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

The changes of parathyroid hormone (PTH) and of vitamin D metabolites after intravenous administration of the bisphosphonate APD were studied in ten patients with Paget's disease of bone and in ten patients with tumour-induced hypercalcaemia. After APD all patients with Paget's disease became hypocalcaemic and showed an increase in both N-PTH and C-PTH values. Patients with malignancies had a nearly six-fold greater decrease in serum calcium but rises in N-PTH and C-PTH were observed only in those who developed hypocalcaemia. Overall, a clear rise in PTH was found when serum calcium fell below 2.20 mmol/l. Basal 25-hydroxy- and 24,25-dihydroxyvitamin D concentrations were similar in the two groups and showed no change after APD treatment. Circulating 1,25-dihydroxyvitamin D, however, increased in all patients with Paget's disease and in six of the hypercalcaemic patients. It is concluded that the main regulator of PTH secretion is the concentration of calcium per se rather than the magnitude or the rate of its change. The production of 24,25-dihydroxyvitamin D is not affected by wide variations in serum calcium while that of 1,25-dihydroxyvitamin D is sensitive to these changes.
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PMID:Effects of decreasing serum calcium on circulating parathyroid hormone and vitamin D metabolites in normocalcaemic and hypercalcaemic patients treated with APD. 350 18

Bisphosphonates (or diphosphonates) constitute a major advance in the treatment of tumor-associated hypercalcemia and also have the potential to prevent or reverse osteolysis in normocalcemic patients. Available information on adequate therapeutic doses and potential toxicity is, however, very fragmentary. This report describes a phase I study of one of the most promising bisphosphonates currently available, aminohydroxypropylidene bisphosphonate (AHPrBP or APD), in tumor-associated hypercalcemia. Only patients remaining hypercalcemic after 48 hours of rehydration were evaluated, and antineoplastic therapy was delayed at least until a normal serum calcium level was reached. AHPrBP was given as two-hour daily infusions for three days, and three different patients were treated at each of the six following dosage levels: 0.01, 0.05, 0.25, 0.75, 1.5, and 3.0 mg/kg per day. The two lowest dosages levels were insufficient to normalize serum and urinary calcium levels, but the efficacy of the four other dosages was very similar. Plasma immunoreactive parathyroid hormone levels increased as a function of calcium levels, whereas urinary hydroxyproline levels did not prove to be a very useful measure of AHPrBP's effects on bone resorption. The drug was generally very well tolerated: only six patients had transient fever and/or decreases in lymphocyte count that were not clearly related to AHPrBP dosage. The only real problem was observed at the highest dosage of 3.0 mg/kg per day in an obese woman in whom high fever and hypotension developed. Efficacy and tolerance in dehydrated patients were verified by treating seven other patients, not previously rehydrated, at 1.0 mg/kg per day for three days. In summary, the therapeutic range of AHPrBP, given for three days as a two-hour infusion daily, lies between 0.25 and 1.5 mg/kg per day. Fasting urinary calcium levels are probably the most reliable and easily measured parameter to monitor AHPrBP's inhibition of bone resorption in normocalcemic patients.
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PMID:Dose/response study of aminohydroxypropylidene bisphosphonate in tumor-associated hypercalcemia. 357 65

The effect of a single dose of APD on hypercalcaemia has been studied in advanced breast cancer. Twenty-five patients were rehydrated intravenously for 48 h. Twenty-three remained hypercalcaemic and received 5-15 mg APD as a 2 h infusion. Eighteen patients achieved normocalcaemia, 15 after a dose of less than or equal to 15 mg. One patient died within 24 h from rapidly advancing disease and 4 remained hypercalcaemic. Urinary calcium excretion increased during rehydration as glomerular function improved and tubular reabsorption of calcium fell. After APD, calcium excretion fell to normal in 22/24 patients reflecting inhibition of bone resorption. Hydroxyproline excretion remained high. The effect of a single dose of APD on hypercalcaemia lasted a median of 11 days (range 7-17). Transient fever occurred in 2 patients, but there were no other side effects. The possibility of long-term control of osteolysis using a 2 weekly schedule of APD administration is now being studied.
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PMID:3(Amino-1,1-hydroxypropylidene) bisphosphonate (APD) for hypercalcaemia of breast cancer. 368 64

Twenty patients with malignant hypercalcemia were treated with aminohydroxypropylidene bisphosphonate (AHPrBP, previously APD) a potent inhibitor of osteoclast-mediated bone resorption. To assess the efficacy of oral vs intravenous therapy, the patients were divided into two groups: group A received AHPrBP intravenously (30 mg/day), and group B received the drug orally (1200 mg/day) for 6 days. In both groups all the patients responded to AHPrBP with a rapid decrease in plasma calcium concentration after a mean time lag of 1 day. Within 9 days plasma calcium concentration fell from 3.42 +/- 0.13 (mean +/- SEM) to 2.26 +/- 0.13 mmol/l in group A and from 3.28 +/- 0.12 to 2.24 +/- 0.09 mmol/l in group B. There was no significant difference in plasma Ca level between both groups on days 4, 6, and 9, and plasma Ca was within the normal range in all patients on day 9. On both treatment regimens urinary calcium excretion fell dramatically and similarly. Plasma phosphate concentration decreased significantly on AHPrBP in both groups of patients, reaching values slightly below the normal range from day 4 to day 9. TmP/GFR decreased progressively on AHPrBP. However, this decrement was significant at day 6 only. Plasma parathyroid hormone concentration rose significantly in both groups from day 4 to day 9. We conclude that at the doses used in the present study treatment of tumor-induced hypercalcemia with AHPrBP is equally effective whether given orally or intravenously.
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PMID:Oral versus intravenous AHPrBP (APD) in the treatment of hypercalcemia of malignancy. 376 3

We report a case of sarcoid hypercalcaemia treated with the bisphosphonate, APD [(3-amino-1-hydroxypropylidene)-1,1-bisphosphonate]. Investigations showed that the hypercalcaemia was associated with a high plasma 1,25 dihydroxy vitamin D concentration. A low dietary intake of calcium partially corrected the hypercalcaemia but APD rapidly normalized plasma calcium without reducing the elevated 1,25 dihydroxy vitamin D concentration. The case demonstrates that hypercalcaemia in sarcoidosis results from the effects of 1,25 dihydroxy vitamin D on bone as well as on calcium absorption and that prolonged suppression of the effect on bone occurs with APD treatment.
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PMID:Hypercalcaemia due to sarcoidosis corrects with bisphosphonate treatment. 377 26

In a group of thirty patients with tumour-induced hypercalcaemia the effects of volume repletion and intravenous (3-amino-1-hydroxypropylidene)-1, 1-bisphosphonate (APD) were examined. Volume repletion was only partially effective in lowering serum calcium and raising glomerular filtration rate and it increased the tendency towards hypomagnesaemia. In twenty-nine of the patients serum calcium, serum magnesium, and glomerular filtration rate were rapidly restored to normal by intravenous APD, in doses of 1.75-30 mg/day. Tubular reabsorption of phosphate was lower than normal in five of nine patients in whom it was studied and remained unchanged despite correction of hypovolaemia and serum and urine calcium levels or changes in parathyroid hormone. These findings suggested that tumours may produce a phosphate-lowering factor. The improvement in clinical condition with volume repletion depends on its ability to adjust calcium excretion to the abnormal production of calcium from bone. APD, in contrast, returns pathological bone destruction to normal without any undesirable side-effects.
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PMID:Comparison of intravenous (3-amino-1-hydroxypropylidene)-1, 1-bisphosphonate and volume repletion in tumour-induced hypercalcaemia. 613 76

The diphosphonates (DP) represent a new class of therapeutic agents, the main property of which is to block bone resorption, irrespective of its stimulus. Apart from their remarkable results in Paget's disease of the bone, DP are very effective in the treatment of hypercalcaemia the osseus origin of which is nearly always essential. In malignant hypercalcaemia, EHDP, C12 MDP and APD, the three DP tested in man, cause a fall in serum calcium in a few days when administered intravenously. The latter two preparations are also effective when given orally. DP are also valuable in controlling hypercalcaemia in primary hyperparathyroidism. Research is under way to determine the role of DP in the prevention of malignant osteolysis, as distinct from the effects of chemotherapy.
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PMID:[Diphosphonates in the treatment of hypercalcemia]. 624 Jul 53

The treatment of tumour-induced hypercalcemia (HCa) by diphosphonates appears to be safe and reliable with very mild side effects. We have tested APD as sole treatment in 14 patients with cancer and symptomatic HCa. APD was given i.v. in a dose of 0.38 +/- 0.03 mg/kg BW/day until two subsequent normal plasma calcium (Ca) levels were obtained (Ca determined daily). The mean duration of treatment was 5.56 +/- 1.9 (4 to 11 days). As expected, there was a significant correlation between initial Ca and duration of therapy (p less than 0.001). Mean Ca fell from 3.38 +/- 0.19 mmol/l before APD to 2.43 +/- 0.09 after 4 days of treatment and remained normal four weeks after the start of treatment. Four patients relapsed 11 to 31 days after the end of treatment during a one-month follow-up. This recurrence did not depend on initial Ca, length of treatment and duration of remission. Two of these patients were treated successfully with a second course of APD, while in the other two no further treatment was undertaken. Both mean UCa and UHydroxyproline decreased significantly when measured seven days after the beginning of the treatment. Plasma PTH values remained in the normal range, while NcAMP rose significantly after a week of treatment from low to normal values. Plasma phosphorus decreased significantly (p less than 0.005) during the treatment while TRP % increased, suggesting a positive phosphorus balance. We conclude that short treatments with APD of tumour-induced HCa are effective and sufficiently sustained, even if they are interrupted as soon as normal Ca is obtained.
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PMID:[Simple treatment of tumor-induced hypercalcemia: i.v. aminohydroxypropylidene biphosphonate]. 631 6

For 2 weeks 27 patients with hypercalcemia received a standard oral treatment with (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate (APD) as the sole agent. Results were grouped according to causes of hypercalcemia and compared with effects of APD in 13 normocalcemic patients with Paget's disease of bone and 7 with osteoporosis. In 12 hypercalcemic patients with osteolytic bone lesions and in the 20 normocalcemic patients, the mean serum calcium decreased to final levels that were subnormal and significantly lower than those obtained after treatment of 8 patients with primary hyperparathyroidism. In 3 patients with myeloma and in 4 tumor patients without bone lesions, serum calcium did not always decrease to the normal range. Implications of these observations for the mechanism of hypercalcemia are discussed.
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PMID:Efficacy of amino-hydroxypropylidene bisphosphonate in hypercalcemia: observations on regulation of serum calcium. 681 19

In view of previous animal studies showing that pamidronate (Aredia) can cause renal damage, and human data indicating that pamidronate in doses of 60-90 mg is more effective in the control of tumor-induced hypercalcemia than when given at lower doses, we decided to investigate whether pamidronate 90 mg infused over 60 minutes at weekly intervals had any adverse effects on renal function in patients with bone metastases. Twelve patients, 7 female (all with breast cancer) and 5 male (4 with prostate cancer, 1 with bladder cancer) were entered into the trial. Each patient received weekly intravenous infusions of pamidronate 90 mg in 250 ml normal saline over 60 minutes for 4 weeks. 51Cr-EDTA clearances showed no significant changes in renal function. Urinary N-acetyl-B-D-glucosaminidase/creatinine ratios fluctuated considerably, but no consistent changes were found. No patient with a normal level of urinary beta 2-microglobulin had elevated levels at the end of the trial. Serum creatinine levels did not change significantly, though 1 patient had a corrected serum calcium level of < 2 mmol/L on a single occasion on day 8. No evidence of renal toxicity was detected. However, the possibility that neprohtoxicity would ultimately appear cannot be excluded, and these favourable short-term results cannot be extrapolated to patients with impaired renal function.
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PMID:Intravenous pamidronate: infusion rate and safety. 787 59


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