Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:APRD00964 (EHDP)
 496 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thirteen cases of advanced Paget's Disease of bone were treated with Sodium Etidronate (EHDP) at 20 mg/kg/day for 6 months and followed at 2 to 3-month intervals for 20 months with serum alkaline phosphatase, 24-hour urinary hydroxyproline, radiographic skeletal survey, whole-body scanning with Tc-99m-Sn-EHDP and F-18, external body counting with the same radiopharmaceuticals over preselected areas, skin temperature, densitometry of normal phalanges and bone biopsies. Sodium etidronate had a marked effect on Pagetoid bone in all cases with reduction of bone turnover demonstrated by the chemistries, scanning, external counting, skin temperature and X-ray diffraction studies of the bone biopsies. Normal bone did not appear to be materially affected by the drug. Complications drug dose-related included new pain in 6 cases, two fractures in Pagetoid areas and one case of severe demineralization. There was one case of spinal cord compression unlikely to be drug related. All complications cleared or were successfully treated by the end of the study. Some patients continued to show reduction in bone turnover to the end of the study, as long as 14 months after stopping EHDP. Long-term follow-up is needed for final evaluation of the efficacy of the drug. Sodium etidronate shows promise as an agent in the treatment of Paget's Disease. Smaller doses or shorter courses of therapy or combination of EHDP and calcitonin may be just as efficacious and may avoid complications.
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PMID:Evaluation of sodium etidronate in the treatment of Paget's disease of bone. Osteitis deformans. 40 46

Low-titre antibodies to synthetic human calcitonin (hCT) were detected in a 69-year-old woman suffering from Paget's disease who was treated for 16 months with hCT and the diphosphonate EHDP. Levels of antibody were highest between 10 and 18 months after commencement of therapy, slowly decreased after completion of treatment and were later no longer measurable. There was no immunological response to a single re-injection of hCT 14 months after discontinuation of therapy. Formation of antibodies to hCT in man is a very rare event, this being the first recorded case of an immune response to synthetic human calcitonin, whereas synthetic salmon calcitonin induces an immune response in a high percentage (up to 78%) of the patients treated with this hormone.
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PMID:Formation of antibodies to synthetic human calcitonin during treatment of Paget's disease. 51 48

Severe hypercalcemia is a medical emergency requiring urgent treatment. It most commonly is caused by malignant tumors, as in the case study, but can also be caused by advanced hyperparathyroidism or high serum levels of vitamin D. The patient described in the case study shows clinical evidence of volume contraction due to hypercalcemia-related anorexia and vomiting. His elevated serum concentrations of urea nitrogen and creatinine reflect intravascular volume depletion and hypercalcemia-induced reduction of renal perfusion. He is also likely to have irreversible renal damage as a result of nephrocalcinosis. His central nervous system depression is most likely a result of hypercalcemia, but other central nervous system disorders such as cerebral metastases should be considered. Appropriate treatment would include intravenous fluids to correct volume depletion, dilute extracellular fluid calcium, and promote renal calcium excretion. Before waiting for the effects of volume expansion, the first dose of an inhibitor of bone resorption should be given. The agent of choice now (this may change when second-generation bisphosphonates become available) is plicamycin. Etidronate is a reasonable second choice. Because both drugs require at least 48 hours before their hypocalcemic action is manifest, calcitonin could be used to accelerate the rate of decline of the serum calcium. As the patient becomes more alert, weight-bearing and ambulation should be encouraged. With this combination of therapeutic modalities, this patient's serum calcium level should be corrected within 3 to 5 days. Intermittent injections of mithramycin or etidronate could be given on an outpatient basis approximately once a week in order to maintain the serum calcium within the normal range. One of the most important aspects of treatment in hypercalcemic patients is eradication of the underlying disease, which usually calls for specific antitumor therapy, including chemotherapy, radiation therapy, or surgery. Most of the agents currently available for the correction of hypercalcemia have cumulative toxicities or are only transiently effective and, therefore, their use should be considered a temporizing measure until specific treatment directed at the primary disease takes effect.
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PMID:Management of severe hypercalcemia. 200 13

The advent of potent new bisphosphonates (diphosphonates) now makes it possible to restore and maintain normal bone turnover in many patients with Paget's disease of bone (osteitis deformans). This has necessitated a reappraisal of the indications for treatment, the ways in which disease activity and response are assessed, as well as the place of existing therapies. Measurements of urinary hydroxyproline and serum alkaline phosphatase remain the most useful markers of disease activity. Pyridinium crosslinks may prove to be more specific than hydroxyproline in the assessment of bone resorption but osteocalcin has been disappointing in monitoring the effect of treatment on bone formation. Etidronic acid (disodium etidronate), the first bisphosphonate introduced for clinical use, is a potent inhibitor of osteoclastic bone resorption but its potential is limited by the development of defective mineralisation with high dosage (10 to 20 mg/kg/day). The newer bisphosphonates, clodronic acid (clodronate) and pamidronic acid (pamidronate, APD), are free from this problem and appear able to control a wide range of disease activity. A small number of patients appear resistant to the agents but the underlying mechanism is unclear. The efficacy and safety of these bisphosphonates makes it likely that the threshold for treating asymptomatic patients will fall in the hope of preventing long term complications. These developments will lead to a reappraisal of the role of calcitonin which can now be administered by both the parenteral and intranasal routes. One focus of interest will be on the quality of the bone laid down during treatment. Meticulous radiographic studies have shown that calcitonin improves bone architecture and this may have particular relevance to the treatment of lytic disease. The relative merits of the different forms of therapy for Paget's disease need further evaluation, particularly with respect to the identification of specific advantages of individual drugs.
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PMID:Advances in the management of Paget's disease of bone. 207 98

We report serum 25-hydroxyvitamin D (25-OHD), 24,25-dihydroxyvitamin D [24,25-(OH)2D], and 1,25-dihydroxyvitamin D [1,25-(OH)2D] levels in untreated Paget's disease and the effect of treatment with either calcitonin (CT) or etidronate (EHDP) on these levels. In untreated Paget's patients serum 25-OHD (73 +/- 29 nmol/liter, n = 36, mean +/- SD) and 24,25-(OH)2D (0.3-12.9 nmol/liter, median 2.2, n = 36) levels were significantly lower than in age-matched controls (94 +/- 30 nmol/liter, n = 32, p less than 0.005, and 1.3-16.4 nmol/liter, median 5.3; n = 32, p less than 0.001, respectively). Also, the 24,25-(OH)2D levels correlated with the 25-OHD levels in the untreated Paget's patients (r = 0.56, p less than 0.01) and in the controls (r = 0.39, p less than 0.05). The percentage molar ratio of 24,25-(OH)2D to 25-OHD in Paget's patients had a median value of 3.7% (range 0.4-14.3%), which was not significantly different from controls, who had a median value of 5.6% (range 2.2-18%). There was no difference between the 1,25-(OH)2D, and immunoreactive PTH (iPTH) levels of Paget's patients and control subjects. The percentage molar ratio of 1,25-(OH)2D to 25-OHD in untreated Paget's patients (0.157 +/- 0.09%) was not significantly different from controls (0.124 +/- 0.05%) despite lower 25-OHD levels in Paget's patients. There was a significant inverse correlation between the severity of Paget's disease as measured by plasma alkaline phosphatase (AP) levels and 25-OHD levels (r = 0.392, p less than 0.02); however, 24,25-(OH)2D and 1,25-(OH)2D levels were not correlated with AP.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alterations in vitamin D metabolites during treatment of Paget's disease of bone with calcitonin or etidronate. 212 1

18 patients with Paget's disease resistant to calcitonin and/or to EHDP (ethane-hydroxy bisphosphonate) were treated with APD (disodium amino-hydroxypropylidene-bisphosphonate). The efficacy of the product was judged by the decrease in serum alkaline phosphatases and of hydroxyproline in the 24-hour urine specimen. The treatment lasted for a maximum of 6 months. Administration of APD was stopped before six months if he hydroxyproline content in the urine returned to normal (except in the case of four patients where the early interruption of treatment was due to lack of supplies). Of the 14 patients who followed the regular course of treatment, the urine hydroxyproline became normal between the first and the sixth month of treatment in 11 patients: at the start, all had a 24-hour urine hydroxyproline content equal to or less than 2.1 mmol/l 24 h (275 mg/24 h). The baseline 24-hour urine hydroxyproline in the remaining three patients was higher (3.55; 2.30; 3.28 mmol/24 h), but the level was reduced by 50% after 6 months of treatment. Alkaline phosphatases were reduced in the same proportions but the decrease occurred at a slightly later date. The residual activity was evaluated in 9 subjects who had not received any treatment for one year: in 8 out of the 9 patients the parameters used for measuring bone activity had not appreciably altered. Treatment with APD was restarted in 4 patients after a period of 12 to 36 months without therapy, and its efficacy was found to be comparable to that of the drug's first use. In all, APD demonstrated remarkable efficacy in pagetic patients resistant to both calcitonin and/or EHDP.
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PMID:[Amino-hydroxy-propylidene biphosphonate in the treatment of Paget's disease resistant to calcitonin and/or etidronate]. 249 60

Paget's disease of bone occurs in elderly people and resembles no other disease. The most frequent diagnostic errors are made when it is discovered in young adults, especially after an injury. Forms with osteolysis of the lower limbs are the most misleading, and it is better to avoid biopsies in such cases, as they may be followed by fractures. In geriatric pathology the failure to recognize that cerebral, spinal cord and cardiac manifestations are due to a specific vascular disorder of pagetic origin is a serious error as it deprives the patient of calcitonin which is the only effective therapy. Errors in the interpretation of laboratory results are easily avoided if a low hydroxyproline diet is prescribed during the week that precedes the tests. The biochemical activity should be correlated with the pagetic bone mass. Histology may wrongly suggest primary hyperparathyroidism, but patients with Paget's disease have no hypercalcaemia unless they are bedridden. Treatment relies on calcitonin and/or disodium etidronate (EHDP). Only 50% of the patients require this treatment the indications of which must carefully be weighed. EHDP may have adverse effects on bones, including fractures and pseudosarcomatous osteolysis, notably when it is given in high doses or for limited and/or osteolytic lesions. Pre and post-operative calcitonin therapy is recommended in patients undergoing surgery.
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PMID:[Paget's disease: errors to be avoided]. 249 20

Specific treatment of osteitis deformans (OD, Paget's disease of bone) is indicated when symptoms are associated with signs (biochemical or by bone scintigraphy) of active disease. OD in the base of the skull and osteolytic lesions in weight-bearing bones should be treated irrespective of symptoms. The effect of calcitonin (CT) on symptoms and skeletal blood-flow is achieved rapidly and healing of osteolytic lesions may occur. However, CT is only effective in approximately 60%, is discontinued due to side effect in 20% of patients, and must be administered parenterally. EHDP (Etidronate) is administered orally but the use of even small doses carries a risk of mineralisation defect and possibly fracture. EHDP should, therefore, be given intermittently and should not be used in osteolytic lesions of weight-bearing bones. Second-generation bisfofonates are devoid of this side effect and are very effective in OD. The effect of mithramycin is only transient and because of the risk of serious side effects the use should be restricted to severe cases of OD resistant to the other lines of treatment.
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PMID:[Treatment of Paget's osteitis deformans]. 252 92

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

In order to determine the prevalence of secondary hyperparathyroidism in patients with Paget's disease of bone, we measured serum parathyroid hormone levels (N-terminal assay) in 39 patients with a wide range of pagetic activity. All patients had normal serum calcium levels. A total of 30 patients were either untreated or had received no treatment for 6 months or longer when studied; the other 9 were receiving either salmon calcitonin (3) or EHDP (6). The results showed that in 7 of the 39 patients (18%) parathyroid hormone levels were increased above normal. These were among the most severely affected cases, as manifested by the degree of elevation of three pagetic biochemical indices: serum alkaline phosphatase, plasma bone Gla protein, and 24 h urinary hydroxyproline-creatinine ratios. Levels of 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 were normal. We examined the relationships between parathyroid hormone and each of the three pagetic indices as well as serum calcium for the entire group of 39 patients. Parathyroid hormone values did not correlate with serum calcium measurements (r = -0.241, p = NS) but did correlate significantly with serum alkaline phosphatase (r = 0.496, p less than 0.001), plasma bone Gla protein (r = 0.537, p less than 0.001), and urinary hydroxyproline (r = 0.450, p less than 0.011). We conclude that relative or absolute increases in parathyroid hormone may occur in moderately active Paget's disease, possibly in the setting of greater calcium demands during periods of increased pagetic new bone formation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Parathyroid function in Paget's disease of bone. 271 81


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