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)

Changes of bone turnover with aging are responsible for bone loss and play a major role in osteoporosis. Although an increase of bone turnover has been documented at the time of menopause, the subsequent abnormalities of bone resorption and formation and their potential role in determining bone mass in the elderly have not been investigated. To address this issue, we have measured a battery of new sensitive and specific markers of bone turnover in a population-based study of 653 healthy women analyzed cross-sectionally, including 432 women postmenopausal from 1 to 40 years, and the data were correlated with bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) at different skeletal sites. Bone formation was assessed by serum osteocalcin (OC), serum bone-specific alkaline phosphatase (B-ALP), serum C-propeptide of type I collagen (PICP), and bone resorption by the urinary excretion of two pyridinoline cross-linked peptides (NTX and CTX). Bone turnover increased in perimenopausal women with both irregular menses and elevated serum follicle stimulating hormone (FSH). Menopause induced a 37-52% and 79-97% increase in the bone formation and bone resorption marker levels, respectively (p < 0.0001 except for PICP). In postmenopausal women, bone formation markers did not decrease with age. When resorption markers were corrected by whole body bone mineral content (BMC), the fraction of bone resorbed per day was not correlated with age in postmenopausal women and remained elevated for up to 40 years after menopause. In premenopausal women, the bone turnover rate accounted for only 0-10% of the variation in whole body BMC, total hip, distal radius, and lumbar spine BMD. With increasing time after menopause, the importance of the bone turnover rate as a determinant of bone mass increased at all sites and accounted for up to 52% of the BMD variance in elderly women. Thus, in women 20 years or more postmenopause, bone turnover was higher in those in the lowest quartile than in those in the highest quartile of BMD. In elderly women, 20 years since menopause and over, but not in younger ones, serum PTH was negatively correlated with serum 25-hydroxyvitamin D (r = -0.22, p < 0.05) and explained only 5-8% of the bone turnover variance (p < 0.01-0.001). These data indicate that the overall rates of both bone formation and bone resorption remain high in elderly women. The rate of bone turnover appears to play an increasing role as a determinant of bone mass with increasing time since menopause with a high bone turnover rate being associated with a low bone mass. Thus assessing bone marker levels may be useful in the evaluation of osteoporosis risk. In elderly women, secondary hyperparathyroidism caused in part by reduced serum 25-hydroxyvitamin D appears to be a marginal determinant of an increased bone turnover rate.
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PMID:Increased bone turnover in late postmenopausal women is a major determinant of osteoporosis. 885 44

In Paget's disease of bone, the normal lamellar bone is replaced by a woven structure with an irregular arrangement of collagen fibers. In this study, we investigated whether the degree of beta-isomerization within C-telopeptide of alpha 1 chain of type I collagen was altered in Paget's disease compared with other bone diseases with no alteration of bone structure. In Paget's disease (n = 26), but not in patients with primary hyperparathyroidism (n = 6) or hyperthyroidism (n = 17), the urinary excretion of nonisomerized (alpha) fragments derived from degradation of type I collagen C-telopeptide (CTX) was markedly increased compared with beta-isomerized CTX (+ 13-fold vs. + 3.5-fold over controls) resulting in an urinary alpha CTX/beta CTX ratio 3-fold higher than in controls (2.6 +/- 1.0 vs. 0.8 +/- 0.3, p < 0.001). In five pagetic patients in complete remission, as demonstrated by normal total alkaline phosphatase activity, the alpha CTX/beta CTX ratio was normal. The immunohistochemistry of normal and pagetic human bone sections showed a preferential distribution of alpha CTX within woven structure, while lamellar bone was intensely stained with an anti-beta CTX antibody, suggesting a lower degree of beta-isomerization of type I collagen in the woven pagetic bone. In collagenase digest of human bone specimens, we found a lower proportion of beta-isomerized type I collagen molecules in pagetic bone (40% of beta CTX) than in normal bone taken from trabecular (68%) and cortical compartments (71%). In conclusion, we found that in Paget's disease the alpha CTX/beta CTX ratio in bone and in urine is markedly increased. This altered beta isomerization can be accurately detected in vivo by measuring urinary degradation products arising from bone resorption.
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PMID:Decreased beta-isomerization of the C-terminal telopeptide of type I collagen alpha 1 chain in Paget's disease of bone. 928 56

The effect of exercise training, particularly relatively brief periods, on bone turnover markers in adolescents has been poorly studied. Thirty-eight healthy males (16+/-0.7 years) participated in a 5-week summer school program in which 20 subjects were randomly assigned to a training group consisting of 2 h/day, 5 days/week of endurance exercise, and 18 subjects were assigned to a control group. Bone formation was assessed by measurements of circulating osteocalcin, bone-specific alkaline phosphatase (BSAP), and the C-terminal procollagen peptide (PICP). Bone resorption was assessed by urinary levels of free deoxypyridinoline cross-links (dPYR) and the C-(CTX) and N-terminal (NTX) telopeptide cross-links. Prior to training, there was a weak positive correlation between fitness and PICP (r = 0.27, p < 0.05), but no correlations were observed between fitness and either the other markers of bone formation or bone resorption. Training led to a significant increase in (1) osteocalcin (15+/-4%, p < 0.03), (2) BSAP (21+/-6%, p < 0.02), and (3) PICP (30+/-11%, p < 0.03) and to a significant decrease in NTX (-21 +/- 3%, p < 0.05). These bone turnover markers did not change in the control subjects (osteocalcin, 0+/-4%; BSAP, 2+/-4%; PICP, -4 +/- 6%; NTX, -6 +/- 4%). There was no change in urinary dPYR and CTX in either control or trained subjects. Fitness is only weakly, if at all, correlated with bone formation, but a relatively brief period of endurance training leads to a substantial increase in bone formation markers in adolescent males. School-based, short-term exercise training programs could play a role in enhancing bone formation in adolescents.
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PMID:Evidence for increased bone formation following a brief endurance-type training intervention in adolescent males. 933 32

To evaluate the clinical utility of recently developed biochemical markers in the assessment of bone metabolism during GnRH agonist (GnRHa) treatment, we compared five bone resorption markers [C-telopeptide (CTX) and N-telopeptide (NTX) of type I collagen, hydroxyproline (Hpr), pyridinoline (Pyr), and deoxypyridinoline (Dpyr)] and two bone formation markers [total alkaline phosphatase (Alp) and osteocalcin (OC)]. Sixty-eight normally menstruating women were injected with a long-acting GnRHa once a month for 24 weeks for the treatment of endometriosis or leiomyoma. The mean percentage bone loss at the lumbar spine was 3.79% at the end of treatment. Although levels of all markers increased significantly as the treatment progressed, CTX and NTX exhibited the highest correlation coefficients between bone loss at 24 weeks and the seven markers measured at 0, 4, 12, 16, and 24 weeks of treatment. Serum estradiol levels were similarly suppressed during the treatment in both fast losers (whose bone loss was more than the mean) and slow losers (whose bone loss was less than the mean). However, significantly higher z-scores of bone resorption markers, but not of bone formation markers, were observed in the fast losers at 24 weeks of treatment, suggesting a more accelerated bone resorption in this group. Whereas the three highest z-scores at 24 weeks of treatment were CTX, NTX, and Dpyr (in that order), the highest z-score (P < 0.05) was observed for CTX in the fast losers. The subjects in the highest quartile of CTX, the highest, and second highest quartiles of NTX at 24 weeks of treatment experienced 2.1, 2.2, and 1.7 times more bone loss (P < 0.001), respectively, than those in the lowest quartiles. Furthermore, the subjects in the highest quartile of both CTX and NTX experienced 3.6 times more bone loss (P < 0.001) than those in the lowest quartile of both markers. These results indicate that both CTX and NTX are useful and sensitive markers for bone resorption in a hypoestrogenic state induced by GnRHa.
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PMID:The effect of gonadotropin-releasing hormone agonist on type I collagen C-telopeptide and N-telopeptide: the predictive value of biochemical markers of bone turnover. 946 36

Long-term spaceflights induce bone loss as a result of profound modifications of bone remodeling, the modalities of which remain unknown in humans. We measured intact parathyroid hormone (PTH) and serum calcium; for bone formation, serum concentrations of bone alkaline phosphatase (BAP), intact osteocalcin (iBGP), and type 1 procollagen propeptide (PICP); for resorption, urinary concentrations (normalized by creatinine) of procollagen C-telopeptide (CTX), free and bound deoxypyridinoline (F and B D-Pyr), and Pyr in a 36-year-old cosmonaut (RTO), before (days -180, -60, and -15), during (from days 10 to 178, n = 12), and after (days +7, +15, +25, and +90) a 180-day spaceflight, in another cosmonaut (ASW) before and after the flight. Flight PTH tended to decrease by 48% and postflight PTH increased by 98%. During the flight, BAP, iBGP, and PICP decreased by 27%, 38%, and 28% respectively in CM1, and increased by 54%, 35%, and 78% after the flight. F D-Pyr and CTX increased by 54% and 78% during the flight and decreased by 29% and 40% after the flight, respectively. We showed for the first time in humans that microgravity induced an uncoupling of bone remodeling between formation and resorption that could account for bone loss.
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PMID:Bone formation and resorption biological markers in cosmonauts during and after a 180-day space flight (Euromir 95). 951 Aug 65

To determine the mechanism of bone loss after cardiac transplantation (CTX), we studied 50 men 0.5-47 months after CTX (ages 18-64 years) who received prednisolone and cyclosporin to prevent rejection, and 40 healthy men as controls (ages 20-70 years). We measured bone mineral density (BMD) using dual-energy X-ray absorptiometry (DXA), bone resorption using urinary cross-linked N-terminal telopepides of type I collagen (NTx), and bone formation using osteocalcin (BGP) and bone alkaline phosphatase (BAP). The results from the controls were used to calculate z scores. BMD was significantly decreased at the lumbar spine, femoral neck, and total body, and bone turnover was significantly increased as assessed by NTx/creatinine, BGP, and BAP as compared with controls (p < 0.01 for all measurements). To evaluate the cause of the increased bone turnover we measured serum parathyroid hormone (PTH) by IRMA, and this was also elevated (p < 0.001). There was a significant correlation between serum PTH and BGP (r = 0.58, p < 0.01). To evaluate the cause of the increase in PTH, we measured serum calcium and it was decreased (p < 0.001), serum phosphorus was increased (p < 0.001), serum creatinine was increased (p < 0.001), and serum 1,25-dihydroxyvitamin D3 [1,25(OH)2D, RIA] was decreased (p = 0.03). Serum PTH correlated weakly with serum calcium (r = -0.41, p < 0.003) and with serum creatinine (r = 0.35, p = 0.01). There was a weak, but significant, correlation between serum creatinine and 1,25(OH)2D3 (r = 0.33, p = 0.03). Serum levels of testosterone and dehydroapiandrosterone sulfate were decreased after CTX but did not correlate with any other parameters. There was a weak negative correlation between prednisolone daily dose and serum BGP level (r = 0.29, p = 0.06) in those patients whose prednisolone current dose was >7.5 mg/day. We conclude that: (1) the low BMD found after CTX is associated with increased bone turnover which results, in turn, from renal impairment; (2) prednisolone is involved in rapid bone loss, whereas mild secondary hyperparathyroidism may be a major contributor to disorder of bone remodeling after this rapid loss; and (3) decreased androgen levels may not be a major factor resulting in bone loss in men after CTX.
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PMID:Mechanisms of bone loss after cardiac transplantation. 951 19

Biochemical markers of bone metabolism (bone markers) are used increasingly to monitor response to therapy and may be predictors of bone loss and fractures. The relationship between fracture rates, which differ between countries, and the rate of bone turnover has not been examined. Therefore, we explored the geographic variability of bone turnover in a selected, healthy study population of 619 postmenopausal women, ages 40-61, participating in a clinical trial of raloxifene hydrochloride for osteoporosis prevention. The subjects were distributed among 38 investigative sites in 10 countries (9-211 subjects/country) on four continents (North America, n = 277, Europe, n = 168, Australia, n = 125, and Africa, n = 49). Specimens for serum osteocalcin (OC), bone-specific alkaline phosphatase (BSAP), and urine type I collagen fragment/urinary creatinine ratio (CTX) were handled in a uniform fashion and assayed in a central laboratory. Mean levels of OC (P < 0.001), BSAP (P = 0. 006), and CTX (P < 0.001) varied significantly by country (ANOVA), with the lowest values typically in German and Spanish subjects and the highest in American and Canadian subjects. The consistent pattern and wide ranges of mean bone marker values (OC 1.6-fold, BSAP 1.7-fold, CTX 3.1-fold) between countries suggest clinically significant differences in bone turnover. Geographic differences in bone markers were not explained by the determined potential confounders of age, years posthysterectomy, total serum cholesterol, and serum follicle stimulating hormone (FSH). We conclude that bone marker values vary substantially by country in this selected study population, suggesting systematic geographic differences in bone metabolism that potentially relate to osteoporotic fracture rates.
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PMID:Geographic differences in bone turnover: data from a multinational study in healthy postmenopausal women. 974 83

To examine the ability of commercially available biochemical markers of bone formation and resorption to predict hip bone loss, we prospectively obtained serum and timed 2-h urine specimens from 295 women age 67 years or older who were not receiving estrogen replacement therapy. Serum was assayed for two markers of bone formation: osteocalcin (OC) and bone-specific alkaline phosphatase (BALP). Urine specimens were assayed for four markers of bone resorption: N-telopeptides (NTX), free pyridinolines (Pyr), free deoxypyridinoline (Dpyr), and C-telopeptides (CTX). Measurements of hip bone mineral density were made at the time the samples were collected and then repeated an average of 3.8 years later. Higher levels of all four resorption markers were, on average, significantly associated with faster rates of bone loss at the total hip, but not at the femoral neck. Women with OC levels above the median had a significantly faster rate of bone loss than women with levels below the median, but there was no significant association between levels of BALP and hip bone loss. The sensitivity and specificity of higher marker levels for predicting rapid hip bone loss was limited, and there was considerable overlap in bone loss rates between women with high and low marker levels. We conclude that higher levels of urine NTX, CTX, Pyr, Dpyr, and serum OC are associated with faster bone loss at the hip in this population of elderly women not receiving estrogen replacement therapy, but these biochemical markers have limited value for predicting rapid hip bone loss in individuals.
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PMID:Biochemical markers of bone turnover and prediction of hip bone loss in older women: the study of osteoporotic fractures. 1045 73

Anorexia nervosa (AN) is a very extended pathology among adolescent girls nowadays. These patients show a high degree of osteopenia; hence, study of their bone remodelling is of great interest. Serum bone alkaline phosphatase (bAP) and aminoterminal propeptide of procollagen I (PINP) provide good sensitivity in the analysis of bone alterations in postmenopausal osteoporosis. The aim of this study was to compare the usefulness of bAP and PINP in the study of bone remodelling in AN, and their possible correlation with the degree of osteopenia in this pathology. In order to help in the interpretation of the results, levels of the beta-isomer of urinary carboxyterminal propeptide of collagen I (beta-CTX) have also been included. Serum bAP (IRMA) Tandem R-Ostase, Hybritech), PINP (RIA, Orion Diagnostica) and CTX (CrossLaps ELISA, Osteometer) were determined in 41 girls with AN, aged 18.5+/-2.2 years (mean+/-SD) and in 31 healthy control women, aged 19+/-2.3 years. Bone mineral density (BMD) in lumbar spine was measured by DEXA in the AN group. We found that 41 of the 43 patients had BMD z-scores under -2. No significant differences were found in the levels of serum bAP nor in PINP and beta-CTX levels between controls and patients, although values in the AN group were highly variable. All the BMD z-score values were negative, and their absolute value correlates positively with bAP (P = 0.0279) and almost with beta-CTX (P = 0.0921) but not with PINP (P = 0.4627). Bone AP correlates with PINP in control girls (P = 0.017), but not in the AN group (P = 0.3573). Patients with AN were divided into three groups according to their levels of bAP: low (I), normal (II) or high (III). Patients with the highest bAP levels also presented the highest increase in bone resorption, according to their beta-CTX levels, and the highest degree of osteopenia. However, values of PINP were similar in the three groups of patients. The bAP/beta-CTX ratios in subgroups I, II and III of AN patients were 0.035, 0.065 and 0.073, a finding that suggests that bAP is not indicating the real degree of bone mineralization in these patients, because it is a contradiction that the formation/resorption ratio should be higher in the patients who have the highest bone loss. These results could suggest that bone loss in AN is produced by an increase in bone resorption (beta-CTX), without variations in bone matrix formation (PINP); bAP levels are a good marker in the follow-up of osteopenia degree, but not a real indicator of bone mineralization, a similar situation to that of osteomalacia.
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PMID:A variation in Bone Alkaline Phosphatase levels that correlates positively with bone loss and normal levels of aminoterminal propeptide of collagen I in girls with anorexia nervosa. 1048 28

The objective of this study was to evaluate the effect of surgical menopause and hormone replacement therapy (HRT) on the new biochemical markers of bone turnover. Fourteen women who had undergone surgical menopause and began HRT 3 months after surgery were recruited for a 1-year study. Results were compared with a control group of 31 healthy premenopausal women of similar age. Serum samples were obtained to determine total alkaline phosphatase, bone alkaline phosphatase, propeptides carboxy- and amino-terminal of type I procollagen (PICP, PINP), osteocalcin, tartrate-resistant acid phosphatase, and carboxy-terminal telopeptides of type I collagen (ICTP and serum CTX). Urine samples were analyzed for hydroxyproline, pyridinoline, deoxypyridinoline, alpha- and beta-carboxy-terminal telopeptides of type I collagen (alpha-CTX and beta-CTX), and amino-terminal telopeptide of type I collagen (NTX). Determinations were performed after 3 months of surgical menopause and after 3 and 9 months of HRT. All biochemical markers increased after menopause, and most of them normalized after 9 months of HRT. Serum PINP showed the highest proportion of increased values after surgery among bone formation markers (62%), as well as the highest mean percent increase (101%). Among bone resorption markers in postmenopausal women, urinary beta-CTX, alpha-CTX, NTX, and serum CTX showed the highest proportion of increased values (100%, 67%, 58%, 58%, respectively) as well as the greatest mean percent increase. They were also the markers with the most marked response to HRT. In conclusion, serum PINP is the most sensitive marker of bone formation, whereas beta-CTX is the most sensitive marker of bone resorption after surgical menopause. In addition, both markers showed the highest response after HRT.
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PMID:Biochemical markers of bone turnover after surgical menopause and hormone replacement therapy. 1049 39


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