Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020437 (hypercalcemia)
 10,293 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prostaglandins of the E series, primarily E2 and E1, have the greatest activity in bone. Following discovery of their potent ability to stimulate bone resorption in vitro, clinical investigations have placed prostaglandins at sites of localized bone resorption associated with inflammatory or space occupying lesions in vivo. These studies have shown that prostaglandin production at such sites may be increased by cytokines such as interleukin-1 but the mechanisms by which prostaglandins stimulate bone resorption are not yet known. Observation of periosteal bone formation in patients given, pharmacological doses of prostaglandin has led to investigation of its bone forming activity. Young, growing rats have increased metaphyseal bone formation and this is accompanied by increased periosteal and endocortical bone formation in older animals. In the mature animals there is a generalized activation of remodelling with increased formation in the remodeling cycle. This is also seen in oophorectomized rats and results in repletion of the lost bone in this model of osteoporosis. In animal models of localized disuse osteopenia, prostaglandins are found to be elevated at the site of bone loss and prostaglandin inhibitors at least partially protect against the exaggerated resorption that occurs. This is also seen in models of orthodontic tooth movement, periodontitis and osteomyelitis. Prostaglandin synthesis inhibitors have been shown to delay healing of bone and this has led to limitations on their use clinically in some situations. Exogenously administered prostaglandins have been found to enhance periosteal callus formation, but healing is not uniformly enhanced. Prostaglandins have also been associated with hypercalcemia in certain animal tumors that model human hypercalcemia of malignancy but are probably most important in this condition as mediators in the localized resorption of bone at tumor sites. These in vivo studies have shown that prostaglandins are involved with increases in both bone formation and bone resorption. In vitro studies have shown that prostaglandins stimulate osteoblasts as well as osteoclastic bone resorption but understanding these effects under in vivo conditions will require further investigation.
 ...
PMID:The role of prostaglandins in bone in vivo. 228 Nov 18

We report results for adjusted ionized calcium (at pH 7.4) and actual ionized calcium (at actual pH) in capillary blood from 183 patients with disorders of calcium metabolism (primary hyperparathyroidism, secondary hyperparathyroidism of malabsorption, primary hypoparathyroidism, Paget's disease, acromegaly, hypercalcemia of malignancy, osteoporosis, sarcoidosis, idiopathic hypercalciuria, and familial hypocalciuric hypercalcemia). The correlation and the equation for the linear regression between adjusted ionized calcium (y) and actual ionized calcium (x) were y = 1.011x + 0.005 mmol/L, r = 0.992, Sy,x = 0.021 mmol/L. Results were similar within each diagnostic group. Consistent agreement between adjusted and ionized calcium was observed in 96.7% of patients representing a variety of the most frequently encountered disorders of calcium metabolism. Thus we find adjusted ionized calcium to be as useful as actual ionized calcium for evaluation of patients with such disorders. Adjusted ionized calcium may therefore also be a logical choice for establishing agreement between laboratories for reference intervals in healthy adults.
 ...
PMID:Adjusted ionized calcium (at pH 7.4) and actual ionized calcium (at actual pH) in capillary blood compared for clinical evaluation of patients with disorders of calcium metabolism. 231 Dec 30

Prevention of postmenopausal osteoporosis is an alternative to the currently problematic goal of reversing the trabecular plate thinning and perforation that constitute the major pathologic defects in patients with established osteoporosis. 1,25(OH)2D3 (calcitriol) has been suggested as a drug that may decrease bone resorption sufficiently to preserve trabecular structure in perimenopausal women. In the present study, we compared the effects of calcitriol and an investigational analog, 1,25,26-(OH)3delta22-D3 (Ro-23-8525), to those of an inert vehicle in maintaining the bone mass of oophorectomized adult beagles. In these studies, we used dual-energy radiography to serially quantitate the bone density of control and treated animals. Treatment for 1 year with either agent resulted in no evidence of hypercalcemia or decreased renal function. Moreover, calcitriol and Ro-23-8525 effectively abolished the loss of bone mass observed in untreated oophorectomized controls. Indeed, treated animals displayed variations in bone density similar to that observed in sham-operated untreated animals. These data suggest that calcitriol and Ro-23-8525 may be potentially effective agents for prophylaxis of postmenopausal osteoporosis.
 ...
PMID:Role of calcitriol in prevention of osteoporosis: Part I. 232 66

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.
 ...
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.
 ...
PMID:Action of 1,25-dihydroxyvitamin D3 on calcium balance and bone turnover and its effect on vertebral fracture rate. 232 69

In order to assess the long-term effects of calcitriol treatment in postmenopausal osteoporotic patients, 1.0 micrograms/d of calcitriol was administered in two divided doses for 1 to 8 years to 270 women with symptomatic, histologically proven postmenopausal osteoporosis. No calcium supplementation was given. Clinically, the treatment resulted in substantial relief from pain, with improvement of ambulancy. Intestinal calcium absorption, which was lower than normal at baseline, increased significantly and remained higher than the baseline value as long as calcitriol was administered. Urinary calcium absorption also increased, but hypercalcemia occurred, exceptionally and transiently, in only a few patients. Urinary hydroxyproline excretion did not increase, indicating that hypercalciuria was not of resorptive origin. Total-body density, determined by dual-photon total-body absorptiometry in 56 patients, showed an increase after 18 to 24 months of therapy in most cases. The occurrence of nontraumatic, clinically relevant fractures decreased noticeably as compared with the period preceding calcitriol treatment. No change occurred in renal function, and no renal stones developed. Calcitriol was an effective and safe treatment of postmenopausal osteoporosis.
 ...
PMID:Long-term treatment with calcitriol in postmenopausal osteoporosis. 232 71

An ongoing randomized clinical trial of 3 years duration is being undertaken to evaluate the recurrent fracture rate and safety profile associated with low-dose calcitriol versus calcium supplementation in women with at least 3 years postmenopausal osteoporosis who are under the age of 80 years. A total of 856 patients were submitted for possible inclusion in the study by 123 primary care physicians, and 636 met all entry requirements. Each patient was randomly allocated to receive either 0.25 micrograms of calcitriol twice daily or calcium supplementation of 1,000 mg/d. If significant hypercalcemia developed (greater than 2.6 mmol/L) or a deterioration in renal function was observed, the dose of trial medication was to be halved or stopped if laboratory values did not return to normal. Patients were given no specific instructions regarding dietary calcium intake. To date, 528 patient-years experience with calcitriol and 527 patient-years experience with calcium the calcium supplementation have been accumulated. Thus far, low-dose calcitriol has not been observed to cause hypercalcemia, deterioration in renal function, or nephrocalcinosis. At 1 year, a loss in total anterior height (P less than .05) has been detected in the calcium-treated group compared with the calcitriol-treated group. Thus, calcitriol appears to preserve spinal height. Long-term follow-up of all patients for 2 or 3 years will be continued.
 ...
PMID:Low-dose calcitriol versus calcium in established postmenopausal osteoporosis. 232 72

The development of accurate methods for measuring bone density has made it possible to evaluate more effectively methods for the prevention and treatment of osteoporosis. Calcium supplements are not required in early life for people with a normal dietary intake of the substance, but may reduce the risk of fractures in postmenopausal women. The role of oestrogens in the reduction of postmenopausal bone loss is well established. Vitamin D and its metabolites are of doubtful efficacy in this situation and carry the risk of side effects associated with hypercalcaemia. Treatment with sodium fluoride increases bone density, but its effect on the incidence of fractures remains uncertain. Bone rarefaction can be reduced with calcitonin but administration remains a problem. Elderly patients can be effectively treated with anabolic steroids with relatively small risk of long term side effects. Coherence therapy is a promising new approach which has yet to be fully evaluated. There is no doubt that physical exercise reduces bone loss and increases skeletal density.
 ...
PMID:Osteoporosis. 240 51

Vitamin D has complex effects in bone: it stimulates matrix formation and bone maturation but also enhances osteoclastic activity and may influence differentiation of bone cell precursors. Calcitonin inhibits the function of osteoclasts, reducing bone resorption, thus, the combination of vitamin D and calcitonin could result in a positive bone balance. We tested the hypothesis that chronic treatment with high doses of vitamin D (150,000 U/week), moderate doses of salmon calcitonin (120 MRC U/week), and adequate Ca supplementation (1 g/day) could be beneficial in osteoporosis. Thirteen women with postmenopausal osteoporosis received this treatment for 2-6 years (mean 3.5 years). No side effects, hypercalcemia, or hypercalciuria occurred. There was marked reduction in bone pain. The fracture rate in 11 patients with vertebral compression fracture was 240/1,000 patient years, threefold lower than the reported 834 fractures for untreated patients of similar age. Single photon bone densitometry of the radius did not change. Iliac crest bone biopsies obtained at the initiation and conclusion of the study showed a 43% increment in trabecular bone volume (P = 0.0003), without changes of the normal osteoid thickness, surface, and volume. Because single photon densitometry reflects mostly cortical bone, the data suggest that the combination of vitamin D and calcitonin increases trabecular bone mass and prevents the fall of cortical bone mass in osteoporosis. Previous reports suggest that calcitonin alone or with small doses of vitamin D increased bone mass for about 2 years. The present study suggests a prolonged beneficial effect of the combination of high doses of vitamin D with rather moderate (less than 150 MRC U/week) doses of calcitonin in postmenopausal osteoporosis.
 ...
PMID:Effect of calcitonin and vitamin D in osteoporosis. 250 3

Forty-one patients in chronic end-stage renal failure and 4 patients with a functioning kidney transplant presented with spontaneous hypercalcemia or intolerance to vitamin D3 sterols and/or oral calcium supplements. Bone iliac crest biopsy with aluminum staining and Tc-pyrophosphate bone scintigraphy with determination of Fogelman score were performed in all cases. Two patients had aluminum-induced osteomalacia (AL O). Thirty-eight biopsies showed renal osteodystrophy (secondary hyperparathyroidism or various combinations of osteitis fibrosa and osteomalacia): 19 with positive staining for aluminum (RO + AL) and 19 without aluminum deposits (RO). The series also comprised 2 cases of pure osteomalacia (OM), 2 cases of osteoporosis (OP), and 1 case of osteoporosis with aluminum accumulation (OP + AL). Mean Fogelman score in RO patients (9.1 +/- 0.3) was significantly higher than in all other categories (5.9 +/- 0.5 for RO + AL, and scores ranging from 0 to 8 in the last 7 patients, p less than 0.01). Patients with massive aluminum accumulation in bone (greater than 75% of the total trabecular surface) showed no or very low uptake of the isotope by the skeleton. Fogelman scores of 9 or higher were always associated with histological secondary hyperparathyroidism. 99mTc-pyrophosphate bone scintigraphy is helpful to distinguish aluminum intoxication from secondary hyperparathyroidism in uremic patients.
 ...
PMID:Differential diagnosis between secondary hyperparathyroidism and aluminum intoxication in uremic patients: usefulness of 99mTc-pyrophosphate bone scintigraphy. 254 46


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>