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

---

Query: EC:3.1.3.1 (alkaline phosphatase)
47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acromegaly is characterized by growth hormone (GH) hypersecretion and insulin-like growth factor-I (IGF-I) excess, both of which stimulate osteoblast proliferation. At diagnosis, GH excess has usually been present for years. Furthermore, impaired gonadotropin secretion with hypogonadism is frequent. To date, studies of changes in bone mineral density (BMD) in acromegaly have been limited and the available data inconsistent. To investigate the effects of GH excess on proximal femur and lumbar spine BMD, a case series of 25 patients with acromegaly (8 eugonadal, 17 hypogonadal) documented by high plasma GH and IGF-I concentrations was studied. BMD was measured using dual-photon absorptiometry, hormonal and biochemical measurements, which included GH, IGF-I, serum calcium, phosphate, alkaline phosphatase, 1,25 dihydroxy vitamin D and urinary calcium and hydroxyproline excretion. Seven patients were re-studied after IGF-I was suppressed for six months by the somatostatin analog 201-995 (five patients) or pituitary adenomectomy (two patients). BMD was normal in 22 patients and was decreased at one site each in one eugonadal and two hypogonadal patients. BMD was similar between the eugonadal and hypogonadal groups at all sites. Urinary hydroxyproline excretion was equally increased in both groups. There was no correlation between any of the hormonal or biochemical parameters and the age, sex, race and body mass index matched Z-scores of BMD at any site. Following normalization of IGF-I for 6 mo in seven patients, there was no significant change of BMD. We conclude that proximal femoral and lumbar spine BMD is normal in most patients with active acromegaly, including those who are hypogonad. Successful treatment of acromegaly does not result in major short-term changes in BMD.
...
PMID:Bone mineral density of the axial skeleton in acromegaly. 151 33

We present iliac bone histomorphometric data after in vivo double tetracycline labeling and related biochemical data from 14 nonalcoholic men referred for evaluation of symptomatic spinal osteoporosis. Six patients had previously undiagnosed hypogonadism, and 8 had normal gonadal function and no evident etiology for osteoporosis. Bone histomorphometry revealed no differences in structural measurements or resorption indices between the 2 groups. However, compared to reference values for normal postmenopausal women, osteoblast surface, mineralizing surface, and formation rate were normal or modestly increased in the hypogonadal men and significantly reduced in the idiopathic group. There were significant corresponding differences between the 2 groups in the fasting urinary hydroxyproline to creatinine ratio, an index of bone resorption, and serum total alkaline phosphatase, an index of bone formation. Plasma 25-hydroxyvitamin D levels did not differ between the 2 groups and were above 10 ng/mL in all patients. Plasma 1,25-dihydroxyvitamin D [1,25-(OH)2D] levels were normal in the hypogonadal group and significantly reduced in the idiopathic group, but did not correlate with any histological measurements. The formation indices fell substantially in 3 of 4 hypogonadal men after 7-14 months of therapy with testosterone and a calcium supplement. We conclude the following. In vitamin D-replete hypogonadal men with osteoporosis, 1,25-(OH)2D synthesis is normal, and bone remodeling is modestly increased and correctable by hormone replacement therapy, as in normal postmenopausal women. In middle-aged men with idiopathic osteoporosis, there is impairment of 1,25-(OH)2D synthesis and of the recruitment and activity of teams of osteoblasts, as in postmenopausal osteoporosis.
...
PMID:Bone histomorphometry in hypogonadal and eugonadal men with spinal osteoporosis. 358 99

During the past two decades, the essentiality of zinc for man has been established. Deficiency of zinc in man due to nutritional factors and several diseased states has been recognized. High phytate content of cereal proteins decreases availability of zinc; thus the prevalence of zinc deficiency is likely to be high in a population subsisting mainly on cereal proteins. Alcoholism is known to cause hyperzincuria and thus may play a role in producing zinc deficiency in man. Malabsorption, cirrhosis of the liver, chronic renal disease and other chronically debilitating diseases may similarly induce zinc deficiency in human subjects. A severe deficiency of zinc has recently been recognized to occur in patients with sickle cell anemia and a beneficial effect of zinc therapy in such patients has been reported. Growth retardation, male hypogonadism, skin changes, poor appetite, mental lethargy and delayed wound healing are some of the manifestations of chronically zinc-deficient human subjects. Taste abnormalities, correctable with zinc supplementation, have been observed in uremic subjects. Recently, abnormal dark adaptation related to zinc deficiency in patients with cirrhosis of the liver and sickle cell disease has been reported. In severely zinc-deficient patients, dermatological manifestations, diarrhea, alopecia, mental disturbances and intercurrent infections predominate and if untreated the condition becomes fatal. Zinc deficiency is known to affect testicular functions adversely in man and animals. This effect of zinc is at the end organ level and it appears that zinc is essential for spermatogenesis and testosterone steroidogenesis. Zinc is involved in many biochemical functions. Several zinc metalloenzymes have been recognized in the past decade. Zinc is required for each step of cell cycle in microorganisms and is essential for DNA synthesis. Thymidine kinase, RNA polymerase, DNA-polymerase from various sources and RNA-dependent DNA polymerase from viruses have been shown to be zinc-dependent enzymes. Zinc also regulates the activity of RNase; thus the catabolism of RNA appears to be zinc-dependent. The effect of zinc on protein synthesis may be attributable to its vital role in nucleic acid metabolism. The activities of many zinc-dependent enzymes have been shown to be affected adversely in zinc-deficient tissues. Three enzymes, alkaline phosphatase, carboxypeptidase and thymidine kinase, appear to be most sensitive to zinc restriction in that their activities are affected adversely within three to six days of institution of a zinc-deficient diet to experimental animals.(ABSTRACT TRUNCATED AT 400 WORDS)
...
PMID:Zinc deficiency in human subjects. 636 78

Acquired hypogonadism is being increasingly recognized in adult men. However, the effects of long term testosterone replacement on bone density and body composition are largely unknown. We investigated 36 adult men with acquired hypogonadism (age, 22-69 yr; median, 58 yr), including 29 men with central hypogonadism and 7 men with primary hypogonadism, and 44 age-matched eugonadal controls. Baseline evaluation included body composition analysis by bioimpedance, determination of site-specific adipose area by dual energy quantitative computed tomography scan (QCT) of the lumbar spine, and measurements of spinal bone mineral density (BMD) using dual energy x-ray absortiometry, spinal trabecular BMD with QCT, and radial BMD with single photon absorptiometry. Percent body fat was significantly greater in the hypogonadal men compared to eugonadal men (mean +/- SEM, 26.4 +/- 1.1% vs. 19.2 +/- 0.8%; P < 0.01). The mean trabecular BMD determined by QCT for the hypogonadal men was 115 +/- 6 mg K2HPO4/cc. Spinal BMD was significantly lower than that in eugonadal controls (1.006 +/- 0.024 vs. 1.109 +/- 0.028 g/cm2; P = 0.02, respectively). Radial BMD was similar in both groups. Testosterone enanthate therapy was initiated in 29 hypogonadal men at a dose of 100 mg/week, and the subjects were evaluated at 6-month intervals for 18 months. During testosterone therapy, the percent body fat decreased 14 +/- 4% (P < 0.001). There was a 13 +/- 4% decrease in subcutaneous fat (P < 0.01) and a 7 +/- 2% increase in lean muscle mass (P = 0.01) during testosterone therapy. Spinal BMD and trabecular BMD increased by 5 +/- 1% (P < 0.001) and 14 +/- 3% (P < 0.001), respectively. Radial BMD did not change. Serum bone-specific alkaline phosphatase and urinary deoxypyridinoline excretion, markers of bone formation and resorption, respectively, decreased significantly over the 18 months (P = 0.003 and P = 0.04, respectively). We conclude that testosterone therapy given to adult men with acquired hypogonadism decreases sc fat and increases lean muscle mass. In addition, testosterone therapy reduces bone remodeling and increases trabecular bone density. The beneficial effects of androgen administration on body composition and bone density may provide additional indications for testosterone therapy in hypogonadal men.
...
PMID:Increase in bone density and lean body mass during testosterone administration in men with acquired hypogonadism. 895 42

The etiology of osteoporosis in most men without a history of alcohol abuse, hypogonadism, or glucocorticoid excess is unknown. Several histomorphometric reports have demonstrated a reduction in indices of bone formation. We tested the hypothesis that the putative reduction in bone formation in men with idiopathic osteoporosis may be related to deficiencies in skeletal mechanisms that are mediated by insulin-like growth factor I (IGF-I). Twenty-four middle-aged men (50.5 +/- 1.9 yr) with severe idiopathic osteoporosis (mean lumbar spine T-score -3.5 +/- 0.16) were studied. The following biochemical indices were all normal: serum calcium, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, testosterone, osteocalcin, carboxyterminal propeptide of type I collagen, bone specific alkaline phosphatase, urinary calcium, and collagen crosslinks. Parathyroid hormone level was in the lower range of normal, 25 +/- 2 pg/mL (nl: 10-65). Mean serum IGF-I level was also in the lower range of normal, 157.9 +/- 7.6 ng/mL (normal age-matched range, 140-260 ng/mL). Eight men had IGF-I levels that were below 140 ng/mL. The mean IGF-IZ score was -0.75, significantly different from the expected mean of zero (P = 0.0002). IGF-I was correlated negatively with age (r = -0.49, P < 0.02). With age held constant, serum IGF-I accounted for 15% of the variance in lumbar bone mineral density (BMD; P < 0.001). The osteocalcin concentration correlated well with bone density at the distal 1/3 radius (r = +0.44; P < 0.002). Histomorphometric analysis of bone biopsy specimens showed significant reductions in cancellous bone volume (31%; P < 0.001), cortical width (28%; P < 0.05), osteoid surface (33%; P < 0.01), and bone formation rate (54%; P < 0.01) when results were compared with age-matched control subjects. Percent eroded surface was normal and was correlated inversely with serum IGF-I levels (r = -0.5; P < 0.04). These results suggest that serum IGF-I levels are reduced in men with idiopathic osteoporosis and that IGF-I correlates with and may contribute to the reduction in lumbar spine bone mass density (BMD). The low IGF-I levels may reflect the reduction in bone formation demonstrated by histomorphometry. Insights into the etiology of idiopathic osteoporosis in men may be revealed by further studies of the IGF-I axis.
...
PMID:Insulin-like growth factor-I in men with idiopathic osteoporosis. 928 97

Transplantation of solid organs including heart, kidney, and liver is associated with rapid bone loss and increased rate of fracture; data on bone marrow transplantation recipients (BMT) are scarce. The purpose of the present study was to examine the magnitude, timing, and mechanism of bone loss following allogeneic BMT, and to study whether bone loss can be prevented by calcium with or without calcitonin. Sixty-nine patients undergoing allogeneic BMT for malignant blood diseases were enrolled into the study. Forty-four (22 women, 22 men) completed 6 months, and 36 patients 1 year follow-up. They were randomized to receive either no additional treatment (n = 22), or oral calcium 1 g twice daily for 12 months (n = 12) or the same dose of calcium plus intranasal calcitonin 400 IU/day for the first month and then 200 IU/day for 11 months (n = 10). Bone mineral density (BMD) at the lumbar spine and three femoral sites (femoral neck, trochanter, Ward's triangle) was measured by dual-energy X-ray absorptiometry (DXA). Bone turnover rate was followed with markers of bone formation and resorption (serum bone-specific alkaline phosphatase (B-ALP), type I procollagen carboxyterminal (PICP) and aminoterminal propeptide (PINP), serum type I collagen carboxyterminal telopeptide (ICTP)). Serum testosterone was assayed in men. Calcium with or without calcitonin had no effect on bone loss or bone markers; consequently the three study groups were combined. During the first 6 post-transplant months BMD decreased by 5.7% in the lumbar spine and by 6.9% to 8.7% in the three femoral sites (P < 0.0001 for all); no significant further decline occured between 6 and 12 months. Four out of 25 assessable patients experienced vertebral compression fractures. Markers of bone formation reduced: B-ALP by 20% at 3 weeks (P = 0.027), PICP by 40% (P < 0.0001) and PINP by 63% at 6 weeks (P < 0.0001), with a return to baseline by 6 months. The marker of bone resorption, serum ICTP was above normal throughout the whole observation period, with a peak at 6 weeks (77% above baseline, P < 0.0001). In male patients serum testosterone decreased reaching a nadir (57% below baseline) at 6 weeks (P = 0.0003). In conclusion, significant bone loss occurs after BMT. It results from imbalance between reduced bone formation and increased bone resorption; hypogonadism may be a contributing factor in men. Bone loss can not be prevented by calcium with or without calcitonin.
...
PMID:A prospective study of bone loss and turnover after allogeneic bone marrow transplantation: effect of calcium supplementation with or without calcitonin. 1010 May 79

The effects of orchidectomy on bone metabolism in male beagle dogs were examined using twelve 2-year-old dogs that were orchidectomized. The dogs' bilateral iliac bones, double-labeled with tetracycline and calcein for the histomorphometry, were obtained from three dogs prior to orchidectomy and at 3, 6, 9, and 12 months afterwards. The serum biochemical constituents related to bone metabolism were examined before and every month after orchidectomy. Between 1 and 6 months after orchidectomy, the value of serum testosterone decreased (1 month), while the levels of parathyroid hormone, calcitonin, total calcium, osteocalcin, and alkaline phosphatase activity increased significantly, indicating a high bone turnover. The mean trabecular thickness and the fraction of labeled osteoid surface decreased significantly 3 months after orchidectomy, but other histomorphometric parameters were unchanged. In the period 7-12 months after orchidectomy, the parathyroid hormone level increased ever and above that of the first 6-month period, while the levels of calcitonin, osteocalcin, alkaline phosphatase activity, and phosphorus decreased. The bone volume, mean trabecular thickness, and the fraction of labeled trabecular surface decreased significantly compared with the pre-orchidectomy values. These findings indicate an imbalance in bone metabolism (i.e. bone resorption > bone formation). These results indicate that a loss of bone volume accompanied the fall in sex hormone levels following orchidectomy and suggest that the orchidectomized dog is available as an animal model for studying osteoporosis caused by hypogonadism and the decline of sex functions in men.
...
PMID:Effects of orchidectomy on bone metabolism in beagle dogs. 1067 93

The present study investigates the role of sex steroids, especially serum estradiol and serum testosterone in male osteoporosis patients and their association to established markers of bone turnover as also to BMD results and histomorphometric findings. Included were patients with secondary osteoporosis due to steroid medication, anticonvulsive medication and alcohol consumption, and heavy smoking patients. 100 males aged from 30 to 78 years were investigated for osteodensitometry (DEXA) and assessment of biochemical bone turnover markers (venous blood samples, 24 hour urine samples). In 40 of these patients bone biopsies were taken for histomorphometry. Laboratory investigations were made for serum Ca, P, parathyroid hormone (PTH), osteocalcin (OC), carboxyterminal extension peptide of type I procollagen (PICP), bone specific alkaline phosphatase (B-ALP), 25OH-vit.D, testosterone, estradiol, gonadotropines, and deoxypyridinoline and hydroxyproline from 24-hour urinary collection. Regions of interest for osteodensitometry with DEXA technique were the lumbar spine L1-L4 and the femoral neck (Ward's triangle). All of the patients examined had low bone mineral density (BMD) values compared to age- and sex-matched controls. Results from descriptive statistics showed hypogonadism in 26.4%, 25 OH-vitamin D deficiency in 26.2% and high serum estradiol in 59.1% of patients, compared to age- and sex-matched controls. 8.5% had elevated PTH levels. Multivariate analysis of data showed no significant correlation between BMD and semiquantitative histomorphometric findings (scaled from 1-5), neither a significant correlation between serum testosterone/estradiol and BMD. A significant correlation was observed between testosterone and estradiol values (r = 0.389, p = 0.008), and between OC and BMD results at ward's triangle (p = 0.008). In steroid treated patients (n = 12) significant differences were found for PTH (P < 0.01), 25 OH-Vit.D (p < 0.05) and urinary deoxypyridinoline (p < 0.05) as compared with the other patient group (n = 88). In summary we found high serum estradiol in 59.1% of our patients collective with low BMD, there was no correlation between BMD and histomorphometric findings. We observe a significant positive correlation between testosterone and estradiol values, but we did not find any association to bone turnover markers or BMD results.
...
PMID:Sex steroids, biochemical markers, bone mineral density and histomorphometry in male osteoporosis patients. 1112 45

Hypogonadism is associated with osteoporosis in men. GnRH- agonist-induced hypogonadism increases bone turnover and bone loss in men, but the mechanism underlying these changes is unknown. To determine whether gonadal steroid deprivation increases the skeletal sensitivity to PTH or blunts the ability of PTH to promote 1,25-dihydroxyvitamin D formation, we infused human PTH-(1-34) at a dose of 0.55 U/kg.h for 24 h, in 11 men (ages, 50-82 yr) with locally advanced, node-positive, or biochemically recurrent prostate cancer but no evidence of bone metastases. PTH infusions were performed before initiation of GnRH agonist therapy (leuprolide acetate, 22.5 mg im, every 3 months) and again after 6 months of confirmed GnRH agonist-induced hypogonadism. Serum osteocalcin (OC), bone- specific alkaline phosphatase (BSAP), N-telopeptide (NTX), whole-blood ionized calcium, and 1,25-dihydroxyvitamin D were measured at baseline and every 6 h during each PTH infusion. Urinary NTX and free deoxypyridinoline (DPD) were assessed on spot morning samples before PTH infusion and on 24-h samples collected during the PTH infusions. Sex steroid levels were lowered to the castrate range in all subjects. Baseline serum NTX levels (drawn before PTH infusion) increased from 9.1 +/- 3.7 before leuprolide therapy to 13.9 +/- 5.0 nmol bone collagen equivalents (BCE)/L after leuprolide therapy (P = 0.003). Spot urine NTX collected before PTH infusion increased from 28 +/- 8 before leuprolide therapy to 49 +/- 17 nmol BCE/mmol creatinine after leuprolide therapy (P < 0.001), and urinary DPD increased from 4.7 +/- 1.1 to 7.4 +/- 1.8 nmol BCE/mmol creatinine (P < 0.001). Baseline serum OC and BSAP levels drawn before each PTH infusion did not change before vs. after leuprolide therapy. Serum NTX levels increased significantly during PTH infusion pre-GnRH agonist therapy (P < 0.001), and the rate of increase was greater after 6 months of GnRH agonist-induced hypogonadism (P < 0.01 for the difference in rates of change before and after GnRH agonist administration). Serum OC and BSAP levels decreased during PTH infusion (P < 0.001 for OC and P = 0.002 for BSAP), but the rates of decrease did not differ before or after leuprolide therapy (P = 0.45 for OC and P: = 0.19 for BSAP). Whole-blood ionized calcium levels increased during PTH infusion (P < 0.001), and the rate of increase was greater after GnRH agonist-induced hypogonadism (P = 0.068). Serum 1,25-dihydroxyvitamin D levels increased in response to PTH infusion before leuprolide therapy (P = 0.022), but there was no difference in the rate of increase before or after leuprolide therapy (P = 0.66). The incremental increase in urinary NTX excretion, but not DPD, during PTH infusion was greater after 6 months of leuprolide therapy (P = 0.029 for NTX, P = 0.578 for DPD). We conclude that suppression of sex steroids in elderly men increases the skeletal responsiveness to the bone resorbing effects of PTH infusion but does not affect the response of bone formation markers or 1,25-dihydroxyvitamin D to PTH. Changes in skeletal sensitivity to PTH may play an important role in the pathogenesis of hypogonadal bone loss in men.
...
PMID:Effects of gonadal steroid suppression on skeletal sensitivity to parathyroid hormone in men. 1115 1

Bone disease in patients with thalassaemia major is a multifactorial and still poorly understood process. The present study evaluated 45 thalassaemic patients using dual X-ray absorptiometry at three sites (lumbar spine, head of femur and forearm) to assess bone mineral density, in parallel with a series of biochemical markers to measure bone formation and bone resorption. To identify possible interfering factors, our patients were grouped according to whether or not they needed transfusion therapy; the presence of hypogonadism was also considered. Our results showed that patients on regular transfusions had a markedly low bone mineral density in contrast to those not requiring blood support and that this finding was more pronounced in the hypogonadic group, irrespectively of sex. The decrease of bone mineral density values was more prominent in the forearm, thus making this site particularly interesting for such studies. Bone formation, as evidenced by the levels of serum alkaline phosphatase and osteocalcin, did not appear to be impaired, while bone resorption was grossly increased in all patient groups. The latter process was clearly evident using the recently introduced measurement of the urinary N-terminal peptides of collagen type I, the sensitivity of which has already been established in other groups of osteoporotic patients. Our conclusion is that, in spite of the severe bone destruction that occurs in thalassaemia major, the fact that bone formation remains intact calls for a more intensive treatment comprising hormonal replacement, bisphosphonates and other agents.
...
PMID:Bone resorption is increased in young adults with thalassaemia major. 1116 80


1 2 3 Next >>

---