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)

Calcitonin-secreting cells, 'C cells', have specific receptors for calcitriol, thus the calcitriol deficiency in uraemia may affect calcitonin secretion and/or production. The aim of the present study was to evaluate in CAPD patients the effect of calcitriol replacement (4 weeks of oral calcitriol, 0.5 micrograms/day) on both, basal calcitonin concentration and calcitonin response to calcium infusion (calcium gluconate, 3 mg/kg/h). Calcitriol replacement produced a normalization of serum calcitriol level without a significant change in serum calcium concentration. After calcitriol replacement, basal calcitonin increased from 78 +/- 15 to 101 +/- 13 pg/ml, P < 0.05. The increment in calcitonin induced by a calcium infusion was lower after (15 +/- 4 pg/ml) than before (29 +/- 4 pg/ml) calcitriol replacement. In addition, calcitriol administration induced a decrease in serum PTH level. Replacement of calcitriol in CAPD patients produced an increase in serum calcitonin concentration and a decrease in the calcitonin response to hypercalcaemia.
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PMID:Effect of calcitriol replacement on serum calcitonin and parathyroid hormone levels in CAPD patients. 772 33

1. 1,25-Dihydroxyvitamin D3, the biologically active form of vitamin D, in addition to regulating calcium homeostasis, also has antiproliferative and prodifferentiating effects. 2. Most studies concerning the therapeutic potential of analogs of 1,25(OH)2D3, which are antiproliferative and prodifferentiating but do not cause hypercalcemia, have been done using leukemic cells. 3. Recent evidence from both in vivo and in vitro studies has indicated that 1,25(OH)2D3 or analogs of 1,25(OH)2D3 can inhibit the growth of breast cancer cells, thus suggesting the therapeutic potential of analogs of 1,25(OH)2D3 in the treatment of breast cancer.
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PMID:Vitamin D and breast cancer. 772 55

Intravenous calcitriol is generally considered to be more efficient than oral administration in the treatment of secondary hyperparathyroidism of chronic renal failure, although a comparative and prospective study employing the same doses and modality of drug administration is lacking. We therefore evaluated 12 hemodialysis (HD) patients (51.7 +/- 9.4 years, mean +/- SD, HD for 8.7 +/- 4.7 years) with marked secondary hyperparathyroidism. Based on basal humoral and bone histologic parameters, we divided these patients into 2 comparable groups. Calcitriol (0.015 micrograms/kg) was given at the end of each dialysis intravenously in group A and orally in group B. Humoral parameters were evaluated basally and after 1, 2, 4 and 8 months. Ax bone biopsy was taken at the start and at the end of the study. From the first month of treatment, group A showed an increment in ionized calcium (from 1.28 +/- 0.08 to 1.37 +/- 0.12 mmol/l, p < 0.01), with a reduction in intact parathyroid hormone (from 470.1 +/- 349.5 to 255.5 +/- 256.5 pg/ml; p < 0.0003) and alkaline phosphatase (from 615.1 +/- 696.3 to 445.3 +/- 577.7 mU/ml, p < 0.001). The occurrence of hypercalcemia prompted a reduction in dialysate calcium content in 4 of 6 patients after 4 months, and of the calcitriol dose in 2 of 4 patients after 6 months. Ionized calcium then turned to 1.32 +/- 0.11 (p = n.s. compared to basal) while the intact parathyroid hormone concentration tended to revert (363.3 +/- 360 pg/ml, p = n.s. compared to basal) and alkaline phosphatase remained low (420 +/- 638 mU/ml, p < 0.0005).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intravenous versus oral calcitriol therapy in renal osteodystrophy: results of a prospective, pulsed and dose-comparable study. 781

A synthetic form of calcitriol (1,25-dihydroxycholecalciferol; 1,25-dihydroxyvitamin D3), the most physiologically active metabolite of vitamin D, has shown efficacy in the treatment of postmenopausal osteoporosis and promise in corticosteroid-induced osteoporosis. Although results of small studies investigating calcitriol in the treatment of postmenopausal osteoporosis have been conflicting, a clinical trial in 622 women with postmenopausal osteoporosis demonstrated that patients with mild to moderate disease who received calcitriol (0.25 microgram twice daily) had a significant 3-fold lower rate of new vertebral fractures after 3 years of treatment, compared with patients receiving elemental calcium 1000 mg/day. In patients commencing long term treatment with prednisone or prednisolone, calcitriol 0.5 to 1.0 micrograms/day plus calcium 1000 mg/day, administered with or without intranasal calcitonin 400 IU/day, prevented steroid-induced bone loss. Overall, calcitriol is well tolerated. As shown in clinical studies, at recommended dosages hypercalcaemia is infrequent and mild, generally responding to reductions in calcium intake and/or calcitriol dosage. The narrow 'therapeutic window' of calcitriol requires that its use be adequately supervised, with periodic monitoring of serum calcium and creatinine levels. However, significant renal toxicity has not been seen in patients with osteoporosis treated with calcitriol in high dosages for several years in comparative and noncomparative trials. In conclusion, as with other drugs currently used in the management of patients with osteoporosis, questions remain to be answered regarding the efficacy of calcitriol relative to other agents, and its tolerability in such patients during the very long term. Nonetheless, at this stage, calcitriol should be considered a useful treatment option in patients with mild to moderate postmenopausal osteoporosis.
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PMID:Calcitriol. A review of its use in the treatment of postmenopausal osteoporosis and its potential in corticosteroid-induced osteoporosis. 782 99

1,25-Dihydroxyvitamin D3 (1,25-(OH)2D3) has been shown to inhibit breast cancer cell growth both in vitro and in vivo. A major drawback is that high doses of 1,25-(OH)2D3 are needed which may result in undesirable side effects like the development of hypercalcemia and an increased risk of bone metastases due to the stimulation of bone resorption by 1,25-(OH)2D3. Several newly developed 1,25-(OH)2D3 analogs have a reduced calcemic activity, but their direct effects on bone resorption have not yet been examined. Presently, the antiestrogen tamoxifen is the most important endocrine therapy for breast cancer. Recent studies have demonstrated the benefit of the combination tamoxifen and 1,25-(OH)2D3/analogs for the inhibition of breast cancer cell growth. Besides inhibition of breast cancer growth tamoxifen appeared to have beneficial effects on bone. The purpose of the present study was to investigate the effect of tamoxifen on 1,25-(OH)2D3- and analogs (EB1089 and KH1060)-stimulated bone resorption in an in vitro model. Bone resorption was stimulated by 1,25-(OH)2D3 and analogs in a dose-dependent manner with KH1060 and EB1089 being more potent and 1,25-(OH)2D3. Tamoxifen caused a strong dose-dependent inhibition (70% at 10 microM) of 1,25-(OH)2D3- and EB1089-stimulated bone resorption. KH1060-stimulated bone resorption was also inhibited by tamoxifen but to a lesser extent (36%). Also the pure antiestrogen ICI164,384 but not 17 beta-estradiol inhibited 1,25-(OH)2D3-stimulated bone resorption. Together, this study demonstrates that tamoxifen considerably reduces 1,25-(OH)2D3/analogs-stimulated bone resorption and therefore may be useful to reduce the risk of bone metastases. This together with the observed beneficial effects on breast cancer cell growth indicates that tamoxifen together with 1,25-(OH)2D3/analogs is an interesting combination for the treatment of breast cancer. The mechanism of the bone resorption inhibitory action is not yet known but seems to be independent of the estrogen pathway.
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PMID:Antiestrogens inhibit in vitro bone resorption stimulated by 1,25-dihydroxyvitamin D3 and the vitamin D3 analogs EB1089 and KH1060. 783 15

Calcitriol is increasingly used for therapy of secondary hyperparathyroidism in patients with end-stage renal disease. Its therapeutic efficacy, however, often has been limited by the associated increase in intestinal calcium and phosphorus absorption. Previous studies reported that these side effects could be avoided by intermittent administration of calcitriol in high doses, subsequently referred to as pulse therapy. The present study was designed to investigate pulse oral calcitriol therapy in a patient subgroup especially susceptible to the development of hypercalcemia and hyperphosphatemia under standard continuous calcitriol treatment. We examined 15 peritoneal dialysis patients with moderate degrees of hyperparathyroidism (intact parathyroid hormone [iPTH] levels, 150 to 903 pg/mL) ingesting between 1.5 and 6 g of calcium salts as the sole phosphate binders. Treatment consisted of 0.5 microgram calcitriol twice weekly. Eight of these patients had been previously converted to low calcium dialysate to tolerate the necessary doses of phosphate-binding calcium salts. During the study period, comprising 8 pretreatment weeks and 8 weeks of therapy, dialysates and doses of calcium salts were not changed, so that only calcitriol influenced the determined parameters. As expected, iPTH levels decreased rapidly in all patients (P < 0.0001). However, within 4 weeks of treatment a marked increase in calcium phosphorus products was observed (P < 0.0001). Overt hypercalcemia developed in five patients. We concluded that pulse oral calcitriol has to be carefully monitored in peritoneal dialysis patients receiving high doses of calcium salts because of the increased risk for hypercalcemia and hyperphosphatemia.
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PMID:Limitations of pulse oral calcitriol therapy in continuous ambulatory peritoneal dialysis patients. 784 57

To examine the most effective route (intravenous vs. "pulse" oral), dose (physiologic vs. pharmacologic) and long-term efficacy of calcitriol therapy for secondary hyperparathyroidism in patients with end-stage renal disease (ESRD), we randomized 19 hemodialysis patients with severe hyperparathyroidism to receive over a 36-week study period either pulse orally administered calcitriol and intravenous placebo (pulse oral group; N = 9) or intravenous calcitriol and oral placebo (intravenous group; N = 10). Calcitriol was given intermittently in a double-blinded fashion at an initial dose of 2 micrograms thrice weekly and increased as tolerated up to a maximum dose of 4 micrograms per treatment. All patients received similar daily calcium supplementation (2.5 g of elemental calcium) and low dialysate calcium (1.25 mmol/liter) throughout the study period. At the maximum tolerated calcitriol dose, serum 1,25-dihydroxyvitamin D levels were significantly greater 60 minutes following intravenous (389 pmol/liter) compared to oral administration (128 pmol/liter). In spite of the different pharmacologic profiles, intravenous and oral administered calcitriol resulted in similar reductions of serum PTH over the 36 week period of observation (P = 0.300), achieving an overall maximum average PTH reduction of 43% (P = 0.016). Long-term intensive calcitriol therapy (independent of administration route), however, failed to decrease parathyroid gland size as assessed by high resolution ultrasound and/or magnetic resonance imaging. Calcitriol therapy also failed to alter the calcium sensitivity as assessed by serial PTH measurements in response to calcium loading. Increases in serum calcium, but not calcitriol dose or parathyroid gland size, predicted decrements in serum PTH, whereas hyperphosphatemia and the level of PTH suppression derived from the PTH/ionized calcium response curves predicted refractoriness to calcitriol therapy. Episodes of hypercalcemia and hyperphosphatemia were similar in both treatment groups and limited the dose of calcitriol that could be administered. These data indicate that intermittent intensive calcitriol therapy, regardless of administration route, is poorly tolerated, fails to correct parathyroid gland size and functional abnormalities, and has a limited ability to achieve sustained serum PTH reductions in end-stage renal failure patients with severe hyperparathyroidism.
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PMID:Prospective trial of pulse oral versus intravenous calcitriol treatment of hyperparathyroidism in ESRD. 793 19

Intermittent bolus administration of calcitriol--i.e., 1,25-dihydroxycholecalciferol or 1,25-(OH)2D3--is highly efficacious in dialysis patients. In experimental studies, intermittent administration of calcitriol is superior to continuous administration in suppressing preproparathyroid hormone (PTH) mRNA and circulating PTH concentrations. In a randomized, prospective, open multicenter trial 45 dialysis patients with elevated 1,84-iPTH (> or = 20 pmol/l, normal 1-6 pmol/l) levels were randomly allocated to daily administration of 0.75 microgram calcitriol (continuous) or twice weekly administration (intermittent); the two protocols provided an identical total weekly doses of 5.25 micrograms calcitriol. Patients were dialyzed with a dialysate Ca concentration of 1.75 mmol/l and had oral CaCO3 or Ca acetate. 1,84-iPTH (immunoradiometric assay) and serum Ca and Pi levels were measured weekly. At the beginning of the study, the median 1,84-iPTH value was 37 pmol/l (range 20-115) in the intermittent versus 36 pmol/l (range 21-72) in the continuous calcitriol group. After 2 weeks, the median 1,84-iPTH level was 18.5 pmol/l (range 1.4-106) versus 18 pmol/l (range 1.2-48). After 12 weeks, 11 of 21 of the patients in the intermittent and 18 of 24 patients in the continuous group had reached the treatment goal, i.e., 1,84-iPTH < or = 10 pmol/l without hypercalcemia or hyperphosphatemia. There were seven episodes of hypercalcemia (> 2.7 mmol/l) in the intermittent versus two in the continuous group; the mean peak Ca level was 2.8 mmol/l (range 2.76-3.0) versus 2.9 mmol/l (range 2.74-3.06). There were 21 versus 17 episodes, respectively, of hyperphosphatemia (> 2.2 mmol/l).
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PMID:Comparison of intermittent and continuous oral administration of calcitriol in dialysis patients: a randomized prospective trial. 805 67

1,25-Dihydroxyvitamin D [1,25(OH)2D3, calcitriol] can inhibit the proliferation of some human prostate cancer cells but its clinical use is limited by hypercalcemia. We therefore explored the bioactivity of less calcemic vitamin D analogs. We studied the effects of calcitriol and 3 synthetic analogs at concentrations of 10(-6) to 10(-12) M on the in vitro proliferation of 3 human prostate carcinoma cell lines: DU 145, PC-3, and LNCaP. Calcitriol and analogs showed significant antiproliferative activity on PC-3 and LNCaP cells. DU 145 cells were inhibited by the analogs only. We conclude that vitamin D analogs warrant further investigation as therapeutic agents in prostate cancer.
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PMID:Human prostate cancer cells: inhibition of proliferation by vitamin D analogs. 807 53

Ca2+ binds to a parathyroid cell Ca2+ receptor, which is G protein-coupled and activates inositol triphosphate production. Mutations in the Ca(2+)-sensing receptor gene cause familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism. Chronic hypocalcemia increases parathyroid hormone messenger RNA levels and parathyroid cell hyperplasia. Parathyroid cells in vitro are heterologous in their response to Ca2+. The concept of a higher Ca2+ set-point in secondary hyperparathyroidism is controversial. Calcitriol is more effective than the less hypercalcemia analogues in decreasing parathyroid hormone messenger RNA and immunoreactive parathyroid hormone levels, and its kinetics are well established. Phosphate and estrogens regulate the parathyroid independently of 1,25 dihydroxyvitamin D3 and Ca2+. The physiology of the effects of endothelin and insulin-like growth factors on the parathyroid need to be established. Important advances are being made in understanding the regulation of parathyroid hormone synthesis and secretion, which are relevant to both normal physiology and the pathogenesis and treatment of diseases such as the secondary hyperparathyroidism of renal failure and osteoporosis.
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PMID:New aspects in the control of parathyroid hormone secretion. 807 41


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