1,25-二羟维生素D3与维生素D受体的研究

维生素D对于人体健康具有重要作用。本文就维生素D的重要活性形式1,25-二羟维生素D_2及维生素D受体两者关系作一综述,为进一步研究维生素D提供参考。     

Vitamin D status among postmenopausal Malaysian women

Serum levels of 25-hydroxyvitamin D (25 (OH) D) were determined in 276 (103 Malays and 173 Chinese) postmenopausal women, aged 50 to 65 years. The level of 25 (OH) D was significantly lower in the postmenopausal Malay women (44.4 +/-10.6 nmol/L) compared to the Chinese women (68.8 +/- 15.7 nmol/L) (P<0.05). There were 27% Malay women with serum 25 (OH) D in the range of 50 - 100 nmol/L (defined as lowered vitamin D status, or hypovitaminosis D) and 71% with levels in the range of 25 - 50 nmol/L (defined as vitamin D insufficiency) compared to 87% and 11% Chinese women respectively. Serum 25 (OH) D was found to significantly correlate with BMI, fat mass and PTH level. Multivariate analyses showed that race has a strong association with vitamin D status. The high prevalence of inadequate levels of serum vitamin D found in our study may have important public health consequences and warrants the development of a strategy to correct this problem in the older adult Malaysian population.     

Vitamin D intake and status in Irish postmenopausal women

OBJECTIVE: The objective of this study was to assess vitamin D status during late-summer and late-winter/early-spring in postmenopausal Irish women, and whether it was influenced by vitamin D-containing supplement use. DESIGN: A longitudinal observational study. SETTING: Cork City, Ireland (51 degrees north). SUBJECTS: A total of 59 apparently healthy, free-living, postmenopausal women aged between 51 and 69 y were sampled during February/March 2002. Of these, 48 and 47 returned during August/September 2002 and February/March 2003, respectively. None of the women were suffering from any medical condition likely to affect vitamin D status. Fasting serums were collected and analysed for 25-hydroxyvitamin D (25 (OH) D) and parathyroid hormone (PTH) by enzyme immunoassays. RESULTS: Mean daily intake of vitamin D was 3.2 microg from food sources alone and 5.8 microg when vitamin D-containing supplements were included (P<0.01). Serum 25 (OH) D was significantly lower (P<0.001) during February/March 2002 than both August/September 2002 and February/March 2003. Serum 25 (OH) D was also significantly higher (P < or = 0.05) in women who were vitamin D-containing supplement users than nonusers during all three sampling points. Between 17 and 36% of women had inadequate vitamin D status (defined as serum 25 (OH) D <40 nmol/l) during late-winter, but only 4% had inadequate vitamin D status during late-summer. Serum 25 (OH) D was inversely related to serum PTH (r = -0.33; P = 0.028). CONCLUSION: Suboptimal vitamin D status is common in postmenopausal Irish women during winter. Vitamin D supplementation is associated with improved vitamin D status, even during summertime.     

Elevated serum parathyroid hormone, calcitonin, and 1,25-dihydroxyvitamin D in lactating women nursing twins

The roles of vitamin D, calcitonin, and parathyroid hormone in calcium metabolism during lactation may be more evident in women secreting very large amounts of milk for a number of months, as in mothers nursing twins. We report significant increases in serum concentrations of parathyroid hormone, calcitonin, and 1,25(OH)2 vitamin D in mothers nursing twins compared to mothers nursing single infants. Serum concentrations of calcium actually increased in both groups during lactation. Maternal intakes of calories, calcium, and phosphorus were significantly higher in mothers nursing twins. Thus, mothers nursing twins were able to compensate for higher calcium losses in breast milk by increased dietary intakes of calcium as well as increased serum concentrations of parathyroid hormone, calcitonin, and 1,25(OH)2 vitamin D.     

Vitamin D, parathyroid hormone, and bone mass in adolescents

This article provides a review of the evidence identifying the factors related to vitamin D status in adolescents. The prevalence of vitamin D deficiency based on 25-hydroxyvitamin D [25(OH)D] of <25 nmol/L ranges from 0 to 32% depending on the season measured and the latitude of the population assessed. The factors that have been reported to affect serum 25(OH)D in adolescents include ethnicity, gender, puberty stage, parathyroid hormone (PTH), dietary vitamin D intake, and sun exposure. Vitamin D supplementation studies are limited to small populations and with supplementation focused on winter months when sunlight may be inadequate. The effects of vitamin D status and supplementation on bone assessment provide varied results. Differences in study design, modalities of bone assessment, and stage of puberty could contribute to disparate findings. Overall, the results from the available literature provide more questions than answers concerning the role of vitamin D in bone accrual in adolescents.     

Vitamin D status and its adequacy in healthy Danish perimenopausal women: relationships to dietary intake, sun exposure and serum parathyroid hormone

We conducted this study to assess the prevalence of vitamin D insufficiency in a population of normal perimenopausal women, to examine the influence of sun exposure and vitamin D intake on the concentration of 25-hydroxyvitamin D (25OHD) and to examine the association between parathyroid hormone (PTH) and 25OHD. A total of 2016 healthy women aged 45-58, who had recently undergone a natural menopause, were enrolled over a 2.5-year period in the Danish Osteoporosis Prevention Study. A marked seasonal fluctuation of 25OHD was seen, with an abrupt rise in June and high values until October. The fluctuation could be related to number of hours of sunshine per month with a two months time lag. Dietary vitamin D intake, vitamin supplementation, sunlight exposure, and use of sun-bed were all significantly related to 25OHD concentrations. Sun exposure seemed to contribute the most. The overall prevalence of vitamin D deficiency (defined as serum ) was 7 %. However, in the subgroup avoiding direct sunshine and abstaining from vitamin D supplementation 32.8 % were vitamin D deficient in the winter-spring period. Although mean PTH was increased in the group with low serum 25OHD, PTH was not a sensitive marker of hypovitaminosis D in the individual, as only 16 % of those with vitamin D deficiency had PTH levels above normal range. Thus, we have shown, that healthy middle-aged Danish women are prone to vitamin D insufficiency in the winter-spring period, if they avoid sun exposure in the summer period and abstain from vitamin D supplementation.     

Vitamin D status and its relationship with parathyroid hormone and bone mineral status in older adolescents

Osteoporosis is an important contributor to the global burden of disease, and in the UK alone results in one in three women and one in twelve men aged >50 years experiencing a fragility fracture. Optimising peak bone mass in early adulthood is thought to reduce osteoporosis risk by offsetting bone losses in later life. Ensuring sufficient vitamin D status (measured as 25-hydroxyvitamin D (25OHD) in plasma), among other factors, is believed to facilitate the achievement of optimum peak bone mass. Lower 25OHD is associated with a higher plasma concentration of parathyroid hormone (PTH). As PTH is associated with increased bone turnover and bone loss, maintenance of sufficient 25OHD is thought to have a protective effect on bone health. However, there is a lack of consensus internationally on what constitutes an optimum 25OHD concentration, and values between 30 and 80 nmol/l have been suggested. These values have been based on findings from various studies in adults in which PTH has been observed to plateau at a 25OHD concentration of >30 nmol/l; however, not all studies have found such a plateau. Although studies in younger adolescents (14-16 years) have shown an inverse relationship between PTH and 25OHD, the concentration of 25OHD required for achievement of optimum peak bone mass is unknown. The present review examines the evidence defining vitamin D insufficiency thresholds, and the relevance of such thresholds to adolescent bone health.     

Vitamin D status, parathyroid hormone and sunlight in Turkish, Moroccan and Caucasian children in The Netherlands

At the end of the winter circulating concentrations of 25-hydroxyvitamin D (25-OHD) in Asian and Mediterranean immigrants in northwestern European countries are usually very low. This may lead to vitamin D deficiency and eventually to rickets. Children are more prone to develop vitamin D deficiency. The vitamin D status of 8-year-old Turkish, Moroccan and Caucasian children was assessed by measuring plasma concentrations of 25-OHD and parathyroid hormone (PTH) and related to the cumulated global sun radiation (CGSR). The study population was selected from school children in The Hague and Rotterdam (The Netherlands). In each city blood samples were examined from 40 migrant children and a Caucasian reference group (n = 40) (matched for age and sex). Children in The Hague were examined at the end of the winter and early spring (February/April) and those in Rotterdam in late spring and early summer (May/June). Mean plasma 25-OHD concentrations for the migrant children in both cities were significantly lower than for the Caucasian reference group. The lowest 25-OHD values were measured in migrant children in The Hague: 42 per cent of the Turkish and 23 per cent of the Moroccan children had plasma levels less than 20 nmol/l. In these groups hyperparathyroidism (PTH greater than 85 pmol/l) was significantly more prevalent. With all pooled data a significant correlation between plasma 25-OHD and PTH was observed (r = -0.24; P less than 0.001). Regression analysis indicated that the relationship between both variables did not differ among the three ethnic groups. As expected, 25-OHD concentrations were higher for increased CGSR. Differences in 25-OHD level are mainly explained by differences in skin pigmentation and calcium intake between Mediterranean and Caucasian children. The secondary hyperparathyroidism observed in some children confirms that migrant children have a higher risk of developing nutritional rickets when living in areas with a moderate climate.     

Vitamin D and bone health in postmenopausal women

Osteoporosis, a disease of increased skeletal fragility, is becoming increasingly common as the U.S. population ages. Adequate vitamin D and calcium intake is the cornerstone of osteoporosis prevention and treatment. Age-related changes in vitamin D and calcium metabolism increase the risk of vitamin D insufficiency and secondary hyperparathyroidism. Although longitudinal data have suggested a role of vitamin D intake in modulating bone loss in perimenopausal women, studies of vitamin D and calcium supplementation have failed to support a significant effect of vitamin D and calcium during early menopause. There is a clearer benefit in vitamin D and calcium supplementation in older postmenopausal women. Vitamin D intake between 500 and 800 IU daily, with or without calcium supplementation, has been shown to increase bone mineral density (BMD) in women with a mean age of approximately 63 years. In women older than 65, there is even more benefit with vitamin D intakes of between 800 and 900 IU daily and 1200-1300 mg of calcium daily, with increased bone density, decreased bone turnover, and decreased nonvertebral fractures. The decreases in nonvertebral fractures may also be influenced by vitamin D-mediated decreases in body sway and fall risk. There are insufficient available data supporting a benefit from vitamin D supplementation alone, without calcium, to prevent osteoporotic fracture in postmenopausal women.     

Vitamin D status and parathyroid hormone concentrations in Chinese women and men from north-east of the People's Republic of China

STUDY OBJECTIVE: To evaluate vitamin D status of young and old women and men living in Shenyang, north-east People's Republic of China in early spring and to explore the relationship between vitamin D metabolites and parathyroid hormone (PTH) in this population. DESIGN: Cross-sectional study. SETTING: Shenyang, north-east China. SUBJECTS: 194 healthy volunteers: 48 young women and 48 young men aged 25-35 y, and 48 old women and 50 old men aged 65-75 y. RESULTS: Fasting blood samples were used to measure plasma 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)2D) and PTH using radioimmunoassays. The proportion of subjects who could be regarded as vitamin D deficient (<25 nmol/l) was 48%, 29%, 15% and 13% for old men, young men, old women and young women, respectively. There was no association between plasma 1,25(OH)2D and 25(OH)D concentrations. PTH concentrations were elevated in both old women and men compared with young subjects (P<0.01). A negative association between PTH and 25(OH)D was only found in old women (P<0. 001), but not in old men, nor in young subjects. CONCLUSIONS: Vitamin D status was poor in this population in early spring, especially in men. There was no clear evidence to show that the secretion of PTH and the conversion of 1,25(OH)2D were affected by the low 25(OH)D concentration. SPONSORSHIP: Partly supported by the Sandoz Foundation for Gerontological Research and the Nestlé Foundation, Switzerland, and Medical Research Council, UK. European Journal of Clinical Nutrition (2000) 54, 68-72     

Optimal vitamin D status and serum parathyroid hormone concentrations in African American women

BACKGROUND: Optimal vitamin D status for the prevention of osteoporosis has been inferred from examinations of the serum 25-hydroxyvitamin D [25(OH)D] concentration below which there is an increase in serum parathyroid hormone (PTH). OBJECTIVE: The objectives of the study were to ascertain whether a threshold for serum 25(OH)D exists below which serum PTH increases and whether persons with 25(OH)D above this threshold have lower rates of bone loss than do persons with 25(OH)D below the threshold. DESIGN: The relation of serum 25(OH)D to serum PTH was analyzed in 208 African American women studied longitudinally for 3 y. These healthy women in midlife were randomly assigned to receive placebo or 800 IU vitamin D3/d; after 2 y, the vitamin D3 supplementation was increased to 2000 IU/d. Both groups received calcium supplements to ensure an adequate calcium intake. A systematic literature review found a wide range of threshold values in part due to varied calcium intake. RESULTS: A Loess plot suggested a breakpoint between 40 and 50 nmol/L for serum 25(OH)D. A line-line model was fitted to the data, and it showed a spline knot at 44 nmol/L. A heuristic approach verified that PTH does not decline as rapidly when the serum concentration of 25(OH)D is >40 nmol/L as when it is <40 nmol/L. We found no significant difference in rates of bone loss between persons with 25(OH)D concentrations above and below 40 nmol/L. CONCLUSION: Although a threshold for 25(OH)D can be identified, we suggest that it should not be used to recommend optimal vitamin D status.     

Vitamin D status and its association with parathyroid hormone concentrations in women of child-bearing age living in Jakarta and Kuala Lumpur

OBJECTIVE: To describe the vitamin D status of women living in two Asian cities,--Jakarta (6 degrees S) and Kuala-Lumpur (2 degrees N), to examine the association between plasma 25-hydroxyvitamin D and parathyroid hormone (PTH) concentrations, and to determine a threshold for plasma 25-hydroxyvitamin D above which there is no further suppression of PTH. Also, to determine whether dietary calcium intake influences the relationship between PTH and 25-hydroxyvitamin D. DESIGN: Cross-sectional. SETTING: Jakarta, Indonesia and Kuala Lumpur, Malaysia. PARTICIPANTS: A convenience sample of 504 non-pregnant women 18-40 years. MAIN MEASURES: Plasma 25-hydroxyvitamin D and PTH. RESULTS: The mean 25-hydroxyvitamin D concentration was 48 nmol/l. Less than 1% of women had a 25-hydroxyvitamin D concentration indicative of vitamin D deficiency (<17.5 nmol/l); whereas, over 60% of women had a 25-hydroxyvitamin D concentration indicative of insufficiency (<50 nmol/l). We estimate that 52 nmol/l was the threshold concentration for plasma 25-hydroxyvitamin D above which no further suppression of PTH occurred. Below and above this concentration the slopes of the regression lines were -0.18 (different from 0; P=0.003) and -0.01 (P=0.775), respectively. The relation between vitamin D status and parathyroid hormone concentration did not differ between women with low, medium or high calcium intakes (P=0.611); however, even in the highest tertile of calcium intake, mean calcium intake was only 657 mg/d. CONCLUSION: On the basis of maximal suppression of PTH we estimate an optimal 25-hydroxyvitamin D concentration of approximately 50 nmol/l. Many women had a 25-hydroxyvitamin D below this concentration and may benefit from improved vitamin D status.     

Serum parathyroid hormone in healthy Japanese women in relation to serum 25-hydroxyvitamin D

The aim of this work was to clarify levels of serum parathyroid hormone (PTH) in healthy adult women and to study the relationship between PTH and 25-hydroxyvitamin D [25(OH)D]. One hundred sixty-nine healthy women aged 40 years or older in a community were studied. The average age of the subjects was 65.3 years (SD 8.2). All subjects had normal serum creatinine levels. Serum intact PTH and 25(OH)D were measured in these subjects. The mean intact PTH concentration was 2.19 pmol/l (SD 1.02). High intact PTH levels above the reference range were observed in four women (2.4%), all of whom were aged 70 years or older. Intact PTH increased with age with a correlation coefficient of 0.192 (p = 0.013). However, there was no correlation (r = -0.125, p = 0.105) between intact PTH and 25(OH)D whose concentrations were more than 37.5 nmol/l. In conclusion, PTH levels of healthy adult Japanese women are lower than previous reports from Western countries, which may be due to the high 25(OH)D levels of the present subjects and/or an ethnic difference. In addition, there is no association between serum 25(OH)D and PTH levels in this Japanese population, supporting a cutoff level of 25(OH)D less than 37.5 nmol/l for the elevated PTH level.     

Vitamin D inadequacy in Belgian postmenopausal osteoporotic women

Background  

Inadequate serum vitamin D [25(OH)D] concentrations are associated with secondary hyperparathyroidism, increased bone turnover and bone loss, which increase fracture risk. The objective of this study is to assess the prevalence of inadequate serum 25(OH)D concentrations in postmenopausal Belgian women. Opinions with regard to the definition of vitamin D deficiency and adequate vitamin D status vary widely and there are no clear international agreements on what constitute adequate concentrations of vitamin D.     

Vitamin D status: effects on quality of life in osteoporosis among Turkish women

Background and objectives Vitamin D deficiency causes muscle weakness, impairs bone formation and neuromuscular coordination thus leading to an increase in fracture risk. It has been found that inadequate levels of vitamin D are present in most of the osteoporosis patients. However, very few studies investigate the association between vitamin D status and quality of life (QOL). The aim of this study is to investigate the effects of vitamin D on QOL among Turkish women with osteoporosis. Methods 259 patients (61.0 ± 8.9 years) with osteoporosis were evaluated by physical activity level, back pain, bone turnover markers, 25-hydroxyvitamin D [25(OH)D], parathyroid hormone levels and bone mineral density. QOL was assessed using QOL Questionnaire of the European Foundation for Osteoporosis (QUALEFFO). 25(OH)D levels below 20 ng/ml was defined as vitamin D insufficiency, below 12 ng/ml as vitamin D deficiency. Results Mean 25(OH)D level was 22.7 ± 12.6 ng/ml and mean total QUALEFFO score was 43.3 ± 14.9. Vitamin D levels were significantly correlated with all subscales and total score of QUALEFFO (r = −0.25, P = 0.0001). Vitamin D insufficiency was determined in 132 patients (51%). In vitamin D deficient (<12 ng/ml) group all subscales and total QOL were found to be poorer when compared with the groups whose vitamin D levels were ≥12 and <20 ng/ml and ≥20 ng/ml (effect sizes 0.41 and 0.62 respectively, P = 0.0001 for total QOL). Vitamin D level, education, concomitant diseases, physical activity level and pain severity were found to be significantly associated with QOL in multiple linear regression analysis model. Conclusions Vitamin D insufficiency affects physical, social and mental functions of osteoporosis patients and impairs QOL. Vitamin D was found to be one of the factors affecting QOL.     

Vitamin D status in a rural postmenopausal female population

BACKGROUND: Inadequate vitamin D nutritional status is increasingly recognized as common in North American and European populations, but the extent of the shortfall and the parameters of the distribution for populations of interest remain uncertain. PURPOSE: To report the distribution of values for serum 25-hydroxyvitamin D [25(OH)D] in a population of rural postmenopausal women, together with quantification of factors related to vitamin D status. SETTING: Nine largely agrarian counties in eastern Nebraska (approximately 41 degrees N). PARTICIPANTS: A population-based sample of 1,179 women 55 years of age and older recruited into a four-year trial of calcium and vitamin D supplementation. METHODS: Baseline biochemical, dietary, and anthropometric measurements obtained on entry into trial. RESULTS: Serum 25(OH)D concentration at baseline varied cyclically with season, with the solar cycle explaining 2.9% of the total variance (P < 0.001). Mean seasonally adjusted 25(OH)D concentration was 71.1 nmol/L. Serum 25(OH)D also exhibited the expected inverse curvilinear relationship with serum parathyroid hormone (PTH), with the inflection point of the curve located at approximately 80 nmol/L. Supplements containing vitamin D were regularly taken by 59% of the cohort (median dose: 200 IU/d). Nevertheless, approximately 4% of all women had values below the laboratory reference range and more than two-thirds fell below 80 nmol/L. Seasonally adjusted serum 25(OH)D concentration was positively correlated with the size of daily vitamin D supplement dose, and negatively with age, weight, and body mass index (P < 0.01 for all). In stepwise multiple linear regression models, weight, age, and supplement dose were independently correlated with seasonally adjusted serum 25(OH)D, and together explained 19% of the total variance of adjusted 25(OH)D concentration. Women taking supplements had only one-sixth the chance of having a 25(OH)D value below the reference limit of the assay, compared to women who did not use supplements. CONCLUSIONS: Approximately two-thirds of this rural population fell below 80 nmol/L, a value considered to be the lower end of the optimal range. Based on the slope of 25(OH)D on supplement dose observed in these women, it would require an additional vitamin D input of nearly 2000 IU/d to reach the goal of an RDA for vitamin D, i.e., to bring 97.5% of the cohort to levels of 80 nmol/L or higher.     

Protein-binding properties of 22-oxa-1 alpha,25-dihydroxyvitamin D3, a synthetic analogue of 1 alpha,25-dihydroxyvitamin D3

Protein binding properties of 22-oxa-1 alpha,25-dihydroxyvitamin D3 (22-oxa-1,25-D3), a synthetic analogue of 1 alpha,25-dihydroxyvitamin D3 (1,25-D3), were compared with those of vitamin D3 derivatives. The order of binding affinity to the chick embryonic intestinal receptor was 1,25-D3 greater than 22-oxa-1,25-D3 greater than 25-hydroxyvitamin D3 (25-D3) greater than 24R, 25-dihydroxyvitamin D3 (24, 25-D3) greater than vitamin D3 (D3), while that to the rat plasma vitamin D-binding protein (DBP) was 25-D3 greater than 24,25-D3 greater than D3 greater than 1,25-D3 greater than 22-oxa-1,25-D3. The binding potencies of 22-oxa-1,25-D3 to the receptor and DBP were about 1/8 and 1/600 of the respective values of 1,25-D3. When the distribution of the tritiated compounds in human plasma components was examined by an in vitro polyacrylamide gel electrophoretic method, [3H]-22-oxa-1,25-D3 was found to bind only to the lipoproteins including chyromicron. These results suggest that the replacement of a carbon atom into an oxygen atom in the side chain structure of 1,25-D3 results significant decrease in the binding affinity to DBP and that 22-oxa-1,25-D3 is transported as a complex-form not with DBP but with lipoprotein to the target tissues.