Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Organ transplantation is associated with relevant bone loss. Bone loss of up to 20% of pretransplant bone mineral density (BMD) values within the first year after kidney, liver, heart and lung transplantation has been reported. Patients undergoing transplantation of hematopoietic stem cells provide an interesting model to study transplantation-induced bone loss, especially because most patients do not have preexisting bone disease. A longitudinal study was performed in 81 patients undergoing bone marrow or peripheral blood stem cell transplantation. BMD was determined by dual-energy X-ray absorptiometry before transplantation, at discharge from the hospital, and at 6 and 12 months after transplantation in all 81 patients. In 35 patients BMD was re-evaluated 24 months after transplantation. Vitamin D and parathyroid hormone, bone alkaline phosphatase as a marker of bone formation, and N-terminal telopeptide of type I collagen as a marker of bone resorption were assessed before transplantation and in the short-term follow-up 14 and 28 days after transplantation. The majority of patients (72%) showed normal BMD before transplantation. However, lower BMD was observed in patients who had received high-dose cytoreductive chemotherapy before transplantation compared with those who had received no chemotherapy or only hydroxyurea. Despite supplementation with elemental calcium (1000 mg/day) and vitamin D (1000 IU/day), the mean rate of bone loss during the first year was 7.2 +/- 6.3% at the lumbar spine, 11.9 +/- 8.1% at the femoral neck and 3.8 +/- 2.5% at the total body compartment. Evaluation of the pattern of bone loss during the first year demonstrated that the amount of bone loss was largest within the first 40 days after transplantation and small during the second half of the first year after transplantation. The majority of patients showed vitamin D deficiency and secondary hyperparathyroidism. Bone formation was normal before and after transplantation, whereas bone resorption was dramatically increased before and after transplantation. Exposure to glucocorticoids was associated with higher bone loss at spine and femoral neck but not at the total body compartment. Our data demonstrate rapid bone loss in patients undergoing transplantation of hematopoietic stem cells. Bone turnover is characterized by biochemical uncoupling of bone resorption and bone formation, changes interestingly pre-existing before transplantation. The observed alterations in bone mass and metabolism emphasize the importance of clinical trials with antiresorptive agents to prevent and treat post-transplantation osteoporosis in this group of patients.
 ...
PMID:Bone loss in long-term survivors after transplantation of hematopoietic stem cells: a prospective study. 1092 25

It was hypothesized that the widespread structural defect of collagen in connective tissue of vitamin B6 deficient-animals and the consequent alteration in bone biomechanical properties cause an additional stress to their inflamed swollen tibiotarsometatarsal joints. The present study showed a 32% elevation (P < 0.02) in mean plasma free cortisol concentration. Vitamin D metabolism was impaired but without changing plasma calcium homeostasis and bone mineral content. Mean plasma calcitriol [1,25(OH)2D] concentration was significantly reduced (P < 0.001). Because plasma calcidiol concentration did not change, we speculated that either renal 25-hydroxycalciferol-1alpha-hydroxylase activity was reduced or 1,25(OH)2D turnover was increased. Plasma osteocalcin, an index of osteoblast function related to bone formation, was significantly decreased (P < 0.05). This adverse effect on osteoblasts was consistent with the reduction of bone specific alkaline phosphatase activity (another index of bone formation) found in a previous study. The excess of cortisol may have impaired these bone cells functions directly and (or) indirectly via the decline in calcitriol synthesis. Plasma hydroxyproline concentrations in B6-deficient animals were found to be significantly reduced (P < 0.001), suggesting that cortisol in excess had also a suppressive effect on another hydroxylase, namely tissue (mainly bone and liver) prolyl hydroxylase. The bone uncoupling (in formation and resorption) associated with vitamin B6 deficiency seems to be due to secondary hypercortisolism and (or) another unknown factors but not related to a change in bone modulators such as IGF-1 and eicosanoids.
 ...
PMID:Perturbations in factors that modulate osteoblast functions in vitamin B6 deficiency. 1110 Sep 39

In vitro studies and animal experiments suggest that the production of 1,25-dihydroxyvitamin D [1,25-(OH)(2)D] and 24,25-(OH)(2)D is reciprocally controlled by 1,25-(OH)(2)D. To investigate the role of the vitamin D receptor (VDR) in controlling vitamin D metabolism in humans, we studied 10 patients with vitamin D-dependent rickets type II due to a defective VDR. After a period of high dose calcium therapy, 7 of the patients had normal serum calcium, phosphorus, alkaline phosphatase, and plasma PTH levels (PTH-N), and 3 showed increased serum alkaline phosphatase and plasma PTH (PTH-H). Serum calcium, phosphorus, alkaline phosphatase, PTH, vitamin D metabolites, urinary calcium/creatinine, and renal phosphate threshold concentration were compared with unaffected family members that comprised the control group. Vitamin D metabolites were measured before and after an oral load of 50,000 U/m(2) cholecalciferol. Compared with the control group, 1,25-(OH)(2)D levels were significantly higher and 24,25-(OH)(2)D levels were lower in the PTH-N group and even more so in the PTH-H group. 1alpha-Hydroxylase (1-OHase) and 24-OHase activities were estimated by the product/substrate ratio. In the PTH-N group, 1-OHase activity was higher and 24-OHase activity was lower than in controls. In the PTH-H group, 1-OHase activity was even higher, probably due to an additive effect of PTH. Thus, 1,25-(OH)(2)D-liganded VDR is a major control mechanism for vitamin D metabolism, and PTH exerts an additive effect. Assessment of the influence of 1,25-(OH)(2)D shows reciprocal control of enzyme activity in man, suppressing 1-OHase and stimulating 24-OHase activity.
 ...
PMID:The role of the vitamin D receptor in regulating vitamin D metabolism: a study of vitamin D-dependent rickets, type II. 1134 83

Vitamin D status is currently considered among the relevant determinants of skeletal integrity. Since vitamin D levels present seasonal variations, we longitudinally studied young healthy men and women in order to investigate the related physiologic modifications of both calcium homeostasis and bone remodeling. Thirty-two men (mean age 39.4 +/- 7.8 years) and 58 premenopausal women (aged 36.9 +/- 6.4 years) from southern Italy were studied. In all subjects the following parameters were measured both in winter and in summer: serum calcium, phosphorus, creatinine, total alkaline phosphatase activity, 25-hydroxyvitamin D (25OHD), parathyroid hormone (PTH), osteocalcin (BGP), together with urinary calcium (Ca/Cr), total pyridinoline (Pyr/Cr) and deoxypyridinoline (d-Pyr/Cr), corrected for creatinine excretion. In both sexes 25OHD levels were significantly higher in summer, while PTH values were lower, than in winter. The prevalence of hypovitaminosis D, defined by concentrations of 25OHD lower than 30 nmol/l, was 17.8% in winter and 2.2% in summer in the whole sample, while it was 27.8% and 3.4%, respectively, among female subjects. Indeed male subjects did not display hypovitaminosis D, having throughout the year significantly higher calcium and 25OHD levels together with lower PTH values, than the women. Moreover, alkaline phosphatase total activity was more elevated in men both in winter and in summer. In women, during winter, bone remodeling markers levels were higher while urinary calcium levels were lower than in summer. In the whole sample serum 25OHD correlated positively with serum calcium and inversely with PTH. The seasonal percentage variations in PTH were inversely correlated with those of Ca/Cr. Our results show a relatively high prevalence of subclinical vitamin D deficiency among young healthy women from southern Italy. Significant gender-specific differences have been demonstrated in both calcium homeostasis and skeletal remodeling indexes; the seasonal fluctuations in the vitamin D-PTH axis are accompanied by cyclical variations of bone turnover rate, which were more pronounced in women.
 ...
PMID:Longitudinal evaluation of vitamin D status in healthy subjects from southern Italy: seasonal and gender differences. 1184 28

Vitamin D derivatives correct high bone remodeling by decreasing plasma iPTH concentration in uremic patients with secondary hyperparathyroidism. However, without bone biopsy, plasma iPTH alone might not provide sufficient information regarding vitamin D-induced bone changes. Plasma bone-specific alkaline phosphatase (bAP) seems more sensitive than iPTH in assessing the degree of bone remodeling. We prospectively studied the evolution of iPTH and bAP in 14 adult hemodialysis patients treated for 1 year by i.v. alfacalcidol pulses. The mean total alfacalcidol dose was 0.08 +/- 0.02 g/kg/week. Ten patients completed the study, 2 patients had to be parathyroidectomized before week 24 because of hypercalcemia and uncontrolled hyperphosphatemia, and 2 other patients died before week 36. Mean iPTH levels diminished from 826 +/- 300 pg/ml (range 507 - 1,500 pg/ml) at baseline to 436 +/- 371 pg/ml (range 18 - 1,095 pg/ml) after 52 weeks of treatment (48% of decrease). Only 2 patients normalized plasma iPTH levels while 8/10 normalized bAP. Five patients remained with plasma iPTH concentrations higher than 5-fold the normal value. In contrast, plasma bAP levels declined from 47.6 +/- 32.2 ng/ml (range 15.4 - 130.0 ng/ml) at baseline to 17.8 +/- 9.9 ng/ml (range 8.0 +/- 38.0 ng/ml) at week 52 (63% of decrease). Bone histomorphometry was available in 6 patients after 15.8 +/- 5.1 months of alfacalcidol treatment. None of them met the criteria of adynamic bone disease as they had increased bone resorption and marrow bone fibrosis. Bone formation rate was normal in 2 patients and unmeasurable in the other 4. Two patients showed signs of osteomalacia. In conclusion, alfacalcidol preferentially reduced bone formation rate rather than the other histological parameters of secondary hyperparathyroidism. It reduced plasma bAP more efficiently than iPTH.
 ...
PMID:Plasma bone-specific alkaline phosphatase changes in hemodialysis patients treated by alfacalcidol. 1200 42

We observed changes of endothelin content and endothelin mRNA in vivo in vascular calcification and in vitro in calcification of vascular smooth muscle cells to explore the role of endothelin in vascular calcification. Calcification model in vivo was induced by administration of Vitamin D(3) plus nicotine. Calcification of vascular smooth muscle cells (VSMCs) was induced by beta-glycerophosphate. Endothelin content was measured by using radioimmunoassay. Endothelin mRNA amount was determined by using competitive quantitative RT-PCR. The results showed that calcium content, 45Ca(2+) uptake and alkaline phosphatase (ALP) activity were increased in calcified VSMCs, compared with controls, but were decreased, compared with calcified VSMCs plus BQ123 group. The endothelin content in the medium and endothelin mRNA in VSMCs were elevated by 35 and 120% (P<0.05), respectively, compared with those normal VSMCs. Calcium content, 45Ca(2+) accumulation and ALP activity in calcified arteries increased by 5.0-, 1.4-, and 1.4-fold. The endothelin levels in plasma and aorta as well as the amount of endothelin mRNA in calcified aorta were increased by 102, 103, and 22%, respectively, compared with control group. However, calcium content, 45Ca(2+) uptake and ALP activity in VDN plus bosentan group was 33, 36.7, and 40.4% lower than those in VDN group. These results indicated an upregulated endothelin gene expression as well as an increased production of endothelin in calcified aorta and VSMCs with BQ123 and bosentan significantly reducing vascular calcification. This suggested that endothelin might be involved in pathogenesis of vascular calcification.
 ...
PMID:Endothelin-1 is a potent regulator in vivo in vascular calcification and in vitro in calcification of vascular smooth muscle cells. 1461 85

Renal ostedystrophy (ROD) is a major long-term complication in uremic patients. Bone histomorphometry still remains the gold standard for the diagnosis of ROD. However, the low acceptance grade by patients makes bone biopsy a rarely performed and not easily repeatable investigation. No other instrumental assessment has been proved as yet to have sufficient sensitivity for ROD diagnosis. Many biochemical markers have been proposed for a diagnostic role, but few have a real predictive diagnostic value. Serum intact PTH (i-PTH) levels are thought to represent a good predictor of bone lesions. However, although a i-PTH level greater than 450 pg/mL and lower than 120 pg/mL may well predict high and low bone turnover disease respectively, in the wide range of values defined by the above border levels i-PTH does not have a predictive role for ROD. There is as yet no definite proof that the recently developed PTH assays might increase their diagnostic sensitivity. Bone alkaline phosphatase is a more reliable index of bone turnover than i-PTH levels. With regards to Al overload, given that an iron overburden is excluded, serum Al levels lower than 30 ug/L are seldom associated with increased Al deposition; conversely, levels above 60 mg/L are highly diagnostic for Al overload. In the latter condition, a DFO test is recommended. The main goals of ROD treatment are a) to maintain serum i-PTH levels between 120 and 150 pg/mL; b) to bring the phosphate (Pi) concentration under 5.5 mg/dL, Ca concentration between 9.2 and 10.4 mg/dL, and the Ca x Pi product under 55 mg/dL; c) to bring Al concentration under 20 ug/L; and d) to target serum bicarbonate levels between 20 and 24 mmol/L. The main therapeutic approaches include: Dietary Pi intake control (< 1200 mg/day). Intestinal phosphate binding using calcium salts and sevelamer. Calcium salts must be used at a dosage that avoids Ca overload (< 23 g/day). If Pi control is not reached, Mg and Al salts may be added at a dose lower than 2 g/day and for less than 3 months. Appropriate dialysis dose (KT/V > 1.2) and dialysis time (consider increased dialysis duration or session number for a week). Ca concentration in dialysate and infusion fluids can range between 1.25 and 2.00 mmol/L, according to the dialysis technique and to maintain an appropriate Ca balance. Vitamin D should not be used when i-PTH levels are < 120 pg/mL and/or serum Ca > 11 mg/dL and/or Pi > 6.5 mg/dL. The vitamin D dose should be proportional to PTH levels, with a larger dose given as a bolus (23 ug twice or three times per week). The intravenous route should be preferred in the case of very high i-PTH (> 700 pg/mL) or after 3 months of unsuccessful oral treatment. PTX should be prescribed on the basis of the clinical, biochemical, and instrumental data. A 7/8 PTX, when possible, is the most advisable procedure. Bone transplant disease (BTD) is caused by a combination of previous uremic ROD and bone lesions occurring after renal transplantation, mainly secondary to steroid effect. The main clinical result of BTD is the osteopenicosteoporotic syndrome, which frequently results in bone fractures. The most effective treatment of BTD is a reduction of the cumulative steroid dose. No strong evidence has been produced as yet for a preventive role of either bisphosphonates or vitamin D supplementation on BTD.
 ...
PMID:[Renal osteodystrophy Guidelines]. 1466 5

We studied the influence of age, gender, latitude, season, diet and ethnicity on plasma 25-hydroxyvitamin D 25 OHD, PTH, 1,25-dihydroxyvitamin D, vitamin D-binding protein, bone-specific alkaline phosphatase, and osteocalcin levels in 46 Greenlanders living in Nuuk (64 degrees N) on a traditional fare (group A), 45 Greenlanders living in Nuuk on a westernized fare (group B), 54 Greenlanders (group C), and 43 Danes (Group D) living in Denmark (55 degrees N) on a westernized fare. Blood specimens were drawn both summer and winter. Vitamin D insufficiency (plasma 25 OHD <40 nmol/l) was common in all four study groups during summer (23-74%) and winter (42-81%). Compared to groups A and D, vitamin D insufficiency was significantly more frequent in groups B and C. In all groups, summer levels of 25 OHD were above winter levels. Multiple regression analysis revealed a significant effect of ethnicity. Compared to Danes, Greenlanders had higher 1,25-dihydroxyvitamin D levels, but lower 25 OHD and PTH levels despite relatively low plasma calcium concentrations. In addition to ethnicity, 25(OH)D levels were influenced by age, season (summer > winter), and diet (a traditional Inuit diet>westernized diet). Ethnic differences exist between Greenlanders and Danes. Our results suggest that Greenlanders may have an inherent lower "set-point" for calcium-regulated PTH release or an enhanced renal 1,25(OH)(2)D production. In addition to ethnicity, age, season, and diet were important determinants of vitamin D status. Changes from a traditional to a westernized fare are associated with a reduced vitamin D status in Greenlanders. Vitamin D supplementation should be considered.
 ...
PMID:Vitamin D insufficiency in Greenlanders on a westernized fare: ethnic differences in calcitropic hormones between Greenlanders and Danes. 1470 40

There are limited data on vitamin D insufficiency in healthy children. The aim of this study was to describe the prevalence and determinants of vitamin D insufficiency and its association with bone turnover in adolescent boys (N = 136, mean age 16 years). Sun exposure and physical activity were assessed by questionnaire. Vitamin D stores were assessed by serum 25-hydroxyvitamin D3 (25[OH]D3). Bone turnover was assessed by bone-specific alkaline phosphatase (BAP) and urinary pyridinoline (PYR) to creatinine (Cr) ratio (mmol PYR/micromol Cr). The mean 25(OH)D3 level was low (44 nmol/l; 68% < 50 nmol/l; range, 16-87) and was associated with self-reported sun exposure on winter weekends (r = 0.23, p = 0.01), school holidays (r = 0.22, p = 0.01), and weekdays (r = 0.17, p = 0.05). It was also associated with number of sports (r = 0.34, p < 0.001) and vigorous activity (r = 0.22, p = 0.01) but not television, computer, and video watching (r = -0.04, p = 0.68). In multivariate analysis, number of sports but not total sun exposure remained significantly associated with 25(OH)D3. Furthermore, 25(OH)D3 was significantly associated with BAP in cutpoint analysis (cutpoint 55 nmol/l, p = 0.03) but not continuous analysis (r = -0.12, p = 0.16) and PYR in both forms (r = -0.23, p = 0.01, cutpoint 43 nmol/l, p = 0.01). In conclusion, vitamin D insufficiency is common in healthy adolescent boys in winter in our setting, is primarily derived from sports-related sun exposure, and is associated with bone turnover markers. These data suggest that a 25(OH)D3 level of at least 43-55 nmol/l is required for optimal bone health in children.
 ...
PMID:Vitamin D insufficiency in adolescent males in Southern Tasmania: prevalence, determinants, and relationship to bone turnover markers. 1544 89

Vitamin D insufficiency is common in patients with primary hyperparathyroidism (PHPT) and may be associated with more severe and progressive disease. Uncertainty exists, however, as to whether repletion of vitamin D should be undertaken in patients with PHPT. Here we report the effects of vitamin D repletion on biochemical outcomes over 1 yr in a group of 21 patients with mild PHPT [serum calcium <12 mg/dl (3 mmol/liter)] and coexistent vitamin D insufficiency [serum 25 hydroxyvitamin D [25(OH)D] <20 microg/liter (50 nmol/liter)]. In response to vitamin D repletion to a serum 25(OH)D level greater than 20 microg/liter (50 nmol/liter), mean levels of serum calcium and phosphate did not change, and serum calcium did not exceed 12 mg/dl (3 mmol/liter) in any patient. Levels of intact PTH fell by 24% at 6 months (P < 0.01) and 26% at 12 months (P < 0.01). There was an inverse relationship between the change in serum 25(OH)D and that in intact PTH (r = -0.43, P = 0.056). At 12 months, total serum alkaline phosphatase was significantly lower, and urine N-telopeptides tended to be lower than baseline values (P = 0.02 and 0.13, respectively). In two patients, 24-h urinary calcium excretion rose to exceed 400 mg/d, but the group mean 24-h urinary calcium excretion did not change. These preliminary data suggest that vitamin D repletion in patients with PHPT does not exacerbate hypercalcemia and may decrease levels of PTH and bone turnover. Some patients with PHPT may experience an increase in urinary calcium excretion after vitamin D repletion.
 ...
PMID:Vitamin D repletion in patients with primary hyperparathyroidism and coexistent vitamin D insufficiency. 1564


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>