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)

This study investigated the incidence and severity of hepatic osteodystrophy in patients with posthepatitic liver cirrhosis, and the role of hepatocellular injury in bone loss. Twenty-four patients (15 females and 9 males, mean age 49 +/- 13 years) with posthepatitic cirrhosis were enrolled in this study. The control group consisted of 22 healthy age and sex matched adults. The bone mineral density (BMD) was evaluated by dual energy x-ray absorptiometry of the L1-L4 vertebral bodies. A detailed questionnaire was used to assess the epidemiological findings. A statistically significant decrease in BMD of the patients was observed. There were no significant differences in the alkaline phosphatase, parathyroid hormone, calcitonin, 25-hydroxyvitamin D, osteocalcin, free testosterone, luteinizing hormone, follicle stimulating hormone, and estradiol levels, oral calcium intake, urinary calcium, phosphorus and hydroxypyroline excretion between patients and controls. The control group smoked more cigarettes, consumed more coffee and meat, and were exposed the sun light for a longer period than the study group. Multiple regression analysis showed that osteopenia depends significantly on the extent of liver disease. The data shows that the patients with posthepatitic cirrhosis had osteopenia, and that cirrhosis was a direct and independent risk factor.
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PMID:Osteodystrophy in posthepatitic cirrhosis. 1167 84

Renal transplant osteodystrophy encompasses several histologic subtypes. Bone histomorphometric examination reliably distinguishes these groups but is invasive, is time-consuming, and delays diagnosis. Establishing a noninvasive method of correctly predicting histologic subtype in an individual to direct management is an attractive proposition. We identified 19 female renal transplant recipients with histologic evidence of hyperparathyroid bone disease (HPTH) and 14 with adynamic bone (ADB). We evaluated serum osteocalcin and bone-specific alkaline phosphatase as bone formation markers and urinary hydroxyproline (Hypro) and deoxypyridinoline cross-links as bone resorption markers. Mean concentrations for all markers were higher in the HPTH group, reaching significance for Hypro (HPTH, 24.8 +/- 4.2 micromol/mmol creatinine; ADB, 13.2 +/- 5.0 micromol/mmol creatinine; P = 0.01). A cutoff of 16.4 micromol/mmol creatinine for Hypro (Youden's index, 0.65) gave a sensitivity of 93% and specificity and positive predictive value (PPV) of 72% in predicting HPTH. In combination, Hypro greater than 16.4 micromol/mmol creatinine and parathyroid hormone greater than 80 pg/mL gave a specificity of 100%, sensitivity of 32%, and PPV of 100%. Conversely, for predicting ADB, Hypro less than 15.1 micromol/mmol creatinine (Youden's index, 0.45) gave a specificity of 93%, sensitivity of 53%, and PPV of 91%. Hypro less than 15.1 micromol/mmol creatinine plus osteocalcin less than 6.8 microg/L gave a specificity of 84.2%, sensitivity of 64.3%, and PPV of 75%. Significant associations between markers and histomorphometry were evident only for Hypro and osteocalcin (with osteoblast surface) and all markers (except deoxypyridinoline cross-links) with cortical volume. Markers have limited utility in identifying histologic subtype (Hypro was most effective) and, with the exception of Hypro and osteocalcin, showed little association with cell surface markers of bone cell activity.
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PMID:Biochemical measurements in the prediction of histologic subtype of renal transplant bone disease in women. 1214 13

Bone disease is observed in 75-100% of patients with chronic renal failure as the glomerular filtration rate (GFR) falls below 60 ml/minute. Hyperparathyroid (high turnover) bone disease is found most frequently followed by mixed osteodystrophy, low-turnover bone disease, and osteomalacia. With advancing renal impairment, "skeletal resistance" to parathyroid hormone (PTH) occurs. To maintain bone turnover, intact PTH (iPTH) targets from two to four times the upper normal range have been suggested, but whole PTH(1-84) assays indicate that amino-terminally truncated fragments, which accumulate in end-stage renal disease (ESRD), account for up to one-half of the measured iPTH. PTH levels and bone-specific alkaline phosphatase (BSAP) provide some information on bone involvement but bone biopsy and histomorphometry remains the gold standard. Calcitriol and calcium salts can be used to suppress PTH and improve osteomalacia but there is growing concern that these agents predispose to the development of vascular calcification, cardiovascular morbidity, low-turnover bone disease and fracture. Newer therapeutic options include less calcemic vitamin D analogues, calcimimetics and bisphosphonates for hyperparathyroidism, and sevelamer for phosphate control. Calcitriol and hormone-replacement therapy (HRT) have been shown to maintain bone mineral density (BMD) in certain patients with end-stage renal disease (ESRD). After renal transplantation, renal osteodystrophy generally improves but BMD often worsens. Bisphosphonate therapy may be appropriate for some patients at risk of fracture. When renal bone disease is assessed using a combination of biochemical markers, histology and bone densitometry, early intervention and the careful use of an increasing number of effective therapies can reduce the morbidity associated with this common problem.
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PMID:Pathophysiology and recent advances in the management of renal osteodystrophy. 1246 4

A cross-sectional study was developed with 100 of the first-time pre-dialysis patients visiting the Princesa University Hospital's Advanced Chronic Kidney Disease (ACKD) unit, with the aim of analysing various parameters of osteodystrophy at this time. Parameters evaluated were: age, gender, renal function, osteodystrophy serum parameters, comorbidity index (ICED) and the patients' origin to establish correlations between these parameters. Mean iPTH levels were higher irrespective of the patients' origin, and were significantly higher in men than in women, the former also having poorer renal function and higher comorbidity score. The mean levels of calcium, phosphorous, alkaline phosphatase and CO2 did not justify this rise in iPTH. Nutritional parameters NPNA and albumin were adequate in spite of ageing. At early stages of ESRD, iPTH could be elevated and ACKD units play an important part its early detection and subsequent treatment.
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PMID:[Evaluation of osteodystrophy parameters in a pre-dialysis unit]. 1277 53

In spite of essential enrichment of our pathophysiological knowledge in the field of the calcium-phosphate metabolism and bone alterations in renal transplant patients, both diagnosis and therapy of these abnormalities still remain a challenge for nephrologists and transplantologists. The present study aimed to establish the diagnostic value of traditional and contemporary markers of Ca-P metabolism and bone alterations in kidney transplant patients 4 or more years after Tx and the main factors responsible for osteodystrophy after Tx respectively. 61 patients and 21 controls were examined. The assessed parameters were: serum levels of total (Ca) and ionized calcium (Ca2+), serum concentration of phosphorus (P), intact PTH, calcitonin, osteocalcin, 25-OH-D3, collagen type I cross-linked C-telopeptide and activity of alkaline phosphatase (total and bone isoenzyme). In all subjects bone densitometry of the total body, L2-L4 vertebrae and femoral neck were performed. In kidney transplant patients routinely assessed markers of calcium-phosphate metabolism (Ca, Ca2+, P, alkaline phosphatase total and bone fraction) were in the normal range while significantly elevated serum concentrations of PTH, osteocalcin and CTx were found. In more than 20% of renal transplant patients osteoporosis and in further 50% patients osteopenia were found by DEXA. The intensity of bone abnormalities was dependent on the duration of dialysis therapy before Tx, time after Tx, degree of impairment of the graft, intensity of hyperparathyroidism and total dose of corticosteroids. From results obtained in this study estimation of serum concentration of 25-OH-D3, PTH, CTx and the BMD respectively is mandatory to detect Ca-P abnormalities and osteoporosis or osteopenia in Tx patients.
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PMID:[Markers of calcium--phosphate metabolism and bones alterations in long term kidney transplant patients]. 1505 34

Multiple factors can contribute to the development of osteodystrophy in patients with chronic liver disease (CLD). Recently, two new cytokines, osteoprotegerin (OPG) and the receptor activator of nuclear factor-kB ligand (RANKL), have been implicated in the pathogenesis of postmenopausal osteoporosis and other metabolic bone diseases. Therefore, the aim of our study was to evaluate bone metabolism, bone mineral density (BMD) and OPG/RANKL system in 65 male patients with CLD and in 65 healthy controls. Our patients showed lower BMD values than controls both at lumbar and femoral levels. Moreover, they had an unbalanced bone turnover with an increased resorption phase, as shown by high levels of urinary deoxypyridinoline and a decreased formation phase, as shown by the slightly, but significant, low levels of bone-alkaline phosphatase. Patients showed lower plasma levels of free-testosterone than controls and higher - although not significantly so - plasma levels of 17 beta-estradiol. Furthermore, patients with CLD had higher levels of sex hormone-binding globulin and OPG, and lower levels of 25-hydroxyvitamin D (25-HOD) and IGF-I than the control group, while RANKL levels were similar in the two groups. In conclusion, our data do not confirm the hypothesis that the OPG/RANKL system could exert a key role in the pathogenesis of hepatic osteodystrophy, but rather that the observed increase in OPG levels may represent either the result of the inflammatory process per se or a compensation for the observed enhanced bone resorption.
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PMID:Hepatic osteodystrophy: does the osteoprotegerin/receptor activator of nuclear factor-kB ligand system play a role? 1627 62

The aim of this study was to assess the clinical and laboratory correlations of bone mineral density (BMD) measurements among a large population of patients on chronic peritoneal dialysis (PD). This cross-sectional, multicenter study was carried out in 292 PD patients with a mean age of 56 +/- 16 years and mean duration of PD 3.1 +/- 2.1 years. Altogether, 129 female and 163 male patients from 24 centers in Canada, Greece, and Turkey were included in the study. BMD findings, obtained by dual-energy X-ray absorptiometry (DEXA) and some other major clinical and laboratory indices of bone mineral deposition as well as uremic osteodystrophy were investigated. In the 292 patients included in the study, the mean lumbar spine T-score was -1.04 +/- 1.68, the lumbar spine Z-score was -0.31 +/- 1.68, the femoral neck T-score was -1.38 +/- 1.39, and the femoral neck Z score was -0.66 +/- 1.23. According to the WHO criteria based on lumbar spine T-scores, 19.2% of 292 patients were osteoporotic, 36.3% had osteopenia, and 44.4% had lumbar spine T-scores within the normal range. In the femoral neck area, the prevalence of osteoporosis was slightly higher (26%). The prevalence of osteoporosis was 23.3% in female patients and 16.6% in male patients with no statistically significant difference between the sexes. Agreements of lumbar spine and femoral neck T-scores for the diagnosis of osteoporosis were 66.7% and 27.3% and 83.3% for osteopenia and normal BMD values, respectively. Among the clinical and laboratory parameters we investigated in this study, the body mass index (BMI) (P < 0.001), daily urine output, and urea clearance time x dialysis time/volume (Kt/V) (P < 0.05) were statistically significantly positive and Ca x PO(4) had a negative correlation (P < 0.05) with the lumbar spine T scores. Femoral neck T scores were also positively correlated with BMI, daily urine output, and KT/V; and they were negatively correlated with age. Intact parathyroid hormone levels did not correlate with any of the BMD parameters. Femoral neck Z scores were correlated with BMI (P < 0.001), and ionized calcium (P < 0.05) positively and negatively with age, total alkaline phosphatase (P < 0.05), and Ca x P (P < 0.01). The overall prevalence of fractures since the initiation of PD was 10%. Our results indicated that, considering their DEXA-based BMD values, 55% of chronic PD patients have subnormal bone mass-19% within the osteoporotic range and 36% within the osteopenic range. Our findings also indicate that low body weight is the most important risk factor for osteoporosis in chronic PD patients. An insufficient dialysis dose (expressed as KT/V) and older age may also be important risk factors for osteoporosis of PD patients.
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PMID:Bone mineral density and its correlation with clinical and laboratory factors in chronic peritoneal dialysis patients. 1636 3

Reduced bone density is commonly encountered in patients with chronic liver disease. Prior studies have shown that unconjugated bilirubin inhibits osteoblast activity and function in vitro and in animal models of bone mineralization. To determine whether hyperbilirubinemia promotes the development of hepatic osteodystrophy, bone mineral density (BMD) was measured by dual energy X-ray absorptiometry in a cohort of 86 consecutive patients with chronic liver disease referred for liver transplant evaluation. The mean age of the study population was 52 years (range, 22-73), in which 52% were female and 90% were white. Average bone density values were significantly lower than expected for age, race, and sex, with Z-scores for the femoral neck and spine of -0.50 (95% confidence interval [CI] -0.63 to -0.37; p=0.0003) and -0.69 (95% CI -0.85 to -0.52; p=0.0001), respectively. Sixty-one subjects (71%) exhibited reduced BMD (T-score of femoral neck or spine<or=-1 standard deviation [SD] below the young-adult mean), and 18 subjects (21%) met criteria for osteoporosis (T-score<-2.5 SD). Stepwise logistic regression analyses identified significant associations between BMD and serum creatinine, alkaline phosphatase, age, and gender. On the other hand, neither unconjugated, nor conjugated, nor total serum bilirubin levels were found to predict diminished BMD. The lack of association between serum unconjugated bilirubin levels and bone mineralization was validated in hyperbilirubinemic Gunn rats, in which BMD and serum osteocalcin levels were no different than in wild-type rodents. In conclusion, the finding that serum bilirubin levels do not correlate with reduced BMD in patients with end-stage liver disease, and that chronic unconjugated hyperbilirubinemia does not lead to alterations in bone mineralization in Gunn rats, suggests that bilirubin is not a major contributing factor to hepatic osteodystrophy.
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PMID:Hyperbilirubinemia is not a major contributing factor to altered bone mineral density in patients with chronic liver disease. 1673 39

Although renal osteodystrophy and vitamin D analogs may be related to survival in maintenance hemodialysis (MHD) patients, most studies have examined associations between baseline values and survival without accounting for variations in clinical and laboratory measures over time. We examined associations between survival and quarterly laboratory values and administered paricalcitol in a 2-year (July 2001-June 2003) cohort of 58,058 MHD patients from all DaVita dialysis clinics in USA using both time-dependent Cox models with repeated measures and fixed-covariate Cox models with only baseline values. Whereas hypercalcemia and hyperphosphatemia were robust predictors of higher death risk in all models, the association between serum calcium and mortality was different in time-varying models. Changes in baseline calcium and phosphorus values beyond the Kidney Disease Outcome Quality Initiative recommended targets were associated with increased mortality. Associations between high serum parathyroid hormone and increased death risk were masked by case-mix characteristics of MHD patients. Time-varying serum alkaline phosphatase had an incremental association with mortality. Administration of any dose of paricalcitol was associated with improved survival in time-varying models. Controlling for nutritional markers may introduce overadjustment bias owing to their strong collinearity with osteodystrophy surrogates. Whereas both time-dependent and fixed-covariate Cox models result in similar associations between osteodystrophy indicators and survival, subtle but potentially clinically relevant differences between the two models exist, probably because fixed models do not account for variations of osteodystrophy indices and changes in medication dose over time.
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PMID:Survival predictability of time-varying indicators of bone disease in maintenance hemodialysis patients. 1755 57

Normal bone homeostasis involves a balance between osteoblast and osteoclast action, regulated by hormones and cytokine stimuli. Hemodialysis patients appear to have increased production of interleukin-1 (IL-1), interleukin-6 (IL-6) and glycosaminoglycans (GAG) in serum. IL-1 plays a role in the synthesis, degradation and degree of sulphatation of ECM components such as glycosaminoglycans. Also, continuous changes in the ECM involve enzymes such as beta-N-acetyl-d-glucosaminidase (beta-NAG) and beta-d-glucuronidase (beta-GLU) which act on different GAG classes and collagen fibers. We examined the effects of IL-1alpha on ECM synthesis and the related enzymes in human uremic osteoblast cultures. We also measured the levels of IL-1beta, and IL-6 and alkaline phosphatase activity. In biopsies of uremic bone there was less ECM deposition than resorption associated with changes in osteoblast morphology. In vitro osteoblast proliferation was higher (P< or =0.01), and extracellular GAG lower (P< or =0.01) than in controls. The enzyme beta-NAG was high (P< or =0.05) but there were no noteworthy changes in beta-GLU. ELISA of the medium indicated spontaneous production of IL-1beta and IL-6, which significantly increased after IL-1alpha treatment compared to controls. IL-1alpha reduced alkaline phosphatase activity (P< or =0.01) in uremic osteoblast cultures. IL-1 acts on osteoblasts with decreases in GAG synthesis and alkaline phosphatase activity, while beta-NAG increases. This lead to a reduction in the organic component in ECM and its mineralization, and to changes in the regulation of cytokine activity by GAG. The enzymatic breakdown might be facilitated by metabolic acidosis and failed osteoblast differentiation; these factors could be correlated with different degrees of osteodystrophy.
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PMID:Glycosaminoglycan, collagen, and glycosidase changes in human osteoblasts treated with interleukin 1, and osteodystrophy. 1756 66


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