Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

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

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 purpose of this study is to investigate the use of a three-phase bone scan for early detection of HO formation and as a method of evaluating Didronel treatment. A marked vascular blush and blood pool was noted about the hips sometimes with a normal bone scan and normal X-ray of the hips. This appeared to represent the precursor phase of HO formation since, on repeat scans, the bone scan showed accumulation of the bone-seeking radionuclide usually in 2 to 4 weeks and the X-ray revealed ossification. Fifty-two patients treated with Didronel between October 1978 and December 1979 were reviewed to determine the value of Didronel treatment. There were 23 patients in the series who either showed HO by X-ray on admission or developed HO on follow-up X-rays before beginning Didronel therapy. A three-phase bone scan revealed increased vascularity and accumulation of radioactivity on the bone scan in all areas of ossification on the X-ray and in some areas that did not appear to be involved. The other 29 patients had serial three-phase bone scans, X-ray study, and an alkaline phosphatase determination at approximately 2-week intervals. Didronel treatment was started as soon as the precursor phase of HO was demonstrated on the three-phase bone scan in most of these patients. Nine have not developed ossification that could be seen in X-rays during 3 months of continuing study. Six patients seen at follow-Up during the past year had known HO of 4 to 7 years duration. The three-phase bone scan was used to predict the maturity of HO in these patients. Our study in indicates that increased vascularity precedes rather than being secondary to HO formation as is suggested in the literature. Didronel treatment appears to be most effective if initiated during this precursor phase.
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PMID:The use of the three-phase bone scan in the early diagnosis of heterotopic ossification (HO) and in the evaluation of Didronel therapy. 621 9

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

The presentation of Paget's disease varies from a painful or deforming skeletal affliction to an asymptomatic disorder diagnosed on routine biochemical or radiological assessment. When involvement of the peripheral skeleton by Paget's disease is extensive, the clinical diagnosis is usually clear. Affected bones are thickened and deformed and the overlying skin is warm. Bone pain is sometimes severe and malignant change rarely occurs. The new bone formed is structurally abnormal and is consequently liable to deformity and fractures. Serum alkaline phosphatase concentrations and urinary hydroxyproline excretion are raised. Characteristic X-ray changes are seen. Paget's disease should be treated when it causes skeletal pain and tenderness, or when there are neurological symptoms, fractures, marked deformities, or other complications. New therapeutic agents offer both symptomatic relief and some control of the basic disease process. Simple analgesics should be tried before proceeding to the anti-osteoclastic agents, calcitonin, diphosphonates and mithramycin. All are effective in relieving bone pain and improving biochemical indices. The major advantage of the diphosphonates lies in their oral usage and thus, the number of patients who nowadays require calcitonin is small. The majority of patients should be commenced on a course of diphosphonate therapy (EHDP in most instances), but if clinical response is unsatisfactory calcitonin should be tried. Mithramycin should be reserved for special indications e.g. an elderly patient with severe disabling pain.
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PMID:Therapeutic progress--review VII. The medical treatment of Paget's disease. 622 Oct 33

Ten patients with severe Paget's disease of bone and serum alkaline phosphatase (sAP) greater than 900 IU/l were treated for six months with the oral diphosphonate APD, (3-amino-1-hydroxypropylidene-1, 1-bisphosphonate). By the end of the treatment period there was a reduction in the log mean urine hydroxyproline (uHP) and the log mean sAP of 92% and 87% respectively. In four patients both sAP and uHP fell to within the normal range and remained normal for at least six months after therapy was stopped. Bone scintigraphy showed a fall in 99mTc-MDP uptake in sites of active Paget's disease in all patients and histomorphometry showed no increase in osteoid. Repair of radiological osteolytic lesions was observed in 6/6 patients and progression of tibial osteolytic wedges was arrested in 5/5 patients and reversed in four. This improvement persisted six months after completion of therapy but further wedge progression occurred in one patient whose urine HP remained elevated. There were no serious effects though five patients complained of nausea. The clinical and biochemical responses to APD were equivalent to those observed in the same patients during a previous six month course of combined therapy with human calcitonin (CT) + EHDP except that there was additional biochemical and radiological evidence of bone healing. This study confirms PAD as an effective treatment of severe Paget's disease of bone.
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PMID:Effective oral treatment of severe Paget's disease of bone with APD (3-amino-1-hydroxypropylidene-1,1-bisphosphonate); a comparison with combined calcitonin + EHDP (1-hydroxyethylidene-1,1-bisphosphonate). 644 63


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