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 long-term safety and efficacy of synthetic 1,25-(OH)2D3 (calcitriol; Rocaltrol) in the treatment of women with type 1 osteoporosis is being assessed in a randomized trial. Patients were allocated in double-blind fashion to 1,25-(OH)2D3 or matching placebo. Initially, the calcium intake was adjusted to 1,000 mg/d. The study protocol called for increasing the dose of 1,25-(OH)2D3 until patients developed either hypercalcemia or hypercalciuria. However, in order to maintain a higher dose of calcitriol on a long-term basis, the calcium intake had to be reduced to 600 mg/d in those receiving calcitriol; if that was not successful in eliminating hypercalcemia and hypercalciuria, then the dose of 1,25-(OH)2D3 was reduced as necessary. During the hypercalcemic phase, the indices of bone resorption decreased significantly, demonstrating that calcium absorption is solely responsible for hypercalcemia. The maintenance dose was established after 8 to 10 weeks, and the 24-hour urine calcium and creatinine clearance remained constant throughout the remainder of the study period. On a calcium intake of 600 mg/d, the long-term maintenance dose of 1,25-(OH)2D3 averaged 0.675 micrograms/d. Long-term therapy on an average dose of 0.675 micrograms/d was not associated with nephrotoxicity.
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PMID:Metabolic effects of synthetic calcitriol (Rocaltrol) in the treatment of postmenopausal osteoporosis. 232 68

In postmenopausal osteoporotics, malabsorption of calcium is associated with reduced levels of serum 1,25-dihydroxyvitamin D. Metabolic studies have shown that calcium absorption can be normalized and calcium balance improved after administration of oral doses of synthetic 1,25-dihydroxyvitamin D3 (Rocaltrol) 0.25 micrograms twice daily. Further studies performed at two centers compared the effect of Rocaltrol 0.25 micrograms twice daily versus placebo on vertebral fracture rates in osteoporotics. A significant reduction in vertebral fracture rates was seen at the end of 1 year. Those patients who continued on Rocaltrol for a second and third year showed a progressive decrease in vertebral fractures. Rocaltrol, administered at a dose of 0.25 micrograms twice daily, seldom causes hypercalcuria or hypercalcemia in osteoporotic patients on a typical calcium intake of 700 to 800 mg/d. Careful measurements of renal function over a period of 3 years in patients treated with Rocaltrol, 0.25 micrograms twice daily, showed no deterioration in renal function. These data suggest that 1,25-dihydroxyvitamin D3 is a useful therapy in the management of patients with postmenopausal osteoporosis, particularly those who have malabsorption of calcium. We found that it improves calcium balance, reduces the vertebral fracture rate, and is safe to use provided that the dietary calcium is monitored and does not exceed 800 mg/d.
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PMID:Action of 1,25-dihydroxyvitamin D3 on calcium balance and bone turnover and its effect on vertebral fracture rate. 232 69

We studied the effects of acute modifications in plasma calcium on parathormone (PTH) secretion in 23 patients with primary hyperparathyroidism (PHPT). In 12 patients, PTH hypersecretion was autonomous, and basal plasma calcium concentration was positively correlated with maximal serum PTH(1-84) reached during Na2EDTA infusions. In 11 patients, PTH hypersecretion remained suppressible, but with elevated set point value, and basal plasma calcium concentration was positively correlated with set point. Thus, the degree of hypercalcemia seems mainly determined by the magnitude of maximal PTH secretion and set point error in autonomous and suppressible PHPT, respectively. We have previously suggested that high serum calcitriol levels might chronically inhibit PTH hypersecretion in PHPT. We showed that hyperparathyroid patients with renal stone presentation exhibited an abnormally high value of circulating calcitriol and a moderately elevated PTH activity, while patients with severe bone disease presentation displayed a low to normal calcitriol value and a dramatically increased PTH activity. The hypothesis was supported by a recent study from our Unit in one hyperparathyroid patient with severe bone disease and normal serum calcitriol level. Increment of serum calcitriol after daily intravenous Rocaltrol for 5 days directly suppressed PTH hypersecretion without change in plasma ionized calcium.
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PMID:Determinants of parathormone secretion in primary hyperparathyroidism. 269 19

Clinical investigations have shown that 1 alpha-hydroxycholecalciferol (oxydevit, alphacalcidiol) and 1 alpha, 25-dihydroxycholecalciferol (rocaltrol) are act vitamin D3 agents producing a positive clinical effect in different types of osteoporosis and osteomalacia. Clinical improvement of the patients' status (alleviation of the pain syndrome, an increase in motor activity) was noted in 1-2 mos., an x-ray picture of regeneration of the bone structure of both axial and peripheral skeleton--in 6-12 mos. after the initiation of therapy. Therapy was attended by an increase in the serum content of total and ionized calcium, the return of alkaline phosphatase activity to normal, and a decrease in the level of parathormone. During prolonged therapy these agents administered at daily doses of 0.25-2 micrograms caused no pathological side-effects and hypercalcemia. In osteoporotic conditions all these drugs were equal in their clinical effectiveness. Rocaltrol has some advantages in the presence of associated liver pathology.
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PMID:[Comparative evaluation of the effectiveness of vitamin D3 preparations (1-alpha-hydroxy- and 1-alpha,25-dihydroxycholecalciferol in various forms of osteoporosis and osteomalacia]. 276 60

Administration of pulse doses of calcitriol is a better way of conservative treatment of secondary hyperparathyroidism (2HPT), making use of the direct suppression of parathormone (PTH) secretion. In a group of 29 haemodialyzed patients the authors evaluated during a six-month follow-up the effect of intravenous Calcijex in 12 and of oral Rocaltrol in 8 subjects. In responders of the calcijex group the PTH level declined by 67.6%, the mean baseline PTH value being 787.8 pg/ml, as compared with non-responders where the decline of PTH at the end of the investigation was 7.5%, the baseline PTH being 1296.4 pg/ml. The difference was significant (p < 0.05). In patients treated with Rocaltrol the therapeutic effect was apparent also in subjects with a lower baseline PTH. An associated phenomenon of treatment are as a rule parallel changes of kALP and ACP levels with those of PTH. It was however revealed that the drop of serum activities can occur also without a concurrent drop of PTH which indicates a dissociation between the level of bone metabolism and PTH secretion. The therapeutic effect can be influenced not only by the stage of 2HPT but also by the route of administration and quantity of calcitriol doses, as ensues from a long-term follow up of one patient. Moreover, the morphological substrate of the hyperplastic tissue of the parathyroid gland and their receptors for 1,25(OH)2D3 must be taken into account. Successfully performed parathyroidectomy, a still justified therapeutic step, is associated as a rule with rapid restoration of PTH levels. TO CONCLUDE: Pulse doses of calcitriol seem to be at present the effective treatment of diagnosed 2HPT, conventional oral calcitriol doses are useful in 2HPT prophylaxis. 2. The i.v. form should be the last resort of conservative treatment before parathyroidectomy. 3. Calcitriol treatment should attempt to maintain slightly raised PTH levels. 4. The limiting indicators of treatment are hypercalcaemia, hyperphosphataemia and the development of extraosseous calcifications. 5. In order to adhere to these criteria it is necessary to use dietary provisions, the dialyzation technique and check biochemical indicators of bone metabolism and possibly change doses of pharmaceutical preparations.
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PMID:[Pulsed doses of calcitriol in the treatment of secondary hyperparathyroidism in patients on hemodialysis]. 975 Apr 67

Vitamin D(3) affects the immuno response and improves experimental autoimmune diseases. We investigated the effect of 1,25-dihydroxycholecalciferol (1,25[OH](2)D(3)) Rocaltrol as a single immunosuppressive agent and in combination with low-dose cyclosporin A (CsA) in vascularized liver allografts in rats in a high-responder strain combination (ACI-->Lewis). Recipients were placed on a low-calcium diet 7 days before transplantation and were treated with 0.1 or 1 microg/kg/d 1,25(OH)(2)D(3) intraperitoneally beginning 3 days before transplantation. Treatment combining 1,25(OH)(2)D(3) with CsA (2 mg/kg/d) was also tested. Graft function and survival, histologic rejection, and concentrations of interleukin (IL)-2, -4, -10, and -12 in serum and in grafts were measured. 1,25(OH)(2)D(3) increased allograft survival in a dose-dependent manner when compared with controls (P <.05 for both groups). Serum bilirubin, aspartate transaminase (AST), and lactate dehydrogenase (LDH) activities were significantly lower in 1,25(OH)(2)D(3)-treated animals. Vitamin D reduced the concentration of IL-2 and IL-12 in serum and in grafts, and increased IL-4 and IL-10 in the grafts. The rejection activity index 10 days after transplantation was significantly lower in low- and high-dose 1,25(OH)(2)D(3)-treated rats compared with vehicle-treated controls (P <.0001 for both groups). The combination of either low-dose or high-dose vitamin D(3) and CsA prolonged graft survival when compared with low-dose CsA only (P <.05 for both groups). After 3 weeks, hypercalcemia developed in high-dose 1,25(OH)(2)D(3)-treated rats. It is concluded that 1,25(OH)(2)D(3) prolongs survival of liver allografts in rats by decreasing the severity of acute rejection. Analogues of vitamin D with fewer hypercalcemic effects may have potential as immunosuppressive drugs in liver transplantation.
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PMID:1 alpha,25-Dihydroxycholecalciferol reduces rejection and improves survival in rat liver allografts. 1167 63