging population is resulting in more people being diagnosed with cancer, and an increasing number of treatment options means that many patients live significantly longer with their disease. It is anticipated therefore that an increasing number of patients will present to primary and secondary care with acute complications of cancer, or the treatment thereof. Many doctors have limited experience in managing patients with cancer and acute oncological emergencies. This article reviews the diagnosis and management of four common oncological emergencies: febrile neutropenia, metastatic spinal cord compression, superior vena cava obstruction, and malignancy associated hypercalcaemia. It is vital to recognise these conditions, as failure to implement immediate and appropriate treatment may result in significant morbidity or death.
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PMID:Common acute oncological emergencies: diagnosis, investigation and management. 1883 3

Approximately 30 to 40% of patients with advanced lung cancer will develop bone metastases in the course of their disease, resulting in a significant negative impact on both morbidity and survival. Skeletal complications of bone metastases include pain, pathologic fractures, spinal cord compression, and hypercalcemia. Total medical care costs are greater among patients with bone metastases who develop skeletal complications. A randomized phase III trial of the third generation bisphosphonate zoledronic acid has shown clinical benefit in the management of a subgroup of patients with bone metastases from lung cancer. Zoledronic acid treatment was associated with a reduction in both the risk of, and time to, a skeletal-related event. One of the markers of bone resorption, N-telopeptide, is both prognositic for development of skeletal-related events and predictive for benefit from zoledronic acid. In preclinical models, bisphosphonates have also demonstrated antitumor activity and are therefore currently being evaluated in adjuvant trials. Inhibition of the receptor activator of nuclear factor kappa B ligand-RANK pathway can reduce osteoclast-mediated bone resorption, and trials comparing receptor activator of nuclear factor kappa B ligand inhibitors with bisphosphonates are ongoing, including patients with lung cancer. In this article, we review the management of bone metastases and hypercalcemia as well as potential future directions for bone directed therapies in patients with lung cancer.
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PMID:Prevention and management of bone metastases in lung cancer: a review. 1917 5

Bone is one of the most common sites of metastatic disease from cancer, affecting around 400,000 patients each year. Skeletal-related events (SRE) include hypercalcemia, fractures, spinal cord compression or severe bone pain and may occur as a complication of metastasis. Bisphosphonate therapy is crucial in the prevention and treatment of SREs; zoledronic acid and pamidronate have both been shown to significantly reduce the development of SREs. Other agents such as corticosteroids and analgesics are also used in symptomatic management. The use of these agents in conjunction with radiation and surgery can help to improve patient outcomes.
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PMID:The pharmacological management of skeletal-related events from metastatic tumors. 1930 55

The skeleton is the most common site of breast cancer metastasis, which can occur in up to 85% of patients during their lifetime. The morbidity associated with bone metastases in patients with breast cancer includes pathological fractures, bone pain, hypercalcaemia, and spinal cord compression. When breast cancer metastasizes to bone, the balance of bone resorption (mediated by osteoclasts) and bone formation (mediated by osteoblasts) favors bone resorption, which leads to net bone destruction (i.e., osteolysis). Anti-resorptive agents such as bisphosphonates are commonly used to treat bone resorption in osteoporosis or osteolytic cancer patients. However, bisphosphonates by themselves are unable to rebuild lost bone tissue, and can cause severe side effects. In this study, we developed a bovine bone explant culture system and have observed that murine osteoblasts can modulate the activity of osteotropic human breast cancer cells on this substrate. Using markers of bone metabolism, we observe diminished bone turnover in organ culture following the addition of exogenous osteoblasts. The data presented in this study supports further investigation into the use of cytotherapies to limit breast cancer mediated osteolysis.
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PMID:Osteoblasts suppress high bone turnover caused by osteolytic breast cancer in-vitro. 1943 87

Bone metastases place patients at increased risk of skeletal-related events (SREs), including pathologic fractures, spinal cord compression, severe pain requiring radiotherapy or surgery, and hypercalcemia, because of increased osteoclast-mediated bone resorption. Denosumab, a fully human monoclonal antibody, decreases bone resorption by inhibiting RANKL, which mediates osteoclast activity. We compared the effects of denosumab in two phase 2 studies in patients with bone metastases naive to intravenous bisphosphonate therapy (IV BP; n = 255) and those with elevated levels of the bone resorption marker urinary N-telopeptide (uNTX) despite ongoing IV BP treatment (n = 111). Patients were randomized to receive IV BP every 4 weeks or subcutaneous denosumab every 4 weeks (30/120/180 mg) or every 12 weeks (60/180 mg). Patients treated with denosumab experienced a rapid and sustained reduction in bone turnover regardless of prior IV BP exposure. After 25 weeks, the median uNTX reduction was 75% (IV BP-naive) and 80% (prior IV BP) after denosumab treatment and 71% (IV BP-naive) and 56% (prior IV BP) in the IV BP arms. Denosumab patients with prior IV BP exposure had marked suppression of the osteoclast marker TRAP-5b (median reduction: denosumab 73%, IV BP 11%). SRE incidence was low across both studies. In patients previously treated with BPs, the rate of first on-study SRE was lower in the denosumab groups (8%) than the IV BP group (17%). Denosumab appeared to be well tolerated in both studies. Denosumab suppresses bone resorption markers independently of prior BP treatment, even in patients who appear to respond poorly to BPs.
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PMID:Effects of denosumab in patients with bone metastases with and without previous bisphosphonate exposure. 2020 Sep 89

Breast cancer frequently metastasizes to bone. Metastases result in skeletal morbidity including pathologic fractures, the need for radiation or surgery to bone, spinal cord compression and hypercalcemia. The pathophysiology of bone destruction is related to activation of osteoclasts by tumor-derived and bone marrow microenvironmental factors. One prominent osteoclast-activating factor associated with breast cancer is parathyroid hormone-related peptide (PTHrP). Bisphosphonates have been shown to impair osteoclast activity by decreasing recruitment from the monocyte macrophage cell line, inhibiting osteoclast function at the bone site and causing osteoclasts to undergo apoptosis. Clinical studies with bisphosphonates show an improvement in the control of hypercalcemia and a reduction in skeletal related morbidity with administration of pamidronate and zoledronic acid. Bisphosphonates have become the standard of care for osteolytic metastases associated with breast cancer. Recent data with zoledronic acid found that skeletal related morbidity may be reduced regardless of the radiographic picture of skeletal metastases. Thus, zoledronic acid may be valuable in osteolytic and osteoblastic disease as well as in disease with an osteolytic or osteoblastic radiographic appearance. In breast cancer with osteolytic disease, zoledronic acid may be more effective than pamidronate in reducing skeletal morbidity and prolonging the time to first skeletal event.
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PMID:The role of bisphosphonates in breast cancer. 1976 82

Bone metastases frequently occur in patients with advanced solid tumors, particularly breast and prostate cancers, and nearly all patients with multiple myeloma have some degree of skeletal involvement. The strides made in treating these primary tumors have extended median survival times and thereby increased patient risk for skeletal-related events (SREs), including pathologic fractures, spinal cord compression, need for palliative radiation therapy or surgery to bone, and hypercalcemia. Bisphosphonates, inhibitors of osteoclastic bone resorption that were first established as treatment of osteoporosis, have been shown to prevent and/or delay SREs related to malignancy. The results of a large, randomized phase 3 study comparing zoledronic acid and pamidronate in breast cancer or multiple myeloma patients with osteolytic lesions showed that the incidence of SREs, time to first SRE, and risk of developing a SRE were similar between treatment groups. However, in patients with solid tumors (excluding breast or prostate cancer) metastatic to the bone, only zoledronic acid has demonstrated clinical efficacy. Although bone turnover marker levels, such as N-telopeptide of type I collagen, have been shown to correlate with clinical response, additional studies are needed to validate their ability to predict response to bisphosphonate therapy.
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PMID:Bisphosphonates in oncology: evidence for the prevention of skeletal events in patients with bone metastases. 1992 Sep 19

Approximately 30-40% of NSCLC patients develop bone metastases. Bone metastases are associated with a significant increase in skeletal-related events (SREs), including severe bone pain, hypercalcemia, pathological fractures, spinal cord compression. These SREs result in impaired mobility, reduced quality of life, and frequently require therapeutic intervention (radiation therapy, surgery and systemic treatments). The normal balance of formation of new bone by osteoblasts and the resorption of old bone by osteoclasts becomes imbalanced and/or uncoupled, leading to the development of lesions that are osteolytic, osteoblastic, or a combination of both. The current National Comprehensive Cancer Network (NCCN) Clinical Practice Giudelines in Oncology recommend palliative external-beam radiotherapy for the treatment of bone metastases in patients with NSCLC and healthcare professionals treating such patients are urged to consider bisphosphonate therapy. Zoledronic acid is the first and only bisphosphonate that has proven efficacy for the treatment of bone metastases from a broad range of solid tumor types, including lung cancer.
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PMID:Treatment of bone metastases in lung cancer: the actual role of zoledronic acid. 2002 33

Bone pain due to skeletal metastases constitutes the most common type of chronic pain among patients with cancer. It significantly decreases the patient's quality of life and is associated with comorbidities, such as hypercalcemia, pathologic fractures and spinal cord compression. Approximately 65% of patients with prostate or breast cancer and 35% of those with advanced lung, thyroid, and kidney cancers will have symptomatic skeletal metastases. The management of bone pain is extremely difficult and involves a multidisciplinary approach, which usually includes analgesics, hormone therapies, bisphosphonates, external beam radiation, and systemic radiopharmaceuticals. In patients with extensive osseous metastases, systemic radiopharmaceuticals should be the preferred adjunctive therapy for pain palliation. In this article, we review the current approved radiopharmaceutical armamentarium for bone pain palliation, focusing on indications, patient selection, efficacy, and different biochemical characteristics and toxicity of strontium-89 chloride, samarium-153 lexidronam, and rhenium-186 etidronate. A brief discussion on the available data on rhenium-188 is presented focusing on its major advantages and disadvantages. We also perform a concise appraisal of the other available treatment options, including pharmacologic and hormonal treatment modalities, external beam radiation, and bisphosphonates. Finally, the available data on combination therapy of radiopharmaceuticals with bisphosphonates or chemotherapy are discussed.
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PMID:Systemic metabolic radiopharmaceutical therapy in the treatment of metastatic bone pain. 2011 78

Certain primary tumours including breast and prostate cancers have a particular propensity for metastasis to bone. Metastatic bone disease can have significant impact on morbidity and mortality of cancer patients. Skeletal-morbidity (spinal cord compression, hypercalcaemia, fracture, need for radiotherapy and surgery to bone) can be effectively reduced by bisphosphonates, a class of anti-resorptive drugs. They are also effective in relieving pain from bone metastases, and may improve survival in patients with accelerated bone resorption. Additionally, there is an exciting body of evidence that suggest these drugs may have anti-tumor effects that may be exploited to prevent or delay the development of bone metastases. Reported effects include inhibition of cancer cell migration, adhesion and invasion as well as anti-angiogenic and immunomodulating effects. The pre-clinical evidence is compelling, and some recently reported randomised clinical studies go part way to support their use in clinical practice at earlier stages of the disease to prevent bone metastases. However, further results are awaited before routine clinical use in the adjuvant setting can be recommended.
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PMID:Prevention and treatment of bone metastases. 2072 24


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