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)

Serum osteocalcin (BGP) is an osteoblast product that probably reflects the rate of bone formation. It is a potential marker of skeletal metastases and, to investigate this, BGP was measured by radioimmunoassay in the serum of normal subjects and patients with breast or prostate cancer. Significantly higher levels were found in patients with metastatic bone disease in comparison to both normal subjects (P less than 0.001) and patients with non-metastatic cancer (P less than 0.05 for breast cancer and less than 0.001 for prostate cancer). The range of values was wide. Levels were higher in sclerotic than lytic bone metastases (P less than 0.01) and lower in patients with hypercalcaemia (P less than 0.001). Serial measurements of BGP were made in 53 patients with skeletal metastases from breast cancer receiving systemic therapy. At 1 month BGP rose by greater than 0.5 ng/ml in 15/16 responding patients compared with 7/23 patients with progressive disease (P less than 0.01). Responding patients also showed a rise in the bone isoenzyme of alkaline phosphatase and a paradoxical deterioration in the bone scan appearance, both reflecting a flare in osteoblast activity. The early increase in responding patients was followed by a gradual decrease over subsequent months as the osteoblast reaction induced by systemic therapy subsided. We conclude that BGP measurements reflect a wide variability of bone formation rates in metastatic bone disease. Bone formation was usually increased, particularly when metastases were sclerotic in appearance, but in patients with hypercalcaemia the low BGP levels suggest uncoupling of bone resorption and formation. Serial measurements of BGP may be useful in monitoring response to treatment.
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PMID:Osteocalcin: a potential marker of metastatic bone disease and response to treatment. 326 63

Assessment of response of skeletal metastases to systemic therapy is currently dependent on radiological evidence of bone healing. We have performed a prospective study of additional response criteria in patients with progressive bone metastases from breast cancer. Changes in these potential markers of response were correlated with the radiological response and the time to treatment failure (TTF). Successful systemic therapy typically led to a transient increase in osteoblast activity ('flare'), a reduction in osteoclast activity and symptomatic improvement. After 1 month a greater than 10% rise in serum osteocalcin (BGP) and alkaline phosphatase bone isoenzyme (ALP-BI) and a greater than 10% fall in urinary calcium excretion were seen in 14/16 patients with radiographic evidence of bone healing (UICC partial responders). In comparison similar biochemical changes at 1 month were seen in only 4/20 patients with progressive disease (P less than 0.001). The predictive value and diagnostic efficiency (DE) of changes at 1 month in biochemical measurements and symptom score has been calculated. The combination of a greater than 10% rise in ALPBI and BGP and a greater than 10% fall in urinary calcium excretion had a DE of 89% for discriminating response from progression, 88% for response from non-response (progressing + no change patients), and 76% for TTF of greater than 6 months from TTF of less than 6 months. Serum calcium, tartrate resistant acid phosphatase (TRP), urinary hydroxyproline excretion and bone scan changes were unhelpful in discriminating between patient groups. Independent confirmation is needed, but our results suggest there are reliable alternatives to plain radiography in the early assessment of response of bone metastases to treatment.
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PMID:Biochemical prediction of response of bone metastases to treatment. 326 66

The effects of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] on alkaline phosphatase (AP) activity and the synthesis of gamma-carboxy-glutamic acid containing protein (BGP) were compared in phenotypically distinct cloned cell lines derived from the osteoblast-like rat osteogenic sarcoma line ROS 17/2-8. 1,25(OH)2D3 stimulated AP activity and BGP synthesis in phenotypes which exhibited relatively low basal AP activity and high basal BGP levels. In contrast 1,25(OH)2D3 inhibited AP activity in phenotypes that exhibited high basal AP activity. The latter cells had undetectable BGP levels and the synthesis of this protein failed to respond to the 1,25(OH)2D3 stimulus. In the cells that responded to 1,25(OH)2D3 with an increase in AP activity the effect of the hormone on AP could be blocked by actinomycin-D. However in the cells that responded to 1,25(OH)2D3 with inhibition of AP the effect of the hormone on AP was not influenced by actinomycin-D. The directly opposite effects of 1,25(OH)2D3 on the AP activity of the respective clones did not change qualitatively at different stages of culture and could not be accounted by differences in the 1,25(OH)2D3 receptor status nor by different effects of the hormone on cell proliferation. These data raise the possibility that the response of AP to 1,25(OH)2D3 in osteoblastic cells depends on their state of phenotypic differentiation. The stimulatory effect of the hormone in low AP-producing cells might be related to differentiation promoting properties of 1,25(OH)2D3. The inhibitory effect of 1,25(OH)2D3 on AP, unlike the stimulatory effect of the hormone does not appear to be mediated by the classical mechanism of 1,25(OH)2D3 action on the genome and might be associated with dedifferentiated osteoblastic cells.
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PMID:Phenotype-associated changes in the effects of 1,25-dihydroxyvitamin D3 on alkaline phosphatase and bone GLA-protein of rat osteoblastic cells. 348 45

Serum bone Gla-protein (S-BGP) and other serum biochemical parameters, including alkaline phosphatase (S-AP) and immunoreactive PTH (S-iPTH), were measured in 42 patients undergoing chronic hemodialysis. Each patient also had a tetracycline-labeled transiliac bone biopsy, allowing correlations between the biochemical and trabecular bone histomorphometric parameters, S-BGP was markedly increased [64.0 +/- 74.8 (+/- SD) vs. 6.2 +/- 2.2 ng/ml in normal subjects] significantly correlated with S-AP (r = 0.53) and S-iPTH (r = 0.55) levels. S-BGP was significantly higher in the 14 patients with high turnover renal osteodystrophy (HT-ROD; S-BGP, 138.5 +/- 90.8 ng/ml) than in the 28 patients with low turnover (LT-ROD; S-BGP, 26.8 +/- 14.8 ng/ml). S-BGP was significantly correlated with the cellular parameters of bone resorption and formation (r = 0.57-0.69) and with the dynamic parameters of bone formation (r = 0.62-0.82). The extent of stainable bone aluminum was significantly negatively correlated with S-BGP (r = -0.51) and serum iPTH (r = -0.33), but not with S-AP. S-BGP measurement allowed better discrimination between LT-ROD and HT-ROD groups than did S-AP measurement. However, in the patients with LT-ROD, S-BGP did not discriminate between patients with or without osteomalacia. We conclude that S-BGP is a valuable marker for evaluating bone remodeling and, more specifically, the bone formation rate at the tissue level in hemodialyzed patients.
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PMID:Serum bone Gla-protein in renal osteodystrophy: comparison with bone histomorphometry. 348 98

The aim of this investigation was to study the bone metabolism in early infancy by establishing the relationship between serum osteocalcin levels and the hormonal vitamin D status of exclusively breast-fed infants during their first month of life. Calcium, phosphorus, alkaline phosphatase, 25-hydroxycalciferol (calcidiol), 1,25-dihydroxycalciferol (calcitriol) and osteocalcin (BGP or GLA-protein) were measured in 22 healthy lactating women and their paired breast-fed infants before and after supplementation (400 IU vitamin D per day). Prior to supplementation calcidiol, calcitriol and osteocalcin remained unchanged. Following supplementation there was an increase in all the parameters with the exception of calcitriol. The administration of vitamin D to breast-fed infants should in fact have an effect on bone activity as reflected by the increase in osteocalcin levels.
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PMID:Relationship between bone GLA-protein (BGP) and calcidiol (25-hydroxycalciferol) in serum of breast-fed infants. 348 5

Serum osteocalcin (BGP) is a new marker of bone turnover that reportedly evaluates bone formation. Thus, its measurement could assess the bone formation rate in tumor-associated hypercalcemia. We measured concentrations of BGP and other parameters of bone metabolism in 54 untreated hypercalcemic cancer patients as compared to 109 healthy subjects. Primary tumor sites were breast (19), lung (11), head and neck (6), multiple myeloma (3), kidney (2), and various (11) or multiple (2). Mean BGP levels were higher in the hypercalcemic subjects, 4.6 +/- 0.4 (SEM) ng/ml, than in the normal subjects, 3.6 +/- 0.1 ng/ml (p less than .05), and were normalized in the 22 patients who could be reevaluated after successful treatment of hypercalcemia with intravenous aminohydroxypropylidene diphosphonate (APD). There was no correlation of BGP levels with age, sex, or renal function. Compared with the Gaussian distribution in the normal subjects, there was a considerable scatter of the data in hypercalcemic patients, suggesting the existence of defined subgroups with abnormally low or abnormally high values. However, we found no significant relationship of BGP concentrations with tumor site or histology or with bone metastatic involvement. We found also no significant correlation between concentrations of serum BGP and total or ionized calcium, alkaline phosphatase, parameters of bone resorption, and indices of parathyroid function. In summary, serum BGP levels were slightly elevated in tumor-associated hypercalcemia and were normalized after successful treatment of hypercalcemia. More importantly, BGP concentrations varied widely even in the subgroups of patients with hypercalcemia accompanying massive bone metastatic involvement or in the patients without detectable skeletal metastases.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serum osteocalcin (BGP) in tumor-associated hypercalcemia. 350 43

Bone mineral metabolism was studied in 10 subjects with familial hypocalciuric hypercalcaemia (FHH) and 10 age-, sex- and surface area matched healthy controls. Bone turnover was estimated by urinary calcium and hydroxyproline excretions relative to creatinine (Ca/Creat and OHPr/Creat, respectively), serum bone Gla-protein (S-BGP) and serum alkaline phosphatase (S-ALP). Bone status was evaluated by measurement of bone mineral content (BMC) on both forearms and X-ray examinations of the hands. Ca/Creat and OHPr/Creat (indices of bone resorption) were both significantly higher in the FHH group than in the controls. S-BGP and S-ALP (indices of bone formation) tended towards a higher level in the FHH subjects, but the differences were not significant. The BMC values were similar in the two study groups and did not change with time. We conclude that these patients with FHH might have a bone turnover higher than normal, and that the increased bone resorption must be paralleled by an increased bone formation.
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PMID:Familial hypocalciuric hypercalcaemia. III: Bone mineral metabolism. 366 25

The gamma-carboxy glutamic acid (Gla)-containing protein of mammalian bone (BGP, also called osteocalcin) is a 49 amino acid polypeptide containing two to three residues of gamma-carboxyglutamic acid. BGP is synthesized by osteoblastlike cells, and plasma BGP in laboratory animals is derived principally from recently synthesized BGP. These data, taken together with observations that plasma BGP levels are elevated in patients with disorders of high bone turnover, suggest that plasma BGP is a marker of osteoblast activity. Since low bone formation rates may play an important role in the loss of bone mass with age, we have examined the determinants of plasma BGP levels in aging subjects, using a region-specific radioimmunoassay for human BGP based on the synthetic C-terminal peptide hBGP37-49. In 147 carefully screened healthy subjects, aged 23-91, BGP did not change with age, whereas alkaline phosphatase (AP) showed a significant positive correlation (r = 0.30, P less than 0.001). Creatinine clearance (GFR) declined by 0.9 ml/min/yr and correlated with both BGP (r = -0.21, P less than 0.001) and AP (r = -0.21, P less than 0.001). However, correlation of AP with age persisted after controlling for GFR. BGP was not correlated with serum PTH, urine Ca/GFR, or urine cAMP/GFR. In 48 patients with known parenchymal renal disease studied for comparison, plasma BGP was increased at a serum creatinine of greater than or equal to 1.8 mg/dl. Our results indicate that plasma BGP, a specific marker of bone metabolism, is not predictably related to age per se. This result is in contrast to the age-related rise in total AP. Subtle changes in renal function can affect plasma BGP levels.
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PMID:Determinants of bone gamma-carboxyglutamic acid-containing protein in plasma of healthy aging subjects. 387 50

Bone gamma-carboxyglutamic acid-containing (Gla) protein (BGP, osteocalcin) is a noncollagenous protein of bone present in plasma and removed by the kidney. Plasma BGP has been shown to be elevated in patients with certain bone diseases. The present study evaluates serum BGP (S-BGP), serum alkaline phosphatase (S-AP), and urinary hydroxyproline excretion (U-OHP) in diseases with differing bone turnover rates, and compares the accuracy of these measurements for estimating bone mineralization (m) and resorption (r) rates. S-BGP, S-AP, U-OHP, and creatinine clearance (Clcr) were measured in patients with primary hyperparathyroidism (n = 13), hyperthyroidism (n = 6), and hypothyroidism (n = 6). Bone mineralization and resorption rates were calculated from a 7-d combined calcium balance and 47Ca turnover study. A highly significant correlation (r = 0.69, P less than 0.001) was found between S-BGP and m. Multiple regression analysis disclosed a partial correlation between S-BGP and m when Clcr was taken into account (r = 0.82, P less than 0.001), and between S-BGP and Clcr when m was taken into account (r = -0.62, P less than 0.005). In accordance with this, a stronger correlation (r = 0.89, P less than 0.0001) was found between S-BGP X Clcr and m than between S-BGP and m. A less significant correlation was found between S-AP and m (r = 0.45, P less than 0.05). Furthermore, U-OHP showed a highly significant positive correlation to r (r = 0.78, P less than 0.001). Thus, in the studied disorders of calcium metabolism, individual serum levels of BGP depend on both mineralization rate and renal function. Serum levels of BGP corrected for alterations in renal function are superior to uncorrected S-BGP and to S-AP levels in the estimation of bone mineralization rates.
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PMID:Estimation of bone turnover evaluated by 47Ca-kinetics. Efficiency of serum bone gamma-carboxyglutamic acid-containing protein, serum alkaline phosphatase, and urinary hydroxyproline excretion. 387 67

Serum osteocalcin (BGP), a vitamin K-dependent gamma-carboxyglutamic acid (GLA) containing bone protein, provides an index of bone turnover in patients with a variety of metabolic bone diseases. BGP increases with increasing age in both sexes, but more so in women. BGP rises above normal when the glomerular filtration rate falls below 30 ml/min. Because of its importance in bone disease, its low mol wt, and the effect of uremia, we measured BGP by RIA in serum and dialysate fluid in patients on hemodialysis (HD) or peritoneal dialysis (PD). In 32 HD patients (22 women and 10 men), serum BGP was not different pre- and postdialysis [67.5 +/- 4.4 (+/- SEM) ng/ml vs. 67.7 +/- 5.2), but was significantly elevated compared to the level in normal subjects (7.3 +/- 0.8 ng/ml). The sex difference previously reported in normal subjects was not found in patients with renal failure. The serum BGP level in 8 PD patients was 49.4 +/- 6.9 ng/ml, with a peritoneal fluid concentration of 27.6 +/- 9.3 ng/ml. The hemodialysate fluid concentration of BGP was 1.7 +/- 0.4 ng/ml, which was significantly lower than the serum BGP levels in the HD patients, the PD patients, and peritoneal fluid (P less than 0.01). A significant correlation existed among BGP, alkaline phosphatase, immunoreactive PTH, creatinine, and blood urea nitrogen. We conclude that BGP is markedly elevated in patients with renal failure, not altered in the serum by HD or PD, but very low in HD dialysate fluid. These findings may reflect a combination of impaired clearance and increased skeletal production. The difference in clearance between the peritoneal and hemodialysis fluid is compatible with the mol wt of BGP. In 15 patients who had successful kidney transplantation, serum BGP was normal despite an elevated serum PTH level.
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PMID:Serum and dialysate osteocalcin levels in hemodialysis and peritoneal dialysis patients and after renal transplantation. 388 31


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