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)

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

The extent to which histomorphometric analysis of bone biopsies correlates with Ca kinetic and biochemical parameters to reflect true bone formation and resorption in adult man remains an unsolved issue. Two groups of patients with either low (osteoporosis), (n = 15) or high (Paget's disease, n = 6) bone turnover were studied before and after sodium fluoride (NaF) and diphosphonate (EHDP) treatment, respectively. Histomorphometry of iliac crest biopsies permitted precise quantitation of the osteoblast layers (SVab), osteoid seams (SVos), the number of osteoclasts (NAocl) and the Howship's lacunae (SVhl). These determinations were correlated with serum alkaline phosphatase (aPh), urinary hydroxyproline (HyPro), Ca accretion rate (Vo+), and Ca mobilization rate (Vo-). In both patient groups bone formation indices were significantly correlated: SVob/Vo+, r = 0.85; SVos/Vo+, r = 0.83; and aPh/Vo+, r = 0.97. Provided that bone matrix formation and mineralization progess at the same rate, bone formation may be assessed by measuring either aPh, Vo+, SVob, or SVos. From these correlations it is not possible to draw any conclusions regarding the absolute "true" value of bone formation, be it in terms of Ca kinetics, alkaline phosphatase, or histomorphometry. However, since Vo+ retains its proportionality to all the other bone formation parameters tested, the so-called "slow exchange," which refers to pure physicochemical Ca exchange processes in the bone mineral, does not perturb Vo+ in an unsystematic way. Vo+ as well as aPh and histomorphometric indices are thus reliable, though not absolute indices of bone formation. Bone resorption indices correlated less well than bone formation indices: NAocl/Vo-, r = 0.68 and SVhl/Vo-, r = 0.63 with both groups. In the osteoporotic group, a negative correlation existed between the empty Howship's lacunae SVhe and Vo+, r = -0.62. Consequently, the overall extent of Howship's lacunae SVhl is influenced both by bone resorption and bone formation. On the other hand, the best correlation of HyPro was with the sum of Vo+ and Vo-, r = 0.97, confirming that HyPro is a sensitive index for the change of bone turnover.
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PMID:Bone remodeling and calcium metabolism: a correlated histomorphometric, calcium kinetic, and biochemical study in patients with osteoporosis and Paget's Disease. 40 1

Subjects (109) with symptomatic Paget's disease of bone were treated with 5, 10, or 20 mg of sodium etidronate (EHDP)/kg body weight - day for 6 to 24 months. Significant decreases in serum alkaline phosphatase and urinary hydroxyproline were noted after 6 months of therapy; no significant further improvement resulted after prolonged therapy. Some patients maintained biochemical remission after withdrawal of EHDP but others showed a relapse, related primarily to the pretreatment severity. Clinical improvement was noted in 61% of the patients. Similar findings were seen after a second course of EHDP. No side-effects were noted in patients treated with 5 mg of EHDP/kg body weight - day. In patients treated with 10 or 20 mg of EHDP/kg body weight - day, severe diarrhea, bone pain, and nontraumatic fractures were noted in 3, 13, and 12 patients respectively. Quantitative histomorphometry showed mineralization delay in patients receiving 10 or 20 mg of EHDP/kg body weight - day but not in those receiving 5 mg/kg body weight - day. Five milligrams of EHDP/kg body weight - day was effective and appears to be safer than the higher doses.
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PMID:Sodium etidronate in the treatment of Paget's disease of bone. A study of long-term results. 41 50

Bone scanning with 99mTc-Sn-HEDP, radiographic skeletal survey and determination of plasma acid and alkaline phosphatase values were carried out in a consecutive series of 90 untreated patients with carcinoma of the prostate. 99mTc-Sn-HEDP provided satisfactory bone imaging and was convenient in use. The addition of bone scanning to radiographic survey increases the detection rate of skeletal metatases by 16%. Radiography increases the accuracy of bone scanning by identifying false positive scans due to benign disease and false negative scans when there are diffuse symmetrical bony metastases. The plasma phosphatases alone are less accurate staging tests. The acid phosphatase data support the validity of scan positive--X-ray negative findings. Bone scan abnormalities due to secondary deposits usually precede elevation of plasma alkaline phosphatase.
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PMID:Bone scanning and plasma phosphatases in carcinoma of the prostate. 75 55

Enzymes have been proposed as tissue receptors that bine 99mTc-stannous diphosphonate and its analogs. Incubation of diphosphonate with several enzymes demonstrated inhibition of acid and alkaline phosphatase activity but showed no effect on glutamic oxalacetic transaminase and lactate dehydrogenase activity. Complete reversal of the diphosphonate-induced inhibition of alkaline phosphatase activity occurred when calcium ion was added to the reaction. The specificity of calcium to induce reversal was dispelled when magnesium ion gave identical results. Diphosphonate-induced inhibition of acid phosphatase, however, was not reversed by calcium or magnesium.
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PMID:Enzymatic inhibition of diphosphonate: a proposed mechanism of tissue uptake. 81 72

16 patients suffering from Paget's disease were studied before, during and after 3 or 6 month treatment with disodium ethydronate (EHDP) per os. An appreciable improvement in pain symptomatology was noted and at times an evident improvement in audiometry; from the metabolic viewpoint there was a fall in serum alkaline phosphatase and urinary excretion of calcium and hydroxyproline. A study of radiocalcium kinetics demonstrated a reduction in the exchangeable calcium pool and the fractional turnover rate. Histological examination following needle biopsy of the iliac crest showed evident diminution in the active bone cell population (osteoclasts, osteoblasts) and, in certain cases, appearance of osteoid borders.
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PMID:[Treatment of Paget's disease with diphosphonate (disodium ethydronate)]. 81 5

Scintigraphic and roentgenological studies in 9 patients, treated for Paget's disease, were evaluated before and during treatment and related to the values of serum alkaline phosphatase. On the initial studies--before treatment--25 lesions were found on both scintigram and roentgenogram. One lesion--proven by biopsy--was only seen on the scintigram. The roentgenograms showed no changes during this period, ranging from 6-16 months, except for one lesion with dubious progression. The scintigrams, carried out using 99Tcm-EHDP, showed both a qualitative and quantitative improvement in 7 cases. The ratios of radionuclide accumulation in Pagetoid bone and normal bone corresponded well with the values of serum alkaline phosphatase. In 4 out of 9 cases, however, the scintigram still demonstrated pathologic uptake of radioactivity, while serum alkaline phosphatase levels had dropped to normal values. It is concluded that bone scintigraphy may be of value for the follow up of patients under treatment for Paget's disease.
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PMID:Evaluation of scintigraphic and roentgenologic studies in Paget's disease under treatment. 82 Oct 96

10 patients with active symptomatic Paget's disease of bone have been treated for 6 months with disodium etidronate (EHDP) at a dose of 20 mg/kg/day. A statistically significant fall in the serum levels of alkaline phosphatase and urinary hydroxyproline was observed. However, only 2 patients experienced a significant reduction of bone pain. 6 patients were partially improved and 2 patients showed no change. Iliac crest biopsies after treatment demonstrated dimunution of the abnormal structure of the pagetic bone, but also a considerable increase in unmineralized osteoid borders. The future potentialities for treatment of Paget's disease are discussed.
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PMID:[Treatment of 10 cases of symptomatic Paget's disease with etidronate (EHDP)]. 82 10

Ethane-1-hydroxy-1, 1-diphosphonate (EHDP) was administered in a dose of 20 mg/kg/d to 21 patients with symptomatic Paget's disease. All patients were treated for 6 months and then followed for an additional 6 months. There was a striking decline in serum alkaline phosphatase and urinary hydroxy-proline excretion observed after 3 months of therapy which was not significantly improved in the succeeding 3 months. Concomitantly there was marked improvement in clinical symptoms and bone scans. Following cessation of therapy, continued biochemical and clinical evidence of remission persisted. Several patients on repeat treatment with EHDP appeared to respond promptly. Side effects were minimal except for a possibly related osteomalacia and increased incidence of pathologic fractures.
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PMID:Diphosphonate treatment of Paget's disease. 97 46

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


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