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)

We measured serum bone alkaline phosphatase (B-ALP) with a new immunoradiometric assay (IRMA) in a large sample of healthy controls comprising 173 women and 180 men, 20-88 yr of age, and in patients with metabolic bone disease. Using serum samples from patients with liver disease and patients with Paget's disease with elevated total alkaline phosphatase (T-ALP) as a source of, respectively, liver and bone isoenzymes, we determined a liver cross-reactivity of the IRMA of 16% that was confirmed by electrophoresis of the circulating alkaline phosphatase isoenzymes. The IRMA was linear for serial sample dilutions, the recovery ranged from 89-110%, and the intra- and interassay variations were below 7% and 9%, respectively. B-ALP increased linearly with age in both sexes, and the mean B-ALP serum levels were not significantly different for women and men (11.3 +/- 4.8 ng/mL for women; 11.0 +/- 4.0 ng/mL for men). The increase in B-ALP after the menopause was significantly higher than that in T-ALP (+77% vs. +24%; P < 0.001). When the values of postmenopausal women were expressed as the SD from the mean of premenopausal women, the mean Z scores were 2.2 +/- 1.8 for B-ALP and 0.9 +/- 1.3 for T-ALP (P < 0.001 between the two). Serum B-ALP was increased from control values in patients with Paget's disease (n = 57; mean, 171.8 +/- 135.6 ng/mL; P < 0.001), in patients with primary hyperparathyroidism (n = 18; mean, 17.2 +/- 5.9 ng/mL; P < 0.001), and in patients with chronic renal failure on hemodialysis (n = 83; mean, 36.6 +/- 35.7 ng/mL; P < 0.001). In patients with Paget's disease, B-ALP was highly correlated with T-ALP (r2 = 0.94; P < 0.001), and the decrease in its serum level was larger than that in T-ALP after treatment with the bisphosphonate pamidronate (-58% vs. -43%; P < 0.03). In patients with various liver diseases, B-ALP was slightly increased, but stayed within the normal range (mean +/- 2 SD) until T-ALP did not exceed 4.5 mu katal/L. We conclude that this new IRMA for B-ALP is reliable, has a low cross-reactivity with the liver isoenzyme, and appears to be more sensitive than T-ALP for the clinical investigation of patients with osteoporosis and other metabolic bone diseases.
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PMID:Assessment of the serum levels of bone alkaline phosphatase with a new immunoradiometric assay in patients with metabolic bone disease. 810 54

Primary hyperparathyroidism (pHPT) is associated with osteopenia. However, the individual variation in recovery in bone mass after surgery is large. Therefore, modes of prediction of the increase in bone mass after parathyroid surgery were investigated. Preoperatively and at one year after surgery bone mineral content (BMC) in the distal radius was measured with single photon absorptiometry technique in 40 patients with pHPT. Serum levels of calcium, intact parathyroid hormone (PTH), alkaline phosphatase, osteocalcin and Vitamin D metabolites were also determined. Preoperatively, Z-score of BMC was -0.85 +/- 1.20 SD below the normal mean. There was a modest association between BMC and serum levels of osteocalcin (r = -0.34; P < 0.05), and dihydroxycholecalciferol (r = -0.35; P < 0.05). At one year after surgery, mean BMC increased by 2% (P < 0.05), but with a wide dispersion. Preoperative Z-score of BMC correlated with the relative change in BMC (r = -0.33; P < 0.05). An increase in BMC with 95% confidence was evident in 10 of the patients. None of these patients had a preoperative Z-score of BMC above the mean expected for age and sex. We conclude that the increase in bone mass after surgery for pHPT is small and evident only in a portion (approximately 25%) of patients. Hence, a decrease in bone mass should not be a major indication for surgery in pHPT.
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PMID:Prediction of changes in bone density after operation for primary hyperparathyroidism. 812 72

Iliac crest biopsies of normals, uremic patients and subjects with primary hyperparathyroidism (pHPT) were investigated. It appeared that serum 1,25- and 24,25-(OH)2-D3 correlated inversely with basal adenylate cyclase (AC) activity and relative PTH-stimulated AC, respectively. Net PTH-elicited AC (dPTH-AC) activation hence reflected individual vitamin D status. The combination variable serum PTH (s-PTH) x dPTH-AC x [H+] correlated well with resorption surface (RS) in both normals, patients with pHPT or subjects with uremia, while s-PTH, dPTH-AC activity or pH as single variables were only marginally related to RS. For all subjects analyzed, osteoid volume (OV) correlated positively with serum alkaline phosphatase but negatively with serum 1,25-(OH)2-D3. OV showed no correlation with dPTH-AC, while the relationship between OV and s-PTH was strong, suggesting that PTH stimulates osteoid deposition via some signalling pathway other than cAMP. In normals, OV was inversely proportional to s-PTH, due to homologous desensitization of this signalling system. Furthermore, s-PTH was negatively correlated with urine cAMP due to homologous desensitization of the effect of PTH on the kidney 25-(OH)-D3 1 alpha-hydroxylase. This phenomenon was absent in uremic patients. Evaluation of variables by artificial intelligence showed that the prototype uremic patient exhibited serum creatinine > 900 microM, RS > 0.12, pH between 7.15 and 7.34 and s-PTH x dPTH-AC x [H+] between 0.5 and 3.7 units with the distinguishability index 'very good' (< 5% overlap) towards normals. Average similarity of uremic patients with the prototype for normal subjects was only 22%. Cluster analysis of all the variables was conducted for comparison and yielded less clinically relevant information. Hence, emulation done by the expert system was superior and clearly indicates that present treatment modalities restore normal bone turnover only to a minor degree or not at all.
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PMID:PTH-stimulated adenylate cyclase activity and bone histomorphometry in iliac crest biopsies in the evaluation of uremic patients: a pilot study with the use of artificial intelligence. 816 16

We developed a sensitive two-site sandwich ELISA for quantitative analysis of human osteocalcin in serum or plasma. Our method is based on two different highly specific antibodies recognizing epitopes at different ends of the protein so that only intact osteocalcin is detected. The method is fast (total analysis time less than 6 h/96 wells), precise (intraassay variation less than 2.3% at four different levels; n = 10, and interassay variation less than 2.5%, n = 5, respectively), and accurate, with a mean recovery of 105%. The detection limit in serum is approximately 0.1 micrograms/liter. The mean concentration of osteocalcin in normal serum with this assay is 3.3 micrograms/liter (SD 3.7 micrograms/liter; range 0.1-13.1 micrograms/liter; n = 41), and the reference range is 0.28-10.1 micrograms/liter (10 and 90% confidence limits). The method shows a reasonable positive linear correlation with other osteocalcin assays (Incstar, r = 0.55, p < 0.05, n = 13; Henning Oscatest, r = 0.52, p < 0.005, n = 34). A good correlation (r = 0.70, p < 0.001) between individual osteocalcin and bone-specific alkaline phosphatase serum concentrations was observed in normal subjects. We found a low or undetectable concentration of intact osteocalcin in serum of all four of our patients with acute primary hyperparathyroidism, and in all five patients with hypocalcemic secondary hyperparathyroidism, which suggests that PTH effectively inhibited the synthesis of osteocalcin in osteoblasts. The serum concentration of intact osteocalcin was elevated in two of three patients with chronic primary hyperparathyroidism.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Two-site enzyme immunoassay for measuring intact human osteocalcin in serum. 819 28

This study was carried out in order to evaluate serum carboxy-terminal propeptide of human type I procollagen (PICP) in patients with primary hyperparathyroidism and to examine its changes following parathyroidectomy. Seventeen patients (four males and 13 famels, aged 53.8 +/- 3.1 SEM years) were studied in basal conditions; six patients also were investigated after successful parathyroid surgery. Mean serum PICP values of patients with primary hyperparathyroidism (194.5 +/- 27 SEM micrograms/l) were significantly higher (p < 0.001) with respect to those found in normal subjects. However, deviations from the norm (Z score values) were significantly less with respect to deviations of serum osteocalcin, alkaline phosphatase and urinary hydroxyproline/creatinine ratio. Following parathyroidectomy, it was possible to observe a discrepancy between markers of bone resorption and those of bone formation. The former tend to decrease, while the latter either do not show any significant change (serum alkaline phosphatase and serum osteocalcin) or increase (serum procollagen). The results of our investigation indicate that in basal conditions the assay of serum procollagen may be of clinical value but it would be better to use it in combination with other biomarkers of skeletal remodelling. The results obtained after parathyroidectomy are the opposite of those obtained following parathyroid hormone infusion and should be ascribed to the effect of acute hormone deficiency on collagen synthesis. The positive biochemical uncoupling following surgery might lend support to the rise of bone mineral density consistently reported in the first few months following parathyroidectomy.
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PMID:Serum carboxy-terminal propeptide of human type I procollagen in patients with primary hyperparathyroidism: studies in basal conditions and after parathyroid surgery. 820 59

Aminohydroxypropylidene diphosphonate (APD), a potent inhibitor of bone resorption, is used to control hypercalcemia in various diseases. It is less effective, however, in the management of hypercalcemia induced by primary hyperparathyroidism. We investigated the effect of APD on the bone metabolism of five patients with parathyroid adenoma. Before parathyroidectomy, 30 mg of APD was administered intravenously. Serum calcium decreased in all cases one to two days after APD administration, although it did not decrease to the normal range. Serum phosphorus also decreased. Urine calcium and hydroxyproline excretion, markers of osteoclasts activity, decreased dramatically. Serum alkaline phosphatase (ALP) and osteocalcin, markers of osteoblast activity, decreased after APD administration. Serum intact parathyroid hormone (PTH) and 1,25-dihydroxy-vitamin D (1,25[OH]2D) increased. These results indicate that APD is partially effective in the management of preoperative serum calcium level in patients with parathyroid adenoma. As osteoclasts activity is inhibited by APD, osteoblasts activity is also suppressed. Elevation of PTH and 1,25(OH)2D after APD-induced decrease in serum calcium level may explain the partial and limited effect of APD on lowering serum calcium in patients with parathyroid adenoma.
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PMID:Effect of aminohydroxypropylidene diphosphonate on the bone metabolism of patients with parathyroid adenoma. 822 4

Primary hyperparathyroidism is usually associated with normal or elevated serum 1,25-dihydroxyvitamin D [1,25(OH)2D] levels. We report a 63-year-old patient with extreme hypercalcemia (ionized serum calcium, 2.51 mmol/l; normal range, 1.19-1.36), very high serum concentrations of intact immunoreactive parathyroid hormone (iPTH) (145 pmol/l; normal range, 1-6.8), radiological lesions of osteitis fibrosa cystica, only mildly impaired renal function (creatinine clearance, 69 ml/min/m2) and very low serum levels of 1,25(OH)2D (28.8 pmol/l; normal range, 72-120). Presurgery normalization of the calcemia with normal saline, salmon calcitonin and pamidronate caused an increase in 1,25(OH)2D serum concentration to 228.3 pmol/l. A negative correlation could be established between ionized calcium and 1,25(OH)2D levels during that period (r2 = 0.80, P < 0.04). While serum calcium decreased with treatment, serum iPTH also decreased to 48.6 pmol/l, suggesting some 1,25(OH)2D inhibition of parathyroid adenoma function. Serum alkaline phosphatase also rose from 309 to 390 units/l (normal range, 25-97), suggesting the beginning of resolution of her osteitis fibrosa cystica prior to surgery. Surgical removal of a parathyroid adenoma was associated with a decrease in serum calcium and iPTH levels. To our surprise, the hypocalcemia could be managed easily with 1500 mg of oral calcium carbonate daily, even if the hungry bone disease became more active with an increase in alkaline phosphatase to 486 units/l. This was explained by the very high levels of serum 1,25(OH)2D (> 200 pmol/l) which prevailed in the postsurgery period and were probably related to decreased bone resorption and increased bone formation. This case illustrates that normalizing serum calcium prior to surgery in patients with primary hyperparathyroidism and osteitis fibrosa cystica can be highly beneficial.
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PMID:Inhibition of 1,25(OH)2D production by hypercalcemia in osteitis fibrosa cystica: influence on parathyroid hormone secretion and hungry bone disease. 827 76

A radioimmunoassay for circulating levels of the pyridinoline cross-linked carboxy-terminal telopeptide of type 1 collagen (1CTP) was developed and can be available as a kit on a commercial base. Using the kits, we evaluated basically and clinically the assay. The assayed values were reproducible and the assay can detect as low as 0.5 ng/ml of 1CTP. In healthy volunteers, circulating level was high under age 24 and over age 46. In patients with bone metastasis, serum levels elevated even in its early stage and correlated well with clinical status. In other bone diseases, such as primary hyperparathyroidism, hyperthyroidism, post-gastrectomy, hypercalcemia of malignancy and myeloma, serum levels elevated according to their clinical conditions. In patients with chronic renal failure, serum levels were high, suggesting decrease of renal clearance of 1CTP. The circulating 1CTP levels seemed to reflect well clinical bone destructive status. A high correlation between serum 1CTP level and urinary pyridinoline (r = 0.884) was shown, whereas essentially no correlation was observed between bone formation markers such as osteocalcin and alkaline phosphatase. Thus, the measurement of circulating 1CTP seems to be a simple and sensitive method to monitor bone destruction.
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PMID:[Radioimmunoassay for the pyridinoline cross-linked carboxy-terminal telopeptide of type 1 collagen (1CTP)--some basic aspects of the RIA kit and clinical evaluation in various bone diseases]. 827 4

Patients with primary hyperparathyroidism have increased bone turnover, but it is less well documented how brief periods of excess parathyroid hormone (PTH) (endogenous or exogenous) affect bone metabolism. In the present double blind study, we examined the effect of either ethylenediaminetetraacetatic acid (EDTA) or placebo on serum levels of PTH and biochemical markers of bone turnover in 15 women and 39 men (aged 41 to 81 years) suffering intermittent claudication due to atherosclerosis. Disodium EDTA was administered as 20 repeated infusions of 3 grams during a period of 5-9 weeks. Serum calcium and serum phosphate decreased following treatment (p < 0.001) and remained unchanged in the placebo group. However, the differences between the groups were insignificant (ANOVA p = 0.13 and p < 0.10, respectively). PTH increased 2 1/2 fold following EDTA treatment (p < 0.001, ANOVA). The change in serum PTH was inversely correlated with the change in serum calcium (r = -0.53, p < 0.01). In the EDTA group, urinary hydroxyproline/creatinine and calcium/creatinine increased after treatment (ANOVA p < 0.001 and p < 0.05, respectively). Serum bone alkaline phosphatase decreased significantly in the EDTA group immediately after treatment (p < 0.001, ANOVA) and returned to baseline level at three months while only an insignificant decrease in serum osteocalcin was seen following treatment. We conclude that EDTA treatment increases endogenous PTH secretion considerably and leads to increased bone resorption. However, no changes in osteoblastic markers indicating increased activation of bone remodeling could be demonstrated. Our findings support that chelation therapy with EDTA is accompanied by bone loss.
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PMID:Effects of intravenous EDTA treatment on serum parathyroid hormone (1-84) and biochemical markers of bone turnover. 829 6

To investigate whether hyperparathyroidism has an effect on blood lead (Pb) concentrations and whether parathyroidectomy will alter blood Pb concentrations, we studied 15 subjects with primary hyperparathyroidism (HPTH) and 7 control subjects with thyroid nodules (TC). Blood Pb concentrations were determined several weeks prior to surgery and then again 4 months later. A reference group (REF) of nonsurgical lab/office workers was examined over the same periods of time. Initial mean blood Pb concentrations were 6.6 +/- 2.8, 6.0 +/- 2.9, and 5.0 +/- 1.7 micrograms/dl for the HPTH, TC, and REF groups (not significantly different), respectively. The mean percentage changes in blood Pb (before vs after) were -13.9, -4.9, and -6.1%. While the paired changes in blood Pb concentrations within the HPTH group were significant (P < 0.05), the percentage changes compared to either of the TC or REF groups were not significantly different. The percentage change in blood Pb correlated with the percentage change in serum calcium across all subjects (r = 0.5176, P = 0.0024, n = 24), although this correlation was not significant within any group alone. The HPTH group demonstrated expected changes in serum calcium, parathyroid hormone, and alkaline phosphatase concentrations. Three of the HPTH subjects received a CaNa2 EDTA chelation challenge (1 g intramuscularly) before and 4 months after surgery. Chelated amounts of Pb (microgram/24 hr before vs after) were 52 vs 38, 42 vs 47, and 60 vs 34. These data indicate that in the high bone turnover state of hyperparathyroidism that Pb concentrations in the blood-soft tissue compartment, and probably Pb mass, are not likely to be different from other individuals. Also parathyroidectomy results in a lowering of blood Pb concentrations possibly due to parallel movements of calcium.
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PMID:Effects of hyperparathyroidism on blood lead concentrations in man. 832 55


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