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)

Forty six patients suffering from Paget's disease in acute exacerbation were treated for three months with 80 u/day of synthetic salmon thyrocalcitonin. A control group of 36 patients received a placebo. A marked improvement in pain was seen in 60% of the treated patients and 15% of the placebo group (p less than 0.001). Functional impairment, when present, was also far more markedly decreased in the treated group (p less than 0.01). In comparison with the control group, the fall in hydroxyprolinuria and alkaline phosphatase levels was highly significant (p less than 0.001). This treatment is active against not only symptoms and signs, but also the biological criteria of activity of the disease. The side-effects of treatment consist above all of hot flashes (35% of cases) and nausea (24%). In only one case was it necessary to stop treatment because of intractable diarrhoea.
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PMID:[Treatment of Paget's disease with salmon thyrocalcitonin. Cooperative double-blind study]. 6 92

19 patients with Paget's disease were treated orally for 6 months with disodium dichloromethylene diphosphonate. 1600 mg/day (10 patients) significantly reduced urine hydroxyproline, serum alkaline phosphatase, urine calcium, and the number of pagetic bone osteoclasts. Tetracycline double labelling revealed undisturbed bone mineralisation. There was improvement on quantitative bone-scans and bone pain diminished. There was a transient increase in parathyroid hormone level in 13 of the 19 patients during treatment, which was associated with a high serum 1,25 (OH)2D3. No adverse clinical side-effects have been observed and biochemical remission has persisted for 9 months.
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PMID:Effects of disodium dichloromethylene diphosphonate on Paget's disease of bone. 9 Feb 15

Fifteen patients with widespread painful osseous metastases from breast cancer unresponsive to other systemic therapy were treated with mithramycin at dose levels usually used for treating Paget's disease. Ten patients had relief of pain, which was marked and rapid in onset in seven. Mobility was greatly improved in four patients. Healing of bone lesions did not occur and new lesions developed while treatment was being given. Clinical response was associated with a decrease in plasma alkaline phosphatase. Toxicity was mild and consisted of nausea in most patients and a slight decrease in platelet count in one patient. Mithramycin is a useful agent for palliation of painful bone metastases and should be considered for further trials of combination chemotherapy for advanced breast cancer with bone metastases.
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PMID:Effect of mithramycin on widespread painful bone metastases in cancer of the breast. 9 11

A significant correlation between the activity of the bone isoenzyme or serum alkaline phosphatase and the urinary hydroxyproline excretion in osteomalacia, osteoporosis, primary hyperparathyroidism with osteodystrophy, Paget's disease, secondary bone tumours, and in a control group was found (P less than 0.001). This close correlation was not observed between these variables in patients with active acromegaly. Diagnosis determined from these indices of formation and turnover of bone matrix agreed with that established by histological and histochemical examination of bone, by X-ray investigation of the skeleton, and by the radionuclear 85Sr test. The relationship between the activity of bone isoenzyme and urinary hydroxyproline excretion differed in metabolic bone diseases with a high bone turnover, in patients with osteoporosis and in patients with early osteoclastic bone metastases.
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PMID:Relationship of the activity of the bone isoenzyme of serum alkaline phosphatase to urinary hydroxyproline excretion in metabolic and neoplastic bone diseases. 10 9

Of 58 patients with Paget's disease treated with disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) in doses of 20 and 10 mg/kg/day, a group of 20 patients with the oligostotic form of the disease showed a significantly greater incidence of complications, such as worsening of bone pains, when compared with a group of 38 patients with the polyostotic disease (P less than 0.05). The group of 32 patients that received 20 mg/kg/day showed a greater although not significant incidence of clinical complications than the group of 26 patients treated with 10 mg/kg/day. Bone biopsies performed in one polyostotic and three oligostotic cases who suffered episodes of bone pain worsening during treatment with 20 mg/kg/day disclosed a severe osteomalacia. Both groups treated with 20 and 10 mg/kg showed a highly significant decrease of urinary hydroxyproline (THP) excretion and of serum alkaline phosphatase (P less than 0.01) after two and six months of treatment although the trend comparison between doses was not significant. It is suggested that the dose of EHDP should be related to the extent of the disease.
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PMID:The treatment of Paget's bone disease with sodium ethidronate. 10 28

There are probably 2.5 million patients with Paget's disease in the U.S.; 125,000 of these have severe disease meriting specific treatment. While the diagnosis can often be made by inspection, or by measurement of the temperature of involved limbs, it is often missed. Nonspecific findings include pain, headaches, deafness, heart failure, neurologic deficits and renal stones. A specific diagnosis can usually be established by radiologic examination of the skeleton and measurement of the serum alkaline phosphatase level. Bone scans are often helpful. In moderate-to-severe symptomatic disease, calcitonin limits the unregulated chaotic bone resorption and exerts highly specific and effective suppressive activity.
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PMID:Paget's disease: New treatment for an old disease. 13 63

The hypothesis that Paget's disease of bone is a low grade neoplastic process led us to use the cytotoxic antibiotic mithramycin in its treatment. The dramatic effects observed on the serum calcium and alkaline phosphatase, and urinary hydroxyproline are compatible with the concept that mithramycin is primarily toxic to osteoclasts. Subjective and objective clinical effects establish this agent as useful in the treatment of Paget's disease despite its observed toxicity to other organ systems.
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PMID:Treatment of Paget's disease of bone with mithramycin. 14 39

Nineteen patients with Paget's disease of bone were studied 7 months to 5 years after therapy with mithramycin in a dose averaging 11.5 microgram/kg body weight daily for 10 days. Thirteen patients, including 3 with the longest followup intervals, remained free of pain. Objective measures of disease activity (serum alkaline phosphatase level and 99mtechnetium pyrophosphate bone scan) were less favorable. There was no evidence of long term toxicity.
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PMID:Long term effectiveness of low dose mithramycin for Paget's disease of bone. 15 31

In ten patients with Paget's disease of bone (Group I) intramuscular injection of 50 MRC units of synthetic Salmon calcitonin (SCT) induced a marked decrease of serum calcium (-1,444 mg%), serum phosphorus (-1,06 mg%), urinary total hydroxyproline (-71%), and a marked increase of urinary cyclic AMP (+ 114%). These changes occur at maximum 6 hours after the injection with a return to the initial values after 24 hours. In six other patients with Paget's disease (Group II) the acute biological effects were of the same nature and magnitude after the injection of 100 MRC units of SCT. In this group a significant but temporary increase of the plasma parathyroid hormone level was demonstrated. The magnitude of the hypocalcemia seems proportional to the initial serum alkaline phosphatase and urinary hydroxyproline levels. After one month of treatment, the alkaline phosphatase and urinary hydroxyproline have more marked and more regular decrease in group II who received 100 MRC units of SCT daily than in group I who received 50 MRC units three times a week. The cellular mechanisms of these biological changes are discussed. A posology of two daily injections of 50 MRC units of SCT is suggested when a quick and maximum stoppage of pagetic remodeling is required.
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PMID:[Short-term biological effects of synthetic salmon calcitonin in Paget's disease. Influence of posology]. 17 38

Paget's disease usually is found in patients past the age of 40. Early presenting symptoms include headache, deafness, tinnitus, and pain due to radicular compression. The diagnosis is confirmed by radiographic features and elevated levels of serum alkaline phosphatase and urinary hydroxyproline. Bony overgrowth results in pressure on nearby soft tissues such as the brain, spinal cord, and certain peripheral nerves. The abnormally soft quality of the calvarial bone permits distortion by the weight of the brain. Dorsal inclination of the plane of the foramen magnum and the projection of the odontoid process into the posterior fossa lead to stretching of the brain stem over the odontoid process and the ventral margin of the foramen. Obstructive hydrocephalus may result. Sarcoma of the crainial vault may develop in cases of Paget's disease. Once cervicomedullary or spinal compression has occurred, surgical decompression may be necessary. Three drugs--calcitonin, disodium etidronate, and mithramycin--have been used with some benefit in the treatment of Paget's disease.
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PMID:Paget's disease and the nervous system. 21 14


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