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)

We have used the cynomolgus macaque as a model for the study of the effects of endogenous and exogenous sex steroid hormones on atherosclerosis and osteoporosis. As in human beings, premenopausal female cynomolgus macaques develop much less extensive coronary artery atherosclerosis than their male counterparts. Furthermore, surgical menopause results in a more atherogenic plasma lipoprotein pattern and an approximate doubling of atherosclerosis extent. Frequent pregnancy, a hyperoestrogenic state, results in an approximate 50% reduction in atherosclerosis extent. Physiological replacement with 17 beta-oestradiol alone or in combination with progesterone prevents the increase in coronary artery atherosclerosis extent associated with ovariectomy. This effect is independent of plasma lipoprotein concentrations and appears to be accounted for, at least in part, by an inhibitory effect of oestrogen replacement therapy on the uptake and degradation of LDL by the artery wall. Also, as in human beings, treatment with certain types of combination oral contraceptives results in marked decreases in plasma HDL-C concentration. Nonetheless, coronary artery atherosclerosis extent is reduced in monkeys by oral contraceptive treatment, and this effect is most pronounced among animals at highest risk due to theoretically adverse plasma lipoprotein profiles. It appears that, as with oestrogen replacement therapy, this effect can be accounted for, at least in part, by an inhibition of the uptake and degradation of low density lipoprotein by the artery wall. The monkey also appears to be a good model for studies of postmenopausal bone loss. As in women, surgical menopause results in significant diminution of bone mineral density and bone mineral content. Also, serum biomarkers of bone turnover (total alkaline phosphatase, acid phosphatase, tartrate-resistant acid phosphatase and osteocalcin) are increased in surgically postmenopausal monkeys, indicating increased bone turnover resulting from the surgical menopause. These increases in bone loss and indices of bone turnover were prevented by physiological oestrogen replacement therapy. Cynomolgus monkeys seem to be exceptionally useful models for studies of the effects of sex steroid hormones on atherosclerosis and osteoporosis, two major public health problems in postmenopausal women.
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PMID:Effects of oestrogens and progestogens on coronary atherosclerosis and osteoporosis of monkeys. 182 26

Recently, bisphosphonates have been used to prevent postmenopausal bone loss. As the effects of bisphosphonates on normal bone metabolism are unknown, 3-amino-1-hydroxypropylidene-1,1-diphosphonate (APD) was studied in healthy subjects. The effects of a single 20-mg APD infusion on biochemical parameters of calcium and bone metabolism were investigated during 2 months in 10 healthy male volunteers. This single moderate dose of APD reduced biochemical parameters of bone resorption during the time of follow-up. After 2 months, urinary hydroxyproline excretion was still below the basal level. The decreased serum calcium levels did not return to basal values. Biochemical parameters of bone formation, serum alkaline phosphatase and osteocalcin, showed a slight increase during the first month after stimulation of the parathyroids and a corresponding increase in serum 1,25-dihydroxyvitamin D. These formation parameters decreased thereafter, probably representing coupling between bone resorption and bone formation.
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PMID:Effect of a single infusion of aminohydroxypropylidene on calcium and bone metabolism in healthy volunteers monitored during 2 months. 198 22

To define the potential role of subclinical vitamin D deficiency in postmenopausal bone loss, we analyzed the levels of circulating 25-hydroxyvitamin D (25OHD) in 539 midwestern caucasian women screened for osteoporosis. Low 25OHD (less than 38 nmol/L) was found in 49 subjects (aged 52-77 yr). Women with low 25OHD had a reduced vertebral bone density (VBD), assessed by quantitative computed tomography, compared to age-matched controls (P less than 0.001). They also had significantly lower levels of serum calcium and phosphate, lower urinary calcium, higher serum alkaline phosphatase, and, in most cases, increased immunoreactive PTH (iPTH) concentrations, suggesting secondary hyperparathyroidism. Furthermore, only in the low 25OHD group did VBD correlate directly with 25OHD (r = 0.41; P less than 0.01), and inversely with iPTH (r = -0.47; P less than 0.01). Multivariate analyses revealed that iPTH was the major determinant of the observed decrease in VBD. Seasonal variations of serum 25OHD were noted only in the control population; in this group the 25OHD levels also correlated with sunlight exposure (r = 0.48; P less than 0.01), as assessed by an outdoor score. Thus, vitamin D deficiency develops when both the endogenous and exogenous sources are insufficient and contributes to a reduced bone mass in elderly women.
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PMID:Subclinical vitamin D deficiency in postmenopausal women with low vertebral bone mass. 199 17

In order to directly evaluate the role of parathyroid hormone (PTH) and its interaction with oestrogens for postmenopausal bone loss, studies were performed where synthetic human (1-38) PTH was infused s.c. over 24 h in 15 healthy females. Measurements were made of serum electrolytes, PTH and biochemical indices of bone turnover: serum osteocalcin and alkaline phosphatase and fasting urinary hydroxyproline and calcium. During the infusion of PTH there were significant increases of serum calcium (15%), fasting urinary calcium (55%) and hydroxyproline (80%) but a reduction of the serum osteocalcin concentrations (15%). There were significant relations between the calcaemic response and the increases of urinary calcium and hydroxyproline and the two latter were also closely related. There was, however, no correlation between the responses to PTH for the formative vs the resorptive indices. Postmenopausal women displayed greater increases of serum calcium and fasting urinary hydroxyproline indicating greater skeletal sensitivity to exogenous PTH. Following treatment with oestrogens the indices of skeletal responsiveness were reversed towards the premenopausal values. The findings demonstrate that during short-term infusion of PTH there is a dissociation between bone resorption and formation and, furthermore, that the menopause is associated with an enhanced skeletal sensitivity for PTH.
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PMID:Skeletal responsiveness to parathyroid hormone in healthy females: relationship to menopause and oestrogen replacement. 206 Jan 42

The present study includes 70 healthy, immediately postmenopausal women stratified according to future rate of bone loss. The stratification was performed by means of four parameters of bone turnover: serum alkaline phosphatase, fasting urinary calcium and hydroxyproline, and body weight, used in an equation developed in a previous study. After the stratification the women were followed without intervention for the next 24 months, with bone mass measurements every 3 months. The bone loss estimated at baseline by means of the equation correlated with the bone loss measured in the forearm (y = 0.72x - 1.52; r = 0.61; P less than 0.001). Plasma bone gla protein (BGP, osteocalcin), which is a new specific marker of bone formation, was now added to the model (replacing body weight). This increased the diagnostic validity (y = x; r = 0.76; P less than 0.001). From the present study we conclude that the postmenopausal bone loss can be predicted by means of four biochemical parameters determined in plasma and urine in women just after the menopause.
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PMID:Screening procedure for women at risk of developing postmenopausal osteoporosis. 213 39

Serum GH, E2, FSH, LH levels, bone mass, serum alkaline phosphatase (AKP), calcium levels and urinary calcium/creatine ratio in 42 postmenopausal women were compared with those in 30 women of fertile age. In thirteen out of the postmenopausal women we also observed these parameters before and after treatment with diethylstilbestrol (DES). The postmenopausal women had significantly reduced serum GH (P less than 0.01) and E2 levels (P less than 0.001) and increased serum FSH(P less than 0.001), LH levels (P less than 0.001), and had lower bone mass (P less than 0.01). They also had increased serum AKP levels (P less than 0.05) and urinary calcium/creatine ratio(P less than 0.01). There were positive correlations between serum E2 and GH levels, between postmenopausal bone loss and serum E2, GH decline. The postmenopausal bone loss began early as menopause commenced. After treatment with DES in 13 postmenopausal women, we observed that GH significantly increased (P less than 0.01) and FSH, LH decreased (P less than 0.001), AKP decreased by 27.58% and urinary calcium/creatine ratio decreased by 43.94% (compared with that before treatment). Our results indicate that bone turnover increased after menopause and resorption exceeded formation. There is bone loss in early postmenopause. The postmenopausal bone loss is related to serum GH, E2 levels. Estrogen replacement therapy is necessary in postmenopausal women and it should be given as early as possible. After treatment with DES, increased serum GH levels, decreased AKP values (27.58%) and urinary calcium/creatine ratio (43.94%) suggest that estrogen may play a definite role in bone metabolism through increased GH.
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PMID:[Relation of serum growth hormone and estradiol levels and osteoporosis in postmenopausal women]. 215 32

In order to establish the role of calcitonin (CT) in postmenopausal bone loss, we studied CT metabolism in 25 pre- and postmenopausal women. Postmenopausal women presented a highly significant reduction of CT basal levels compared to premenopausal females (p less than 0.01). Also, production rates of CT in osteoporotics were significantly lower than in either young premenopausal (18-25 years old), older premenopausal (35-40 years old), or postmenopausal healthy subjects. In a study in rabbits, we found that injection of CT, along with equimolar amounts of anti-SCT antibodies extracted from serum of pagetic patients, did not inhibit the hypocalcemic response to the hormone, thus demonstrating that resistance to CT treatment cannot be accounted for by antibody production. In a subsequent clinical study in patients with Paget's disease of bone, we found that 200 IU/day of salmon CT (SCT), given by nasal spray, improved both clinically and biochemically the activity of the disease, as demonstrated by 37 +/- 4% decrease of serum alkaline phosphatase and 35 +/- 5% fall of urinary excretion of hydroxyproline after six months of therapy. The effectiveness of CT as nasal spray was further tested in healthy women at an early stage of menopause. A 12-month course of intranasal SCT counteracted early postmenopausal bone loss, presumably by inhibiting bone resorption. In conclusion, intranasal CT seems to be a very attractive alternative to be considered for the prevention of postmenopausal osteoporosis.
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PMID:Calcitonin and postmenopausal bone loss. 222 70

Seventy-six healthy, early postmenopausal women (aged 45-54 years) were allocated to 2 years of treatment with a cyclic combination of 2 mg oestradiol valerate (21 d) and 1 mg cyproterone acetate (11 d) or placebo. Sixty-five women (86%) completed the study. In the placebo group the bone mineral content in the forearms (measured by single photon absorptiometry) and the bone mineral content in the lumbar spine and total skeleton (measured by dual photon absorptiometry) decreased significantly and at the same magnitude (P less than 0.001), whereas all bone mass measurements remained unchanged in the hormone-treated group. In the hormone-treated group there was a significant decrease in biochemical estimates of bone turnover (serum alkaline phosphatase, serum phosphate, fasting urinary calcium and hydroxyproline), whereas these values were unchanged in the placebo treated group. We conclude that treatment with a cyclic combination of 2 mg oestradiol valerate and 1 mg cyproterone acetate is effective as prophylaxis of postmenopausal bone loss.
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PMID:Cyproterone acetate, an alternative gestagen in postmenopausal oestrogen/gestagen therapy. 282 Jun 19

10 healthy early postmenopausal women were treated with oestrogen and progestagen for two cycles of 28 days. Serum alkaline phosphatase and bone Gla protein increased during progestagen administration, whereas urinary excretion of calcium and hydroxyproline fell significantly during treatment, independently of progestagen intake. Thus, bone formation increases when progestagen is added to oestrogen treatment, whereas bone resorption may be kept constantly low during oestrogen plus progestagen treatment, leading to a positive calcium balance. This makes possible effective treatment of postmenopausal osteoporosis--treatment of elderly postmenopausal women with substantial bone loss before their bones have fractured or when they have just started to fracture. This study design can be used for easy and rapid screening of potential drugs for the prevention and treatment of postmenopausal bone loss.
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PMID:Uncoupling of bone formation and resorption by combined oestrogen and progestagen therapy in postmenopausal osteoporosis. 286 32

The effect of oral 24R,25(OH)2-vitamin D3 as a prophylactic for postmenopausal bone loss was examined. Fifty-eight healthy, early postmenopausal women entered a double blind therapeutic trial for 2 years. After an initial examination the women were randomized to treatment with 10 micrograms 24R,25(OH)2D3 daily or placebo. Participants were thereafter examined every 3 months (nine examinations in all). In both groups the forearm bone mineral (measured by single photon absorptiometry), the lumbar spine mineral, and the total body mineral (measured by dual photon absorptiometry) fell significantly and at the same magnitude. Furthermore, serum calcium, serum alkaline phosphatase concentration, and fasting urinary hydroxyproline were unchanged, as were the 24-hour urinary calcium excretion and the intestinal radiocalcium absorption. Our findings demonstrate that 24R,25(OH)2D3 treatment has no prophylactic effect on postmenopausal bone loss and does not alter calcium metabolic variables.
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PMID:Does 24R,25(OH)2-vitamin D3 prevent postmenopausal bone loss? 309 22


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