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)

Paget's disease of bone is often discovered incidentally, but can have extensive metabolic and local mechanical complications. Treatment is not required for all patients and should only be undertaken for certain indications, and with a clear understanding of the three types of drugs available. Bone pain unmanageable with analgesics and pathologic fractures are the most common indications, while neurologic symptoms, hypercalcemia and congestive heart failure are less frequent ones. Calcitonin or mithramycin is used for the more urgent indications, and calcitonin or the diphosphonate, etidronate sodium (EHDP), for the more chronic ones. The drugs are generally efficacious and well tolerated.
 ...
PMID:Paget's disease of bone: clinical features and treatment. 315 5

Diphosphonates were administered intravenously to 4 patients with myeloma-induced hypercalcaemia. All patients received EHDP 4.3 mg/kg/day for 3 to 8 days. One of them, whose hypercalcaemia recurred, was later treated with Cl 2 MDP 5 mg/kg i.v. for 8 days. In 2 patients EHDP infusions were followed by EHDP administered orally (5 mg/kg/d) for 3 weeks, after which transiliac bone biopsy was performed. In all patients calcemia fell from 130 +/- 14 to 99 +/- 4 mg/l at the end of the intravenous treatment, with parallel decrease in calciuria. Histomorphometric analysis of the bone biopsies showed few osteoclasts but massive infiltration with plasmocytes. In one case, EHDP probably induced a deficit in mineralization. Intravenous diphosphonates therefore proved to be rapidly effective in the treatment of hypercalcaemia due to malignancy. However prolonged administration of EHDP in high doses is not recommended, as it may result in osteomalacia.
 ...
PMID:[Treatment of hypercalcemia of myelomatous origin with intravenous diphosphonates]. 622 88

The diphosphonates (DP) represent a new class of therapeutic agents, the main property of which is to block bone resorption, irrespective of its stimulus. Apart from their remarkable results in Paget's disease of the bone, DP are very effective in the treatment of hypercalcaemia the osseus origin of which is nearly always essential. In malignant hypercalcaemia, EHDP, C12 MDP and APD, the three DP tested in man, cause a fall in serum calcium in a few days when administered intravenously. The latter two preparations are also effective when given orally. DP are also valuable in controlling hypercalcaemia in primary hyperparathyroidism. Research is under way to determine the role of DP in the prevention of malignant osteolysis, as distinct from the effects of chemotherapy.
 ...
PMID:[Diphosphonates in the treatment of hypercalcemia]. 624 Jul 53

Two diphosphonates, EHDP (disodium etidronate, or ethanehydroxy-diphosphonate) and Cl2MDP (disodium clodronate, or dichloromethylene-diphosphonate) were injected in various doses in six patients with one or multiple episodes of malignant hypercalcemia. All patients responded well to the drugs after a delay period of two to seven days. The tolerance of the drugs was excellent. EHDP, and especially Cl2MDP, are promising agents for treating hypercalcemia and inhibiting bone resorption in malignant disorders.
 ...
PMID:Parenteral diphosphonates for treating malignant hypercalcemia. 645 9

Findings of a 56 year old woman suffering from tumoral calcinosis, who was treated for 6 years, are presented. Under conditions known to lead to negative calcium-phosphorus balance, a reduction in tumor size was seen. Transient hypercalcemia was attributed to immobilization. The process of tumor reduction was not definitely accelerated by treatment with ethane-hydroxy-diphosphonate (EHDP; 500 mg/day for 20 months). Nephrotic syndrome as a consequence of amyloidosis developed. Amyloidosis seems to have resulted from the aseptic histiocytic inflammatory process in the tumors. The possible importance of high cholesterol in very low density lipoproteins in the serum of the patient is discussed.
 ...
PMID:Tumoral calcinosis. Observations during six years. 677 68

Two diphosphonates, EHDP (disodium etidronate, or ethane-hydroxy-diphosphonate) and Cl2MDP (disodium clodronate, or dichloromethylene-diphosphonate) were injected in various doses in 8 patients who had had one or more episodes of malignant hypercalcemia. All patients responded well to the drugs after a time lapse of 2-10 days. Tolerance of the drugs was excellent. EHDP, and especially Cl2MDP, are promising agents for the treatment of hypercalcemia and the inhibition of bone resorption in malignant disorders.
 ...
PMID:[Treatment of hypercalcemia of tumoral origin with two diphosphonates]. 679 98

Etidronic acid is an orally and intravenously active bisphosphonate, which is believed to inhibit resorption of bone via a number of cellular mechanisms, including alteration of osteoclastic activity. In studies of patients with symptomatic Paget's disease, etidronic acid 5 to 20 mg/kg/day administered orally rapidly decreased the biochemical indices of bone turnover. Mineralisation defects in forming bone may be avoided by the use of an initial dosage of 5 mg/kg/day for up to 6 months; dosages above 10 mg/kg/day should be limited to 3 months' duration, and dosages greater than 20 mg/kg/day should be avoided. Although 3-day intravenous therapy with etidronic acid 7.5 mg/kg/day has shown superior efficacy to rehydration and forced diuresis in the management of hypercalcaemia of malignancy, the efficacy of the drug is lower than that of the newer bisphosphonates, pamidronic acid and clodronic acid. Clinical studies involving postmenopausal women with established osteoporosis have indicated that oral etidronic acid 400 mg/day for 14 days as part of a 90-day cycle, repeated for up to 3 years, increases the bone mineral density (BMD) of the lumbar vertebrae and appears to reduce the incidence of vertebral fracture. Published data suggest that etidronic acid shows similar efficacy to hormone replacement therapy (HRT) in these respects. The above dosage also appears to be effective in preventing corticosteroid-induced osteoporosis when administered as part of an intermittent, cyclical regimen. Etidronic acid in higher dosages (10 to 20 mg/kg/day orally) is effective in reducing the incidence of heterotopic ossification and its ensuing complications in both neurological and post-surgical patients. Etidronic acid is well tolerated by the majority of patients, with gastrointestinal complaints reported most commonly, but tends to delay the normal mineralisation of forming bone when administered continuously at higher dosages for prolonged periods. This is of little consequence where short term treatment is involved, but may be detrimental to those patients receiving longer courses of therapy. This effect may be minimised or avoided by using the lowest effective dosage for as short a time as possible (as in the above recommendations for Paget's disease), or by the use of intermittent cyclical therapy (as in the management of osteoporosis). Etidronic acid therefore retains a role in the management of resorptive bone disease, particularly in the treatment of Paget's disease, the prevention of heterotopic ossification, and as a second-line option in postmenopausal osteoporosis. However, the development of newer bisphosphonates requires that these compounds be continually compared and re-evaluated.
 ...
PMID:Etidronic acid. A review of its pharmacological properties and therapeutic efficacy in resorptive bone disease. 785 70

Bisphosphonates regulate bone turnover by inhibiting osteoclastic bone resorption. Due to their pharmacodynamic and pharmacokinetic characteristics, bisphosphonates have a special pharmacotoxicological profile related to their high degree of specificity: low or non-existent distribution in soft tissues and strong affinity for calcified tissues. Some general conclusions may be drawn from the pre-clinical toxicological studies, whose main aim is to identify the toxicity target organ/s and estimate the safety margins of a "prospective therapeutic agent" in laboratory animals. They are based on our own results and on data from the available literature as regards various bisphosphonates: Alendronate, Clodronate, Etidronate, Olpadronate and Pamidronate. Generally, very high doses of bisphosphonates are required to produce in different levels and incidence various extra-skeletical toxic side effects: local reaction, hypocalcemia (and its consequences on the cardiovascular system and the possibility of tetany), affection of the dental structures and renal dysfunction. Most of side effects may be related to the low solubility in biological fluids, the formation of calcium complexes, the potent inhibitory effect of endogenous or induced bone resorption as well as to its main excretion pathway. Some other side effects (on the eye, lungs and liver), may be related to repeated excessive high doses. A safety margin of 200 to 300 : 1 between the "toxic" and "pharmacological" doses may be estimated if the total quantity of Olpadronate given to various animal species in toxicological studies and in pharmacodynamic experimental models (osteopenias due to estrogen deprivation or immobilization and retinoid-induced hypercalcemia) is considered. If the toxic doses in animals are related to the highest doses suggested for human beings, then the ratio increases from 300 to 1000 : 1 depending on the pathology and the route of administration. As regards their effect on the bone, experimental data with the new bisphosphonates suggest a significant dissociation between pharmacologically active doses and those ones producing defective mineralization. The excessive inhibition of bone remodelling, due to the use of high doses in normal animals, is the natural consequence of the pharmacological effect of this family of compounds. A bisphosphonate's toxic potential effect on bone should not be evaluated in normal animals but in particular situations with a high bone turnover. Furthermore, the doses should be adjusted in order to regulate the magnitude of bone remodelling inhibition so as to take it to a normal level without totally suppressing it. Potency, safety margins, doses and proper administration schemes, should be considered as key elements for the optimum use of the therapeutic potentiality of these compounds.
 ...
PMID:[Preclinical toxicology of bisphosphonates]. 956 61

Bisphosphonates are pyrophosphate analogues, in which the oxygen in P-O-P has been replaced by a carbon, resulting in a P-C-P structure. They are characterised by a strong anti-osteoclastic activity and for this pharmacological property they are now considered the treatment of choice for Paget's disease of the bone, malignant hypercalcaemia and bone metastases. Etidronate, clodronate and pamidronate have been registered in several countries for these indications. Etidronate and alendronate are also extensively used for the prevention and treatment of postmenopausal and senile osteoporosis. In this article, we review the most recent findings on the newest bisphosphonates, which will become available in the near future. The aminobisphosphonate risedronate is undergoing a huge programme of clinical development for the treatment of osteoporosis. In a study of the prevention of early postmenopausal bone loss, oral risedronate 5 mg fully prevented the bone loss observed in the placebo group. Similar effects have been observed with an intermittent dosage regimen of oral risedronate 30 mg/day for 2 out of 12 weeks, which corresponds to 5 mg/day in terms of cumulative dose. With lower doses [5 mg on alternate fortnights (2 weeks)] the prevention of bone loss was half that observed with continuous 5 mg/day therapy, indicating that this might not yet be the maximum effective dose. The use of intermittent intravenous bisphosphonates for osteoporosis therapy has been pioneered by studies with clodronate, pamidronate and alendronate. This treatment regimen has been chosen for an extensive clinical development programme for ibandronate. In a phase 2 study, this new bisphosphonate was administered as an intravenous bolus (0.25, 0.5, 1 or 2 mg) every 3 months for a year, with increases in spinal bone mass of 5.2%. Tiludronate, alendronate and risedronate have been recently introduced for the treatment of Paget's disease of bone. Daily doses of tiludronate 400 mg, alendronate 40 mg and risedronate 30 mg for 3 to 6 months have been shown to be superior to etidronate 400 mg/day. The intravenous administration of ibandronate, zoledronate and alendronate (40 mg, 10 mg and 5 mg, respectively) have achieved the normalisation of serum alkaline phosphatase in more than 70% of the patients and these treatments may provide an alternative for patients intolerant oral bisphosphonates. Intravenous ibandronate has been also developed for the treatment of hypercalcaemia of malignancy. The effective doses ranged from 2 to 4 mg. Zoledronate appears to be the most powerful bisphosphonate under investigation, and the effective doses used in cancer hypercalcaemia are as low as 1 to 2 mg. The new generation of bisphosphonates are likely to increase clinical options in terms of administration regimens, but their real advantage over those already available in terms of clinical efficacy remains uncertain.
 ...
PMID:New bisphosphonates in the treatment of bone diseases. 1058 75

Bisphosphonates are used for the treatment of bone resorption, hypercalcemia, osteoporosis and Paget's disease. Etidronate, pamidronate and clodronate also inhibit the development of experimental atherosclerosis without altering serum lipid profile. Bisphosphonates inhibit the arterial calcification, lipid accumulation and fibrosis. They accumulate extensively in arterial walls and suppress macrophages in atheromatous lesions. In macrophage cultures, bisphosphonates inhibit the cellular accumulation and degradation of atherogenic LDL-cholesterol and foam cell formation. Further, they inhibit various enzymes involved in cell signal transduction and cholesterol biosynthesis. Recently, etidronate has been shown to inhibit the thickening of carotid arterial wall even in man.
 ...
PMID:Bisphosphonates and atherosclerosis. 1192 58


<< Previous 1 2 3 Next >>