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)

A controlled therapeutic trial on seventy-four 70-year-old women was carried out with the purpose of finding the optimal treatment for post menopausal osteoporosis. The bone mineral content (BMC) was measured by I-photonabsorptiometry at two sites in the distal part of the forearms, where the trabecular/cortical ratio is 0.25 and 1.5, respectively. Radiographs were done on the right hand to measure the metacarpal bone mass (cortical area/total area=CA/TA. After observing the spontaneous course of bone loss for 6 months the participants were allocated at random to 12 months' treatment with 1,25-dihydroxycholecalciferol [1,25(OH)2D3] and oestrogen/gestagen, alone or in combination, and calcium. The groups treated with oestrogen/gestagen [with or without 1,25(OH)2D3] showed a highly significant increase in BMC. In contrast bone mineral remained unchanged or decreased in both the calcium and the 1,25(OH)2D3 groups with a tendency towards more pronounced negative bone balance in the 1,25-(OH)2D3 group. Seven out of nineteen patients of 1,25(OH)2D3 developed hypercalcaemia, which necessitated a reduction in dosage. It is concluded that the new vitamin D metabolite, 1,25(OH)2D3, given in clinically acceptable doses, is without value in the treatment of post menopausal osteoporosis.
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PMID:Treatment of post menopausal osteoporosis. A controlled therapeutic trial comparing oestrogen/gestagen, 1,25-dihydroxy-vitamin D3 and calcium. 704 20

45Calcium metabolism and circulating levels of iPTH (N-terminal fragment) and iCT were investigated in normocalcemic patients with multiple myeloma (12) in an attempt to ascertain early changes in calcium metabolism, which may occur before hypercalcemia develops. The same parameters were also investigated in patients with senile osteoporosis (11), corticosteroid-induced osteoporosis (6), Paget's disease (6) and controls without bone disorders (13). In the myeloma group, the exchangeable calcium pool (7,678 +/- 321 mg) was significantly higher (P less than 0.01) than in the control group (4,405 +/- 374 mg), the senile osteoporosis group (4,108 +/- 407 mg) and the corticosteroid-induced osteoporosis group (3,015 +/- 161 mg) and nearly as high as in the Paget's disease group (8,876 +/- 1,173 mg). Calcium pool turnover rate was higher in the myeloma group than in controls, as were bone anabolism and bone catabolism, although differences were not statistically significant. There were no statistically significant differences among the groups in the plasma iPTH or iCT, although the mean value of the latter was higher in the myeloma group than in controls (86 +/- 24 vs. 47 +/- 13 pg/ml). These data suggest that an increase in the exchangeable calcium pool and in turnover rate may occur early in the course of multiple myeloma, preceding the development of hypercalcemia. The role of some homeostatic mechanisms in maintaining normal plasma calcium levels in multiple myeloma despite increased bone calcium resorption is discussed.
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PMID:Calcium metabolism in multiple myeloma. 716 1

A series of 38 cases of primary hyperparathyroidism seen at a single hospital within a four a half year period is reported. The importance of hypercalcemia in the diagnosis of this syndrome and its screening in cases of arterial hypertension, gout, osteoporosis, and families with type I multiple endocrine neoplasia are underlined. The patients in the present series had a florid clinical history with a mean duration of 14 years. Main symptoms were urolithiasis (52%), arterial hypertension (28.9%), bone involvement and pain (23.7%), and peptic ulcer (18.4%). There were a high proportion of patients with hyperuricemia (26.3%), some with classical symptoms of gout. One patient presented simultaneous pituitary and pancreatic involvement. Surgical therapy was undertaken in 25 patients, of whom 24 (96%) were cured, one of them after reoperation. There were no cases of relapse, hypoparathyroidism, or postoperative death. Surgery is the only rational and definitive form of treatment of hyperparathyroidism; both experienced surgeons and pathologists are necessary to deal with the anatomic and histologic subtleties of this interesting endocrine disorder.
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PMID:[Comments on a series of 38 cases of primary hyperparathyroidism (author's transl)]. 724 69

Plasma concentrations of 25-hydroxyvitamin D (25-OH-D) were determined in 40 healthy persons and in patients with primary osteoporosis (n = 43), primary hyperparathyroidism (n = 19), intestinal osteopathy (n = 13), and after small intestine bypass operations (n = 8). The control group showed physiologic seasonal variations which must be taken into account in the individual case. Whereas there were no deviations from the normal in patients with osteoporosis, significantly lower values were obtained in the other disease groups. Estimation of 25-OH-D in plasma represents a valuable contribution for the diagnosis of generalized osteopathies and for the differential diagnosis of hypercalcaemia. In addition, the effects of vitamin D treatment may be objectively assessed. Overdosage and intoxication may be recognized in time.
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PMID:[Clinical relevance of 25-hydroxyvitamin D estimation in plasma (author's transl)]. 730 6

After the menopause, a growing proportion of women will have a good chance to add three decades or more to their lifetime. They must decide whether to start long-term hormonal replacement therapy or to accept the risks of osteoporosis, fracture, cardiovascular disease, and a variety of psychological and physical problems as 'natural' destiny. The syndrome of postmenopausal endocrine deficiency is a primary glandular insufficiency, which in principle requires substitution with the secretory product of the gland. Postmenopausal osteoporosis and fractures are consequences of a pathological dysfunction of calcium metabolism. After estrogen withdrawal, the impaired hepatic and renal synthesis of calcitriol will result in a reduced intestinal resorption of calcium. Parathyroid hormone may initiate a vicious circle by acceleration of bone resorption, mobilization of bone calcium and a tendency to hypercalcemia. The failure to preserve circulating calcium due to 'escape' from calcitonin and a decreased renal tubular back-resorption are followed by an increased loss of calcium from a 'renal calcium leak', resulting in hypercalcuria. In order to maintain homeostasis, additional calcium is required, which will be supplied from accelerated bone resorption. Thus, the circle is closed by renewed osteolysis. The process is associated with accelerated bone turnover and a negative balance of calcium and bone. After a variable time interval which depends on the individual bone mass and rate of bone loss, these events will inevitably result in osteoporosis. Estrogen replacement will interrupt the circle, decelerate bone turnover, and re-establish a positive balance of calcium and bone. Estrogen withdrawal also favors an 'atherogenic' set of lipoproteins, which is strongly associated with increased coronary risk. Substitution with estrogens will favor a 'protective' profile of lipoproteins and cut the cardiovascular risk to about one half. Progestogens, in particular the 17 alpha-alkylated 19-nor-steroids, may reduce the favorable effects of estrogens on lipoproteins in a dose-dependent manner; however, they do not impair the antiatherogenic estrogen effects, even in presence of an atherogenic profile of lipoproteins. Thus, these anti-estrogenic effects of progestogens, at least in nonhuman primates, do not have clinical significance.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Sex hormone replacement following menopause--for all women? A plea for prevention using estrogens and gestagens]. 748 82

Cimadronate (YM175) is a novel bisphosphonate with potent inhibitory activity on bone resorption under development for the treatment of tumor-induced hypercalcemia, metastatic bone disease and osteoporosis. We conducted intravenous reproductive toxicity and teratology studies (Segment I, II and III) of this compound in rats and teratology study in rabbits. The test compound was dissolved in physiological saline, which was also given as the vehicle control. Rats were administered at a dosage of 0.06, 0.16 and 0.62 mg/kg/day in the male Segment I study. Dose levels in the other studies in rats including the female Segment I were 0.16, 0.31 and 0.62 mg/kg/day. In the Segment I study, no treatment-related abnormalities were observed in reproductive parameters or fetuses. In the Segment II study, slightly retarded fetal ossification was noted at 0.31 mg/kg/day or more, but the incidence of malformation did not increase. In the Segment III study, death of the dams and abnormal tooth growth of offspring were observed at 0.16 mg/kg/day or more. Further Segment III study showed that the no toxic effect level was 0.003 mg/kg/day. In the rabbit teratology study, dose levels were 0.01, 0.025 or 0.05 mg/kg/day. No toxic effects on pregnant females or their litters were observed at up to 0.05 mg/kg/day.
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PMID:Intravenous reproductive and developmental toxicity studies of cimadronate (YM175), a novel bisphosphonate, in rats and rabbits. 749 Jul 81

Cimadronate (YM175) is a novel bisphosphonate with potent inhibitory activity on bone resorption under development for the treatment of tumor-induced hypercalcemia, metastatic bone disease and osteoporosis. We conducted toxicity studies of cimadronate intravenously, single dose, 30-day repeated dose and 26-week weekly dose in F344 rats. In the single dose study, cimadronate was administered to rats and the animals were observed for 14 days. Major toxic symptoms were decreased motility and piloerection and LD50 values were 23 mg/kg for males and 21 mg/kg for females. In the 30-day study, the animals received cimadronate at doses of 0, 0.16, 0.31, 0.62 or 1.25 mg/kg/day. At 0.16 mg/kg/day or more, an increased amount of primary spongiosa was observed in the femur. At 0.62 mg/kg/day or more, renal and testicular/epididymal toxicity were observed. After a 30-day recovery period, the finding in the kidney disappeared, but the findings remained in the bone, testis and epididymis. In the 26-week weekly dose study, animals received cimadronate at doses of 0, 0.31, 0.62 and 1.25 mg/kg/week. At 0.31 mg/kg/week or more, an increased amount of primary spongiosa was seen in the femur. Renal and testicular/epididymal toxicity, however, were not observed.
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PMID:Intravenous single and repeated dose toxicity studies of cimadronate (YM175), a novel bisphosphonate, in rats. 749 Jul 86

Cimadronate (YM175) is a novel bisphosphonate with potent inhibitory activity on bone resorption under development for the treatment of tumor-induced hypercalcemia, metastatic bone disease and osteoporosis. We conducted intravenous single and repeated dose toxicity studies of cimadronate in beagle dogs. In the single dose study, animals received a single dose of 0.3, 1, 3 or 10 mg/kg of cimadronate and the animals were observed for at least 14 days. At 10 mg/kg, both the male and female dog showed toxic signs such as vomiting, decreased locomotor activities and hypothermia and were killed in extremis within a week after dosing. In the 30-day study, animals received cimadronate at a dosage of 0 (vehicle), 0.03, 0.1, 0.3 or 1 mg/kg/day. At 0.03 mg/kg/day or more, histological findings indicated an increased amount of primary spongiosa in the rib and ilium. At 1 mg/kg/day, degenerative nephropathy, aggregation of spermatozoa and glandular hypoplasia of the prostate gland were observed. On day 16 of dosing one male animal died of acute renal failure. In the 26-week study, animals received cimadronate once weekly at a dosage of 0 (vehicle), 0.31, 0.62, or 1.25 mg/kg. Histopathological examination showed an increased amount of primary spongiosa in the rib at all dosage levels. In addition, similar findings were observed in the lumbar vertebrae at 1.25 mg/kg/week. Histopathological changes in the kidney and male reproductive organs were not observed.
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PMID:Intravenous single and repeated dose toxicity studies of cimadronate (YM175), a novel bisphosphonate, in beagle dogs. 749 Jul 87

Osteoporosis is the most important metabolic bone disease and places an increasing burden on the healthcare system. The condition can be prevented by the early introduction of hormone replacement therapy. The role of bisphosphonates in achieving the same result is being actively explored. The attraction of preventing bone loss is that it preserves the micro-architecture of bone, and therefore its mechanical integrity. The great problem of treating the established condition is that substantial bone loss is accompanied by architectural disintegration. Replacing lost bone may not necessarily restore mechanical integrity and protect against fractures. The management of Paget's disease has been quite revolutionised by the introduction of the bisphosphonates. The condition is a result of a primary increase in osteoclastic bone resorption which can be corrected by bisphosphonates, with considerable symptomatic improvement. The increasing potency and safety margin of the newer agents has meant that the threshold for treatment has fallen. There is now potential for long term control of bone turnover with the hope of preventing late complications. Hypercalcaemia of malignancy is usually the result of both increased bone destruction and decreased urinary calcium excretion. These two components of hypercalcaemia demand different approaches to management. The general availability of an ever-expanding range of increasingly potent bisphosphonates has resulted in a dramatic improvement in the treatment of increased bone resorption associated with malignancy. Many types of tumour, either directly or indirectly, compromise the ability of the kidney to eliminate a calcium load derived from increased bone destruction. Calcitonin is the only agent which is currently available to counter this process.
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PMID:Drugs used in the treatment of metabolic bone disease. Clinical pharmacology and therapeutic use. 750 48

Clodronate (clodronic acid, dichloromethylene bisphosphonate) is a bisphosphonate which has demonstrated efficacy in patients with a variety of diseases of enhanced bone resorption including Paget's disease, hypercalcaemia of malignancy and osteolytic bone metastases. In addition, early reports demonstrating potential efficacy of clodronate in the treatment of osteoporosis suggest a possible role in this debilitating disease. Short term intravenous administration (usually 300 mg/day for 5 days) or longer courses of oral clodronate (usually 1600 mg/day for 6 months) effectively reduced bone pain and/or improved mobility in most patients with Paget's disease, and these effects persisted for up to 12 months after discontinuing clodronate. When administered intravenously (300 mg/day for up to 12 days) to patients with malignant hypercalcaemia, serum calcium levels declined significantly within 2 days of starting treatment and approximately 70 to 95% of patients became normocalcaemic. While there is less experience with oral administration, clodronate (800 to 3200 mg/day) achieved normocalcaemia in the majority of patients, usually within 1 week, and serum calcium levels remained significantly reduced from baseline for up to 6 months with continued treatment. Clodronate is clearly superior to placebo and, based on a retrospective analysis, appears to produce greater and more sustained reductions in serum calcium levels than calcitonin in patients with malignant hypercalcaemia. The few available prospective comparative trials showed that clodronate is at least as effective as etidronate, but comparisons with alendronate and pamidronate produced results of questionable clinical relevance because of low bisphosphonate dosages used in these trials. Nevertheless, single intravenous doses of clodronate 600 mg or alendronate 7.5 mg (both agents repeated on day 3 if necessary) were comparable in efficacy, whereas a single intravenous dose of pamidronate 30 mg was more effective than a single intravenous dose of clodronate 600 mg. Normocalcaemic patients with osteolytic bone metastases due to advanced breast cancer experienced significant reductions in the number of episodes of hypercalcaemia and terminal hypercalcaemia, incidence of vertebral fractures and overall rate of morbid events, including the need for radiotherapy to treat bone-related pain, following treatment with clodronate 1600 mg/day for 3 years in a large placebo-controlled study. A similar large placebo-controlled trial in patients with multiple myeloma demonstrated that clodronate 2400 mg/day orally for 2 years significantly reduced progression of osteolytic bone lesions. Follow-up data from clinical trials revealed that the effects on development of fractures and hypercalcaemia persisted for at least 12 months after the drug was discontinued.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Clodronate. A review of its pharmacological properties and therapeutic efficacy in resorptive bone disease. 752 33


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