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1.
P. R. Ebeling A. L. Yergey N. E. Vieira M. F. Burritt W. M. O'Fallon R. Kumar B. L. Riggs 《Calcified tissue international》1994,55(5):330-334
Recent reports of increases in serum 1,25-dihydroxyvitamin D [1,25(OH2)D] concentration with aging despite no changes or decreases in calcium absorption suggest that elderly women have intestinal resistance to vitamin D action. Thus, in 15 young adult (30±1 year) and 15 elderly (74±1 year) women (mean±SE), we assessed the responsiveness of intestinal calcium absorption to increases in circulating 1,25(OH)2D induced by 4 days of an experimental diet (150 mg calcium and 1600 mg phosphorus daily). True fractional calcium absorption (FCA) (44Ca mixed with food and 42Ca given intravenously, then their ratio in urine measured by mass spectrometry) was determined. Baseline serum intact parathyroid hormone (PTH) concentration was higher in the older women (P=0.01) whereas serum 1,25(OH)2D concentration and true FCA were similar. In both groups, serum 1,25(OH)2D concentrations increased (P<0.002) on the experimental diet. After 4 days on the diet, serum 1,25(OH)2D increased over baseline by 30.5 and 35.6% and, despite these increases, true FCA was 40±3 versus 40±4%/24 hours (NS between groups) in the young and elderly women, respectively. These data suggest that either elderly women have normal intestinal responsiveness to vitamin D or that the resistance to it is too mild to be detected by these methods. 相似文献
2.
To determine the role of the kidney in regulation of 25-hydroxycholecalciferol (25OHD3, metabolism, the effects of 1,25-dihydroxycholecalciferol [1,25(OH)2D3] on 3H-25OHD3 were compared in intact and nephrectomized vitamin D-deficient rats. Sixteen hours after the intravenous administration of 3H-25OHD3, extracts of serum and pooled small intestinal mucosa were fractionated by Sephadex LH-20 column chromatography followed by high performance liquid chromatography. In intact rats, 1,25(OH)2D3 (50 ng/day i.p. for 7 days) increased mean serum 3H-24,25-dihydroxycholecalciferol [3H-24,25(OH)2D3] from 2 +/- 2-210 +/- 80 fmol/ml (mean +/- 1 SD), increased mean serum 3H-25,26-dihydroxycholecalciferol [3H-25,26(OH)2D3] from 2 +/- 2-12 +/- 6 fmol/ml and lowered mean serum 3H-1,25(OH)2D3 from 210 +/- 40-4 +/- 4 fmol/ml. Similarly, in nephrectomized animals, 1,25(OH)2D3 increased mean serum 3H-24,25-(OH)2D3 from 6 +/- 11-115 +/- 30 fmol/ml and increased mean serum 3H-25,26(OH)2D3 from 3 +/- 3-26 +/- 10 fmol/ml. Nephrectomy increased serum 3H-25(OH)D3 in untreated (from 1450 +/- 225-2675 +/- 225 fmol/ml serum) and 1,25(OH)2D3 treated rats (from 1600 +/- 175-3075 +/- 100 fmol/ml). 3H-1,25(OH)2D3 averaged 74 +/- 16% of total radioactivity in intestinal mucosa of untreated intact rats and was not detected in either the serum or intestinal mucosa of nephrectomized animals. The results suggest that in intact animals, extrarenal synthesis can account for substantial 24,25(OH)2D3 production and for most 25,26(OH)2D3 production.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
3.
Effects of oral phosphorus supplementation on mineral metabolism of renal transplant recipients 总被引:2,自引:2,他引:0
Caravaca F; Fernandez M; Ruiz-Calero R; Cubero J; Aparicio A; Jimenez F; Garcia M 《Nephrology, dialysis, transplantation》1998,13(10):2605-2611
Background. Persistent hyperparathyroidism (HPT) is
frequently observed in kidney transplant recipients. Hypophosphataemia is a
common biochemical consequence of HPT. Theoretically, oral phosphorus
administration may induce negative effects on the control of HPT, though
this point has never been demonstrated in kidney-transplant recipients.
This study was designed to evaluate the effects of oral phosphorus
supplementation on the mineral metabolism of successful kidney transplant
recipients. Methods. Thirty-two kidney transplant
recipients with serum creatinine <2 mg/dl and serum phosphate levels
<3.5 mg/dl were included in the study. After a wash-out period in
which oral phosphorus supplementation was discontinued, the following
parameters were determined (F0 period): serum calcium, phosphate, alkaline
phosphatase, uric acid, bicarbonate, PTH, 1,25-dihydroxyvitamin D3
(1,25(OH)2D) and 25-hydroxyvitamin D3 (250HD). Creatinine clearance,
calcium, and phosphate excretion were determined from a 24-h urine sample.
The same determinations were repeated (F1 period) after all patients
received 1.5 g of oral phosphorus for 15 days. For data analysis, patients
were divided into two subgroups (optimal and suboptimal) according to
allograft function (Ccr>or<70 ml/min/1.73
m2). Results. In the F0 period,
only nine of 32 patients had PTH levels within the normal range (<65
pg/ml). The mean concentrations of PTH, 1,25(OH)2D and 25OHD were
132±97 pg/ml, 40.5+16 pg/ml and 12.5±8.2 ng/ml
respectively. Phosphorus supplementation led to significant reductions in
serum calcium and 1,25(OH)2D concentrations, as well as in urinary calcium
excretion in the whole group. On the contrary, serum phosphate, PTH, and
urinary phosphate excretion increased significantly. The percentage
increase in PTH concentrations after phosphorus supplementation were
similar in patients with optimal and suboptimal allograft function (33
vs 36%). The reduction of 1,25(OH)2D concentrations
after phosphorus supplementation was observed mainly in the subgroup with
optimal allograft function (21% reduction with respect to baseline values),
while the mean 1,25(OH)2D concentrations in patients with suboptimal
allograft function scarcely changed (1.4% increase). Changes in 1,25(OH)2D
concentrations after phosphorus supplementation, expressed as a percentage
of the initial concentrations, correlated positively with the percentage
changes in PTH concentrations for the whole group, as well as for each
subgroup. The best determinants for the percentage and the absolute
increase in PTH concentration after phosphorus supplementation was the
final serum phosphate concentration (F=4.84, r=0.37,
P=0.035) and the increase in serum phosphate (F=7.69,
r=0.45, P=0.009) respectively.
Conclusions. Oral phosphorus supplementation led to a
significant increase in the PTH concentration of kidney transplant
recipients. The mean 1,25(OH)2D concentration decreased mainly in
recipients with optimal allograft function. The counterbalance effect of
PTH on 1,25(OH)2D production may account for the relative preservation of
1,25(OH)2D levels in recipients with suboptimal allograft function. 相似文献
4.
Does the vitamin D receptor genotype predict bone mineral loss in haemodialysed patients? 总被引:2,自引:0,他引:2
Karkoszka H; Chudek J; Strzelczyk P; Wiecek A; Schmidt-Gayk H; Ritz E; Kokot F 《Nephrology, dialysis, transplantation》1998,13(8):2077-2080
Background. It has been suggested that the vitamin D
receptor (VDR) gene BsmI-polymorphism is a genetic determinant of bone
metabolism. Design. To test this hypothesis, the
relationship between VDR genotypes, bone mineral density (baseline and
after 18 months) and parameters of calcium metabolism and bone turnover
were investigated prospectively in 88 haemodialysed patients not receiving
active vitamin D metabolites. Methods. Whole body,
lumbar spine and femoral neck bone mineral density (BMD) were assessed by
dual energy X-ray absorptiometry (DEXA). In addition calcium, phosphorus,
25(OH)D3, 1,25(OH)2D3, osteocalcin serum concentrations, alkaline
phosphatase activity and intact, 1,84 PTH levels were measured.
Results. VDR genotype BB, Bb and bb were found in 27,
49 and 24% of patients. Initial BMD (g/cm2) of whole
body, lumbar spine and femoral neck did not differ between genotypes (whole
body: BB 1.055 ± 0.120, Bb 1.082 ± 0.102, bb 1.128
± 0.120; lumbar spine: BB 1.075 ± 0.199, Bb 1.079
± 0.185, bb 1.099 ± 0.170; femoral neck: BB 0.808
± 0.160, Bb 0.862 ± 0.127, bb 0.842 ±
0.125; mean ± SD), but the decrease of whole body and femoral
neck BMD during 18 months was significantly (P
< 0.02) different between the genotype groups (whole body: BB -0.048
± 0.028, Bb -0.031 ± 0.029, bb -0.024 ±
0.023; femoral neck BB -0.044 ± 0.069, Bb -0.032 ±
0.081, bb -0.012 ± 0.029 g/cm2).
Conclusions. This preliminary study suggests faster
mineral loss in BB genotype of VDR in haemodialysed patients. 相似文献
5.
Compensatory Changes in Calcium Metabolism Accompany the Loss of Vitamin D Receptor (VDR) From the Distal Intestine and Kidney of Mice
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1,25 Dihydroxyvitamin D3 (1,25(OH)2D) increases intestinal Ca absorption when dietary Ca intake is low by inducing gene expression through the vitamin D receptor (VDR). 1,25(OH)2D‐regulated Ca absorption has been studied extensively in the small intestine, but VDR is also present in the large intestine. Our goal was to determine the impact of large intestinal VDR deletion on Ca and bone metabolism. We used transgenic mice expressing Cre‐recombinase driven by the 9.5‐kb human caudal type homeobox 2 (CDX2) promoter to delete floxed VDR alleles from the caudal region of the mouse (CDX2‐KO). Weanling CDX2‐KO mice and control littermates were fed low (0.25%) or normal (0.5%) Ca diets for 7 weeks. Serum and urinary Ca, vitamin D metabolites, bone parameters, and gene expression were analyzed. Loss of the VDR in CDX2‐KO was confirmed in colon and kidney. Unexpectedly, CDX2‐KO had lower serum PTH (–65% of controls, p < 0.001) but normal serum 1,25(OH)2D and Ca levels. Despite elevated urinary Ca loss (eightfold higher in CDX2‐KO) and reduced colonic target genes TRPV6 (–90%) and CaBPD9k (–80%) mRNA levels, CDX2‐KO mice had only modestly lower femoral bone density. Interestingly, duodenal TRPV6 and CaBPD9k mRNA expression was fourfold and threefold higher, respectively, and there was a trend toward increased duodenal Ca absorption (+19%, p = 0.076) in the CDX2‐KO mice. The major finding of this study is that large intestine VDR significantly contributes to whole‐body Ca metabolism but that duodenal compensation may prevent the consequences of VDR deletion from large intestine and kidney in growing mice. © 2015 American Society for Bone and Mineral Research. 相似文献
6.
Dr. Russell T. Turner Richard C. Avioli Norman H. Bell 《Calcified tissue international》1984,36(1):274-278
Summary To determine the role of the kidney in regulation of 25-hydroxycholecalciferol (25OHD3, metabolism, the effects of 1,25-dihydroxycholecalciferol [1,25(OH)2D3] on3H-25OHD3 were compared in intact and nephrectomized vitamin D-deficient rats. Sixteen hours after the intravenous administration of3H-25OHD3, extracts of serum and pooled small intestinal mucosa were fractionated by Sephadex LH-20 column chromatography followed
by high performance liquid chromatography. In intact rats, 1,25(OH)2D3 (50 ng/day i.p. for 7 days) increased mean serum3H-24,25-dihydroxycholecalciferol [3H-24,25(OH)2D3] from 2±2–210±80 fmol/ml (mean±1 SD), increased mean serum3H-25,26-dihydroxycholecalciferol [3H-25,26(OH)2D3] from 2±2–12±6 fmol/ml and lowered mean serum3H-1,25(OH)2D3 from 210±40–4±4 fmol/ml. Similarly, in nephrectomized animals, 1,25(OH)2D3 increased mean serum3H-24,25-(OH)2D3 from 6±11–115±30 fmol/ml and increased mean serum3H-25,26(OH)2D3 from 3±3–26 ± 10 fmol/ml. Nephrectomy increased serum3H-25(OH)D3 in untreated (from 1450±225–2675±225 fmol/ml serum) and 1,25(OH)2D3 treated rats (from 1600±175–3075±100 fmol/ml).3H-1,25(OH)2D3 averaged 74±16% of total radioactivity in intestinal mucosa of untreated intact rats and was not detected in either the serum
or intestinal mucosa of nephrectomized animals. The results suggest that in intact animals, extrarenal synthesis can account
for substantial 24,25(OH)2D3 production and for most 25,26(OH)2D3 production. Further, the observed stimulation of production of 24,25(OH)2D3 and 25,26(OH)2D3 by 1,25(OH)2D3 in anephric — D rats providesin vivo evidence for regulation of extrarenal 25OHD3: 24- and 26-hydroxylases. 相似文献
7.
Dusso AS 《Kidney international. Supplement》2003,(85):S6-S9
8.
M. Ishibe T. Nojima T. Ishibashi T. Koda K. Kaneda R. N. Rosier J. E. Puzas 《Calcified tissue international》1995,57(6):430-435
It is well known that 17-estradiol (E2) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) have important roles in bone metabolism. This study was undertaken to examine E2 regulation of 1,25(OH)2D3 receptor (VDR) expression and the biological action of 1,25(OH)2D3 in human osteoblast-like cells. When human osteosarcoma-derived osteoblast-like cells were treated with varying concentrations of E2, the VDR levels increased by up to 100% in a dose-dependent manner. VDR levels significantly increased at 10 nM E2 and this increase plateaued at 100 nM E2. E2-dependent increase of VDR was time dependent, plateauing, at 24 hours and was maintained for at least 48 hours in human osteoblast-like cells. Scatchard analysis showed that E2 increased the number of VDR (12.3±0.4 versus 26.5±0.3 fmol/mg protein; mean ±SE of three independent experiments) rather than the Kd (0.15±0.02 versus 0.16±0.01 nM; mean±SE of three independent experiments). Tamoxifen (50 nM), a specific competitor with E2, completely abolished the E2-induced increase of VDR. The levels of VDR mRNA (4.5 kb) from the cells increased in a dose-dependent manner after E2 treatment. With regard to the biological effects, E2 increased by 10–25% the inhibitory effect of 1,25(OH)2D3 on cell growth. However, E2 did not increase the stimulation of alkaline phosphatase activity by 1,25(OH)2D3. The present study suggests that E2 modulates the biological action of 1,25(OH)2D3 through VDR levels in bone cells. 相似文献
9.
N. M. Wright N. Papadea B. Wentz B. Hollis S. Willi N. H. Bell 《Calcified tissue international》1997,61(2):101-103
To assess the effects of growth hormone (GH) on serum 1,25-dihydroxyvitamin D [1,25(OH)2D], we performed the following prospective crossover study in six healthy, young, adult, white men. During each of two admissions
for 2? days to a general clinical research center, subjects were placed on a daily dietary calcium intake of 400 mg. Serum
calcium, phosphorus, 1,25(OH)2D, immunoreactive intact parathyroid hormone (PTH), insulin-like growth factor I (IGF-I), IGF binding protein 3 (IGFBP3),
tubular reabsorption of phosphate (TRP), and maximum tubular reabsorption of phosphate (TMP/GFR) were measured. Recombinant
human GH (rhGH, Humatrope) (25 μg/kg/day subcutaneously for 1 week) was administered prior to and during one of the admissions.
Results are expressed as mean ± SEM. Whereas serum 1,25(OH)2D (58.9 ± 7.7 versus 51.6 ± 7.4 pg/ml, P < 0.01), serum phosphorus (4.5 ± 0.1 versus 3.7 ± 0.1 mg/dl, P < 0.01), TRP (92.0 ± 0.5 versus 87.8 ± 0.7 mg/dl, P < 0.005), TMP/GFR (4.6 ± 0.1 versus 3.5 ± 0.2, P < 0.005), and urinary calcium (602 ± 49 versus 346 ± 25 mg/day, P < 0.001) increased significantly, serum PTH decreased significantly (19.9 ± 1.9 versus 26.8 ± 4.0 pg/ml, P < 0.05) and serum calcium did not change when subjects received rhGH. These findings indicate that in humans, GH affects
serum 1,25(OH)2D independently of circulating PTH and that this effect is mediated by IGF-I. We propose, therefore, that one potential mechanism
by which GH stimulates increases in bone mass is via modest increases in serum 1,25(OH)2D.
Received: 2 May 1996 / Accepted: 18 October 1996 相似文献
10.
11.
P. Oelzner A. Müller F. Deschner M. Hüller K. Abendroth G. Hein G. Stein 《Calcified tissue international》1998,62(3):193-198
In several studies on patients with rheumatoid arthritis, an association of bone loss with a persistently high disease activity
has been found. The aim of our study was to investigate the relation between disease activity and serum levels of vitamin
D metabolites, parathyroid hormone (PTH), and parameters of bone turnover in patients with rheumatoid arthritis. A total of
96 patients (83 women and 13 men) were divided into three groups according to disease activity measured by serum levels of
C-reactive protein (CRP). In the whole group, serum levels of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) (P < 0.001) and PTH (P < 0.05) were negatively correlated to disease activity. The urinary excretion of collagen crosslinks—pyridinoline (Pyd) (P < 0.001) and deoxypyridinoline (Dpd) (P < 0.05)—showed a positive correlation with disease activity. The inverse correlation between serum 1,25(OH)2D3 and disease activity was separately evident in patients with (P < 0.001) and without (P < 0.01) glucocorticoid treatment, in pre- (P < 0.01) and postmenopausal (P < 0.001) women, and in men (P < 0.01). 1,25(OH)2D3 and PTH serum levels were positively correlated to serum bone alkaline phosphatase (ALP) (P < 0.01). The results indicate that high disease activity in patients with rheumatoid arthritis is associated with an alteration
in vitamin D metabolism and increased bone resorption. The decrease of 1,25(OH)2D3 levels in these patients may contribute to a negative calcium balance and inhibition of bone formation. Furthermore, low
levels of 1,25(OH)2D3 as an endogenous immunomodulator suppressing activated T cells and the proliferation of cells may accelerate the arthritic
process in rheumatoid arthritis.
Received: 3 February 1997 / Accepted: 26 June 1997 相似文献
12.
Dr K. Sakhaee A. Zisman J. R. Poindexter J. E. Zerwekh C. Y. C. Pak 《Osteoporosis international》1993,3(4):209-214
It was previously shown that the stimulation of intestinal calcium absorption by exogenous 25-hydroxyvitamin D (25-OHD) in postmenopausal women with osteoporosis was attenuated when thiazide was added, probably due to the suppression of endogenous synthesis of 1,25-(OH)2 vitamin D (1,25-(OH)2D). To test whether the above attenuation could be averted if exogenous 1,25-(OH)2D replaced 25-OHD, 10 women with postmenopausal osteoporosis participated in a three-phase study comprising control (pretreatment), treatment with 1,25-(OH)2D 0.5 µg/day for 4 weeks, and combined 1,25-(OH)2D and trichlormethiazide (TZ) 2 mg/day for 4 weeks. The 1,25-(OH)2D treatment significantly increased serum 1,25-(OH)2D from 60±7.2 (SD) to 154±48 pmol/1, fractional intestinal calcium absorption () from 0.386 ±0.055 to 0.613±0.081, and urinary calcium from 3.7±0.8 to 6.6±1.9 mmol/day. Addition of TZ significantly reduced urinary calcium from 6.6±1.9 to 4.8±1.3 mmol/day, without changing (0.613±0.081 to 0.584±0.070), serum calcium or 1,25-(OH)2D (154±48 to 154±38 pmol/1). Thus, estimated calcium balance (absorbed minus urinary calcium, increased marginally to +5.6 mmol/day on 1,25-(OH)2D alone (p=0.028) and significantly to +6.8 mmol/day on 1,25-(OH)2D+TZ, from the control value of +4.0 mmol/day. Seven patients who were treated long-term with combined 1,25-(OH)2D and TZ for 11–29 months maintained their a (0.593±0.099) and a marginally more positive estimated calcium balance (+6.4 mmol/day,p=0.025 from the control phase). Moreover, there was a stability of bone density of radial shaft, femoral neck, and lumbar spine. In conclusion, when exogenous 1,25-(OH)2D is provided, TZ does not lower serum 1,25-(OH)2D and in patients with postmenopausal osteoporosis. Thus, the hypocalciuric action of TZ may lead to improved calcium balance and may potentially attenuate further bone loss. 相似文献
13.
Kuwahara M Inoshita S Nakano Y Terada Y Takano Y Sasaki S 《Clinical and experimental nephrology》2007,11(1):34-40
Some researchers have speculated that a decrease in bone type 1 PTH receptor (PTH1R) may be among the causes of “skeletal
resistance” in chronic renal failure (CRF). Indeed, the down-regulation of PTH1R mRNA has been identified in uremic bones.
However, few studies have identified the patterns of PTH1R protein expression. In this article we compare the bone expression
of PTH1R protein and mRNA under control and CRF conditions. Sprague–Dawley rats underwent 5/6 nephrectomies (Nx) or sham operations
(control), and were killed 16 weeks later. Blood urea nitrogen (BUN), serum Cr, P, and parathyroid hormone (PTH) were higher
in the Nx group than in the controls, while serum Ca and 1,25(OH)2D3 were lower in the Nx group. Immunohistochemical images of lumbar bone samples were analyzed by an image processing system.
PTH1R was essentially identified in all osteoblasts. The expression of osteoblast PTH1R protein was quantified based on the
gray value of PTH1R staining. The mean gray scale of osteoblasts was 25% lower in Nx rats than in control rats (P < 0.01), whereas osteoblast cell counts and cell sizes were not significantly different between the two groups. Thus, down-regulation
of PTH1R protein expression under the CRF condition appeared likely. Total RNA extracted from the bone samples was reverse
transcribed for real-time polymerase chain reaction (PCR). PTH1R mRNA expression was 33% lower in the Nx group than in the
control group in the quantitative PCR analysis (P < 0.05). Our findings suggested that osteoblast PTH1R expression is down-regulated at both the protein and mRNA levels in
the steady state of CRF. 相似文献
14.
Synthesis of vitamin D takes place in the skin under the effect of sunlight. The Indian subcontinent is situated between 8.4° N and 37.6° N latitudes and has adequate sunshine throughout the year. Thus, it has been presumed that Indians are vitamin D sufficient. We measured serum 25-hydroxy vitamin D [25(OH)D] (n=92) and 1,25-dihydroxy vitamin D [1, 25(OH)2D] (n=65) levels in healthy hospital staff, using 125I radioimmunoassay. Serum intact parathyroid hormone (PTH) concentration was estimated by immunoradiometric assay. Bone mineral density was estimated using a dual energy X-ray absorptiometer (HologicR QDR 4500A). Using a serum 25(OH)D level of 15 ng/ml as a cutoff, 66.3% (61/92) of the subjects were found to be vitamin D deficient. Of these, 20.6% (19/92) subjects had severe vitamin D deficiency (<5 ng/ml), 27.2% (25/92) had moderate vitamin D deficiency (5–9.9 ng/ml), while 18.5% (17/92) had mild vitamin D deficiency (10–14.9 ng/ml). When a serum 25(OH)D level of 20 ng/ml was used as a cutoff, 78.3% subjects were diagnosed to be vitamin D deficient/insufficient. The serum 1,25(OH)2D level was within the normal range (40.6±20.1 pg/ml; mean ± SD). Mean (±SD) serum intact PTH, estimated in a limited number of subjects (n=15), was 72.3 (±21.0) pg/ml (range 36–100 pg/ml). There was a significant correlation between daily sun exposure and 25(OH)D levels (r=0.731, P<0.001). The serum 25(OH)D level correlated with BMD at the femoral neck and Ward's triangle (r=0.50, P=0.020 and r=0.46, P=0.037, respectively). Our findings show that vitamin D deficiency is common in urban north Indian hospital staff. The possible reasons include inadequate sunlight exposure and skin pigmentation in Indians. The serum 1,25(OH)2D level is not a good indicator of vitamin D deficiency. A low serum 25(OH)D level is possibly one of the reasons for lower bone mineral density among Indians. 相似文献
15.
16.
Dr C. L. Benhamou D. Tourliere J. B. Gauvain G. Picaper M. Audran P. Jallet 《Osteoporosis international》1995,5(2):103-107
The effects of age on calciotropic hormones are not completely understood. The presence of secondary hyperparathyroidism has previously been demonstrated, particularly in patients with hip fracture. The role of a disturbance of vitamin D metabolism, especially a defect in l-hydroxylation, is debated. The aim of this study was to compare serum parathyroid hormone (PTH), osteocalcin and vitamin D metabolites (25(OH)D and 1,25(OH)2D) in osteoporotic elderly patients with hip fracture (HF) and in elderly controls. We studied 57 HF patients aged 83.9±5.9 years (mean±SD) and 68 controls aged 82.5±5 years recruited during two periods: 1 January and 30 April 1988 and 1989. Patients with chronic renal failure (serum creatinine above 150, µmol/l), cancer, or other metabolic bone disease were excluded. Thirty healthy young adults were studied in 1989 only for measurement of 1,25(OH)2D. (1,25(OH)2D was measured by different laboratories in 1988 and 1989 for technical reasons.) We also measured serum PTH, osteocalcin, total calcium and ionized calcium. 1,25(OH)2D levels were not statistically different between HF patients and controls for the two years, nor between HF patients and young healthy adults in 1989. 25(OH)D was decreased in HF patients (p<0.003), as was ionized calcium. Serum PTH levels were higher in HF patients than in controls (p<0.01). A positive correlation has been found between PTH and age in HF patients (r=0.29;p<0.03) and in the whole group of HF patients and controls. There was a significant decrease in osteocalcin in HF patients versus elderly controls (p<0.04). Our results confirm the high levels of intact PTH in elderly HF patients, this elevation of PTH being known to increase bone resporption. Low serum osteocalcin in HF patients seems to reflect decreased bone formation. Thus, this association contributes to the accelerated bone loss in hip fracture. This study also suggests that 1,25(OH)2D is not significantly lowered in case of hip fracture, and l-hydroxylase is not deficient, in spite of a lack of the substrate of this enzyme (25(OH)D). Therefore, a defect of 1,25(OH)2D does not appear to be a pathogenetic factor in bone aging. 相似文献
17.
Sherri‐Ann M Burnett‐Bowie MD MPH Maria P Henao Melissa E Dere Hang Lee Benjamin Z Leder 《Journal of bone and mineral research》2009,24(10):1681-1685
Fibroblast growth factor 23 (FGF23) promotes phosphaturia and suppresses 1,25‐dihydroxyvitamin D [1,25(OH)2D] production. PTH also promotes phosphaturia, but, in contrast, stimulates 1,25(OH)2D production. The relationship between FGF23 and PTH is unclear, and the acute effect of pharmacologically dosed PTH on FGF23 secretion is unknown. Twenty healthy men were infused with human PTH(1‐34) [hPTH(1‐34)] at 44 ng/kg/h for 24 h. Compared with baseline, FGF23, 1,25(OH)2D, ionized calcium (iCa), and serum N‐telopeptide (NTX) increased significantly over the 18‐h hPTH(1‐34) infusion (p < 0.0001), whereas serum phosphate (PO4) transiently increased and then returned to baseline. FGF23 increased from 35 ± 10 pg/ml at baseline to 53 ± 20 pg/ml at 18 h (p = 0.0002); 1,25(OH)2D increased from 36 ± 16 pg/ml at baseline to 80 ± 33 pg/ml at 18 h (p < 0.0001); iCa increased from 1.23 ± 0.03 mM at baseline to 1.46 ± 0.05 mM at hour 18 (p < 0.0001); and NTX increased from 17 ± 4 nM BCE at baseline to 28 ± 8 nM BCE at peak (p < 0.0001). PO4 was 3.3 ± 0.6 mg/dl at baseline, transiently rose to 3.7 ± 0.4 mg/dl at hour 6 (p = 0.016), and then returned to 3.4 ± 0.5 mg/dl at hour 12 (p = 0.651). hPTH(1‐34) infusion increases endogenous 1,25(OH)2D and FGF23 within 18 h in healthy men. Whereas it is possible that the rise in PO4 contributed to the observed increase in FGF23, the increase in 1,25(OH)2D was more substantial and longer sustained than the change in serum phosphate. Given prior data that suggest that neither PTH nor calcium stimulate FGF23 secretion, these data support the assertion that 1,25(OH)2D is a potent physiologic stimulator of FGF23 secretion. 相似文献
18.
Sutin Sriussadaporn Man-Sau Wong Wesley J. Pike Murray J. Favus M.D. 《Journal of bone and mineral research》1995,10(2):271-280
Dietary phosphorus restriction up-regulates intestinal vitamin D receptor (VDR), but the tissue specificity of the up-regulation and the mechanism of receptor accumulation remain unknown. Therefore, the effects of low phosphorus diet (LPD) on VDR content in intestine, kidney, and splenic monocytes/macrophages were examined. Male Sprague-Dawley rats weighing 50–100 g were fed a normal diet (NPD; 0.6% Ca, 0.65% P) as controls followed by an LPD (0.6% Ca, 0.1% P) for 1–10 days (D1-D10). LPD rapidly decreased serum P levels by D1 from 11.11 ± 0.19 mg/dl (mean ± SE) to 4.98 ± 0.37 mg/dl (n = 9). LPD increased total serum Ca from 10.54 ± 0.09 mg/dl to 11.63 ± 0.15, 12.17 ± 0.15, and 12.39 ± 0.18 mg/dl by D1, D2, and D3, respectively, and then remained stable. Serum 1,25-(OH)2D3 rapidly increased from 123 ± 5.4 pg/ml to 304 ± 35 pg/ml by D1, reached a plateau through D5, and then gradually increased to 464.9 ± 27.7 pg/ml by D10. Intestinal VDR quantitated by ligand binding assay increased 3.5-fold from 169.6 ± 13.7 fmol/mg of cytosol protein in rats fed NPD (n = 12) to a peak of 588.3 ± 141.88 fmol/mg of protein by D3 (n = 6; p < 0.001) and then decreased to a plateau level of 2.5-fold greater than NPD (p < 0.05) during D5 to D10. In contrast, LPD did not up-regulate kidney or splenic monocyte/macrophage VDR. Northern blot analysis showed that intestinal VDR mRNA increased 2-fold by D2 (n = 3) of LPD and then gradually decreased to control levels after D5. In contrast, kidney VDR mRNA levels did not change during the first 5 days of P restriction and then subsequently decreased to 50% of NPD controls. The results of these studies indicate that VDR up-regulation during dietary phosphorus restriction is tissue-specific and that the mechanism of the up-regulation is time-dependent. Acutely (D1-D5), phosphorus restriction up-regulates intestinal VDR through increased VDR gene expression, whereas chronic (D5-D10) phosphorus restriction appears to alter VDR metabolism through nongenomic mechanisms that are consistent with prolongation of the half-life of the receptor. The nature of the tissue-specific regulation of VDR during phosphorus restriction remains to be determined. 相似文献
19.
S. Adami W. B. Frijlink O. L. M. Bijvoet J. L. H. O'Riordan T. L. Clemens S. E. Papapoulos 《Calcified tissue international》1982,34(1):317-320
Summary In 10 patients with Paget's disease of bone and 2 patients with osteoporosis, we studied the effects of hypocalcemia and hypophosphatemia
induced by disodium-(3-amino-1-hydroxypropylidene)-1,-bisphosphonate (APD) treatment on the serum concentration of PTH and
1,25-dihydroxyvitamin D [1,25(OH)2D3] and on calcium absorption and balance. The fall in serum calcium and phosphate was associated with a rise in the serum concentration
of PTH and 1,25(OH)2D3, coupled with increases in net calcium absorption and calcium balance. The concentration of 1,25(OH)2D3 was significantly related (P<0.001) to the serum calcium (r=0.66), the serum phosphate (r=0.78), and the serum PTH (r=0.71), confirming the interrelated control of these parameters on 1,25(OH)2D3 production. Moreover, the rise in 1,25(OH)2D3 caused an appropriate rise in calcium absorption (r=0.74) and calcium balance (r=0.86), showing that this vitamin D metabolite contributes as a hormone to calcium homeostasis. 相似文献
20.
H. K. Kinyamu J. C. Gallagher J. A. Knezetic H. F. DeLuca J. M. Prahl S. J. Lanspa 《Calcified tissue international》1997,60(6):491-495
It is well established that bone mineral density is under strong genetic control. Recently it was reported that the Bsm I
restriction fragment length polymorphism of the vitamin D receptor (VDR) gene could account for up to 75% of the genetic variance
in bone mineral density. However, the physiological basis for such an effect has not been established. The VDR gene codes
for the vitamin D receptor protein which regulates intestinal calcium absorption. In order to assess the biochemical basis
we studied the effect of common allelic variation of the VDR gene on intestinal VDR protein concentration, calcium absorption,
and serum 1,25 dihydroxyvitamin D (1,25(OH)2D). Ninety-two Caucasian women were genotyped for Bsm I and Taq I polymorphism at the VDR gene locus. From these we compared
49 young women aged 25–35 years and 43 elderly women aged 65–83 years, who had all three measurements performed. There were
no significant differences in intestinal VDR protein concentration, serum 1,25(OH)2D, or radioactive calcium absorption among VDR genotype groups. Therefore, the small intestine does not seem to be a target
for VDR gene polymorphism.
Received: 12 August 1996 / Accepted: 3 January 1997 相似文献