Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.3.1 (alkaline phosphatase)
47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Response to acute and chronic administration of calcitonin and calcium and of biphosphonates (EHDP) was evaluated in 14 patients with Paget's bone disease who were grouped on the basis of homogeneous disease activity, as appraised by bone involvement and alkaline phosphatase and hydroxyproline levels. At first, 100 MRC U of calcitonin followed 4 hours later by 500 mg of elemental calcium were given for 10 days; a significant (p less than 0.001; paired and unpaired Student t test) reduction in alkaline phosphatase (-25%) and hydroproline (-55%) was observed. Subsequently, 5 mg/kg/day of EHDP was given for 20 days. Both parameters increased to levels similar to basal values. These increases were significant (p less than 0.001 for the paired and unpaired Student test) compared with those obtained after calcitonin administration; alkaline phosphatase rose +27% and hydroxproline +135%. After this, patients were divided into 2 groups (A and B). Group A was treated with calcitonin and calcium, at the dosage indicated above, for 10 days a month during 6 months. Group B continued with the same protocol with the addition of EHDP for the 20 days during which calcitonin and calcium were not given. The results of 6 months of treatment showed that calcitonin was more active and suggested that EHDP diminishes hormonal effects. These results also demonstrate a short-term absence of EHDP activity.
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PMID:Biochemical assessment of acute and chronic treatment of Paget's bone disease with calcitonin and calcium with and without biphosphonate. 313 91

Clinical effects of EHDP on relief of bone pain, changes in bone lesions on X-ray and 99mTc-MDP scintigram and performance status were investigated in 19 patients with bone metastasis from urogenital cancers (4 renal cell cancers, 1 renal pelvic cancer, 4 bladder cancers and 10 prostatic cancers). EHDP was effective in relieving bone pain in prostatic cancer patients with osteoblastic lesions. Bone lesions on X-ray and 99mTc-MDP scintigram were slightly improved in prostatic cancer patients with osteoblastic lesions. Administration of EHDP did not improve the performance status. Changes in laboratory data such as serum alkaline phosphatase, serum calcium and urinary total hydroxy-proline following EHDP administration indicated inhibition of osteolytic activity with no effect on bone formation in the early period of treatment (in 4 weeks) and development of both osteolytic activity and bone formation in the later period (from 8 to 12 weeks). No marked side effects were observed. EHDP seems to be effective in relieving bone pain in prostatic cancer patients with osteoblastic bone metastasis. Moreover, some diphosphonate groups including EHDP are expected to be useful to the patients with malignant hypercalcemia.
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PMID:[Effects of etidronate disodium (EHDP) on urogenital malignancies with bone metastasis: a multicentered collaborative evaluation]. 313 34

A double-blind randomized study of 29 patients with symptomatic Paget's disease was conducted comparing the clinical, biochemical, and histomorphometric responses to 3-month treatment with placebo (10 patients), low-dose disodium etidronate (EHDP) (5-7 mg/kg/day) (10 patients), and low-dose EHDP plus 1 alpha-hydroxyvitamin D3 (1 alpha D3) 0.5 mcg daily (9 patients). In placebo-treated patients no significant changes were observed in symptoms, biochemistry, or bone histomorphometry. Histologically apparent mineralization defects developed after 3 months of therapy in 90% of patients in the EHDP group, compared with 45% of patients in the EHDP/1 alpha D3 group. In 19% of the patients treated with active medication, the mineralization defects in pagetic bone were accompanied by histological evidence of continued osteoclastic resorption. The development of mineralization defects was not related to serum levels of vitamin D metabolites, alkaline phosphatase, or intestinal calcium absorption but did correlate with the occurrence of hyperphosphatemia during treatment, which was most marked in patients treated with EHDP alone. Although mineralization defects were less frequent in the EHDP/1 alpha D3 group, these patients also responded less well symptomatically, thus limiting the potential usefulness of this drug combination in Paget's disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of 1 alpha-hydroxyvitamin D3 on the mineralization defect in disodium etidronate-treated Paget's disease--a double-blind randomized clinical study. 313 73

In contrast to prevention, the therapy of manifest osteoporosis remains a clinically significant problem. So far all therapeutic attempts have yielded unsatisfying results. For this reason we have tried to achieve a positive bone balance by sequential stimulation and inhibition of the osseous metabolism. The therapy consisted of six 14-day courses with 400 units (1-38)hPTH per day and, in addition, starting with the 2nd week of PTH therapy, EHDP 5 mg per kg body weight per day for a total of 2 weeks. Already the initial therapeutic course resulted in a stimulation of decreased bone metabolism which could be documented by an increase in the calcium-47 accretion rate (six patients). An increase of the alkaline phosphatase could be noted (four patients); this, however, did not correlate with the calcium accretion. A positive calcium balance could, nonetheless, only be attained in four of eight patients within this period, while neither the alkaline phosphatase nor the kinetics would allow a prediction of this effect. Changes of the balance coincided with equal changes in the net calcium absorption. The urinary calcium excretion increased temporarily during the therapeutic phase. We were not able to detect an influence on the vitamin D metabolites. Histomorphometric studies did not demonstrate an increase in bone mass in the iliac creast after six therapeutic courses. Nevertheless, progressive deformations of vertebral bodies did not occur. We conclude that already after 2 weeks this therapeutic concept can lead to a stimulation of bone metabolism.
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PMID:Results of a stimulatory therapy of low bone metabolism in osteoporosis with (1-38)hPTH and diphosphonate EHDP. Protocol of study I, osteoporosis trial Hannover. 314 72

Dialysis osteomalacia is characterized by distinctive, although not pathognomonic, clinical and biochemical features. Symptoms and signs may include musculoskeletal pain, arthralgias, proximal muscle weakness, and spontaneous fractures. Biochemical characteristics may be hypercalcemia and normal serum alkaline phosphatase activities. Vitamin D administration may induce early severe hypercalcemia. Plasma phosphate and immunoreactive parathyroid hormone concentrations may be at any level. Only bone histology allows to establish the diagnosis of dialysis osteomalacia with certainty. Diphosphonate bone scan, however, enables to distinguish between severe osteitis fibrosa and dialysis osteomalacia. The diagnostic value of desferrioxamine administration with subsequent measurement of plasma aluminium remains to be determined. The complex interactions existing between parathyroid hormone and aluminium are not yet fully understood.
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PMID:Dialysis osteomalacia: clinical aspects and physiopathological mechanisms. 391 57

The effects of EHDP (20 mg/kd/day) and APD (4.5 mg/kg/day) given for three months to patients with severe symptomatic Paget's disease have been compared in an open trial of 17 patients. Both drugs were equally effective in producing a prompt reduction in pair scores, urine hydroxyproline, and serum alkaline phosphatase levels. The remission was maintained for a variable period after stopping treatment. Both drugs were well tolerated, and a one-month course of either drug was not effective. Comparison with published responses from previous studies indicates that EHDP given at this dose as a relatively short course is more effective than a lower dose for a longer period of time; the present study does not suggest that APD has significant advantages.
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PMID:Clinical experience with the use of two diphosphonates in the treatment of Paget's disease. 391 13

13 patients with polyosseous Paget's disease were treated for a mean period of 7 months with disodium etidronate (EHDP, ethylidene-1-hydroxy-1,1-diphosphonate); the average daily dosage was 5 mg/kg body weight. Subjectively, all patients reported a considerable improvement, in particular with regard to pain. Objectively, a significant decrease in plasma alkaline phosphatase activity and in urinary hydroxyproline excretion was observed. Bone scintigraphy showed a decreased activity of bone lesions after therapy, but no clear-cut regression was found radiologically. No serious side-effects were observed during treatment with EHDP and oral administration of the drug proved to be advantageous.
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PMID:[EHDP (ethylidene-1-hydroxy-1,1-diphosphonate) in the treatment of polyosseous Paget disease]. 392 24

This report presents clinical pictures of 11 patients with Paget's disease of bone treated at our clinic since 1977 and discusses the disease progress in seven patients who were given Elcatonin and EHDP and followed-up for a mean period of four years and eight months. All the patients responded to the drugs and the main clinical effect was disappearance of pain. They did not develop side effects which were especially a problem. Although both of the drugs exerted excellent effect on Paget's disease of bone, they have both strong and weak points with respect to administration route and side effects. These drugs should be selected with combined therapy, clinical effectiveness, side effects and other factors taken into account. Bone scintigram, serum alkaline phosphatase and urinary hydroxyproline were employed as therapeutic effect of these drugs. However, their handiness and reliability were unsatisfactory. More convenient parameters reflecting the disease activity more accurately are needed.
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PMID:[Treatment of Paget's disease of bone]. 393 94

Fifty-four patients with Paget's bone disease have been treated with the bisphosphonate APD. Twenty-six patients had not previously received treatment for Paget's disease; and 28 had been treated before with EHDP alone or in combination with calcitonin. APD was given orally in a mean dose of 500 mg daily (congruent to 6.8 mg/kg of body weight) for 4 to 12 months. Bone pain diminished or disappeared in 34 of 39 patients with symptoms. A very significant diminution of the biochemical indices of bone turnover was observed in all patients, but the responses were faster in patients who had not previously received treatment for Paget's disease. After 4 months of treatment the serum levels of alkaline phosphatase of previously untreated patients diminished from 58.8 +/- 8.0 to 20.0 +/- 3.9 KA units (P less than 0.001) and urinary excretion of hydroxyproline diminished from 108.6 +/- 16.9 to 42.4 +/- 8.3 mg/24 h (P less than 0.001). In 23 of 26 previously untreated patients the biochemical indices decreased to the normal range (complete response). A reduction of 50% or more without reaching the normal range was observed in the other 3 patients (partial response). Actuarial analysis of the duration of the effect 12 months after stopping APD disclosed that 63% of patients who had achieved a complete response but only 23% of those with a partial response were in biochemical remission. A second course of APD was administered to 11 patients. The results were as effective during the second as the first course in 9 patients, whereas 2 patients had no response to retreatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Efficacy of the bisphosphonate APD in the control of Paget's bone disease. 409 79

The main features of Paget's disease are described, together with the indications for medical treatment. A brief summary is given of the drugs available for treatment of Paget's disease with particular emphasis on sodium etidronate (EHDP, ethylidene-1-hydroxy-1, 1-diphosphonate). Sodium etidronate, given at doses between 5 and 20 mg per kilogram per day for 3-6 months, causes a progressive reduction in the biochemical abnormalities (raised plasma alkaline phosphatase and urinary hydroxyproline) and in the histological abnormalities of bone. Clinical symptoms also improve. The usual dose is 5 mg per kilogram body weight per day to be given for not longer than 6 months. Higher doses (10 and 20 mg per kilogram per day) may cause impairment of normal bone mineralisation and should be given for short periods only (1-3 months). Sodium etidronate also has a limited place in the treatment of certain disorders of ectopic calcification, notably heterotopic ossification after spinal cord injury or hip surgery. At the present time there is insufficient evidence to justify its use in the treatment of renal stones or in osteoporosis other than that due to immobilisation after spinal cord injury.
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PMID:Paget's disease of bone: diagnosis and management. 622 Jan 90


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