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)

Renal bone disease was assessed for an average of 5.5 years in 9 patients on maintenance haemodialysis. The investigative methods included serial biochemical estimations, radiographic skeletal surveys and quantitative bone histology. Repeated bone mineral analyses and neutron activation analyses of a hand were also performed in order to monitor changes in skeletal calcium content. Before treatment, progressive osteodystrophy was demonstrated by all techniques. Following therapy with the vitamin D analogues, all patients noted symptomatic improvement; serum alkaline phosphatase reverted to normal and serum parathyroid hormone concentrations decreased. Radiographically, subperiosteal erosions healed while the histological features of osteomalacia and osteitis fibrosa were abolished. Both bone mineral and neutron activation analyses indicated that progressive skeletal demineralisation had been halted. However, a sustained increase in the overall mineral content of bone was not demonstrated. Thus, vitamin D therapy although improving the biochemical, radiological, and histological features of renal osteodystrophy may not restore bone mass to osteopenic bone.
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PMID:Renal osteopenia - an assessment of long-term therapy with vitamin D analogues. 23 16

Six long-term hemodialysis patients with progressive skeletal deterioration during long-term pharmacologic vitamin D2 therapy were treated for six to 12 months with oral 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) to determine its therapeutic effectiveness in vitamin D2-unresponsive osteodystrophy. On bone biopsy, three of the patients had severe osteomalacia and three showed predominant osteitis fibrosa. Previous therapies, including phosphate binders and dialysis schedules, were maintained. The three patients with osteomalacia and the two with osteitis fibrosa showed clinical deterioration. There was no significant change in serum calcium, phosphate, alkaline phosphatase, bone densitometry, immunoreactive parathyroid hormone levels or bone histology. Roentgenograms showed multiple new fractures of ribs and femoral necks in the patients with osteomalacia and increased bone resorption in two of three patients with osteitis fibrosa. 1,25-(OH)2D3 dosage had to be decreased in all patients because of hypercalcemia with a mean tolerated dose of 0.22 microgram/day. In these patients, 1,25-(OH)2D3 was not effective therapy for progressive osteodystrophy unresponsive to pharmacologic vitamin D2.
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PMID:Experience with 1,25-dihydroxycholecalciferol therapy in undergoing hemodialysis patients with progressive vitamin D2-treated osteodystrophy. 38 92

During the hemodialysis treatment of 543 uremic patients for 10 years, significant complications concerning metabolic calcium disturbances, subperiosteal resorption, calcification of soft tissue or peripheral vessels, and fractures were noted. Significant elevation of alkaline phosphatase was induced for 5 years under hemodialysis using 5.0--6.0 mg/dl dialysate calcium, but not under 7.5 mg/dl dialysate calcium. Plasma immunoreactive parathyroid hormone (iPTH) values were abnormally high with a few exceptions, without relationship to serum calcium levels. Among the patients with chronic renal failure on dietary control, osteomalacic changes were predominant, but their iPTH values were not always elevated. When the patients were treated for a long time with hemodialysis, the mixed type of osteomalacia and osteites fibrosa appeared. Administration of dihydrotachysterol and 1 alpha-hydroxycholecalciferol to the patients on hemodialysis changed the mixed type of osteomalacia and osteitis fibrosa to the osteomalacic type with the marked reduction of osteoid seam thickness.
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PMID:Azotemic renal osteodystrophy; clinical features and bone pathology. 46 54

The effects of 25-OHD3 on renal osteodystrophy have been studied in 6 patients on maintenance haemodialysis. Administration of 25-OHD3, 50 microgram/day, did not improve biochemical data and intestinal absorption of calcium. With a dose of 100 microgram/day in all patients an increase in blood calcium levels eventually reaching hypercalcemic values was observed. In two cases a fall in alkaline phosphatase toward normal values was noted. In the same cases the treatment-induced hyperphosphatemia, uncontrolled by AI(OH)3 supplementation and similarly high iPTH levels were observed. In two cases repeated bone biopsy following 8 months treatment and not show substantial improvement of bone lesions. In one case addition of 1,25-(OH)2D3 to the treatment with 25-OHD3 led to a more rapid improvement in biochemical parameters and iPTH serum levels. Doses of 25-OHD3 capable to correct blood calcium levels and intestinal absorption of calcium, may have minimal benefit on the osteitis fibrosa component of the bone lesion.
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PMID:25-hydroxycholecalciferol in the treatment of renal osteodystrophy in haemodialysed patients. 51 68

Patients with severe symptomatic renal osteodystrophy were treated with either 1,25(OH)2D3 or 1 alpha(OH)D3. In 39 instances, there was either reversal of symptoms and/or a marked fall in plasma alkaline phosphatase. Bone biopsies showed improvement of either osteomalacia or osteitis fibrosa, and serum iPTH often fell. In thirteen patients, no improvement occurred. In seven patients, bone biopsy disclosed osteomalacia, and serum iPTH was normal or only slightly elevated. Thus, there was a defect in mineralisation. apparently unrelated to the lack of 1,25(OH)2D3 and in the absence of evidence of phosphate depletion. The other 'treatment failure' group showed osteitis fibrosa on biopsy and iPTH levels were markedly elevated. They are presumed to have marked secondary hyperparathyroidism. These 'treatment failure' groups had higher pre-treatment levels of serum Ca and Mg than in those showing a favourable response; also, hypercalcaemia developed rapidly during 1,25(OH)2D3 treatment. Thus, 1,25(OH)2D3 is efficacious in treating symptomatic osteodystrophy in many uraemic patients, and in other patients, it may help identify bone disease of other, as yet unknown, pathogenesis.
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PMID:Use of 1,25(OH)2-vitamin D3 to separate 'types' on renal osteodystrophy. 60 Sep 61

(1) The bone histology of 233 non-dialysed and 276 haemodialysed patients with chronic renal failure is reviewed. In non-dialysed patients osteitis fibrosa occurred in 83.7% and osteomalacia in 23.6% of patients. Osteomalacia was not found in the absence of osteitis fibrosa. In haemodialysed patients there was a more variable bone histology, sometimes resembling non-dialysed bone disease, but in general with a greater incidence of osteomalacia, especially with increasing time on dialysis. In some patients there was a predominance of osteomalacia accompanied by no or only mild osteitis fibrosa and the serum alkaline phosphatase was normal. (2) The results of treating twenty-six haemodialysed patients with 1alpha-hydroxyvitamin D3 (1alpha-OHD3) are described. Patients with osteomalacia and minimal or no osteitis fibrosa and a normal serum alkaline phosphatase (Group I) in general failed to respond and it is suggested that 1,25-dihydroxyvitamin D3 deficiency is not the sole factor responsible for the osteomalacia in these patients. In contrast, 1alpha-OHD3 therapy was effective in improving osteitis fibrosa and osteomalacia in some patients with moderate to severe degrees of osteitis fibrosa and osteomalacia (Group IIa) and in improving osteitis fibrosa where this occurred alone (Group IIb).
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PMID:Histopathology of renal osteodystrophy with particular reference to the effects of 1alpha-hydroxyvitamin D3 in patients treated by long-term haemodialysis. 60 22

Twenty-three patients with bone disease and chronic renal failure were treated for periods of 4--28 months with 1alpha-hydroxyvitamin D3 (1alpha-OHD3). Improvements in bone histology were consistently seen in patients with features both of osteitis fibrosa and osteomalacia but were not invariably observed in patients with osteitis fibrosa or osteomalacia alone (37 and 50% improved respectively). Several factors influencing the outcome of treatment were assessed on the basis of histological responses in bone. A low level of plasma calcium before treatment, rather than the dose of 1alpha-OHD3 tolerated, was the major detectable factor which favourably affected the histological outcome. Other factors examined, including initial plasma concentrations of phosphate, immunoreactive parathyroid hormone and alkaline phosphatase, and treatment with haemodialysis or dietary supplements of calcium did not apparently influence the response.
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PMID:Factors influencing the response to 1alpha-hydroxyvitamin D3 in patients with renal bone disease. 60 25

Six patients with chronic renal disease and variable degrees of renal osteodystrophy were treated for three weeks with either 1alpha,25-dihydroxyvitamin D3 (1alpha25(OH)D3) or 1alpha,hydroxyvitamin D3 (1alpha(OH)D3) and both the biochemical and osseous responses measured. The most consistent changes seen were an increase in serum calcium concentration to normal, a decrease in immunoreactive parathyroid hormone toward normal, an increase in the extent of the calcification front and a decrease in the extent of fibrous dysplasia in the marrow cavity. Two important parameters which did not change significantly were serum alkaline phosphatase activity and the osteoid volume. These data, in conjunction with that from previous studies, indicate that therapy with 1alpha,25(OH)2D3 or 1alpha(OH)D3 does not heal the osteomalacia of renal osteodystrophy, but that it does suppress the secondary hyperparathyroidism, and ameliorate the osteitis fibrosa seen in patients with chronic renal disease. They raise the likelihood that additional factors, such as metabolites of vitamin D other than 1alpha,25(OH)2D3, play a role in regulating bone formation and/or mineralization.
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PMID:The effect of 1alpha(OH)D3 and 1alpha,25(OH)2D3 on the bone in patients with renal osteodystrophy. 62 25

This paper explores in patients with dialysis osteodystrophy the relationship between clinical features and histological, radiological, and biochemical findings. Eighty-five patients treated by hemodialysis for more than 6 months were studied. The following conclusions were drawn: 1) Bone pain in patients on regular hemodialysis is usually a symptom of developing osteomalacia but not of hyperparathyroidism or osteoporosis. 2) Many patients with histological osteomalacia and radiological features of osteomalacia, such as fractures or Looser zones, have no symptoms. 3)In dialysis patients, biochemical and radiological abnormalities are not a reliable means of predicting the presence of osteomalacia, but a raised serum alkaline phosphatase is a good indicator of the presence of osteitis fibrosa. For early detection of osteomalacia, bone biopsy in necessary. 4)A number of our dialysis patients develop an unusual form of osteomalacia characterized by absent or minimal histological osteitis fibrosa, a normal serum alkaline phosphatase, and a high incidence of myopathy and fractures.
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PMID:Hemodialysis bone disease: correlation between clinical, histologic, and other findings. 68 26

Successful treatment of osteitis fibrosa with 1alpha-hydroxycholecalciferol (1alpha-OHD3) in 9 patients with end-stage chronic renal failure was associated with a significant increase in plasma levels of immunoreactive calcitonin (iCT) independently of changes in plasma calcium, and a decrease in levels of parathyroid hormone (iPTH). In 9 further patients whose plasma alkaline phosphatase activity failed to suppress with 1alpha-OHD3, changes in iPTH were associated with proportionate changes in iCT. This suggests that a rise in endogenous calcitonin (CT) secretion contributes to the success of treatment with 1alpha-OHD3. In 13 further patients, injections of salmon CT induced a fall in plasma calcium and phosphate which was proportional to the prevailing level of plasma alkaline phosphatase. These data provide further evidence that bone resorption can be effectively inhibited when CT levels are raised either by exogenous CT or its endogenous stimulation.
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PMID:Biological activity of endogenous and exogenous calcitonin in patients with osteitis fibrosa and chronic renal failure. 74 Jun 83


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