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

In order to determine the prevalence of secondary hyperparathyroidism in patients with Paget's disease of bone, we measured serum parathyroid hormone levels (N-terminal assay) in 39 patients with a wide range of pagetic activity. All patients had normal serum calcium levels. A total of 30 patients were either untreated or had received no treatment for 6 months or longer when studied; the other 9 were receiving either salmon calcitonin (3) or EHDP (6). The results showed that in 7 of the 39 patients (18%) parathyroid hormone levels were increased above normal. These were among the most severely affected cases, as manifested by the degree of elevation of three pagetic biochemical indices: serum alkaline phosphatase, plasma bone Gla protein, and 24 h urinary hydroxyproline-creatinine ratios. Levels of 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 were normal. We examined the relationships between parathyroid hormone and each of the three pagetic indices as well as serum calcium for the entire group of 39 patients. Parathyroid hormone values did not correlate with serum calcium measurements (r = -0.241, p = NS) but did correlate significantly with serum alkaline phosphatase (r = 0.496, p less than 0.001), plasma bone Gla protein (r = 0.537, p less than 0.001), and urinary hydroxyproline (r = 0.450, p less than 0.011). We conclude that relative or absolute increases in parathyroid hormone may occur in moderately active Paget's disease, possibly in the setting of greater calcium demands during periods of increased pagetic new bone formation.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Parathyroid function in Paget's disease of bone. 271 81

Hyperphosphatasia, or hereditary bone dysplasia with hyperphosphatasaemia, is a rare genetic disorder which is characterised by failure to transform woven into lamellar bone. Clinical, radiological and histological features establish the diagnosis, fractures, deformities, diffuse sclerosis on radiographs and high serum alkaline phosphatase being characteristic. We report the case of a 27-year-old man with follow-up at the same hospital for 20 years. Attempts at treatment with calcitonin and disocium etidronate (EHDP) failed, but stapling of the growth plates at the knee was successfully performed. Transverse "brittle" fractures of the humerus, lower leg and ribs healed normally, but internal fixation and late bone grafting were required for a subtrochanteric stress fracture of the femur at the age of 24 years. At present the patient has no clinical problems and leads a normal life.
 ...
PMID:Idiopathic hyperphosphatasia with dermal pigmentation. A twenty-year follow-up. 300 27

Paget's disease of bone is now regarded as a slow virus disease of the skeleton presenting with localized manifestation. The affected areas show increased turnover with irregular structure (mosaic pattern in histology). The bones are thickened but have decreased mechanical strength. The disease most frequently affects the pelvis, femora, and tibiae, followed by the calvarium, the lumbar vertebrae and others. Diagnosis is made by X-ray examination. The differential diagnosis is rarely so difficult that a bone biopsy is required. Bone scintigraphy reveals asymptomatic lesions. Alkaline serum phosphatase mirrors the activity of the disease. Indications for treatment are pains, bending, deformities, fractures, skull base involvement, nerve damage and very high alkaline phosphatase. Calcitonins and bisphosphonates are used for treatment. Single-agent therapy reduces alkaline phosphatase to 50% of the initial level. If more intensive treatment is desired, a combination of calcitonin and EHDP can be used. Paget's sarcoma develops in less than 1% of patients with Paget's disease of bone; it is uncertain whether this complication can be prevented or delayed by the therapeutic regimens currently in use.
 ...
PMID:[Paget's disease of the skeleton]. 305 12

12 patients with symptomatic Paget's disease of bone were treated with the diphosphonate EHDP during a 6 month period and underwent a follow up of 12 months. 6 patients received a daily dose of 5 mg/kg, 6 patients a daily dose of 10 mg/kg. All patients reported a remarkable improvement of their clinical symptoms. The decline of the serum-alkaline-phosphatase level served as an objective criterium for reduced bone turn-over metabolism. After three months of treatment with the high dose of EHDP the serum level of the alkaline phosphatase was reduced to 52% of the initial value. After 6 months of therapy a similar good result was achieved with the lower dose of EHDP. The serum alkaline-phosphatase level remained low up to 12 months after cessation of therapy in both groups of patients. So far similar long periods of remission have not been achieved by calcitonin, which is considered to be the standard therapy of Paget's disease. Another advantage of EHDP over calcitonin is the oral route of application. If a fast initial effect is desired, a daily dose of 10 mg/kg of EHDP should be used over a period of 3 months instead of the usually recommended dose of 5 mg/kg.
 ...
PMID:[Long-term experience using EHDP (ethylidene-1-hydroxy-1,1-diphosphonate) in the treatment of Paget's disease]. 310 38

Nineteen patients with Paget's disease and four patients with hypercalcemia of malignancy underwent hypocalcemic therapy with etidronate disodium (etidronate) administered intravenously. The dosage for patients with Paget's disease was 4.3 mg/kg/day, infused on each of seven consecutive days. Nine of the 19 patients also received oral etidronate 5 mg/kg/day for three months after administration of intravenous therapy. Etidronate administered orally sustained the decreases in urinary hydroxyproline produced by the infusions, whereas levels returned to pretreatment values in most patients receiving only the intravenously administered drug. Serum alkaline phosphatase levels were not reduced in the 10 patients receiving only intravenously administered etidronate, but they declined by approximately 50 percent in the nine patients who received the additional orally administered etidronate. Transiliac-crest bone biopsy specimens obtained three months after intravenous therapy revealed a regular lamellar structure, compared with the characteristic woven pattern of pagetic bone. In all four patients with hypercalcemia of malignancy, normocalcemia was achieved by the 10th day of treatment using a dosage of 4.3 mg/kg/day. Oral etidronate therapy was beneficial in maintaining normocalcemia.
 ...
PMID:Intravenous disodium etidronate therapy in Paget's disease of bone and hypercalcemia of malignancy. Effects on biochemical parameters and bone histomorphometry. 310 38

Quantitative bone scans were performed with 99mTc-EHDP in 170 untreated pagetic patients (93 men, 77 women; mean age, 65.4 years). The distribution of 863 pagetic skeletal locations was analyzed. Bone scans demonstrated 8.3% more pagetic sites than roentgenograms. The extent of Paget's disease was evaluated in each patient by a scintigraphic skeletal index. This index correlated with serum alkaline phosphatase (SAP) and urinary hydroxyproline (HyPro) levels, and also with hypocalcemic acute response to calcitonin. The correlation of SAP with an index of activity (extent index adjusted by uptake ratios) was better than with the nonadjusted index. Only 30.6% of pagetic sites were responsible for clinical symptoms. No correlation was found between age and skeletal index of the disease.
 ...
PMID:Skeletal distribution and biochemical parameters of Paget's disease. 310 64

To examine whether either of the two known active vitamin D metabolites 1,25(OH)2D3 or 24,25(OH)2D3 could reverse the mineralization defect induced by 1-hydroxyethylidene-1,1-bis phosphonate (EHDP), a model of EHDP-induced rickets was used. Rats at the age of 31 days were injected for 10 consecutive days with EHDP (10 mg/kg). Other littermates were treated with a combination of EHDP and either 1,25(OH)2D3 or 24,25(OH)2D3 or were treated following 10 days of EHDP, with either of the vitamin D metabolites for an additional 72 hr. Samples of cartilage fluid (Cfl) and of blood were removed prior to sacrifice for biochemical studies of some parameters of calcification. These parameters were correlated with the results of light and electron microscope studies of growth plate cartilage and bone. EHDP-treated rats revealed signs of typical rickets, manifested by widened growth plates and impaired bone mineralization. Transmission electron microscope (TEM) examination revealed matrix vesicles distributed throughout the growth plate; however, there appeared to be an arrest of the spread of the crystals at the provisional zone of calcification. Treatment with either 1,25(OH)2D3 or 24,25(OH)2D3 failed to reverse the rachitic condition of the animals. Serum calcium blood levels were elevated in the 1,25(OH)2D3 and EHDP-treated group. 1,25(OH)2D3 and 24,25(OH)2/D3 further increased the already elevated serum alkaline phosphatase levels observed in EHDP rats, although the increase observed with 1,25(OH)2D3 was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:EHDP-induced rachitic syndrome in rats is not reversed by vitamin D metabolites. 312 78

The biochemical responses to salmon calcitonin (SCT: 100 MRC units thrice weekly) and disodium etidronate (EHDP: 400 mg daily) alone and in combination for 6 months were compared in 72 patients with symptomatic Paget's disease of bone unresponsive to simple analgesic agents. SCT produced a 53% reduction in alkaline phosphatase (AP) and a 38% reduction in 24 h urinary hydroxyproline excretion (HYPRO). The response to EHDP was not significantly different--56% reduction in AP and 48% reduction in HYPRO. Their use in combination produced a significantly greater reduction of 71% in AP (P less than 0.002) and 69% reduction in HYPRO (P less than 0.0001). In those that remained symptomatic with increased disease activity treatment for longer than 6 months had a unpredictable effect and normal bone turnover was rarely achieved. Once therapy was withdrawn AP and HYPRO increased rapidly in those given SCT alone, returning to initial levels within 6 months. More sustained control of disease activity was achieved in those given EHDP either alone or with SCT but the combination retained the advantage obtained during treatment. Combinations of SCT + EHDP may find a place in the treatment of very active Paget's disease.
 ...
PMID:Biochemical response to combination of disodium etidronate with calcitonin in Paget's disease. 312 15

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.
 ...
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.
 ...
PMID:[Effects of etidronate disodium (EHDP) on urogenital malignancies with bone metastasis: a multicentered collaborative evaluation]. 313 34


<< Previous 1 2 3 4 5 6 Next >>