Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020437 (hypercalcemia)
 10,293 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The major clinical manifestations of multiple myeloma are related to the loss of bone. This bone loss often leads to pathologic fractures, spinal cord compression, hypercalcemia, and bone pain. This article reviews the cytokine network involved in myeloma bone disease; describes the signaling cascade involved in osteoclastogenesis and mechanisms of action of novel therapeutic options for myeloma bone disease such as osteoprotegerin, RANK human immunoglobulin fusion protein, the proteasome inhibitor PS-341, and bisphosphonates; and summarizes the latest clinical trial results using oral and intravenous bisphosphonates for bone disease in multiple myeloma.
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PMID:Advances in the biology and treatment of myeloma bone disease. 1252 Apr 79

Bony pathology in the cancer patient represents a significant source of morbidity and mortality. Complications include insufficiency and pathological fractures resulting from either medical treatments or bony metastases that can cause significant functional limitations. Additional complications include spinal cord compression, hypercalcemia, and bone marrow failure. Rehabilitation management of such conditions is reviewed, with an emphasis on diagnostic and therapeutic management. Bracing and focused rehabilitation programs facilitate maximal participation and functional outcomes, which can result in an enhanced quality of life. Specific rehabilitation goals and strategies are discussed, with an emphasis on tailoring these according to the functional staging of the patient.
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PMID:Bony pathology in the cancer patient. 1257 36

Multiple myeloma (MM) is a plasma cell malignancy characterized by infiltration of bone marrow, bone destruction, infiltration of soft tissues with plasma cells, and suppression of normal hematopoiesis. The production of monoclonal immunoglobulins with or without light chains is a major feature of the disease. Full spectrum of plasma cell dyscrasias include monoclonal gammapathy of undetermined significance, smouldering myeloma, indolent multiple myeloma, and fully developed, symptomatic multiple myeloma. The usual presenting features of MM include bone pain, weakness, fatigue, fever and infection. Neurologic symptoms are less common but one must not forget that MM may present with a neurologic disease. Careful neurologic history and examination are mandatory in patients with MM. Neurologic symptoms may be a direct manifestation of MM or may be due to the immune effect of monoclonal proteins directed against different neural structures. Finally, metabolic consequences (uremia, hypercalcemia, hyperviscosity) of MM may produce a broad spectrum of different neurologic symptoms including headache, blurring of vision, drowsiness, precoma, coma, vertigo, ataxia, hemiparesis and epileptiform seizures. The most common location of bone changes in MM is the thoracic spine, where it causes osteolytic changes with consequent compressive fractures. The most disastrous sequel is paraplegia. Multiple vertebral involvement with the evidence of osteolytic changes in other bones is usual, but solitary vertebral myeloma may occur. Myeloma usually involves the bone of the vertebral body and then spreads into the extradural space. However, patients with solitary extradural myeloma have been reported. Skull myeloma is frequently asymptomatic. It may grow externally or, rarely, there is intracranial expansion. Involvement of the cranial nerves is not rare, with II, V, VI, VII and VIII cranial nerves being most often affected. Isolated intracerebral plasmacytomas are extremely rare. Diagnostic approach includes plain X-rays of the skeleton, which was found to be the method of choice for demonstration of osteolytic changes, whereas magnetic resonance with gadolinium enhancement most reliably displays the degree of vertebral involvement and demonstrates any associated soft tissue mass. Current treatment of osteolytic changes in multiple myeloma include chemotherapy, radiotherapy in combination with dexamethasone, monthly infusions of bisphosphonates, surgical decompression, and kyphoplasty. Therapeutic approach is dictated by the presenting symptoms. In case of pain as the predominant symptom, treatment with chemotherapy and radiotherapy may be appropriate. Compressive symptoms are relieved with dexamethasone followed by radiotherapy and chemotherapy. Surgical decompression is used in patients with vertebral collapse and vertebral instability. Kyphoplasty is a new method used in the treatment of osteolytic changes of vertebral bodies. A viscous cement is injected into the cavity by a balloon-like inflatable bone tampon. It has been successfully employed to improve the quality of life, to reduce pain, and to increase overall functioning in patients with vertebral compression fractures by restoring most of the original height of the vertebral body. Bisphosphonates reduce pain associated with osteolytic changes in multiple myeloma, but also significantly reduce skeletal events (pathologic fracture, spinal cord compression, surgery or irradiation of bone) via unknown mechanism. It seems that bisphosphonates, by inhibiting bone resorption, alter the microenvironment in which the MM cells grow.
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PMID:[Neurologic sequelae of bone changes in multiple myeloma and its therapy]. 1263 Mar 41

Multiple myeloma is characterized by bone destruction mediated by osteoclastic bone resorption. Skeletal complications of myeloma, including bone pain, fractures, spinal cord compression and hypercalcemia, result in significant morbidity. Gallium nitrate was shown in a small, randomized trial to attenuate the rate of bone loss in patients with myeloma treated with chemotherapy. In a retrospective analysis, we found that patients with advanced multiple myeloma treated with chemotherapy plus gallium nitrate had markedly prolonged median survival compared with similar patients treated with chemotherapy alone (87+ months v 48 months, respectively). These data suggest that gallium nitrate may have a positive, indirect benefit on survival in myeloma by decreasing the rate of bone resorption. Further evaluation of gallium nitrate to attenuate progression of disease in patients with multiple myeloma is warranted.
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PMID:Gallium nitrate in multiple myeloma: prolonged survival in a cohort of patients with advanced-stage disease. 1277 56

Patients with metastatic cancer and bone involvement are at chronic risk of skeletal complications, including bone pain, fractures, spinal cord compression and hypercalcaemia of malignancy. Therapies targeting the primary malignancy are often unable to prevent skeletal complications, which often require orthopaedic surgery, radiation therapy and analgesics. Intravenous bisphosphonates can reduce the risk of skeletal complications and the requirement for palliative radiation therapy. Since its broad regulatory approval, zoledronic acid (ZOMETA, Novartis Pharma AG/Novartis Pharmaceuticals Corporation) 4 mg by 15-minute intravenous infusion has become widely used to treat bone metastases from all solid tumours and is becoming the standard of care for advanced breast cancer and multiple myeloma. Additionally, cancer treatment-induced bone loss is an emerging problem in clinical oncology, and bisphosphonates -- particularly intravenous bisphosphonates -- may provide benefits even before bone lesions develop. Further investigations of bisphosphonates in these and other indications are ongoing.
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PMID:Bisphosphonate therapy in the oncology setting. 1466

The skeleton is the third most common site for cancer to spread to after the liver and lungs. Malignancies that can cause destruction of skeletal bones include multiple myeloma and metastatic disease of the breast, prostate, and lung. Bone metastases are problematic for patients with cancer because accelerated bone breakdown occurs with many associated complications. One or more of the following problems may occur: pain, hypercalcemia, pathologic fractures, myelosuppression, and spinal cord compression with subsequent progressive immobility. Quality of life is affected negatively, and associated feelings of fear, grief, anger, despair, anxiety, and depression can occur. Management of malignancies of the bone involves a multimodal approach. Therapies include analgesia, hormone therapy, chemotherapy, surgery, radiation therapy, and the use of bisphosphonates. Nurses can be instrumental in promoting positive outcomes for patients with bone metastases.
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PMID:Advances in the treatment of bone metastases. 1470 79

Patients with multiple myeloma often experience skeletal-related complications including pathological fractures, hypercalcemia, spinal cord compression, pain requiring surgery or radiotherapy. Myeloma bone disease is characterized by the presence of lytic lesions due to increased osteoclastic activity, which is not accompanied by a comparable increase in bone formation. Targeting osteoclastic bone resorption therefore represents an important approach to treating patients with myeloma-related bone disease. Bisphosphonates are potent inhibitors of osteoclast activity and function. Recent large, placebo-controlled clinical trials have shown the efficacy of bisphosphonates in reducing skeletal complications in multiple myeloma and suggest that these agents may also alter the overall course of the disease. In this review, we summarize the data covering the effect of different types of bisphosphonates on myeloma bone disease, their mode of action and the future implications of their use.
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PMID:Bisphosphonate treatment for multiple myeloma. 1498 68

Bisphosphonate drugs are a group of pyrophosphate analogues which bind avidly to hydroxyapatite bone mineral surfaces and their major action is to inhibit osteoclast activity and thus bone resorption. In oncology, their role in metastatic bone disease is well established, but there is increasing interest in their potential role in preventing and treating cancer-induced bone loss and their possible anti-tumour effects. Metastatic bone disease is associated with a variety of skeletal complications, including pathologic fractures, bone pain, impaired mobility, spinal cord compression and hypercalcaemia. Intravenous bisphosphonates, particularly zoledronic acid, in conjunction with rehydration, are now established as the treatment of choice for hypercalcaemia. For treatment of bone pain, it has also been shown that bisphosphonates can be an effective supplementary approach to radiotherapy. In breast cancer and myeloma, bisphosphonates have now become part of standard therapy to treat and prevent skeletal-related events (SRE) and, until recently, treatment was largely with intravenous pamidronate or oral clodronate. However, large, randomised, multicentre trials using intravenous administration of the highly potent bisphosphonate zoledronic acid every 3-4 weeks have recently demonstrated a reduction of 20% in the risk of developing an SRE compared with pamidronate for patients with breast cancer. Moreover, these trials have demonstrated, for the first time, that a bisphosphonate significantly reduces the occurrence of skeletal events in hormone-refractory prostate cancer and in non-small cell lung cancer and a range of other solid tumours. Investigations into the potential of the relatively low potency bisphosphonate, clodronate, for the prevention of bone metastases in breast cancer have produced conflicting data. Further large, randomised studies with clodronate and zoledronic acid are planned and until the results are available it is not possible to identify a definite adjuvant role for bisphosphonates. Evidence is accumulating in vitro that bisphosphonates are also able to directly affect tumour cells, in addition to their effects on osteoclasts, with zoledronic acid being particularly potent. Over recent decades there has been a significant improvement in cure rates and survival times in certain cancers and the use of chemotherapy and hormone therapy has expanded greatly, leading to increasing numbers of long-term survivors who have received these treatments. Management of treatment-induced bone loss is therefore assuming a greater importance and bisphosphonates represent an attractive treatment option in such patients. Several placebo-controlled trials using oral clodronate, oral risedronate, intravenous pamidronate and intravenous zoledronic acid have all now demonstrated benefits in reducing the loss in bone mineral density.
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PMID:The role of bisphosphonates in breast and prostate cancers. 1516 99

Patients with cancer who have bone metastases may live for several years following diagnosis. However, skeletal disease significantly impacts quality of life, causing bone pain, pathologic fractures, spinal cord compression, and hypercalcemia. This program covered the challenges of treatment, new standards of care, advances in nursing, responsibilities in supportive care, and current trials investigating options for treatment-induced bone loss. The program ended with a call to nurses to become more active as patient advocates.
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PMID:Current topics in bone metastases. 1547 78

Bone metastasis are a frequent complication of cancer, occurring in up to 70% of patients with advanced breast or prostate cancer. The consequences of bone metastasis are often devastating. Osteolytic metastasis can cause different kinds of skeletal related events including severe pain, pathologic fractures, life-threatening hypercalcemia, spinal cord compression, and other nerve-compression syndromes. These skeletal-related events are the result of the resorption of mineralized bone by osteoclasts. Bisphosphonates are synthetic analogues of naturally occurring pyrophosphate compounds that inhibit bone resorption. Potent bisphosphonates, pamidronate and, more importantly zoledronic acid may cause hypocalcemia, but mostly asymptomatic, mild, transient in most cases. Sufficient calcium and vitamin D intake needs to be ensured in patients with malignancy who have borderline or low levels of calcium when commencing treatment with bisphosphonates. Vitamin D itself induce the formation of osteoclasts by increasing the expression of RANKL on marrow stromal cells. Local calcium also promotes tumor growth and the production of parathyroid hormone-related peptide which in turn stimulates bone resorption. Vitamin D and calcium supplementation during bisphosphonate administration for the purpose of elimination of the side effects related to hypocalcemia in patients with bone metastasis may increase the bone resorption and decrease the efficacy of bisphosphonates. Therefore, vitamin D and calcium supplementation must not be routinely recommended during bisphosphonate administration.
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PMID:Calcium and vitamin D supplementation during bisphosphonate administration may increase osteoclastic activity in patients with bone metastasis. 1569 11


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