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)

Observational studies suggest that statin use may be associated with lower incidence of fracture. However, there are conflicting data for their effects on bone remodeling parameters and bone mineral density (BMD). In the present study, we aimed to investigate the effects of simvastatin on bone metabolism and BMD in subjects with hypercholesterolemia (>240 mg/dl). For this purpose, 32 postmenopausal osteopenic subjects who were given simvastatin treatment (20 mg/day) and not on osteoporosis treatment were included in the study. During the 1-year follow-up period, the total cholesterol level decreased from 262.1+/-30.9 to 202.2+/-30.1 mg/dl (p<0.0001). At a period as early as the 3rd month, levels of the anabolic markers, e.g., bone-specific alkaline phosphatase (BSAP) and osteocalcin (OCL), were found to be significantly increased (from 120.8+/-56.6 to 149.5+/-57.6 IU/l, p=0.008, and from 20.8+/-12.6 to 34.7+/-18.4 microg/l, p=0.015, respectively) while no significant change was observed in the resorptive marker of serum N-telopeptide of type I collagen (CTX). At the 6th and 12th month, BSAP and OCL were both found to be decreased below the pretreatment values. While a significant reduction was found in BSAP levels (from 120.8+/-56.6 to 55.9+/-18.8 IU/l, p<0.001), no significant change was observed in CTX levels after the 6-month treatment period. Parathyroid hormone showed a gradual profound increase during the follow-up period (from 62.7+/-41.5 to 108.4+/-51.7 pg/ml, p<0.001). No significant change was found in BMD levels at the spine, femoral neck, Ward's triangle, and trochanter at the end of the 1-year follow-up period. In conclusion, simvastatin treatment showed a short-lasting anabolic effect on bone metabolism. However, this effect was lost by prolongation of therapy. The decrease in both anabolic and resorptive markers at the 6th and 12th month suggests that simvastatin affects bone metabolism mostly in favor of inhibition of the bone turnover in a long-term observation period although this inhibitory effect was not reflected in BMD.
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PMID:Effects of simvastatin on bone mineral density and remodeling parameters in postmenopausal osteopenic subjects: 1-year follow-up study. 1574 22

Studies determining the association between hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) and bone metabolism are mixed. We conducted a systematic review to assess the potential impact of statins on fractures, bone mineral density and bone markers. We searched Medline, Embase, the Cochrane Library, and Federal Research in Progress (FEDRIP). Inclusion criteria consisted of human studies with measurable outcomes, which were rated as good or fair according to the United States Preventive Services Task Force (USPSTF) criteria. The effects of statins on bone mineral density (BMD), bone markers and fracture risk were independently extracted by two reviewers and were combined by use of a random-effects model. The 31 analyzed studies included 24 observational studies and seven randomized controlled trials. Overall, statin use was associated with fewer hip fractures (OR 0.60, 95% CI 0.45-0.78) and improved hip BMD (Z score 0.12, 95% CI 0.05-0.19), with a non-significant reduction in vertebral fractures and no effect on vertebral BMD. In subgroup analysis of studies that involved only women there was a reduction in hip fractures (OR 0.75, 95% CI 0.60-0.95) and improvement in hip BMD (Z score 0.11, 95% CI 0.04-0.18). Vertebral BMD was unchanged, and only one study reported on vertebral fractures, finding improvement. Statins had only small effects on bone markers, with a decrease in alkaline phosphatase [standardized mean difference (SMD) -0.18, 95% CI -0.34 to -0.01], an increase in NTX (SMD 0.39, 95% CI 0.07-0.71), with no effect on osteocalcin or CTX. The statistically significant improvement in hip fracture risk was seen only in case-control trials, not in either the eight prospective trials or the two randomized controlled trials (RCTs). Statins may have a beneficial impact on bone metabolism and fracture risk; randomized controlled trials are needed to explore this association.
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PMID:Hydroxymethylglutaryl-coenzyme A reductase inhibitors and osteoporosis: a meta-analysis. 1574 53

In striving to refine the clinical utility of different markers of bone metabolism, we should take into account numerous confounders, many of which are well known, such as sampling time, fasting status, and bone density. One further confounder may be ongoing fracture healing and/or post-fracture immobilization, which at least theoretically should impose an increased bone formation and resorption. Since both recent fracture and high bone turnover are independent predictors for new fracture, we thought it of importance to define the potential influence of such fracture on markers of bone turnover. From a population-based cohort of 1604 women, all 75 years old (the OPRA-study), 1024 women attended a clinical examination. The bone metabolism was assessed in serum, by three markers of bone formation [bone-specific alkaline phosphatase (S-Bone ALP), intact and N-Mid osteocalcin (S-Total OC), and total carboxylated osteocalcin (S-cOC)], two markers of bone resorption [C-terminal cross-linked telopeptides of type I collagen (S-CTX) and tartrate-resistant acid phosphatase type 5b (S-TRACP5b)], and in urine by one marker of bone resorption [deoxypyridinoline/creatinine (U-DPD/crea)] and two putative markers of bone resorption [urinary osteocalcins (U-OC/crea)]. Current physical activity and retrospective fracture data were recorded by questionnaires. The fracture data, for the entire cohort of 1604 women, were validated with radiographic referrals and reports, saved since the beginning of the last century. All data provided, except date of occurrence of retrospectively sustained fracture, were thus obtained cross-sectionally and in all women at the age of 75. Fracture had ever been sustained by 727 of the entire cohort (n = 1604), and by 523 of the attending women (n = 1024). All markers were marginally higher (significant only for U-DPD/crea, P = 0.027) in women who had ever sustained fracture, compared to women without fracture. In women with recent retrospective fracture (since 2 years) (n = 100), the levels of all markers, except the two S-OCs, were significantly higher (r = 0.20-0.33, P = 0.049-0.001) the more recently the fracture had been sustained. Women with low current physical activity had elevated levels of U-DPD/crea (P < 0.001) and one U-OC (P = 0.014), while the other markers were unaffected.
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PMID:Biochemical markers of bone turnover are influenced by recently sustained fracture. 1580 93

Bone density, bone turnover and fracture susceptibility were evaluated in 1,132 randomly recruited women, all 75 years old. Seventy-four of the women had diabetes, while 1,058 women did not. Areal bone mineral density (aBMD) of the hip and lumbar spine was investigated by dual energy X-ray absorptiometry (DXA), and bone mass of the calcaneus was measured by ultrasound. Urinary deoxypyridinoline/creatinine (U-DPD/Crea) and serum C-terminal cross-linked telopeptide of type 1 collagen (S-CTX) were assessed as markers of bone resorption. Serum bone-specific alkaline phosphatase (S-bone ALP) and serum osteocalcin (S-OC) were assessed as markers of bone formation. Also, serum 25(OH) vitamin D and serum parathyroid hormone (S-PTH) were assessed. Fracture susceptibility was evaluated retrospectively and prospectively for up to 6.5 years. In diabetic women, the aBMD of the femoral neck was 11% higher (p<0.001), and BMD of the lumbar spine was 8% higher (p=0.002) than in non-diabetic women. There was no difference in bone mass by ultrasound of the calcaneus. Women with diabetes had higher BMD of the femoral neck (p<0.001) and lumbar spine (p=0.03) also after correction for differences in body weight. In diabetic women, U-DPD/Crea, S-CTX, and S-OC were decreased when compared with non-diabetic women (p=0.001 or less). After correction for covariance of body weight and plasma creatinine, S-CTX (p<0.001) and S-OC (p<0.001) were still lower in the diabetic women. Diabetic patients had hypovitaminosis D (p=0.008), a difference explained by differences in time spent outdoors and body weight. S-PTH did not differ between the groups. Women with diabetes had no more lifetime fractures (52%) than women without diabetic disease (57%), (p=0.31). This study shows that elderly women with diabetes and without severe renal insufficiency have high bone mass and low bone turnover. The high bone mass and low bone turnover is not likely to have a strong influence on fracture susceptibility.
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PMID:Increased bone density and decreased bone turnover, but no evident alteration of fracture susceptibility in elderly women with diabetes mellitus. 1582 89

In the Western world, increased consumption of carbonated soft drinks combined with a decreasing intake of milk may increase the risk of osteoporosis. This study was designed to reflect the trend of replacing milk with carbonated beverages in a group of young men on a low-calcium diet and studies the effects of this replacement on calcium homeostasis and bone turnover. This controlled crossover intervention study included 11 healthy men (22-29 years) who were given a low-calcium basic diet in two 10-day intervention periods with an intervening 10-day washout. During one period, they drank 2.5 l of Coca Cola per day and during the other period 2.5 l of semi-skimmed milk. Serum concentrations of calcium, phosphate, 25-hydroxycholecalciferol, 1,25-dihydroxycholecalciferol (1,25(OH)2D), osteocalcin, bone-specific alkaline phosphatase (B-ALP) and cross-linked C-telopeptides (CTX), plasma intact parathyroid hormone (PTH) and urinary cross-linked N-telopeptides (NTX) were determined at baseline and endpoint of each intervention period. An increase in serum phosphate (P<0.001), 1,25(OH)2D (P<0.001), PTH (P=0.046) and osteocalcin (P<0.001) was observed in the cola period compared to the milk period. Also, bone resorption was significantly increased following the cola period, seen as increased serum CTX (P<0.001) and urinary NTX (P<0.001) compared to the milk period. No changes were observed in serum concentrations of calcium or B-ALP. This study demonstrates that over a 10-day period high intake of cola with a low-calcium diet induces increased bone turnover compared to a high intake of milk with a low-calcium diet. Thus, the trend towards a replacement of milk with cola and other soft drinks, which results in a low calcium intake, may negatively affect bone health as indicated by this short-term study.
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PMID:Short-term effects on bone turnover of replacing milk with cola beverages: a 10-day interventional study in young men. 1588 60

Population studies have shown that about 3-5% of perimenopausal women already have osteoporosis according to the WHO definition of osteoporosis for postmenopausal women ( t -score<or=-2.5). In general, this bone loss arises from well-characterized diseases or conditions that affect acquisition of peak bone mass and/or the rate of bone loss after peak bone mass has been attained. However, there often remains a subset of these women, with no identifiable cause of bone loss. This group has so far been little studied. We prospectively evaluated a group of 60 perimenopausal and early postmenopausal women (mean age 52.2+/-2.5 years) who were found to have apparently unexplained low bone mass, and we compared them to 120 controls matched for age and menopausal status. These women were extensively investigated, including by detailed questionnaire and laboratory testing. Of the 60 women with osteoporosis, only three were found to have previously undiagnosed disorders (two with subclinical hyperthyroidism and one with elevated serum PTH levels) that might have contributed to their low bone mass. On the other hand, osteoporotic patients were characterized by a significantly lower body weight, higher prevalence of personal and parental histories of fractures and a higher level of bone turnover as assessed by increased serum osteocalcin and bone alkaline phosphatase levels and urinary type I collagen C-telopeptide (CTX) excretion, as compared to controls. These findings support theories of a genetic contribution to osteoporosis and underline the predictive value of a previous history of personal and familial fracture in the identification of osteoporosis in early postmenopausal women.
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PMID:Osteoporosis in otherwise healthy perimenopausal and early postmenopausal women: physical and biochemical characteristics. 1602 26

An increase in parathyroid hormone (PTH) levels in chronic renal failure (CRF) induces bone abnormalities known as renal osteodystrophy (ROD). The aim of the present study was to evaluate alternative biochemical methods to bone biopsy, to evaluate changes in bone remodeling in renal patients. Intact PTH (iPTH) and bone markers were measured in 43 predialysis (PD), 49 hemodialysis patients (HD) and 185 controls. betaCTXs, bone alkaline phosphatase (bAL), iPTH were higher and creatinine clearance (Ccr) was lower in PD and HD compared with controls (p < 0.0001). In both renal groups, a positive correlation was found between iPTH and both betaCTXs and bAL (p < 0.0001) and between betaCTXs and bAL (p < 0.002). PD patients with Ccr < 40 ml/min had higher iPTH, bAL and betaCTXs (p<0.004, p<0.05 and p<0.001, respectively) than patients with Ccr > 40 ml/min. betaCTXs (p < 0.05) in PD and betaCTXs and bAL in HD patients were higher than controls, even when iPTH was within normal range (< 65 pg/ml). Patients with severe secondary hyperparathyroidism showed higher bone markers than patients with normal or moderately increased iPTH (p < 0.001). These results suggest that even when there is no increase in iPTH, bone remodeling increases (possibly due to other factors) exhibiting higher bone resorption, and betaCTXs would seem to be an adequate non-invasive tool to assess early bone changes in CRF and prevent future fractures. Bone marker measurements in ROD would be useful to identify patients who may require bone biopsy. However, further studies comparing both methods must be performed before replacing bone biopsy with serum beta-CTX.
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PMID:[Serum beta-type I collagen carboxyterminal telopeptide (beta-CTXs) and bone involvement in chronic renal failure]. 1619 10

The goal of the present study was to compare mobilization rate of calcium (Ca) from bone in pregnant and lactating goats and sheep. Blood samples were collected from goats and sheep monthly during pregnancy and at 1, 2, and 4 weeks postpartum (pp) and monthly during lactation until 6 months after parturition. Total bone mineral content (BMC) and total bone mineral density (BMD) were quantified using peripheral quantitative computed tomography at the same intervals as the blood was taken. Bone resorption was assessed by immunoassays quantitating two epitopes of the carboxyterminal telopeptide of type I collagen (ICTP, CTX). Bone formation was estimated by quantifying serum osteocalcin (OC) and bone-specific alkaline phosphatase (bAP). In addition, Ca and 1,25-dihydroxy vitamin D (1,25-VITD) concentrations were determined in serum. Mean ICTP and CTX concentrations of both animal species increased the first week after parturition. By the second week pp, the concentrations of both markers had decreased toward early gestation levels. In contrast, mean OC concentrations continually decreased until the 1st week pp. By the 2nd week pp, the mean concentrations of OC started to increase again. Mean bAP activities decreased during gestation and reached a nadir in the first week pp in goats and 4 weeks pp in sheep. Afterwards, mean bAP activities increased again in goats and sheep. 1,25-VITD concentrations peaked the first week pp and returned to early gestation values thereafter. Total BMC and BMD decreased from the 4th month of pregnancy until the 1st week pp in both species. Afterwards, BMC increased throughout the first month pp in goats and the first 3 months pp in sheep. BMD levels of sheep and goats returned to prepartum levels during lactation. The resorptive phase of bone remodeling is accelerated at parturition and in early lactation and is uncoupled from the process of bone formation. This allows the animal to achieve Ca homeostasis at the expense of bone. Increased bone remodeling during lactation may represent physiological mechanisms to help replace the maternal skeleton lost as the animal adapted to enormously increased Ca losses to the fetus and milk in late gestation and early lactation.
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PMID:The effects of first gestation and lactation on bone metabolism in dairy goats and milk sheep. 1636 7

Osteoporosis associated with estrogen deficiency results from an imbalance between bone resorption and formation, causing deterioration of bone architecture and decreased bone mass. Anti-osteoporotic therapies that have been developed so far include either anticatabolic or anabolic drugs. Strontium ranelate is a newly developed drug that induces opposite effects on bone resorption and formation. This dual original mode of action was demonstrated in experimental studies on bone cells and pharmacological studies in animals. In vitro, strontium ranelate was shown to decrease bone resorption. This effect resulted from a decreased differentiation and resorbing activity of osteoclasts and increased osteoclast apoptosis. In contrast, strontium ranelate was shown to enhance preosteoblastic cell replication and collagen synthesis in culture without affecting bone mineralization. In vivo, strontium ranelate promoted bone formation and reduced bone resorption in intact mice, an effect which resulted in increased vertebral bone mass. Additionally, strontium ranelate was found to reduce resorption and long bone loss induced by hind limb immobilization in rats. Finally, strontium ranelate administration decreased bone resorption and maintained bone formation in adult ovariectomized rats, which resulted in prevention of bone loss. In clinical trials (Spinal Osteoporosis Therapeutic Intervention [SOTI]), bone alkaline phosphatase levels increased, whereas C cross-linking telopeptide of type I collagen (CTX) levels decreased in patients treated with strontium ranelate compared with placebo at all time points. These pharmacological and clinical studies suggest that strontium ranelate acts by increasing bone formation and decreasing bone resorption and that these effects result in improved bone mass in vivo.
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PMID:Strontium ranelate: a physiological approach for optimizing bone formation and resorption. 1643 91

The purpose of this study was the investigation of serum concentration of serum C-telopeptide of type I collagen (s-CTX) and bone alkaline phosphatase (BALP) in Polish healthy children aged 2-18 years. We studied 141 healthy children (64 girls, 77 boys) divided into 3 age groups of both genders: prebubertal, pubertal and postpubertal. The level of s-CTX was determined by Serum CrossLaps One Step ELISA kit (Osteometer Bio Tech, Denmark) and the activity of BALP was measured using an enzyme immunoassay Alkphase-B kit (Metra Biosystems, USA). We observed that both markers of bone turnover showed sigmoid regression curves with increasing age. The peak values of s-CTX and BALP occurred during puberty in the girls aged 8-13 years (2266 +/- 368 ng/ml; 113.4 +/- 21.9 U/L) and in the boys aged 10-15 years (2139 +/- 489 ng/ml; 117.8 +/- 24.7 U/L). In all children after puberty, we observed a gradual lowering of both markers. However, girls showed decreased postpubertal values of s-CTX and BALP 2-3 years earlier than boys, reflecting the earlier completion of puberty in girls. The correlation between s-CTX and BALP was statistically significant (r = 0.578; p < 0.0001) in tested children. The results of this study will be useful in the diagnosis and monitoring of therapy in bone diseases.
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PMID:[Some bone turnover markers in serum of healthy children and adolescents in relation to age and gender]. 1652 55


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