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)

Parathyroidectomy (PTx) is indicated in hemodialysis (HD) patients who have severe osteitis fibrosa unresponsive to vitamin D therapy or in whom the latter treatment is contraindicated. Immediately after PTx, plasma immunoreactive parathyroid hormone, calcium and phosphorus concentrations decline abruptly. However, little is known in such patients about the short-term effects of PTx on plasma alkaline phosphatase (AP) activity and plasma aluminum (Al) levels. The present, preliminary study was performed to determine such parameters in 37 HD patients, and to correlate them with data of bone histology. Mean plasma AP activity started to increase after PTx from day 4 onwards. Thus, AP values significantly higher than pre-PTx values were observed at day 7 and 14 (415 +/- 54 vs. 619 +/- 77 and 749 +/- 83 IU/liter, means +/- SEM; N = 37; P less than 0.05 and 0.001, respectively). This increase, in the absence of changes in liver function, was mainly due to the bone-specific iso-AP. Moreover, the degree of increase in plasma AP activity was higher in the subgroup with negative (group I, 21 patients) than in that with positive bone Al staining (group II, 16 patients). However, plasma osteocalcin (BGP) did not change after PTx (N = 8). Basal plasma Al levels were significantly higher in group II both before and two weeks after surgery.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Short-term effects of parathyroidectomy on plasma biochemistry in chronic uremia. 257 18

Osteitis fibrosa, a frequent complication of chronic renal failure, is characterized by increased rates of bone formation and bone resorption due to increased secretion of parathyroid hormone (PTH). Effective treatment with oral calcitriol is often impossible in patients with osteitis fibrosa, because low doses may cause hypercalcemia. Because short-term infusions of intravenous calcitriol are capable of suppressing the secretion of parathyroid hormone in patients with uremia without causing hypercalcemia, we evaluated the effectiveness of long-term intermittent calcitriol infusions (1.0 to 2.5 micrograms three times weekly, during dialysis) in treating severe osteitis fibrosa in 12 consecutive patients on hemodialysis whose disease was refractory to conventional therapy. After a mean (+/- SE) treatment period of 11.5 +/- 1.4 months, the mean bone-formation rate declined from 1642 +/- 277 to 676 +/- 106 microns 2 per square millimeter per day (P less than 0.01) in the 11 patients who successfully completed the study. Similar reductions occurred in the osteoblastic osteoid (18 +/- 3 to 9 +/- 2 percent; P less than 0.01) and the degree of marrow fibrosis (6.2 +/- 1.7 to 3.5 +/- 1.3 percent; P = 0.01). Concomitant serum biochemical changes included increased calcium levels (2.55 +/- 0.03 to 2.67 +/- 0.05 mmol per liter; P less than 0.01), decreased alkaline phosphatase levels (489 +/- 77 to 184 +/- 32 U per liter; P less than 0.001), and decreased levels of PTH (amino-terminal, 172 +/- 34 to 69 +/- 16 ng per liter in five patients, P less than 0.03; and carboxy-terminal, 1468 +/- 467 to 1083 +/- 402 ml-eq per liter in six patients, P not significant). Although the majority of the patients had transient episodes of asymptomatic hypercalcemia, this complication could be quickly reversed by temporarily halting treatment or decreasing the dose of calcitriol. We conclude that long-term intermittent infusions of intravenous calcitriol are effective in ameliorating osteitis fibrosa in patients on dialysis. Patients whose osteitis fibrosa is refractory to oral calcitriol and who are candidates for parathyroidectomy should be considered first for intravenous calcitriol therapy.
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PMID:Intravenous calcitriol in the treatment of refractory osteitis fibrosa of chronic renal failure. 274 71

In addition to the well-documented hyporesponsiveness of the kidney, resistance to parathyroid hormone (PTH) has been postulated for bone in pseudohypoparathyroidism type I (PHP). In some of these patients reduced bone density and even frank osteitis fibrosa suggest osteoclastic overactivity. To address the possibility that the skeletal system of patients with PHP may be affected by their increased PTH secretion we measured intact serum PTH and three biochemical markers of bone turnover in a large number of patients with PHP (n = 20). The results were compared with subjects with low (hypoparathyroidism, HP n = 29), normal (controls, n = 31) and high (primary hyperparathyroidism, 1 degree HPT, n = 13) PTH secretion. Both markers of osteoblastic bone formation, alkaline phosphatase activity and osteocalcin concentration in serum, and one index of osteoclastic bone degradation, the urinary hydroxyproline/creatinine ratio (OH-P/Cr), were decreased in HP and increased in 1 degree HPT, whereas only OH-P/Cr was elevated in patients with PHP. Although intact serum PTH was significantly more increased in PHP than in 1 degree HPT, the markers of bone turnover were not significantly different in these two groups, suggesting some bone resistance in the patients with PHP. In these subjects intact serum PTH was elevated even at normocalcaemia during vitamin D treatment with a negative correlation with the respective serum calcium concentration (r = -0.69, P less than 0.001), indicating an elevated set-point for the suppression of their parathyroid glands. OH-P/Cr was negatively related to serum calcium in PHP, it normalized in most patients during normocalcaemia induced by vitamin D treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Biochemical markers of bone turnover, intact serum parathyroid horn and renal calcium excretion in patients with pseudohypoparathyroidism and hypoparathyroidism before and during vitamin D treatment. 274 15

Six patients with progressive chronic renal failure not yet requiring dialysis and not consuming supplemental calcium or vitamin D developed hypercalcemia. Three had proven and 1 suspected tertiary hyperparathyroidism, 1 parathyroid carcinoma and 1 aplastic bone. None of the 3 patients who underwent bone biopsy had heavy bone aluminum staining. The patients with proven parathyroid-mediated hypercalcemia had marked elevation of C-terminal parathyroid hormone and alkaline phosphatase values and, when performed, radiographs consistent with osteitis fibrosa. When these findings are absent or the diagnosis is otherwise uncertain, a bone biopsy may provide a definitive diagnosis and guide management.
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PMID:Hypercalcemia in patients with advanced chronic renal failure not yet requiring dialysis. 275 79

Three patients receiving maintenance hemodialysis therapy for end-stage renal failure presented with spontaneous rupture of the quadriceps tendon(s). Biochemical data and the skeletal roentgenograms were compatible with secondary hyperparathyroidism. Histological examination of the excised quadriceps tendon specimens suggested that repeated minor avulsion fractures of the bone cortex at the tendon insertion site had preceded the final total tendon rupture and that osteitis fibrosa was responsible for these minor fractures. Serum alkaline phosphatase level had been increasing continuously for approximately five years prior to the tendon rupture in all three patients, indicating that uncontrolled osteitis fibrosa due to secondary hyperparathyroidism over these years preceded the tendon rupture.
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PMID:Spontaneous rupture of the quadriceps tendon in patients on maintenance hemodialysis--report of three cases with clinicopathological observations. 279 66

Two boys aged six and four with the syndrome of hereditary resistance to 1,25-dihydroxyvitamin D3 with rickets alopecia and growth retardation are presented. After unsuccessful therapeutic trials with pharmacologic doses of vitamin D or its active metabolites, the patients were treated by long-term intracaval infusions of calcium through an implantable catheter. A total of 0.5 to 0.9 g of elemental calcium was infused daily for 18 months and the serum calcium concentration was maintained at 9 to 10 mg/dl. Bone pain subsided within one week of treatment. Serum phosphorus, immunoreactive parathyroid hormone, and 1,25-dihydroxyvitamin D concentrations and alkaline phosphatase activity were normalized within four to nine months. Radiographs of the knees and hands revealed progressive healing of rickets with complete resolution after one year of treatment. The patients gained 12 cm and 8 cm per year in height as compared with 3 cm and 2 cm, respectively, in the previous year. A transilial bone biopsy obtained from one patient prior to treatment revealed severe osteomalacia associated with osteitis fibrosa. A follow-up biopsy examined after 12 months of therapy showed almost complete healing of osteomalacia and normal mineralization. These observations indicate the following: (1) Long-term intracaval calcium infusions are an effective mode of therapy for these patients, and (2) When adequate serum calcium and phosphorus concentrations are maintained, healing of rickets and normal growth rate could be achieved even in the absence of a normal 1,25-dihydroxyvitamin D3 receptor-effector system.
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PMID:Long-term intracaval calcium infusion therapy in end-organ resistance to 1,25-dihydroxyvitamin D. 282 6

Histopathology of mandibular swellings in two women aged 68 and 73 years respectively provided a diagnosis of Paget's disease. The complementary biological tests (phosphorus-calcium metabolism, alkaline phosphatase, hydroxyprolinuria) performed showed the increase in bone metabolism, while imaging techniques (conventional radiography, scintigraphy, CT scan) demonstrated numerous subclinical bony foci. Treatment of the facial deformity, if desirable esthetically or functionally necessary (alveolitis, osteitis) can only be surgical. If there is biological bone hypermetabolism, medical (diphosphonate, calcitonin) can be discussed with the rheumatologists. Evolutive risks are represented by rare sarcomatous transformations, osteomyelitis on Paget and monstrous deformities of the face, as in one of the patients reported who had refused all treatment over 37 years.
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PMID:[Clinical and therapeutic aspects of maxillofacial lesions of Paget's disease]. 316 48

An 86-year-old woman with a history of treated hyperthyroidism and a 20-year history of untreated primary hyperparathyroidism developed generalized bone pain and a pseudofracture of the midshaft of the left femur. Laboratory examinations revealed elevated serum calcium, alkaline phosphatase, and C-terminal parathyroid hormone levels. Serum inorganic phosphate was below normal and 25-hydroxyvitamin D levels were low-normal. An undecalcified transiliac bone biopsy specimen following tetracycline double labeling revealed osteomalacia and osteitis fibrosa. Following treatment with vitamin D and phosphate, the serum inorganic phosphate level rose to normal. There was a decrease in bone pain, and the pseudofracture healed. However, the serum calcium, alkaline phosphatase, and C-terminal parathyroid hormone levels remained elevated. Longstanding primary hyperparathyroidism causes chronic hypophosphatemia and may lead to osteomalacia. Osteomalacia and its consequences may be part of the spectrum of bone disease seen in patients with longstanding primary hyperparathyroidism.
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PMID:Osteomalacia as a very late manifestation of primary hyperparathyroidism. 334 77

We report on a 5-year, prospective, double-blind trial of 1,25 dihydroxycholecalciferol (calcitriol) versus placebo in 76 hemodialysis patients without biochemical or radiological evidence of bone disease. Calcitriol, 1 microgram daily, regularly induced hypercalcemia. Doses of 0.25 microgram daily or less proved satisfactory in most patients. During calcitriol treatment, plasma calcium concentration was significantly higher and serum parathyroid hormone concentration significantly lower than on placebo. There was no difference in the rates of development or of progression of vascular calcification in the two groups. Significantly more patients on placebo (17 vs. 6, p less than 0.05) developed a sustained elevation of plasma alkaline phosphatase concentration. Calcitriol appeared to protect against the development of histological evidence of osteitis fibrosa but not of osteomalacia, but accumulation of aluminum in bone occurred during the study. We conclude that calcitriol delays and may prevent the development of osteitis fibrosa in patients receiving regular hemodialysis and may reasonably be prescribed routinely in hemodialysis patients without biochemical or radiological abnormality, unless there is a substantial prospect of early renal transplantation.
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PMID:Controlled trial of calcitriol in hemodialysis patients. 353 32

Bone histologies and serum concentrations of calcium, phosphate, alkaline phosphatase, iPTH, 25 OHD, 1,25(OH)2D3, and aluminum were obtained from 113 chronically hemodialyzed patients free of symptoms and signs of renal osteodystrophy. All patients had a pathologic bone histology; in 69.0%, a mixed form with predominant osteitis fibrosa and concomitant osteoidosis. In 30.1%, we found pure hyperosteoidosis, nearly half of these cases showing osseous aluminum deposits. Hyperosteoidosis was much more frequent in women (35.7%) than in men (20.9%), although the prescribed intake of aluminum-containing phosphate binders was the same. It is possible that female hemodialysis patients were more prone to aluminum accumulation or that they had a better compliance in taking the aluminum hydroxide. Serum parameters alone were not very helpful in predicting the underlying bone disease. Mean iPTH concentrations tended to be lower in the patients with hyperosteoidosis than in those with the mixed lesion, but there was wide variation. Serum aluminum was only predictive for aluminum deposits in the bone when concentrations exceeded 100 micrograms/L.
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PMID:Renal osteodystrophy in asymptomatic hemodialysis patients: evidence of a sex-dependent distribution and predictive value of serum aluminum measurements. 381 72


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