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)

Complications of breast cancer involving the skeleton include hypercalcaemia, bone pain and fracture. These complications arise because of progressive osteolysis which is in turn dependent on the activation of osteoclasts by tumour and host tissues. Clodronate is a powerful inhibitor of osteoclastic bone resorption which led us to evaluate its potential in metastatic breast cancer. When given intravenously it lowers serum calcium in the majority of hypercalcaemic patients. A convenient regimen is 600 mg iv as a single dose infused over several hours. We have additionally shown in a double-blind cross-over study that this regimen also has a significant effect on bone pain. This had led us to assess the longer term effects of clodronate by mouth in a prospective double-blind study of patients with established skeletal metastases. These studies are not yet complete but the agent appears to prevent hypercalcaemia and trends are emerging which indicate that the incidence of bone pain and fractures may also decrease.
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PMID:Treatment of skeletal disease in breast cancer with clodronate. 172 12

Osteolytic bone metastases secondary to breast cancer are extremely common, occurring in more than 50% of breast cancer patients. The resulting increased bone resorption leads to significant symptomatic morbidity caused by bone pain, hypercalcaemia and pathological fracture. Clodronate, an anti-osteolytic agent, inhibits osteoclastic bone resorption and has considerable therapeutic value. Recent studies have shown that clodronate is effective in the treatment of malignancy hypercalcaemia, relief of bone pain and decreases the risk of pathological fracture. The use of clodronate in the future, other than as a palliative therapy, may focus upon the prevention of osteolytic bone metastases at the time of primary diagnosis or later in the disease progression in those patients at risk, for example, those with non-osseous relapse. Since patients with bone metastases secondary to breast cancer often have an increased duration of survival, any agent that would decrease the symptomatic morbidity would have a significant impact upon quality of life, even more so if the actual development of osteolytic bone metastases was delayed or prevented.
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PMID:Clodronate: the potential for the future. 172 14

The intravenous administration of Clodronate, a strong inhibitor of osteoclastic activity provides a safe and very effective treatment of hypercalcemia whether secondary to bone metastasis or due to paraneoplastic syndrome. Its action is fast, exclusively osseous and lasts up to 7 days. The response is incomplete when increased renal absorption is the predominant mechanism of hypercalcemia. The data published by Elomaa et al on osteolytic metastases in breast cancer patients show a significant improvement with regard to pain reduction, prevention of fractures as well as hypercalcemia. The results obtained using a 1-yr oral treatment need further confirmation.
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PMID:[Value of Clodronate in the treatment of bone metastasis]. 183 87

The bisphosphonate clodronate has been widely used in the treatment of hypercalcaemia and osteolytic bone metastases. It can normalize plasma calcium in most hypercalcaemic, rehydrated cancer patients when increased bone resorption is the prevailing disturbance of calcium metabolism. When given intravenously either as a single infusion or as repeated daily administrations, serum calcium levels fall to normal 3-5 days after the onset of therapy. Long-term maintenance treatment must be adjusted individually since relapse appears to depend upon the tumour type, the degree of malignancy and any anticancer therapy. In patients in whom increased tubular calcium reabsorption is the prevailing disturbance of calcium metabolism, the effect of clodronate on plasma calcium is incomplete, despite the normalization of bone resorption. This type of therapeutic response can be reproduced experimentally in bisphosphonate-treated animals receiving a constant infusion of parathyroid hormone-related peptide, a peptide isolated from various tumour types including lung, kidney, breast and neuroendocrine tumour of the pancreas. In patients having a good response to clodronate, the fall in plasma calcium is accompanied by an increase in the calcium-regulating hormones, parathyroid hormone and 1,25-dihydroxyvitamin D3. This homeostatic response probably explains why hypocalcaemia occurs rarely in clodronate-treated patients. No serious side-effects of treatment have been reported. Clodronate appears to be a safe and effective treatment for the hypercalcaemia of malignancy, where increased bone resorption is the major mechanism disturbing the homeostasis of extracellular calcium.
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PMID:Treatment of hypercalcaemia of malignancy with clodronate. 183 97

Bone metastases secondary to myeloma, are characterized by severe bone pain, pathological fractures, hypercalcaemia and hypercalciuria. Histological and biochemical investigations have shown a wide spectrum of abnormalities in bone turnover in patients with multiple myeloma. The increased osteoclast activity caused by various osteoclast activating factors secreted by myeloma cells, is responsible for the diffuse localized osteolytic lesions. These lesions are responsible for the symptoms and respond poorly to standard chemotherapy, justifying the use of a bone-sparing agent. Clodronate is a potent inhibitor of osteoclast activity and does not impair bone mineralization. Several studies have shown that clodronate can normalize serum calcium in hypercalcaemic patients with metastatic bone disease, and a similar response is seen in multiple myeloma. In a long-term (18 months) placebo-controlled study we have shown that clodronate, given orally at a daily dose of 1.6g, can decrease both the incidence of pathological fractures and the activity of osteoclasts, as judged by measurements in iliac crest biopsy. These results, along with those from two other studies, are promising and suggest that clodronate may inhibit the progression of osteolytic lesions in multiple myeloma.
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PMID:The use of clodronate in multiple myeloma. 183 98

We have examined the effects of the diphosphonate, clodronate, in 9 haemodialysis patients with severe hyperparathyroid bone disease. Clodronate (300-600 mg infused after dialysis on 5 consecutive occasions) significantly decreased mean serum calcium, phosphate and hydroxyproline. This was associated with an increase in serum immunoassayable parathyroid hormone and activity of alkaline phosphatase. These changes reversed 2-4 weeks after stopping treatment but were sustained when treatment with oral clodronate (1.6 g daily) was supplemented for 2 weeks. Our findings suggest that intravenous clodronate is capable of inhibiting osteoclast-mediated bone resorption in chronic renal failure. The therapeutic potential of clodronate alone or with vitamin D derivatives merits further evaluation, particularly in patients with severe hyperparathyroidism, when the use of D metabolites alone is precluded by the presence of hypercalcaemia.
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PMID:Effects of clodronate in severe hyperparathyroid bone disease in chronic renal failure. 214 21

Increased bone resorption and increased renal tubular reabsorption of calcium are involved in the pathogenesis of hypercalcemia of malignancy. Clodronate and calcitonin inhibit bone resorption and have been used as therapy for malignancy-associated hypercalcemia. Both drugs induce significant reductions of serum calcium but the decrease is greater with clodronate, particularly when given intravenously. While the response to calcitonin generally is of short duration, clodronate can maintain normal serum calcium values over several weeks when oral administered. Thus, from the clinical point of view clodronate is a very useful adjunct to the available therapy.
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PMID:Use of clodronate and calcitonin in hypercalcemia due to malignancy. 252 99

The distribution of 14C-labeled clodronate (dichloromethylene bisphosphonate), a new bisphosphonate for the treatment of osteolytic bone metastases and hypercalcemia, was studied in mice by whole-body autoradiography and by measuring the 14C activities in various tissues [14C]Clodronate was administered into the tail vein, and its distribution was followed from 5 min to 90 days after the injection. The drug disappeared promptly from the plasma and accumulated intensively in the bone and moderately in the spleen. In both tissues, relatively high radioactivities were measured as late as 90 days after the [14C]clodronate administration. Small amounts of 14C activity were also detected in the liver for 90 days. The results agree well with the previous observations that bisphosphonates deposit rapidly in the bone. Our findings indicate further that clodronate accumulates in the bone and the spleen for several months.
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PMID:Distribution of [14C]clodronate (dichloromethylene bisphosphonate) disodium in mice. 295 50

Clodronate (dichlormethylene diphosphonate) was administered to 21 patients with hypercalcemia due to malignant tumor. The drug was initially given intravenously, then orally. In 20 patients the serum calcium level had been reduced to the normal range within one week of the start of treatment (from 3.3 +/- 0.5 mmol/l to 2.4 +/- 0.3 mmol/l). With oral administration there was a renewed rise in calcium levels in some patients, which had to be treated with higher oral doses or intravenous administration. Parallel with the reduction in calcium levels there was an improvement in the originally impaired renal function. The serum level of intact parathormone(1-84) and 1.25-dihydroxy-vitamin-D3 (calcitriol) rose significantly from usually lowered initial levels. There was a non-linear inverse correlation between parathormone and calcium. No side effects were noted, even after long-term administration.
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PMID:[Treatment of tumor hypercalcemia with clodronate. Effect on parathormone and calcitriol]. 295 79

Clodronate can be used in animals to prevent the effects of immobilization on bone. For this reason we have studied the effects of this agent on immobilisation bone loss in man. We administered clodronate by mouth to 14 paraplegic patients (400 mg/d, n = 7; 1600 mg/day, n = 7), and compared its effect with a placebo (n = 7). Treatment was given for 100 days, 5-29 days after spinal cord injury. Our results suggest that clodronate, given early after immobilization, prevents the acute bone loss observed in immobilization as judged by its effects on serum and urine calcium and hydroxyproline, bone mineral content, trabecular bone volume, and the number of osteoclasts present in bone. No mineralization defect or other side-effects were observed during or after treatment. In addition, a total of 70 patients, with comparable degrees of immobilization, were studied with a variety of antiosteoclastic drugs comprising controls (n = 16), etidronate (n = 20), salmon calcitonin (n = 20) and clodronate 400 mg/d (n = 7) or 1600 mg/d (n = 7). Clodronate, at the dose of 1600 mg/d appeared the most effective drug on bone resorption, together with calcitonin. Unlike calcitonin, clodronate can be administered orally. The mineralisation defects observed during prolonged treatment with etidronate at high doses were not observed with clodronate. We conclude that clodronate 1600 mg/d is a promising agent for the treatment of bone loss and the resorptive hypercalcaemia and hypercalciuria noted in immobilisation.
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PMID:Effects of clodronate on immobilization bone loss. 296 57


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