Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020438 (hypercalciuria)
 2,502 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fifteen patients, 13 women and 2 men (mean age 60 years) with osteoporosis of different types have been under treatment with 1 alpha-hydroxyvitamin D3 and calcium. The responses were observed clinically and by the use of roentgen morphometry, photon absorptiometry and by blood and urine chemical analyses. The treatment had beneficial clinical effect in all but 3 patients. The intestinal calcium absorption rate increased significantly. Slight hypercalcemia and a significant hypercalciuria occurred during treatment. Serum and urine phosphate levels, alkaline phosphatase and parathyroid hormone values were within normal ranges. The bone mineral content increased significantly during treatment. 1 alpha-hydroxyvitamin D3 and calcium was well tolerated by the patients. Three patients had coincidental acute attacks of spinal pain and 2 had further vertebral crush fractures. A period of time longer than one year is necessary to further evaluate the effects of 1 alpha-hydroxyvitamin D3 therapy on the clinical course of severe osteoporosis.
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PMID:Interim report on treatment of osteoporotic patients with 1 alpha-hydroxyvitamin D3 and calcium. 70 36

Osteolytic lesions and pathological fractures are common in multiple myeloma. Because clodronate inhibits osteoclastic resorption, we did a randomised, controlled trial in 350 patients from 23 hospitals. All patients received standard melphalan-prednisolone, and were randomised to receive clodronate 2.4 g daily or placebo for 24 months. The proportion of patients with progression of osteolytic bone lesions was twice as high in the placebo group (n = 168 at baseline) than in the clodronate group (n = 168 at baseline) in an intention-to-treat analysis (24 vs 12%, p = 0.026). Progression of vertebral fractures was lower in the clodronate group, but the difference was not significant (30 vs 40%). Serum calcium and urinary calcium excretion decreased significantly in both groups, but the changes were greater in the clodronate group. The percentage of patients feeling no pain increased more in the clodronate group (from 24 to 54%, p < 0.001) than in the placebo group (from 29 to 44%, p < 0.01). Side-effects were similar in both groups. We conclude that clodronate is an effective and safe adjunct in the management of multiple myeloma. The drug delays osteolytic bone lesions, reduces the degree of hypercalcaemia and hypercalciuria, and decreases pain.
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PMID:Randomised, placebo-controlled multicentre trial of clodronate in multiple myeloma. Finnish Leukaemia Group. 809 68

The geminal bisphosphonates are a new class of drugs characterised by a P-C-P bond. Consequently, they are analogues of pyrophosphate, but are resistant to chemical and enzymatic hydrolysis. The bisphosphonates bind strongly to hydroxyapatite crystals and inhibit their formation and dissolution. This physicochemical effect leads in vivo to the prevention of soft tissue calcification and, in some instances, inhibition of normal calcification. The main effect is to inhibit bone resorption, but in contrast to the effect on mineralisation, the mechanism involved is cellular. These various effects vary greatly according to the structure of the individual bisphosphonate. The half-life of circulating bisphosphonates is very brief, in the order of minutes to hours. 20% to 50% of a given dose is taken up by the skeleton, the rest being excreted in the urine. The half-life in bone is far longer and depends upon the turnover rate of the skeleton itself. Bisphosphonates are very well tolerated; the relatively few adverse events that have been associated with their use are specific for each compound. Bisphosphonates have been used to treat various clinical conditions, namely ectopic calcification, ectopic bone formation, Paget's disease, osteoporosis and increased osteolysis of malignant origin. The three compounds commercially available for use in tumour-induced bone disease are in order of increasing potency, etidronate, clodronate and pamidronate. Most data have been obtained with the latter two agents. By inhibiting bone resorption, they correct hypercalcaemia and hypercalciuria, reduce pain, the occurrence of fractures, as well as the development of new osteolytic lesions, and in consequence improve the quality of life. In view of these actions, of their excellent tolerability and of the fact that they are active for relatively long periods, these compounds are, after rehydration, the drugs of choice in tumour-induced bone disease and an excellent auxiliary to the drugs used in oncology.
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PMID:Bisphosphonates. Pharmacology and use in the treatment of tumour-induced hypercalcaemic and metastatic bone disease. 172 40

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.
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PMID:Long-term treatment with calcitriol in postmenopausal osteoporosis. 232 71

The pathogenesis, clinical features, indications for therapy, and current pharamacologic management of Paget's disease are reviewed. Paget's disease is a bone disorder of unknown etiology primarily affecting the elderly. Overactive bone resorption leads to the accelerated formation of disorganized, weak bone. Pain and fractures are common clinical features. Neurologic, cardiovascular, metabolic, and neoplastic complications are also reported. Because most patients are asymptomatic, the disease is often detected during routine roentgenography or laboratory tests. Primary indications for pharmacologic intervention include bone pain, neural compression, immobilization hypercalcemia or hypercalciuria, cardiac failure, and orthopedic surgery. Recurrent or non-healing fractures and rapidly progressing complications are additional indications. Drugs used in the management of Paget's disease include calcitonin, etidronate disodium, and plicamycin. Although these agents are efficacious, each has disadvantages. Clinical resistance to animal calcitonins may develop, and the cost of therapy may be prohibitive. Etidronate may induce ostemalacia. The use of plicamycin is limited by potentially severe toxicities. Dichloromethylene and aminohydroxypropylidene are promising diphosphonate compounds but are still investigational In those patients who are unresponsive to single-agent regimens, combination therapy may prove effective. Although many patients with Paget's disease do not require pharmacologic therapy, calcitonin and etidronate are the agents of choice when it is indicated.
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PMID:Pharmacologic management of Paget's disease. 266 12

The relation between signs and symptoms of Paget's disease of bone was studied in 180 patients consecutively submitted for treatment. In these patients 826 lesions were identified by scintigraphy. The intensity of scintigraphic uptake was correlated with long-term calcium uptake in bone. The frequency distribution of lesions over the patients was compatible with a 65 per cent chance of local disease once the patient had been exposed to an extraneous agent. The spatial distribution within a skeleton was related to the local density of the osteoclast population. The particular frequency distribution resulted in a log-normal distribution diagram for anatomical spread. Within lesions, increases in numbers of osteoclasts and osteoblasts were proportional and these too had a log-normal distribution. Increases of alkaline phosphatase levels and hydroxyproline excretion were closely related and reflected anatomical spread on the one hand and local activity on the other. They were also closely correlated with overall calcium fluxes. It was shown that alkaline phosphatase is the more sensitive and hydroxyproline the more accurate of the biochemical signs. Maximum values, corresponding to total skeletal disease, were approximately 25 times the upper limit of normal. Equilibrium between bone formation and resorption was not always maintained. There were, indeed, wide variations of urinary calcium, which were significantly related to the difference between bone formation and resorption, but the extracellular calcium homeostasis was generally maintained. This may explain the frequent occurrence of normocalcaemic and hypercalcaemic hyperparathyroidism. The hypercalciuria constitutes an additional risk for urolithiasis in men. The most frequent complaint was pain (86 per cent). Extent of lesions was important, but a major decisive factor was the specific nature of the bone affected. The findings allowed assessment of the relative importance of the various signs, symptoms and locations as criteria of disease severity and as indications for treatment.
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PMID:Relation between signs and symptoms in Paget's disease of bone. 371 67

Ten women with skeletal metastases from breast carcinoma received dichloromethylene diphosphonate (Cl2MDP), an inhibitor of osteoclast function, in a placebo-controlled, double-blind, crossover study. Eight of these patients had either hypercalcemia or hypercalciuria, and all 10 had elevated urinary hydroxyproline levels as evidence of active skeletal disease. Eight patients had moderate to severe bone pain. After eight weeks of oral dichloromethylene diphosphonate treatment (3,200 mg per day), either preceded by or followed by an eight-week placebo period, seven of eight patients with hypercalciuria had significant reductions in urinary calcium levels, and nine of 10 had reductions in urinary hydroxyproline levels (significant in eight) when the dichloromethylene diphosphonate treatment periods were compared with prestudy or placebo periods. Additionally, seven of eight subjects had decreased pain with dichloromethylene diphosphonate. There were no adverse effects other than transient diarrhea in some patients. We conclude that oral dichloromethylene diphosphonate can significantly inhibit osteoclast-mediated bone destruction in patients with bone metastases from breast cancer.
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PMID:Effects of dichloromethylene diphosphonate in women with breast carcinoma metastatic to the skeleton. 621 77

Dichloromethylene diphosphonate (Cl2MDP), an inhibitor of oestoclast activity, was evaluated for its ability to decrease the excessive mobilization of skeletal calcium that complicates multiple myeloma. Ten patients with active myeloma, wide-spread bone disease, and hypercalciuria were studied in a double-blind, placebo-controlled, crossover-designed trial in which they took Cl2MDP for eight weeks and placebos for eight weeks. Two patients died during the placebo phase; of eight patients who received Cl2MDP, seven had rapid, sustained, and highly significant (P less than 0.001) decreases in urinary excretion of calcium. Six also had significant decreases in hydroxyproline excretion, and five reported lessening of skeletal pain. On patient did not respond. Although the patients received concurrent chemotherapy during the study, concentrations of myeloma proteins actually increased or decreased only slightly, indicating the declines in hypercalciuria resulted from Cl2MDP and not from improvement in the underlying disease. We conclude that Cl2MDP is a potentially useful inhibitor of osteoclast-mediated bone erosion in multiple myeloma.
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PMID:Effects of dichloromethylene diphosphonate on skeletal mobilization of calcium in multiple myeloma. 644 41

Clinical course of the idiopathic juvenile osteoporosis (IJO) was monitored in the group of 45 patients of both sexes with diagnosed disease, verified during follow-up period. The aim of the study was to evaluate the relationship between clinical symptoms and the results of biochemical, anthropometric, and densitometric measurements. An analysis of the obtained data enabled to distinguish the acute and chronic IJO phases. Evolution of the acute phase into chronic one was manifested by the cessation of pain and pathological gait stereotype, normalization of muscular strength, anthropometric parameters and urinary Pyr and DPyr excretion, as well as improvement in bone density. Hypercalciuria and increased urinary excretion of Pyr and DPyr, observed in the acute phase of IJO, may indicate that bone resorption exceeded bone formation. Tendency to maintain of alkaline phosphatase activity within lower limits of the normal values with slight increase during an improvement of densitometric parameters suggested transient osteoblast dysfunction.
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PMID:[Dynamics of the course of idiopathic juvenile osteoporosis]. 830 31

Hyperprostaglandin E syndrome is a rare disease usually presenting with renal symptoms such as polyuria, polyhydramnios, hypercalciuria, hypokalaemia, and recurrent episodes of extreme fever, diarrhoea, and convulsions. We report a severe variant of this syndrome with obvious pain and prostaglandin E2 (PGE2)-stimulated hyperthyroidism, an association not previously described. Urinary excretion of PGE2 and its metabolite 7 alpha-hydroxy-5,11-diketotetranorprosta-1,16-dioic acid were markedly increased above normal levels (to 53.3 and 1895 ng/h per 1.73 m2, respectively). We studied oxidative capacity of peroxisomes and mitochondria, the sites where PGE2 oxidation takes place. A generalized mitochondrial disease could be ruled out and no deficiency was found in liver peroxisomal oxidases. The basic pathology of hyperprostaglandin E syndrome remains unsolved.
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PMID:Severe hyperprostaglandin E syndrome with hyperthyroidism--studies of pathogenetic mechanisms. 889 27


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