Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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 skeletal manifestations of hyperparathyroidism are due to the stimulation of osteoclast-mediated bone resorption by high circulating concentrations of parathyroid hormone (PTH). Since diphosphonates inhibit PTH-mediated bone resorption, we assessed the effects of clodronate in 42 patients with hypercalcaemia and increased bone resorption due to primary hyperparathyroidism (20 patients), secondary hyperparathyroidism in chronic renal failure (12 patients on haemodialysis replacement therapy) and tertiary hyperparathyroidism following successful renal transplantation (10 patients). Clodronate (0.8-1.6 g daily by mouth or 300 mg given as an intravenous infusion following five consecutive dialysis treatments) significantly decreased serum calcium and biochemical indices of bone resorption in the three groups studied. In primary and tertiary hyperparathyroidism, serum calcium values remained above the upper limit of the reference range despite suppression of bone resorption due to the unopposed effect of PTH on renal tubular reabsorption of calcium. Prolonged treatment (3 months) was associated with a partial recurrence of hypercalcaemia in 8 of 12 patients with primary hyperparathyroidism despite continued effects on bone resorption, possibly due to a secondary decrease in bone formation. These studies indicate that clodronate is capable of suppressing PTH-mediated bone resorption in disorders of parathyroid secretion and may prove to be a useful adjunct in their medical management.
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PMID:Clodronate in the medical management of hyperparathyroidism. 296 58

Dichloromethylene bisphosphonate (clodronate, Cl2MDP) is a synthetic analogue to pyrophosphate, which inhibits increased bone resorption. This drug was given to 12 patients with hypercalcemia secondary to advanced malignant disease. Clodronate in a daily dose of 1.6 to 3.2 g generally caused a return of the serum calcium values to normal within 5-10 days with a concomitant improvement of symptoms related to the hypercalcemia. Side effects were few. Thus, clodronate appears to be a valuable adjunct for the medical management of patients with malignancy-associated hypercalcemia.
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PMID:Treatment with clodronate in patients with hypercalcemia secondary to malignancy. 296 87

We have assessed the effects of clodronate (dichloromethylene diphosphonate; Cl2MDP 0.8-3.2g daily by mouth for up to 3 months) in 17 episodes of hypercalcaemia and osteolysis due to carcinoma. Clodronate reduced serum calcium in 14 episodes and bone resorption in all patients. These remained suppressed for the duration of treatment, but recurred promptly when treatment was stopped. Clodronate may be a useful measure for controlling hypercalcaemia and osteolysis in patients with carcinoma.
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PMID:Treatment of malignant hypercalcaemia with clodronate. 315 26

Clodronate (clodronic acid, dichloromethylene bisphosphonate) is a bisphosphonate which has demonstrated efficacy in patients with a variety of diseases of enhanced bone resorption including Paget's disease, hypercalcaemia of malignancy and osteolytic bone metastases. In addition, early reports demonstrating potential efficacy of clodronate in the treatment of osteoporosis suggest a possible role in this debilitating disease. Short term intravenous administration (usually 300 mg/day for 5 days) or longer courses of oral clodronate (usually 1600 mg/day for 6 months) effectively reduced bone pain and/or improved mobility in most patients with Paget's disease, and these effects persisted for up to 12 months after discontinuing clodronate. When administered intravenously (300 mg/day for up to 12 days) to patients with malignant hypercalcaemia, serum calcium levels declined significantly within 2 days of starting treatment and approximately 70 to 95% of patients became normocalcaemic. While there is less experience with oral administration, clodronate (800 to 3200 mg/day) achieved normocalcaemia in the majority of patients, usually within 1 week, and serum calcium levels remained significantly reduced from baseline for up to 6 months with continued treatment. Clodronate is clearly superior to placebo and, based on a retrospective analysis, appears to produce greater and more sustained reductions in serum calcium levels than calcitonin in patients with malignant hypercalcaemia. The few available prospective comparative trials showed that clodronate is at least as effective as etidronate, but comparisons with alendronate and pamidronate produced results of questionable clinical relevance because of low bisphosphonate dosages used in these trials. Nevertheless, single intravenous doses of clodronate 600 mg or alendronate 7.5 mg (both agents repeated on day 3 if necessary) were comparable in efficacy, whereas a single intravenous dose of pamidronate 30 mg was more effective than a single intravenous dose of clodronate 600 mg. Normocalcaemic patients with osteolytic bone metastases due to advanced breast cancer experienced significant reductions in the number of episodes of hypercalcaemia and terminal hypercalcaemia, incidence of vertebral fractures and overall rate of morbid events, including the need for radiotherapy to treat bone-related pain, following treatment with clodronate 1600 mg/day for 3 years in a large placebo-controlled study. A similar large placebo-controlled trial in patients with multiple myeloma demonstrated that clodronate 2400 mg/day orally for 2 years significantly reduced progression of osteolytic bone lesions. Follow-up data from clinical trials revealed that the effects on development of fractures and hypercalcaemia persisted for at least 12 months after the drug was discontinued.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Clodronate. A review of its pharmacological properties and therapeutic efficacy in resorptive bone disease. 752 33

The use of bisphosphonates in hypercalcemia is fully accepted, but the long term therapy with bisphosphonates is still controversial. The aim of our study was to evaluate the influence of clodronate on the bone density of myeloma patients. 20 patients were included in the study. A total dose of 3000 mg clodronate was administered in 4 to 6 hourly infusions of 600 mg a day, once in 3 months. The effect of clodronate on bone density was evaluated by CT-densitometry over a period of 6 months. At the beginning of May 1994, 15 patients had completed at least 2 estimations of bone density. The amount of hydroxyapatite had increased in 9 patients, remained unchanged in 1 of them, and decreased in 4 of them during the 6 months. The mean bone density before the administration of clodronate was -2.6 SD (standard deviation of European standard bone density for the respective age and sex). After 6 months of therapy, bone density had increased to -2.3 SD. The mean amount of hydroxyapatite in spongiosa rose from the mean value of 32.71 mg/ml before clodronate administration to 38.91 mg/ml after the 6-month treatment period. The mean increase in calciumhydroxyapatite in trabecular bone mass was 6.2 mg. Clodronate contributed to alleviating bone pain in the majority of patients, but this effect is difficult to evaluate because of other treatment modalities administered concomitantly. The tolerance of clodronate was very good. No impairments of renal function, nor other adverse effects were observed. Only in 2 patients the decrease in calcium concentration caused slight tetania.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Increasing bone density in myeloma patients after the administration of clodronate. 754 57

Clodronate, one of the most investigated bisphosphonates, has been clinically utilised for over 10 years in malignancy. It is the most used, most effective and safest drug in the treatment of hypercalcaemia. It inhibits lytic bone destruction, prevents bone fractures and relieves bone pain. Supportive clodronate therapy may even reduce hypercalcaemia mortality and the morbidity caused by osteolysis. These results have stimulated studies on the patients' quality of life. New methods for the measurement of bone resorption, such as the degradation product of type I collagen (ICTP), may improve the possibility of monitoring the effect of clodronate. Comparative studies with different bisphosphonates in hypercalcaemia and long-term controlled trials using bisphosphonates as supportive therapy in osteolysis due to malignancy are reviewed.
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PMID:Clodronate and other bisphosphonates as supportive therapy in osteolysis due to malignancy. 754 30

The usefulness of bisphosphonates in the treatment of acute hypercalcaemia has been known for some time. The problem of long-term administration of bisphosphonates to patients whose skeleton is afflicted with a malignant tumour is still being discussed. The benefit of ethidronate has not been confirmed. Clodronate and pamidronate administered in i.v. infusions or in adequate amounts by the oral route leads to a reduced incidence of hypercalcaemic crises and the number of pathological fractures. Both mentioned preparations diminish the intensity of pain, increase physical fitness and improve the quality of life of oncological patients. However, they do not prolong the survival period of these patients.
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PMID:[Long-term administration of biphosphonates in oncology patients with bone involvement]. 781 88

The indication of bisphosphonates in hypercalcemia is fully accepted, the long term therapy with bisphosphonates is still controversial. The aim of our study was to evaluate the influence of clodronate on the bone density of myeloma patients. Twenty patients were included in the study. Clodronate is administered in the total dose of 3,000 mg, which is delivered in 4-6 hour infusions, 600 mg/day, once in tree 3 months. The effect of clodronate on bone density is evaluated by CT-densitometry in a period of 6 months. At the beginning of May 1994, 15 patients had completed at least two estimations of bone density. The amount of hydroxyapatite in these six months increased in 9 patients, in one of them there was no change and in 4 of them decreasing bone density was detected. The mean bone density before the administration of clodronate was -2.6 SD (standard deviation of European standard of bone density for age and sex). After 6 months of therapy the bone density increased to -2.3 SD. The mean amount of hydroxyapatite in spongiosa was raised from the mean value 32.71 mg/ml before clodronate administration to 38.91 mg/ml after the 6 month treatment period. The mean increase in calciumhydroxyapatite in trabecular bone mass was 6.2 mg. Clodronate contributed to the amelioration of bone pain in the majority of patients, but this effect is difficult to evaluate because of other treatment modalities administered concomitantly. The tolerance of clodronate was good. No impairments of renal function or other adverse effects were observed. Only in 2 patients the decrease in calcium concentration caused slight tetania. Therefore close monitoring of the calcium level is recommended and in the case of its decrease below the physiological level peroral substitution of calcium was started.
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PMID:[Increased bone density in patients with multiple myeloma treated with clodronate]. 781 97

The precise mechanisms responsible for increased calcium levels in patients with cancer are not fully understood. In a recent study, the participation of interleukin (IL)-6 as an important mediator of key parameters of cancer cachexia in the colon-26 adenocarcinoma was reported. Here, we show that in addition to cachexia, C-26 tumour bearing mice also develop hypercalcemia. Treatment of these mice with 5' deoxyfluorouridine significantly reduces tumour size and inhibits both hypercalcemia, cachexia, and elevated serum IL-6. Moreover, monoclonal antibody to mouse IL-6 prevents both the cachexia and the hypercalcemia and reduces serum IL-6 levels in C-26 tumour bearing hosts. The administration of a bisphosphonate compound (Clodronate) reverses the hypercalcemia but has no effect on tumour burden, serum IL-6 levels, or wasting. We conclude that tumour-derived IL-6 plays a role in the pathogenesis of the C-26 associated hypercalcemia, and that the increase of serum calcium does not by itself mediate cachexia.
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PMID:Mechanisms of paraneoplastic syndromes of colon-26: involvement of interleukin 6 in hypercalcemia. 814 2

The effects of clodronate, a bisphosphonate for the treatment of hypercalcemia, on the progress of atherosclerosis were studied in rabbits fed with a high-cholesterol (1%) diet and treated simultaneously with disodium clodronate 0 (saline), 1, 5, or 25 mg/kg intravenously twice a week for 6, 9, and 12 weeks. In 9 to 12 weeks, plasma total cholesterol increased from 0.8 +/- 0.3 mmol/L (mean +/- SD) in rabbits fed the standard diet to 46 +/- 17 mmol/L in animals subjected to high-cholesterol diet. Clodronate did not influence the cholesterol concentration in plasma. None of the parameters studied were changed by clodronate within 6 weeks after beginning the treatment. In 9 to 12 weeks (n = 7 to 9), plasma total Ca++ concentration was decreased from 3.55 +/- 0.12 mmol/L in the saline group to 3.36 +/- 0.16 mmol/L in the group on the greatest clodronate dose (p < 0.05). Free and esterified cholesterol and total Ca++ concentrations in the wall of thoracic aorta were reduced by the greatest dose of clodronate, compared with the groups treated with saline solution or smaller doses of the drug (p < 0.05). At 12 weeks, the greatest dose of clodronate also reduced the visible and lipid-stained atheromatous areas in the thoracic and abdominal aorta, compared with those in the saline and the other clodronate dose groups (p < 0.05). The results suggest that a high dose of clodronate inhibits the development of diet-induced atherosclerosis in rabbits.
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PMID:Effects of clodronate (dichloromethylene bisphosphonate) on the development of experimental atherosclerosis in rabbits. 819 83


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