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)

In this prospective study, we aimed to evaluate the effect of simvastatin on bone metabolism and the correlation between changes in bone turnover parameters and serum cytokine levels. For this purpose, 38 postmenopausal subjects with hypercholesterolemia (>240 mg/dl), not on osteoporosis treatment, were studied. Simvastatin was started at a dose of 20 mg daily and continued for 3 months. Six patients were excluded from the study during the follow-up period. Pre- and post-treatment samples were analyzed for bone alkaline phosphatase (BAP) and osteocalcin (OCL), as markers of bone formation; for carboxyterminal telopeptide of collagen I (CTX), as a marker of bone resorption; and for interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) cytokine levels. Total cholesterol level was decreased from 262.1 +/- 30.9 to 210.2 +/- 35.6 mg/dl after simvastatin treatment (P < 0.0001). While no significant change was observed in serum CTX level, BAP and OCL levels were 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). In the analysis of cytokines, while no significant change was observed in IL-6 levels, the TNF-alpha level was found to be significantly decreased after simvastatin treatment (from 77.9 +/- 31.6 pg/ml to 23.5 +/- 12.6 pg/ml [P = 0.021]). Individual changes in TNF-alpha levels showed a moderate negative correlation with the individual changes in BAP and OCL levels (r = -0.550 [P = 0.001], and r = -0.497 [P = 0.004], respectively). In conclusion; 20-mg daily simvastatin treatment for 3 months significantly increased BAP and OCL levels (markers of bone formation) in hypercholesterolemic postmenopausal subjects, without affecting bone resorption. These findings support the idea that simvastatin has an anabolic effect on bone formation. Additionally, the presence of a negative correlation between TNF-alpha levels and the anabolic bone parameters suggests that a cytokine-lowering effect of simvastatin may also be involved in the remodeling process and could exert some additive beneficial effect on bone metabolism.
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PMID:The effect of simvastatin on serum cytokine levels and bone metabolism in postmenopausal subjects: negative correlation between TNF-alpha and anabolic bone parameters. 1522 96

Our aim was to assess the diagnostic accuracy of bone markers in serum of patients with prostate cancer (PCa) for early detection of bone metastases and their usefulness as predictors of PCa-caused mortality. In sera of 117 PCa patients (pN0M0, n = 39; pN1M0, n = 34; M1, n = 44), 35 healthy men and 35 patients with benign prostatic hyperplasia, bone formation markers [total and bone-specific alkaline phosphatase (tALP, bALP), amino-terminal procollagen propeptides of type I collagen (P1NP), osteocalcin (OC)], bone resorption markers [bone sialoprotein (BSP), cross-linked C-terminal (CTX) and cross-linked N-terminal (NTX) telopeptides of type I collagen, tartrate-resistant acid phosphatase isoenzyme 5b (TRAP)] and osteoclastogenesis markers [osteoprotegerin (OPG), receptor activator of nuclear factor kappaB ligand (RANKL)] were measured. tALP, bALP, BSP, P1NP, TRAP, NTX and OPG were significantly increased in PCa patients with bone metastases compared to patients without metastases. OPG showed the best discriminatory power to differentiate between these patients. Logistic regression analysis resulted in a model with OPG and TRAP as variables that predicted bone metastasis with an overall correct classification of 93%. Patients with concentrations of OPG, P1NP, tALP, bALP, BSP, NTX, TRAP and CTX above cut-off levels showed significantly shorter survival than patients with low marker concentrations. Multivariate Cox proportional hazards regression revealed that only OPG and BSP were independent prognostic factors for PCa-related death. Thus, the importance of serum OPG in detecting bone metastatic spread, alone or in combination with other bone markers, and predicting survival in PCa patients has been clearly demonstrated.
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PMID:Comparison of 10 serum bone turnover markers in prostate carcinoma patients with bone metastatic spread: diagnostic and prognostic implications. 1525 51

Ospemifene is a novel selective estrogen receptor modulator (SERM). Here we studied the effects of ospemifene on bone turnover in postmenopausal women. This was a randomized, double-blind study in which 159 healthy postmenopausal women received 30 (n = 40), 60 (n = 40) or 90 mg (n = 40) of ospemifene or placebo (n = 39) for 3 months. Bone resorption was assessed by measuring the urinary outputs of N- and C-terminal crosslinking telopeptides of type I collagen (NTX and CTX, respectively). Bone formation was assessed by measuring the levels of procollagen type I N propeptide (PINP), procollagen type I C propeptide (PICP), and bone-specific alkaline phosphatase (bone ALP) in serum. All markers were studied at baseline, 3 months, and 2-4 weeks after cessation of the medication. Ospemifene decreased bone resorption dose-dependently, as seen from falls in NTX by 6.1, 9.4 and 12.9% in the 30, 60 and 90 mg ospemifene groups, respectively (p < 0.05 for all dose levels when compared to placebo). CTX values decreased in the 90 mg ospemifene group by 4.8% (p < 0.05). A dose-dependent decrease was also observed in the bone formation markers: PINP values decreased by 9.8 (p < 0.05) and 15.3% (p < 0.01), and PICP values by 12.0 and 11.9% in the 60 and 90 mg ospemifene groups, respectively. Bone ALP decreased in 60 and 90 mg ospemifene groups by 1.9 and 2.6%, respectively (p < 0.05 for both dose levels when compared to placebo). These results show that ospemifene is effective in reducing bone turnover in postmenopausal women.
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PMID:Effects of ospemifene, a novel SERM, on biochemical markers of bone turnover in healthy postmenopausal women. 1525 84

We investigated the bone metabolism of 22 patients (median age 38 years) over 6 years after allogeneic bone marrow transplantation (BMT). Biplanar roentgenograms of the thoracic and lumbar spine were used to diagnose vertebral deformities caused by fractures. The actual bone mineral density (BMD) of the lumbar spine and the femoral neck were measured. Laboratory tests included calcium, phosphate, parathyroid hormone, a marker of bone resorption (beta-crosslaps, CTX), markers of bone formation (osteocalcin, bone-specific alkaline phosphatase), osteoprotegerin (OPG)--antagonist of the osteoclast differentiation factor RANKL, and sex hormone status. One patient had a vertebral fracture. Seven patients (28%) had osteopenia in the lumbar spine while 12 patients (48%) had osteopenia in the femoral neck. Bone resorption was increased in nine patients (43%) and bone formation was increased in four patients (20%). BMT recipients had significantly increased serum levels of OPG (P=0.029). Three women (75%) and four men (25%) were hypogonadal. The data showed that BMD is reduced and bone metabolism is still disturbed more than 6 years after BMT. The RANKL/osteoprotegerin system appears to play an important role in the pathophysiology of late post transplantation osteoporosis.
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PMID:Bone metabolism in patients more than five years after bone marrow transplantation. 1528 95

Retrospective and uncontrolled studies suggest that the lipid-lowering statin class of drugs has either no or beneficial effects on bone density and may reduce fracture risk. We have examined the effects of atorvastatin on serum and plasma markers of bone turnover in 25 patients (age 56 +/- 8 years) with type 2 diabetes (duration: 4.7 +/- 5.0 years, 16 female, 2 insulin-treated, 4 diet alone, and 19 on oral hypoglycemic agents) and baseline hypercholesterolemia (cholesterol 6.6 +/- 0.8 mmol/l) in a double-blind, placebo-controlled, crossover study of 12 weeks of placebo/40 mg of atorvastatin with an 8-week wash-out period. Atorvastatin resulted in a fall in total cholesterol of 2.3 +/- 0.9 mmol/l. There were no effects of active or placebo therapy on total alkaline phosphatase, bone-specific alkaline phosphatase, osteocalcin, or beta C-telopeptide of type 1 collagen (beta-CTX). We conclude that atorvastatin (40 mg/day) has no significant effect on bone turnover in man.
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PMID:The effect of atorvastatin on markers of bone turnover in patients with type 2 diabetes. 1533 14

Classical galactosemia is an autosomal recessively inherited disorder of galactose metabolism. Treatment consists of life-long dietary restriction of galactose. Despite treatment, long-term complications occur such as a decreased bone mineral density (BMD). A decreased BMD might be the result of either dietary deficiencies secondary to the galactose-restricted diet or unknown intrinsic factors. In this study, 40 children with classical galactosemia (13 males and 27 females, aged 3-17 years) on dietary treatment were included to gain insight in the bone metabolism of galactosemics. We found weight and height Z scores significantly decreased in galactosemics. Mean areal BMD Z scores of lumbar spine and of femoral neck as measured by Dual energy X-ray Absorptiometry (DXA) were -0.6 (P < 0.001) and -0.3 (P = 0.066), respectively. Mean volumetric BMD of the femoral neck was significant lower in galactosemics (P < 0.001). The recommended dietary allowances (RDA) for calcium, magnesium, zinc, vitamin D, and protein were met in all patients. Mean serum levels of calcium, phosphate, magnesium, zinc, 1,25-dihydroxy vitamin D (1,25OHD), parathormone (PTH), 17-beta estradiol, bone alkaline phosphatase (BAP), and under-carboxylated osteocalcin (ucOC) were normal. Serum levels of IGF-1 Z score, carboxylated osteocalcin (cOC), N-terminal telopeptide (NTX), and C-terminal telopeptide (CTX) were significantly lower in galactosemics than in control subjects. The different bone markers were strongly correlated. The low levels of IGF-1 Z score, formation marker cOC, and resorption markers NTX and CTX suggest a decreased bone metabolism in galactosemics.
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PMID:Bone metabolism in galactosemia. 1545 6

Glucocorticoid (GC)-induced osteoporosis is the leading form of secondary osteoporosis. Bone loss can be rapid. However, longitudinal studies at the very beginning of treatment are scarce. Patients relapsing from multiple sclerosis are treated with high-dose, short-term iv GCs. A number of them are young, without concomitant disease affecting bone and with no substantial impairment of mobility. Such patients were selected for the present study. Thirteen patients suffering from multiple sclerosis [11 females, two males; age 32 +/- 2 yr (mean +/- se)] and receiving iv methylprednisolone 15 mg/kg daily for 10 d completed the study. We measured serum osteocalcin (OC), aminoterminal propeptide of type I collagen (PINP), bone isoform of alkaline phosphatase (bALP), carboxyterminal telopeptide of type I collagen (CTX), and urinary calcium/creatinine ratio (uCa/Cr) during the 10-d cycle and 3 months later. Dual-energy x-ray absorptiometry and calcaneal quantitative ultrasonometry were performed before and 6 months after therapy. We found an immediate, impressive fall of OC and PINP (-80 +/- 3 and -54 +/- 5% at d 2, respectively), which persisted throughout the whole treatment period (P < 0.0001 for both markers). bALP levels showed only a modest decrease at d 6 (-19 +/- 7%, P < 0.05), with subsequent return to baseline in d 7-10. After 3 months, OC, PINP, and bALP levels rose to +51 +/- 22, +37 +/- 16 (not significant), and +61 +/- 17% (P < 0.01) with respect to baseline, respectively. uCa/Cr and CTX showed a progressive, marked increase during treatment, peaking at d 7-9 (+92 +/- 44 and +149 +/- 63%, respectively), with subsequent decrement at d 10 (P < 0.01 and P < 0.05, respectively) despite continuing GC administration. After 3 months, uCa/Cr and CTX levels were also higher than baseline. No change in quantitative ultrasonometry parameters and bone mineral density was observed 6 months after therapy. In conclusion, high-dose, short-term iv GC regimens cause an immediate and persistent decrease in bone formation and a rapid and transient increase of bone resorption. Our data also support the concept that discontinuation of such regimens is followed by a high bone turnover phase.
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PMID:Immediate fall of bone formation and transient increase of bone resorption in the course of high-dose, short-term glucocorticoid therapy in young patients with multiple sclerosis. 1547 86

The effects of low-level lifetime exposure to cadmium (Cd) on the skeleton mineral status and the risk of bone loss in the elderly were studied in an experimental model of human environmental exposure in non-Cd-polluted areas. Young female Wistar rats were exposed to 1 mg Cd/l in drinking water for 24 months. Bone mineral content (BMC), density (BMD) and area of the lumbar spine (L1-L5) and femur, and total skeleton BMD (T-BMD) were measured densitometrically at the baseline and after 6, 12, 18, and 24 months. Prevalence of osteopenia and osteoporosis was evaluated based on the BMD T score and Z score. Osteocalcin (OC) in the serum and total alkaline phosphatase (total ALP) in the serum, cortical and trabecular bone samples as bone formation markers, and C-terminal cross-linking telopeptide of type I collagen (CTX) in the serum and urine as bone resorption markers were measured. Calcium (Ca) and Cd concentrations in the serum/blood and urine were determined as well. In the Cd-exposed females, the L1-L5 and femur BMC and BMD at all the studied time points were lower compared to control. The exposure to Cd resulted in lower accumulation of peak bone mass, accelerated osteopenia, and enhanced the prevalence of osteoporosis in aged rats. The effect of Cd was more pronounced at the L1-L5 than at the femur. CTX concentration in the urine was decreased after 6 months and next increased compared to control, whereas the urinary loss of Ca was enhanced during the exposure to Cd. After 24 months of the treatment, the serum total ALP activity and the activity of this enzyme in cortical and trabecular bone decreased and serum CTX concentration increased, whereas the concentrations of OC and Ca were unchanged. The study clearly revealed that low-level lifetime exposure to Cd diminishes the accumulation of bone mass during skeletal growth and influences bone metabolism at maturity causing osteopenia, and enhances the age-related bone loss due to high turnover rate leading in consequence to osteoporosis in aged rats. The results together with our previous findings confirm the hypothesis that environmental exposure to Cd may be a risk factor for skeletal diseases.
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PMID:Low-level lifetime exposure to cadmium decreases skeletal mineralization and enhances bone loss in aged rats. 1554 44

Nacre formation is an ideal model to study biomineralization processes. Although much has been done about biomineralization mechanism of nacre, little is known as to how cellular signaling regulates this process. We are interested in whether G protein signaling plays a role in mineralization. Degenerate primers against conserved amino acid regions of G proteins were employed to amplify cDNA from the pearl oyster Pinctada fucata. As a result, the cDNA encoding a novel G(s)alpha (pfG(s)alpha) from the pearl oyster was isolated. The G(s)alpha cDNA encodes a polypeptide of 377 amino acid residues, which shares high similarity to the octopus (Octopus vulgaris) G(s)alpha. The well-conserved A, C, G (switch I), switch II functional domains and the carboxyl terminus that is a critical site for interaction with receptors are completely identical to those from other mollusks. However, pfG(s)alpha has a unique amino acid sequence, which encodes switch III and interaction sites of adenylyl cyclase respectively. In situ hybridization and Northern blotting analysis revealed that the oyster G(s)alpha mRNA is widely expressed in a variety of tissues, with highest levels in the outer fold of mantle and epithelia of gill, the regions essential for biomineralization. We also show that overexpression of the pfG(s)alpha in mammalian MC3T3-E1 cells resulted in increased cAMP levels. Mutant pfG(s)alpha that has impaired CTX substrate diminished its ability to induce cAMP production. Furthermore, the alkaline phosphatase (ALP) activity, an indicator for mineralization, is induced by the G(s)alpha in MC3T3-E1 cells. These results indicated that G(s)alpha may be involved in regulation of physiological function, particularly in biological biomineralization.
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PMID:Cloning and characterization of an mRNA encoding a novel G protein alpha-subunit abundant in mantle and gill of pearl oyster Pinctada fucata. 1558 99

Hypovitaminosis D is common in patients with peripheral arterial disease (PAD). Subsequent secondary hyperparathyroidism and osteomalacia contribute to bone pain and myalgias, and so aggravate clinical symptoms of claudication. We evaluated 95 out of 297 patients with angiographically confirmed PAD stages II (pain in the calves and/or thighs only during exercise) or IV (history of, or presence of local ulcers) and compared them with 44 matched healthy controls regarding their medical history, bone density measurements of the femoral neck and calcaneal bone ultrasound. Bone pain, myalgias and mobility restriction as well as routine laboratory parameters, serum vitamin D [25(OH)D], crosslaps (CTX), parathyroid hormone (PTH), osteocalcin (OC) and alkaline phosphatase (AP) were recorded and analysed. 25(OH)D was significantly lower in PAD IV patients (9.6+/-4.6 ng/ml, P<0.0001) as compared to PAD II stages and controls (19.0+/-7.6 and 19.1+/-9.1 ng/ml), paralleled by lower serum calcium [2.24+/-0.02 mmol/l, P=0.0002 versus PAD II (2.36+/-0.02) and P<0.0001 versus controls (2.39+/-0.02)] and higher iPTH serum levels (66.3+/-3.6 pg/ml, P<0.0001) as compared to PAD II patients (45.3+/-3.5) and healthy controls (38.5+/-2.4). Alkaline phosphatase and serum crosslaps values were significantly higher and age-adjusted bone density and bone ultrasound measurements significantly lower in PAD IV patients, who were also twice as likely to have bone pain and myalgias as PAD II patients. Bone ultrasound measurements correlated significantly with both clinical severity and pain as well as serological parameters of bone metabolism. Underlying PAD has a significant impact on bone density and metabolism as well as on bone and muscular pain. Patients with PAD are at high risk for osteoporosis and osteomalacia and should be regularly monitored and treated for their vitamin D deficiencies.
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PMID:Hypovitaminosis D, impaired bone turnover and low bone mass are common in patients with peripheral arterial disease. 1572 36


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