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)

Pamidronate is one of several powerful bisphosphonates able to produce prolonged remissions of Paget's disease. This study examined to what extent bone scan changes parallel the clinical response and whether there is variability in the behavior of individual lesions. Twenty-five patients with pagetic bone pain for more than 2 yr were examined with bone scintigraphy before and on average 8 mo after six 30-mg infusions of pamidronate given weekly. Serum alkaline phosphatase and urinary hydroxyproline-to-creatinine ratios were measured before and 6 mo after treatment. A second course of pamidronate was given to 13 patients who had clinical or biochemical relapse. Of 136 pagetic lesions, 13 (10%) completely resolved, 90 (65%) improved and 33 (24%) remained unchanged. There was no significant difference in response between bony sites, although less active lesions were more likely to resolve completely. In conclusion pamidronate has a powerful effect on bone scan appearances in Paget's disease. Most lesions improve but complete resolution is uncommon. Less active lesions are more likely to resolve and are less likely to require further therapy.
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PMID:Bone scintigraphy following intravenous pamidronate for Paget's disease of bone. 151 30

We describe the case of a 38-year-old woman with 24 years of progressive skeletal deformities. Radiologic survey showed evidence of generalized skeletal involvement. She presented with secondary osteoarthritis, and her hands showed Heberden's and Bouchard's nodes. Light microscopic examination showed many reversed lines in the trabeculae and increased bone resorption and bone forming areas. On electron microscopic study there were intranuclear inclusions in the osteoclasts. To our knowledge, she is the oldest patient described in the English literature, and the first treated with (3-amino-1-hydroxypropilidene)-1,1 biphosphonate (Pamidronate). She showed a decrease in serum alkaline phosphatase, urinary hydroxyproline. Clinical variables showed good response to medication.
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PMID:Chronic idiopathic hyperphosphatasia. Report of a case treated with pamidronate and a review of the literature. 159 90

We have conducted an open, prospective study to investigate the efficacy of a single 60 mg infusion of pamidronate as alternative therapy in 15 subjects with severe Paget's bone disease refractory to calcitonin. Disease activity was assessed with a visual-analogue score of symptom severity, plasma alkaline phosphatase and quantitative estimation of 99mTc-methylene biphosphonate uptake on bone scan. All indices of disease activity fell after pamidronate, reaching a nadir at 3 months. Although disease activity increased thereafter, only 3 subjects required retreatment within 12 months. Plasma calcium fell after 3 days and remained below baseline levels for 6 months associated with evidence of secondary hyperparathyroidism. Pamidronate was well tolerated; femoral neck fractures occurred in 2 subjects with severe local Paget's disease but were unlikely to be due to the drug. We conclude that pamidronate is an effective and promising alternative for treatment of patients with severe Paget's disease no longer adequately controlled by calcitonin. Calcium supplementation may be prudent to prevent secondary hyperparathyroidism associated with the use of this agent.
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PMID:Single-dose intravenous pamidronate is effective alternative therapy for Paget's disease refractory to calcitonin. 181 3

Several agents are available for treatment of Paget's disease of bone, but their long-term use may be limited by resistance or adverse effects. I have treated two patients with exceptionally severe polyostotic Paget's disease (serum alkaline phosphatase values 25- to 30-fold above normal), in whom salmon calcitonin, sodium etidronate, and plicamycin each had become ineffective or could not be used. Pamidronate (3-amino-1-hydroxypropylidene-1,1-bisphosphonate) decreased serum alkaline phosphatase to normal or near-normal values and almost completely relieved symptoms, without recognizable adverse effects, except for transient mild hypocalcemia. The symptomatic and biochemical responses were maintained through 2 years of treatment and for more than 6 months after the treatment was discontinued. Thus, pamidronate can be very effective in severe, resistant cases of Paget's disease. Further study of this potent agent is needed to define the optimum regimen for maximum effectiveness and minimal long-term toxicity.
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PMID:Successful treatment of resistant Paget's disease of bone with pamidronate. 259 45

Bisphosphonates are strong inhibitors of bone resorption and have become the treatment of choice of Paget's disease of bone. Second generation compounds such as amino-hydroxypropylene bisphosphonate (Pamidronate or APD) have not been found to impair bone mineralization, but to induce sustained remission of Paget's disease after short or medium courses. Gastrointestinal side effects may limit compliance. Therefore, 11 patients with mild but symptomatic Paget's disease of bone were treated with APD administered as a single intravenous infusion of 60 mg over 24 hours. The follow-up, with clinical and biochemical evaluations, was between 6 months and one year. Clinical improvement and normalization of biochemical parameters were observed in all patients. On average, plasma alkaline phosphatase activity fell progressively and significantly from 256 +/- 29 U/l (means +/- SEM) to 97 +/- 6 U/l after 6 months and to 102 +/- 11 U/l after one year (normal less than 120 U/l). Urinary excretion of hydroxy-proline decreased within 7 days to normal (from 4.3 +/- 0.5 mumol/lGF to 1.7 +/- 0.2 mumol/lGF, normal less than 2.2). Thereafter it remained within the normal range until one year later (1.8 +/- 0.2 mumol/lGF after 6 months and 1.9 +/- 0.3 mumol/lGF after 1 year). Side effects were negligible, with only a transient increase in body temperature in 2 patients. When bone scintigraphy was repeated after 6 months it revealed a marked decrease in the activity of the disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[A single infusion of Pamidronate (APD) in Paget's disease of bone]. 271 Nov 57

One three-day course of intravenous pamidronate sodium (3-amino-1-hydroxypropylidene-1,1-bisphosphonate), 30 mg/d, in a patient with calcitonin-resistant Paget's disease resulted in the following: marked clinical improvement within two weeks; normalization of urinary hydroxyproline value; fall of serum alkaline phosphatase value (900 to 250 U/L); a rise in serum osteocalcin value by the tenth week that returned to pretreatment levels in the 16th week; transient hypocalcemia with elevation of parathyroid hormone value; reduction in urinary calcium excretion; and improvement in bone scans. No adverse reactions occurred, with the exception of mild and transient hyperpyrexia for 48 hours during pamidronate administration. White blood cell counts did not change and serum interleukin 1 was undetectable before and after treatment with pamidronate. Pamidronate seems to be highly effective in the treatment of Paget's disease of the bone, but its profound effects on mineral and bone metabolism require close monitoring during the short-term period of intravenous treatment.
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PMID:Pamidronate sodium and calcitonin-resistant Paget's disease. Immediate response in a patient. 278 43

Although the effects of the bisphosphonates on resorption have been well documented, their effects on bone formation are not as clear. Therefore, this investigation was undertaken to elucidate the role played by bisphosphonates in the regulation of bone formation in vitro. To evaluate bisphosphonate-mediated regulation of bone formation in vitro, the effects of two drugs, ethane-1-hydroxy,1-diphosphate (Etidronate) (HEBP), and the second-generation bisphosphonate, disodium-1-hydroxy-1-aminopropylidine-1,1-diphosphate (Pamidronate) (APD), were assessed in the chick periosteal osteogenesis (CPO) model. In this study, drug-induced changes in alkaline phosphatase were assessed at the cellular level by means of quantitative fluorescence histochemistry. Cellular proliferation was quantified by means of autoradiography ([3H]thymidine). Mineralization and matrix production were measured morphometrically, whereas collagen synthesis and degradation were measured biochemically. The data suggest that in addition to their effects on bone resorption, the bisphosphonates have marked and direct effects on bone formation and other parameters of osteogenesis. HEBP may affect cellular proliferation (75-80% reduction, p < 0.05) in zones distant from bone; alkaline phosphatase positive cell numbers were increased in the osteoblastic layer of cells (twofold relative to control, p < 0.05) in 12-day cultures. HEBP, but not APD, prevented mineralization-induced suppression of matrix synthesis in early stages of culture. In 6-day cultures induced to mineralize with beta-glycerophosphate, (GP) cotreatment with HEBP induced a 70% increase in collagen synthesis. In addition, degradation of collagen in the CPO cultures was inhibited by HEBP (25%) and to a lesser extent by APD (8%). Although there were no differences in bone-osteoid areas measured in 12-day cultures treated with various regimens of bisphosphonate or GP, a clear increase in bone-osteoid area was detected in 6-day cultures treated with GP and HEBP as compared to GP only. This may suggest that initially, osteoblasts may be induced to synthesize increased volumes of bone matrix when mineralization is inhibited (e.g., with HEBP), but that over time the osteoblasts make the same amount of matrix. Taken together, these findings indicate that whereas the bisphosphonates do have well-documented effects on bone resorption, their effects on bone formation may also be important.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effects of bisphosphonates APD and HEBP on bone metabolism in vitro. 762 21

Pamidronate is a second generation bisphosphonate that has been used in Europe for the treatment of Paget's disease of bone for several years. It relieves pain and reduces bone turnover in Paget's disease. To assess the effects of pamidronate on Paget's disease of bone, the authors treated 28 patients, aged 45 to 87, with longstanding Paget's disease for a period of 4-18 months. Parameters measured included pain and serum alkaline phosphatase, urinary hydroxyproline, and ionized calcium concentrations. Patients were organized into two groups. Patients in the first group had initial alkaline phosphatase concentrations below 215 U/L, which decreased to normal after one dose of pamidronate. Patients in this group also experienced symptomatic improvement. Patients in the second group had initial alkaline phosphatase values greater than 240 U/L, which did not normalize after 2-11 pamidronate infusions. More patients in this latter group did not report symptomatic improvement. Patients in the second group also had a higher incidence of hypocalcemia. It is concluded that there is a clear relation between initial alkaline phosphatase level in Paget's disease and response to treatment with pamidronate. The authors' current protocol for treating patients with pamidronate is based on this relation. Because pamidronate proved most effective when used in mild Paget's disease, therapy probably should be instituted early in the course of disease.
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PMID:Effects of intravenous pamidronate therapy on Paget's disease of bone. 794 81

The skeletal metabolic effects of androgen withdrawal have been studied in men with metastatic prostate cancer by using a combination of sequential biochemical measurement, quantitative and subjective bone histology and selective osteoclast inhibition with the bisphosphonate Pamidronate. Results showed dissociation in the levels of biochemical markers of bone formation (alkaline phosphatase and osteocalcin) following castration, whilst markers of bone breakdown (urinary hydroxyproline creatinine (OHP) and calcium excretion (CaE)) increased in the majority of patients. The osteolytic response was inhibited by the bisphosphonate Pamidronate (Aminohydroxypropylidene Bisphosphonate (APD)), thus confirming its osteoclastic origin. Histomorphometry of tumour free bone showed an acute drop in bone volume following surgery (p < 0.05). This effect was blocked by Pamidronate suggesting that osteoclastic activity surges immediately following castration, contributing to the acute bone loss. Histology of metastatic areas showed a marked diminution in bone volume due to decreased osteoblast activity and markedly increased osteoclast mediated osteolysis. In 56% of biopsies there were residual foci of active tumour within metastatic areas after orchidectomy. These disturbed metabolic bone activity in a typically localised manner.
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PMID:The effects of orchidectomy on skeletal metabolism in metastatic prostate cancer. 815 20

Pamidronate (APD) is a bisphosphonate that prevents bone loss from a variety of causes. We studied the role of APD in preventing thyroid hormone-induced bone loss. A total of 32 rats were assigned to one of four treatment groups: (1) -APD/triiodothyronine (-T3), (2) -APD/+T3, (3) +APD/-T3, or (4) +APD/+T3. In the first of two studies, the rats received APD for the first week and T3 for the second week, and then their blood was analyzed for alkaline phosphatase and osteocalcin. Alkaline phosphatase and osteocalcin were significantly higher (p < 0.05) in hyperthyroid rats (-APD/+T3, 3.9 +/- 0.25 mukat/liter and 23 +/- 1.6 nM, respectively) than in control animals (2.53 +/- 0.28 mukat/liter and 18.3 +/- 1.4 nM, respectively). Hyperthyroid rats pretreated with APD (+APD/+T3) had levels of alkaline phosphatase and osteocalcin no different from controls. In a second study, rats were divided into the same four groups, except they received APD/placebo and T3/placebo concomitantly for 3 weeks. At the end of the study, bone mineral density (BMD) of the femur, spine, and whole body was measured by dual-energy x-ray absorptiometry, and the calcium content of the femora was measured directly. In hyperthyroid rats (-APD/+T3) BMD was significantly lower than in controls in the spine (0.201 +/- 0.004 versus 0.214 +/- 0.002 g/cm2, p < 0.05) and femur (0.204 +/- 0.003 versus 0.218 +/- 0.002, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Parenteral pamidronate prevents thyroid hormone-induced bone loss in rats. 825 63


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