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)

Bone remodelling is a process by which bone grows and turns over. This process involves a series of highly regulated steps that depend on the interaction of two cell lineages, the osteoclasts and the osteoblasts. Information on metabolic activity of bone tissue are achieved with the determination, in blood and in urine, of biochemical products derived from the activity of this cells. The ability to determine bone turnover with biochemical markers has been enhanced considerably in recent years with the development of new assays for more sensitive and specific markers. These new markers can now replace the outdated and non-specific markers of bone remodeling such as serum total alkaline phosphatase (ALP) and urinary hydroxyproline (Hyp) determination. Biochemical markers of bone turnover can be classified according to the process that underlie in markers of bone formation, products of the osteoblast activity [bone ALP, osteocalcin (OC), procollagene I C- and N-terminal propeptides] and markers of bone resorption, products of the osteocalst activity [pyridinuim crosslinks, collagen I C- and N-terminal telopeptides (CTX-I and NTX-I), tartrate resistent acid phosphatase (TRACP) isoform 5b]. The interpretation of laboratory results should always include the consideration of potential sources of variability. Variation in the results of biochemical markers of bone metabolism can compromise their ability to characterize disorders of bone metabolism. Variation can be categorized into pre-analytical, analytical and biological sources. However, the determination of biochemical markers of bone turnover offers many advantages in clinical practice, since they are non-invasive, can be repeated often, and major changes occur in a short time.
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PMID:Markers of bone turnover: biochemical and clinical perspectives. 1655 Jul 16

Recently, several new bone metabolic markers have been developed and applied for diagnosis of bone metastasis. We have investigated the efficacy of several bone metabolic markers : serum carboxy-terminal telopeptide of type 1 collagen ( I CTP), C-terminal cross-linked telopeptide of type I collagen (CTX) and urinary free deoxypyridinoline (fDPD) as bone resorption markers, serum carboxy-terminal propeptide of type 1 collagen (P I CP), osteocalcin (OC), and bone alkaline phosphatase (BAP) as bone formation markers for diagnosis of bone metastasis. I CTP was most useful for diagnosis of bone metastasis in breast cancer patients because of no increase in postmenopausal osteoporosis. Combination of resorption and formation markers increased sensitivity. In follow-up, bone metabolic markers seemed more useful for predicting therapeutic response of bone metastasis than tumor markers. Bone metabolic markers were also useful for predicting survival or occurrence of skeletal-related events. These findings suggest that bone metabolic markers would be useful to detect, to monitor, and to predict prognosis of bone metastases.
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PMID:[Evaluation of cancer-induced bone diseases by bone metabolic marker]. 1658 8

The present study was undertaken to examine the effect of melatonin (25 microg/mL of drinking water, about 500 microg/day) on a 10-wk long treatment of male rats with methylprednisolone (5 mg/kg s.c., 5 days/wk). Bone densitometry and mechanical properties, calcemia, phosphatemia and serum bone alkaline phosphatase activity and C-telopeptide fragments of collagen type I (CTX) were measured. Both melatonin and methylprednisolone decreased significantly body weight (BW) and the combination of both treatments resulted in the lowest BW values found. Consequently, all results were analyzed with BW as a covariate. Densitometrically, methylprednisolone augmented bone mineral content (BMC), bone area (BA) and bone mineral density (BMD) in the entire skeleton, BMC in cortical bone, and BMC and BMD in trabecular bone. Melatonin increased BMC and BA in whole skeleton and BMC and BMD in trabecular bone. For BMC and BA of whole skeleton, BMC of cortical bone, and BMC and BMD of trabecular bone, the combination of glucocorticoids and melatonin resulted in the highest values observed. Femoral weight of rats receiving methylprednisolone or melatonin increased significantly and both treatments summated to achieve the greatest effect. In femoral biomechanical testing, methylprednisolone augmented ultimate load and work to failure significantly. Rats receiving the combined treatment of methylprednisolone and melatonin showed the highest values of work to failure. The circulating levels of CTX, an index of bone resorption, decreased after methylprednisolone or melatonin, both treatments summating to achieve the lowest CTX values found. Serum calcium increased after methylprednisolone and serum phosphorus decreased after treatment with methylprednisolone or melatonin while serum bone alkaline phosphatase levels remained unchanged. The results are compatible with the view that low doses of methylprednisolone or melatonin decrease bone resorption and have a bone-protecting effect.
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PMID:Melatonin effect on bone metabolism in rats treated with methylprednisolone. 1663 16

Osteolytic bone disease is a major clinical feature of multiple myeloma (MM). Mechanisms of bone destruction are related to increased osteoclastic activity, which is not accompanied by a comparable increase in bone formation, as osteoblasts are functionally exhausted. Thus the lesions rarely heal and bone scans are often negative in myeloma patients with extensive lytic lesions, offering very little in the follow-up of bone disease. Biochemical markers of bone resorption, such as N- and C-terminal cross-linking telopeptide of type I collagen (NTX, CTX/ICTP, respectively), tartrate resistant acid phosphatase isoform-5b, bone formation (bone-specific alkaline phosphatase [BAP]), and osteocalcin provide useful information on bone dynamics. Several studies have shown that NTX, CTX, and ICTP are elevated in myeloma patients, reflect the extent of bone disease, and correlate with survival. Furthermore, they are useful in monitoring bone destruction during antimyeloma or bisphosphonate treatment. Markers of bone formation have produced conflicting results in trials. However, BAP correlates with bone pain, lytic lesions, and fractures in quite a few studies of MM. Novel markers, such as bone sialoprotein, receptor activator of nuclear factor-kappa B ligand (RANKL), osteoprotegerin, osteopontin, dickkopf-1, and soluble Frizzle-related protein-2 have been found of value in assessing bone lytic disease in MM, but their promising results must be confirmed in large trials. In conclusion, although no marker provides optimal analysis of MM or of MM treatments, combinations of markers have at times helped in assessing MM stages and lytic bone disease and in monitoring specific treatment modalities. The need for further research in this field is clear.
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PMID:Biochemical markers of bone metabolism in multiple myeloma. 1668 Aug 33

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


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