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 skeleton is the most common organ to be affected by metastatic cancer, and tumors arising from the breast, prostate, thyroid, lung, and kidney possess a special propensity to spread to bone. Breast carcinoma, the most prevalent malignancy, causes the greatest morbidity. Of great clinical importance is the observation that metastatic bone disease may remain confined to the skeleton. In these patients, the decline in quality of life and eventual death is due almost entirely to skeletal complications and their subsequent treatment. Bone pain is the most common complication of metastatic bone disease, resulting from structural damage, periosteal irritation, and nerve entrapment. Recent evidence suggests that pain caused by bone metastasis may also be related to the rate of bone resorption. Hypercalcemia occurs in 5-10% of all patients with advanced cancer but is most common in patients with breast carcinoma, multiple myeloma, and squamous carcinomas of the lung and other primary sites. Pathologic fractures are a relatively late complication of bone involvement. The clinical courses of breast and prostate carcinoma are relatively long, with a median survival of 2-3 years. For patients with breast carcinoma, good prognostic factors for survival after the development of bone metastases are good histologic grade, positive estrogen receptor status, bone disease at initial presentation, a long disease free interval, and increasing age. In addition, patients with disease that remains confined to the skeleton have a better prognosis than those with subsequent visceral involvement. For patients with prostate carcinoma, adverse prognostic features include poor performance status, involvement of the appendicular skeleton and visceral involvement, whereas for patients with multiple myeloma, the levels of serum beta2-microglobulin and lactate dehydrogenase and the immunologic phenotype are the most important factors. These prognostic factors may be useful in planning the rational use of bisphosphonates in the treatment of advanced cancer.
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PMID:Skeletal complications of malignancy. 936 26

A significant percentage (50-70%) of patients with metastatic breast carcinoma (MBC) will have disease involving the bony skeleton. Clonal selection mediated by parathyroid hormone-related protein and other factors may explain the high incidence of osseous metastases in MBC. The presence of specific growth factors and cytokines in the microenvironment of bone may contribute to the successful establishment and growth of metastatic lesions and also might determine response or resistance of these lesions to chemotherapy or hormonal therapy. Osteolytic bone lesions in MBC frequently give rise to serious clinical problems including bone pain, pathologic fracture, hypercalcemia, and neurologic complications. MBC often is treated with systemic chemotherapy or hormonal therapy. The purpose of this article was to review the recent published literature describing the impact of systemic chemotherapy and hormonal therapy of MBC on the response of bone lesions and their clinical course and complications. Evaluating the response of bone lesions can be problematic and may be complicated by the phenomenon of "tumor flare" that may be observed with either chemotherapy or hormonal therapy. Use of the International Union Against Cancer criteria for the response of bone lesions is recommended. Several studies report objective responses (20-60%) of lytic bone metastases to standard combination chemotherapy regimens such as cyclophosphamide, methotrexate, and 5-fluorouracil and cyclophosphamide, doxorubicin, and 5-fluorouracil, mitoxantrone and 5-FU, newer combinations, and single agents including paclitaxel and docitaxel but responses to vinorelbine may be less frequent. Complete responses of bone lesions to chemotherapy are rare but partial responses and disease stabilization can lead to long term patient benefit. A series from the M. D. Anderson Cancer Center of patients with bone metastases treated with 5-FU, doxorubicin, and cyclophosphamide chemotherapy reported a median duration of response of 14 months. In a recent multicenter study of 195 patients with lytic lesions from MBC treated with chemotherapy, the objective response rate (complete response + partial response) in bone was 18% and 65% of the patients developed at least 1 morbid skeletal event with a median onset of 7.0 months from the start of chemotherapy. Hormone-dependent breast carcinoma has a proclivity to metastasize to bone. In earlier studies comparing aminoglutethimide or medroxyprogesterone acetate with tamoxifen, a higher response rate of bone metastases was observed for the first two agents. However, in more recent studies comparing newer aromatase inhibitors, such as anastrozole, fadrozole, and letrozole, with megestrol acetate, there were no significant differences in rates of response in bone. Patients with MBC with bony lesions respond to both chemotherapy and hormonal therapy and can have a prolonged survival. Therefore such patients are in a more favorable position to benefit from adjunctive supportive therapy such as bisphosphonates intended to reduce skeletal morbidity.
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PMID:Issues concerning the role of chemotherapy and hormonal therapy of bone metastases from breast carcinoma. 936 31

The skeleton is a common site of breast carcinoma metastasis; 75% of patients with breast carcinoma demonstrate bone metastases at autopsy. The lytic destruction of bone in these patients is due to excessive osteoclastic activity. By reducing osteoclastic activity, bisphosphonates inhibit bone resorption. Initial studies of breast carcinoma patients were performed with clodronate, a first-generation bisphosphonate. Studies with small cohorts suggested reduction of pain, analgesic requirement, and development of hypercalcemia. A larger randomized, double-blind, placebo-controlled trial of oral clodronate 1600 mg/day demonstrated a significant reduction of the combined rate of all morbid skeletal events (significant reduction of the incidence of vertebral fractures, rate of vertebral deformity, and hypercalcemic episodes). Trends were observed that favored clodronate for the treatment of nonvertebral fractures and radiotherapy for relief of bone pain. There was no survival difference between the clodronate and placebo groups (Paterson et al., J Clin Oncol 1993;11:59-65). Pamidronate is a second-generation aminobisphosphonate that is a much more potent inhibitor of osteoclastic activity. Phase II studies again suggested an improvement in many of the skeletal complications of breast carcinoma. Two large Phase III studies have recently been completed. Women with Stage IV breast carcinoma who were receiving cytotoxic chemotherapy (380 patients) or endocrine therapy (371 patients) and had at least 1 lytic bone lesion were given either pamidronate 90 mg as a 2-hour infusion monthly for 2 years or a placebo infusion. After the two studies were pooled, 367 patients treated with pamidronate and 384 patients given placebo were available for analysis. The median time to first complication (pathologic fracture, vertebral collapse, spinal cord compression, or treatment of bone with radiation or surgery) was 12.7 months for the pamidronate patients and 7.0 months for placebo patients (P = 0.001). The time to first fracture was 25.2 months for pamidronate patients and 12.8 months for placebo patients (P = 0.003). The proportion of patients with fracture was 40% for pamidronate vs. 52% for placebo (P = 0.002); the proportion with radiation administered to bone was 29% for pamidronate vs. 43% for placebo (P = 0.001); and the proportion with any skeletal event was 51% for pamidronate vs. 64% for placebo (P = 0.001). The skeletal morbidity rate (the number of complications per year) at 24 months was 2.4 for the pamidronate group and 3.7 for placebo (P = 0.001). Pain and analgesic use was decreased among the pamidronate patients. There was no difference in survival between the groups. Not all patients responded to the same dose of bisphosphonate. Recent data suggests that patients who have a normalization of their urinary excretion of N-telopeptide have a reduced risk of progression of disease in bone and fracture. In summary, the addition of pamidronate to standard chemotherapy or endocrine therapy produces a sustained reduction in skeletal complications in breast carcinoma patients with osteolytic bone metastases.
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PMID:Bisphosphonates and breast carcinoma. 936 34

Pamidronate (APD) is a potent inhibitor of bone resorption that is useful in the management of patients with osteolytic bone metastases from breast cancer or multiple myeloma, tumour-induced hypercalcaemia or Paget's disease of bone. After intravenous administration, the drug is extensively taken up in bone, where it binds with hydroxyapatite crystals in the bone matrix. Matrix-bound pamidronate inhibits osteoclast activity by a variety of mechanisms, the most important of which appears to be prevention of the attachment of osteoclast precursor cells to bone. In patients with osteolytic bone metastases associated with either breast cancer or multiple myeloma, administration of pamidronate together with systemic antitumour therapy reduces and delays skeletal events, including pathological fracture, hypercalcaemia and the requirement for radiation treatment or surgery to bone. Pamidronate generally improves pain control. Quality-of-life and performance status scores in pamidronate recipients were generally as good as, or better than, those in patients who did not receive the drug. Overall survival does not appear to be affected by pamidronate therapy. Tumour-induced hypercalcaemia also responds well to pamidronate therapy: 70 to 100% of patients achieve normocalcaemia, generally 3 to 5 days after treatment. Response durations vary, but are commonly 3 weeks or longer, In comparative studies, pamidronate produced higher rates of normocalcaemia and longer normocalcaemic durations than other available osteoclast inhibitors, including intravenous etidronate, clodronate and plicamycin (mithramycin). In most patients with Paget's disease of bone, intravenous pamidronate reduces bone pain and produces biochemical response. Serum alkaline phosphatase levels generally fall 50 to 70% from baseline 3 to 4 months after pamidronate treatment. Biochemical response may be prolonged. Pamidronate is well tolerated by most patients. Transient febrile reactions, sometimes accompanied by myalgias and lymphopenia, occur commonly after the first infusion of pamidronate. Other reported adverse events include transient neutropenia, mild thrombophlebitis, asymptomatic hypocalcaemia and, rarely, ocular complications (uveitis and scleritis). Pamidronate should be considered for routine use together with systemic hormonal or cytotoxic therapy in patients with breast cancer or multiple myeloma and osteolytic metastases. At present, pamidronate is the drug of choice for first-line use in the management of patients with tumour-induced hypercalcaemia. It is an effective treatment for Paget's disease and is the treatment of choice where oral bisphosphonates are not an option.
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PMID:Pamidronate. A review of its use in the management of osteolytic bone metastases, tumour-induced hypercalcaemia and Paget's disease of bone. 950 93

We observed a patient with a giant brown tumor of the iliac bone due to hyperparathyroidism. There was a risk of pathologic fracture due to huge cysts produced by bone absorption. In hyperparathyroid crisis, control of severe hypercalcemia is difficult without resection of the parathyroid gland.
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PMID:Hyperparathyroid crisis in a patient with a giant brown tumor of the iliac bone: a case report. 958 80

The successful use of pamidronate, a bisphosphonate, for the treatment of hypercalcemia and/or osteopenia is reported in three children with renal failure or following renal transplant. Patient 1 was an 11-year-old post renal transplant male who received a single dose of i.v. pamidronate (0.5 mg/kg) for the treatment of acute hypercalcemia associated with a pathological fracture and subsequent immobilization. Prompt resolution of the hypercalcemia was seen. He received a second course of pamidronate (0.5 mg/kg per day for 3 days) for the treatment of osteopenia and has had a subsequent 15% increase in lumbar spine bone mineral content (BMC). Patient 2, a 14-year-old male on peritoneal dialysis, presented with symptomatic hypercalcemia associated with tertiary hyperparathyroidism. A single dose of i.v. pamidronate (0.4 mg/kg) was given with prompt resolution and prolonged control of his hypercalcemia. The third patient was a 16-year-old female, also in renal failure on peritoneal dialysis. Her course had been complicated by marked osteopenia. I.v. pamidronate (0.5 mg/kg per dose) was given on 3 successive days before and after renal transplant in an attempt to stabilize her bone mineral density (BMD) around the time of renal transplantation, when additional glucocorticoid was necessary. Her total body BMC and BMD remained stable pre and post transplant. The treatment was effective and well tolerated in all three patients. Hence pamidronate is safe and effective for the management of hypercalcemia and osteopenia in children with renal failure and/or renal transplant.
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PMID:The use of pamidronate in three children with renal disease. 987 27

Osteolysis, the most common expression of bone tumor, can cause pain, pathological fracture, epidural spinal cord compression and hypercalcemia. Multinucleated osteoclast-like cells, the main agents in bone resorption, are numerous in benign giant cell tumor of bone and can be recruited and activated by various carcinoma cell lines in vitro in animal models. Polykarion macrophages are also able to resorb bone matrix in a favourable tumoral environment. Direct bone resorption by tumor cells has recently been described in vitro and in vivo in animals. The presence of diffusible substances such as hormones, cytokines and growth factors creates a favourable microenvironment for stimulation of osteoclast-like cells and polykarion macrophages functional ability to resorb bone matrix. These mediators act within a complex but still unelucidated network involving high cell production (tumor cells, normal and reactional stroma as well as hematopoietic cells) and many targets (tumor production (tumor cells, normal and reactional stroma as well as hematopoietic cells) and many targets (tumor cells, monocyte/macrophage lineage cells, and osteoclast-like cells). The presence in the same environment of all these stimulating factors for tumor cell growth and resorbing ability could explain the vicious circle of tumoral and osteolytic progression. A better understanding of the complex mechanism of tumor induced osteolysis is essential for improving the conventional surgical approach to this pathology.
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PMID:[Physiopathology of tumor-induced osteolysis]. 1032 68

The bisphosphonates are potent inhibitors of osteoclast-mediated bone resorption and are now the treatment of choice for the management of hypercalcaemia of malignancy. The incidences of hypercalcaemia and other skeletal complications (bone pain, pathological fracture) remain high despite apparent responses to systemic therapy, with particularly high event rates in women with advanced skeletal metastases of breast cancer. This review focuses on studies addressing the long-term efficacy of bisphosphonates to reduce skeletal complications in breast cancer (5 studies) and multiple myeloma (4 studies), with particular reference to controlled studies of sufficient magnitude and duration to allow confidence in the estimation of efficacy. Bearing in mind the limitations of differences in trial design and the lack of direct studies comparing drugs, adequate exposure to a bisphosphonate reduces the incidence of skeletal complication by 30 to 40% in both breast cancer and multiple myeloma. Oral clondronate and intravenous pamidronate have similar efficacy in both diseases, but the duration of efficacy may differ between drugs. Both agents have shown intriguing survival benefits in subgroups of patients. The numbers needed to treat (NNT) to prevent a skeletal complication during one year are lowest in metastatic skeletal disease in breast cancer (NNT < 8) but also compare very favourably with other disease for patients with recurrent nonskeletal breast cancer or multiple myeloma (NNTs 7 to 31 depending on the complication to be prevented). Treatment costs of both breast cancer and multiple myloma are driven by inpatient and outpatient hospital visits so that bisphosphonate regimens should be developed that reduce both. Further research is required to determine if subgroups of patients can be better identified that will derive particular benefit, or perhaps no benefit at all, from bisphosphonate therapy. It is not known whether more potent bisphosphonates will deliver greater clinical efficacy in the future.
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PMID:The clinical and cost considerations of bisphosphonates in preventing bone complications in patients with metastatic breast cancer or multiple myeloma. 1151 Oct 21

Osteitis fibrosa cystica (brown tumors) can be a skeletal manifestation of advanced hyperparathyroidism, including parathyroid cancer. Severe osteitis fibrosa cystica can mimic metastatic bone diseases especially in patients with a history of cancer. Because the treatment and prognosis of these two problems differ greatly considering hyperparathyroidism in the differential diagnosis of patients found to have osteolytic lesions is critical for the appropriate management of these patients. In this case report we describe a patient with a history of renal cell cancer and presumed osteolytic bone metastases. During prophylactic intramedullary rodding to prevent pathologic fracture of her femur she was found to have a benign lesion related to her previously undiagnosed hyperparathyroidism caused by an underlying parathyroid cancer. A detailed review of this disease and the associated bone changes is also included to underscore the importance of an adequate differential diagnosis as well as optimal management. Patients with hypercalcemia or bony lesions should not automatically be treated palliatively for metastatic disease just because of a past medical history of cancer. Hyperparathyroidism is a readily curable problem if properly diagnosed.
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PMID:Disseminated brown tumors from hyperparathyroidism masquerading as metastatic cancer: a complication of parathyroid carcinoma. 1160 52

Acute lymphoblastic leukemia (ALL) is associated rarely with hypercalcemia. This may be due to elevated levels of parathyroid hormone-related peptide (PTHrP). We report a case of an 18-year-old female patient who was presented with a pathological fracture of left intertrochanteric region. Bone scintigraphy was consistent with features of hypercalcemia associated with metastatic calcification. A bone marrow biopsy led to the diagnosis of ALL. The mechanism of hypercalcemia in ALL, metastatic calcification and soft tissue uptake of bone seeking agents in this case are discussed in detail.
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PMID:Soft tissue uptake of Tc99m-MDP in acute lymphoblastic leukemia. 1198 75


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