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)

Following total hip arthroplasty (THA), femoral periprosthetic bone undergoes a remodeling process that results in bone loss in its proximal regions that may compromise the long-term outcome of THA. Periprosthetic bone loss mainly occurs during the first postoperative months. The question is whether a postoperative treatment with alendronate is effective in reducing periprosthetic bone loss and which doses and duration of treatment are required. In a 12-month prospective, randomized double-blind study, 51 patients undergoing cementless THA were treated postoperatively either with a daily dose of 20 mg alendronate for 2 months and 10 mg for 2 months thereafter (group I), with 20 mg of alendronate for 2 months and 10 mg for 4 months thereafter (group II), or treated with placebo (group III). Proximal femoral bone mineral density (BMD) was measured with dual-energy X-ray absorptiometry (DEXA) and serum biochemical markers of bone turnover bone specific alkaline phosphatase, osteocalcin, and C-terminal telopeptides (CTX-I) were assayed. Six months of alendronate treatment significantly reduced (p<0.001) bone loss in proximal medial region (-10%) compared with placebo (-26%). All biochemical markers of bone turnover were suppressed by alendronate. These data suggest that alendronate administered for the first 6 postoperative months following THA was effective in preventing early periprosthetic bone loss.
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PMID:Alendronate prevents femoral periprosthetic bone loss following total hip arthroplasty: prospective randomized double-blind study. 1670 19

The increased bone remodeling in women after menopause induces an imbalance between bone resorption and formation, leading to decreased bone mass, altered bone microarchitecture, and increased fracture risk. Current antiosteoporotic drugs decrease bone remodeling or increase bone formation. Strontium ranelate (Protelos) is a newly developed antiosteoporotic drug that acts by reducing bone resorption and promoting bone formation, thereby inducing a positive bone balance. In rat and mouse culture models, strontium ranelate enhances preosteoblastic cell replication and bone formation markers. In contrast, it decreases rodent osteoclastic cell resorbing activity and human osteoclast differentiation, and increases rabbit osteoclast apoptosis. In vivo, strontium ranelate increases bone formation and reduces bone resorption in mice, resulting in increased vertebral bone mass. In rats, strontium ranelate increases bone mass and improves microarchitecture and bone geometry, resulting in increased bone resistance. In ovariectomized rats, strontium ranelate decreases bone resorption but maintains high bone formation, resulting in improved bone microarchitecture and increased bone mass and strength. In clinical trials, serum alkaline phosphatase levels increased whereas serum CTX levels simultaneously decreased in patients treated with Protelos versus placebo at all time-points. In these trials, histomorphometric analysis of bone biopsies showed that the osteoblast surface and mineral apposition rate increased whereas bone resorption parameters tended to decrease in treated patients compared to the placebo group. These preclinical and clinical data indicate that strontium ranelate acts by increasing bone formation and decreasing bone resorption, thus rebalancing bone turnover in favour of bone formation, an effect that results in increased bone mass and strength.
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PMID:Strontium ranelate: a dual mode of action rebalancing bone turnover in favour of bone formation. 1673 40

The present study was carried out to obtain an experimental model of vitamin D (vit D) insufficiency and established osteopenia (experiment 1) to then investigate whether vit D status, i.e. normal or insufficient, interferes with bone mass recovery resulting from bisphosphonate therapy (experiment 2). Rats (n = 40) underwent OVX (n = 32) or a sham operation (n = 8). The first 15 days post-surgery, all groups were kept under fluorescent tube lighting and fed a diet containing 200 IU% vit D (+D). They were then assigned during an additional 45 days to receive either +D or a diet lacking vit D (-D) and kept under 12 h light/dark cycles using fluorescent or red lighting. Serum 25HOD was significantly lower in -D rats (P < 0.0001). The type of lighting did not induce differences in 25OHD, calcium (sCa), phosphorus (sP), bone alkaline phosphatase (b-AL), CTX, bone density or histology. No osteoid was observed in undecalcified bone sections. Experiment 2 (105 days): rats were fed either +D or -D according to experiment 1 and were treated with either placebo or 16 mug olpadronate (OPD)/100 g rat/week during the last 45 days. Whereas 25HOD was significantly lower (P < 0.0001) in -D/OPD than in +D/OPD rats, no significant differences in sCa, sP, b-AL or CTX were observed. OPD prevented the loss of lumbar spine (LS) and proximal tibia (PT) BMD and the decrease in bone volume (BV/TV) (P < 0.05) and in the number of trabeculae observed in untreated rats. However, +D/OPD animals presented significantly higher values of LS BMD, PT BMD and BV/TV than -D/OPD rats (P < 0.05). No osteoid was observed in undecalcified sections of bone. In summary, this is the first experimental study to provide evidence that differences in vit D status may affect the anticatabolic response to bisphosphonate treatment. However, the molecular mechanism through which vit D insufficiency reduces the effect of the aminobisphosphonate remains to be defined.
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PMID:Vitamin D insufficiency reduces the protective effect of bisphosphonate on ovariectomy-induced bone loss in rats. 1676 65

Ospemifene is a novel selective estrogen receptor modulator (SERM) that is initially being developed for the treatment of vaginal atrophy in postmenopausal women. However, it also shows promise in the prevention and treatment of osteoporosis. As a part of a phase II trial, we compared the effects of ospemifene and raloxifene on bone turnover in postmenopausal women. The study was conducted as a randomized, double-blind study in which 118 healthy postmenopausal women received 30 (n = 29), 60 (n = 30), or 90 mg (n = 30) ospemifene or 60 mg (n = 29) raloxifene for 3 months. Bone resorption was assessed by measuring the urinary outputs of N- and C-terminal cross-linking telopeptides of type I collagen (NTX and CTX, respectively). Bone formation was assessed by measuring bone-specific alkaline phosphatase (bone ALP), osteocalcin (OC), procollagen type I N propeptide (PINP), and procollagen type I C propeptide (PICP) in serum. All markers were studied before and at 3 months and 2-4 weeks after cessation of the medication. Urine NTX outputs decreased in all study groups, and the only statistically significant difference in NTX was observed between raloxifene and 30 mg ospemifene, which was reduced more in the raloxifene group. The output of CTX decreased most clearly in 60- and 90-mg ospemifene groups, but no significant differences between study groups emerged. A significant difference was found between the 90-mg ospemifene group and raloxifene in PINP in favor of ospemifene. No other differences in bone formation markers emerged between ospemifene and raloxifene. The study confirms the bone-restoring activity of ospemifene, which is comparable to that of raloxifene.
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PMID:Effects of ospemifene and raloxifene on biochemical markers of bone turnover in postmenopausal women. 1681 26

Recently the third generation aromatase inhibitors have proved their efficacy and tolerability compared with tamoxifen in the adjuvant treatment of women with hormone responsive early breast cancer. However, there is some concern about the possible negative impact of these drugs on bone. The aim of the study was to evaluate the effects of the steroidal aromatase inactivator exemestane on bone turnover markers and on bone mineral density (BMD). Seventy postmenopausal women (62.0+/-8.9 years) with completely resected breast cancer and who were disease-free following 2-3 years on tamoxifen were randomly assigned to continue tamoxifen (n=36) or switch to exemestane (n=34). Sixty-one patients completed the 2-year study period. Bone alkaline phosphatase (B-ALP) and the carboxy-terminal telopeptide of type I collagen (CTX) were measured at baseline and after 3, 6, 9, 12, 18 and 24 months. BMD at lumbar spine (BMD-LS), at femoral neck (BMD-FN), at total hip (BMD-T) and at whole body (BMD-WB) were measured at 6-monthly intervals. Exemestane-treated women showed significant (p<0.01) increases with respect to baseline in both B-ALP and CTX. The difference between the 2 groups reached the statistical significance at month 6 for CTX (p<0.05) and at month 9 for B-ALP (p<0.01). Moreover, the exemestane-treated women showed an early decrease in PTH serum levels (-20.4%, p<0.01 at month 6). In the E group, the percentage changes were -2.37 (p<0.05) BMD-LS, -1.24 (p<0.05) BMD-FN, -1.1 (n.s.) BMD-T, -1.03 (n.s.) BMD-WB at month 12 and -2.99 (p<0.01) BMD-LS, -1.92 (p<0.01) BMD-FN, -2.01 (p<0.05) BMD-T, -1.3 (n.s.) BMD-WB at month 24. The tamoxifen group did not show significant changes in BMD. The differences between the two groups were significant at all skeletal sites except BMD-WB. Our data suggest that switching postmenopausal women from tamoxifen to exemestane causes a marked increase in bone turnover markers with a consequent reduction in BMD. These findings could be due to both the direct effect of exemestane and to the loss of the protective effect of tamoxifen. Therefore, the postmenopausal women switched from tamoxifen to exemestane should be monitored for bone loss especially if other risk factors for osteoporosis are present.
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PMID:Changes in bone turnover and in bone mass in women with breast cancer switched from tamoxifen to exemestane. 1690 60

The bone alkaline phosphatase (BALP) B1x isoform has previously only been identified in some adults with chronic kidney disease on dialysis and in human bone tissue. Twenty-nine patients, 3-20 years of age, with reduced renal function due to a variety of kidney diseases were examined. We measured parathyroid hormone (PTH), biointact (whole 1-84) PTH, osteoprotegerin (OPG), CrossLaps (CTX), tartrate-resistant acid phosphatase isoform 5b (TRACP 5b) type I procollagen intact amino-terminal propeptide (PINP), osteocalcin, total alkaline phosphatase (ALP), and BALP isoforms B/I, B1x, B1, and B2. Fifty percent higher levels were detected of PTH vs. biointact PTH, demonstrating non-(1-84) PTH fragments detected by the PTH assay. Increased activities were found in five, four, and three patients for total ALP, B1, and B2, respectively. Sixteen (55%) patients had increased B/I levels. B1x was identified in two (7%) patients, who had OPG levels in the higher range independently of age, glomerular filtration rate (GFR), and biointact PTH. B1x was identified prior to and after 9 days of growth hormone (GH) therapy in one patient but not after 1, 3, 6, and 12 months, however. In conclusion, our study demonstrates that the novel BALP B1x isoform is occasionally found to be present in children with kidney disease but to a lesser degree in comparison with adults with chronic kidney disease on dialysis. It is essential to perform bone histomorphometry for future investigations in order to elucidate the exact nature of circulating B1x in patients with kidney disease for accurate classification of type of renal bone disease.
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PMID:The novel bone alkaline phosphatase B1x isoform in children with kidney disease. 1693 97

The effect of bortezomib on bone remodelling was evaluated in 34 relapsed myeloma patients. At baseline, patients had increased serum concentrations of dickkopf-1 (DKK-1), soluble receptor activator of nuclear factor-kappaB ligand (sRANKL), sRANKL/osteoprotegerin ratio, C-telopeptide of type-I collagen (CTX) and tartrate-resistant acid phosphatase isoform-5b (TRACP-5b); bone-alkaline phosphatase and osteocalcin were reduced. Serum DKK-1 correlated with CTX and severe bone disease. Bortezomib administration significantly reduced serum DKK-1, sRANKL, CTX, and TRACP-5b after four cycles, and dramatically increased bone-alkaline phosphatase and osteocalcin, irrespective of treatment response. This is the first study showing that bortezomib reduces DKK-1 and RANKL serum levels, leading to the normalisation of bone remodelling in relapsed myeloma.
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PMID:Bortezomib reduces serum dickkopf-1 and receptor activator of nuclear factor-kappaB ligand concentrations and normalises indices of bone remodelling in patients with relapsed multiple myeloma. 1710 51

The association between quantitative ultrasound (QUS) and bone turnover in postmenopausal women of different ages is an area of continuous investigation. The aim of this study was to investigate the relationship of ultrasound parameters [broadband ultrasound attenuation (BUA) and speed of sound (SOS)] to bone mineral density (BMD) and biochemical markers of bone turnover in three age groups of postmenopausal women. One hundred and twenty-three postmenopausal Caucasian women were divided into three groups according to their age: group A, range 44-54 years, mean age (+/-SD) 48.3 +/- 2.3; group B, range 55-65 years, mean age 59.4 +/- 2.1; and group C, range 66-77 years, mean age 68.2 +/- 3.1. Ultrasound parameters were measured by the DTU-one imaging ultrasonometer in the calcaneus. BMD was assessed by dual-energy X-ray absorptiometry (DEXA) at the lumbar spine, femoral neck, and trochanter. Bone turnover was assessed by serum bone-specific alkaline phosphatase (BAP), urinary excretion of free deoxypyridinoline, N-telopeptides (NTX), and C-telopeptide breakdown products of type I collagen (CTX). QUS and BMD were significantly correlated in all sites, except hip BMD in group A. The most significant correlation was observed between BUA and femoral neck BMD in group C (r = 0.626, p < 0.01). BUA correlated significantly with BAP, NTX, and CTX (r = -0.434, -0.511, -0.478, respectively; p < 0.01), and SOS with BAP and NTX (r = -0.351 and -0.356, respectively; p < 0.05) only in group C. In groups A and B, ultrasound parameters did not correlate significantly to biochemical markers. Ultrasound parameters were better correlated to hip BMD and to biochemical markers of bone turnover in elderly postmenopausal women. These ultrasound measurements could be used as a screening test for bone status, either in nonambulatory third aged women or in those living in rural areas where attending medical centers with DEXA equipment and biochemical laboratories is difficult.
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PMID:Quantitative ultrasound is better correlated with bone mineral density and biochemical bone markers in elderly women. 1711 63

The fundamental role of Vitamin D has been long known in regulating calcium homeostasis and bone metabolism. An increased contribution of Vitamin D was recently described in association with a lower incidence of Rheumatoid Arthritis (RA). This must not be surprising, as the immunomodulating effects of Vitamin D are clear, which have been attributed protective effects in autoimmune disorders such as some chronic inflammatory bowel diseases, multiple sclerosis and type I diabetes. An interaction was suggested between Vitamin D metabolism and inflammation indexes through mediation of TNF-alpha which is also especially involved in osteoclastic resorption and therefore in bone loss processes. Some preliminary data would indicate an association between seasonal changes of Vitamin D serum levels, latitude and disease activity (DAS28) in RA patients. Consequently, the Osteoporosis and Metabolic Bone Diseases Study Group of SIR believes that there are grounded reasons for assessing the Vitamin D status of RA patients in order to investigate whether this is to be related to physiopathological and clinical aspects of disease other than those of bone involvement. Primary end point of the study will be to assess the levels of 25 OH Vitamin D in RA patients. Secondary endpoints will include correlation with dis-ease activity, densitometry values and bone turnover. The cross-sectional study will enroll patients of both sex genders, age ranging between 30 and 75 years according to the 1988 ACR criteria, onset of symptoms at least 2 years prior to study enrollment. Patients will be excluded suffering from osteo-metabolic diseases, liver and kidney insufficiency and those administered Vitamin D boli in the previous 12 months. Disease activity will be evaluated with the HAQ. Hemato-chemical tests and femoral and lumbar bone densitometry will be performed, unless recently undergone by patients. Blood levels of 25 OH C Vitamin D and PHT and of the two bone remodelling markers (bone alkaline phosphatase and serum CTX) will be measured, as well. Patient enrollment will start on February 2007 and will last 4 months. By the end of 2007 the study will be concluded and results will be published.
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PMID:[Study of vitamin D status of rheumatoid arthritis patients. Rationale and design of a cross-sectional study by the osteoporosis and metabolic bone diseases study group of the Italian Society of Rheumatology (SIR)]. 1721 21

Biochemical measurements of bone turnover provide an objective assessment of disease activity and the response to treatment. Alkaline phosphatase is the best characterized of the bone turnover markers and reflects the extent and activity of Paget's disease. However, in addition to bone-specific alkaline phosphatase (Bone ALP), there is also osteocalcin (OC) and procollagen type 1 N-terminal propeptide (P1NP) as formation markers. A variety of telopeptides (C-terminal telopeptide of type I collagen, [CTX], N-telopeptide of type I collagen [NTX]) or cross-link breakdown products of type 1 collagen can be used to assess bone resorption. Total alkaline phosphatase (Total ALP), Bone ALP, and P1NP all perform similarly in diagnosis and in evaluating the response to treatment, but the general availability, low interassay variation, and inexpensiveness of Total ALP makes it the best test for routine use. Measurement of the biological variability of the different markers in stable, untreated Paget's disease indicates how great a change (critical difference) is needed to define a true alteration in disease activity. Bone ALP, P1NP, and NTX show the highest therapy induced change/critical difference ratio during antiresorptive treatment. Some of the resorption markers show more complex changes in response to treatment. Pyridinoline (PYD) or deoxypyridinoline (DPD) cross-links of type 1 collagen are excreted in urine either as free or as peptide bound moieties, but it is the latter which decrease by the greatest amount in response to bisphosphonate therapy. Newly formed type 1 collagen contains an aspartyl-glycine motif (alphaCTX), which undergoes spontaneous isoaspartyl formation to betaCTX as the bone ages. In untreated Paget's disease, the alphaCTX is raised proportionately more (16-fold) than betaCTX (3-fold) and decreases in response to bisphosphonate therapy to a greater extent than betaCTX (measured in the sCTX assay). As bisphosphonates have become more potent, the aim of treatment has shifted toward the achievement of a rate of bone turnover in the lower part of the reference range. This is important because the duration of remission of disease activity is strongly determined by the post treatment nadir bone turnover.
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PMID:Biochemical assessment of Paget's disease of bone. 1722 3


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