Vitamin D(3) and vitamin K(1) supplementation of Dutch postmenopausal women with normal and low bone mineral densities: effects on serum 25-hydroxyvitamin D and carboxylated osteocalcin

OBJECTIVE: Improvement of vitamin D and K status of about 60 -y-old postmenopausal Dutch women. DESIGN: In a randomized study postmenopausal women with normal (T-score >-1; n=96) and low (T-score< or =-1; n=45) bone mineral density (BMD) of the lumbar spine, were supplemented with 350-400 IU vitamin D(3), 80 microg vitamins K(1) vitamins K(1)+D(3), or placebo for 1 y. Serum 25-hydroxyvitamin D [25(OH)D] and percentage carboxylated osteocalcin (%carbOC) were measured at baseline and after 3, 6 and 12 months. RESULTS: Baseline %carbOC of the entire study population was positively correlated with BMD of the lumbar spine and femoral neck. Correspondingly, women with low BMD had lower %carbOC at baseline than women with normal BMD but this difference disappeared after 1 y of supplementation with vitamin K(1) ((mean+/-s.d.) 68+/-11% (95% CI, 64. 5-71.2%) vs 72+/-6% (95% CI, 70.1-72.9%), respectively). One year of supplementation with vitamin D(3) showed maximum increases in 25(OH)D of 33+/-29% (95% CI, 24.8-41.8%) and 68+/-58% (95% CI, 50.1-84.6%) in women with normal and low BMD, respectively. During winter, however, a 29% decline in maximum 25(OH)D levels was not prevented in women with low BMD. CONCLUSION: Daily supplementation of Dutch postmenopausal women with >400 IU vitamin D(3) is indicated to prevent a winter decline in 25(OH)D and to control serum parathyroid hormone levels. Daily supplementation with 80 microg vitamin K(1) seems to be necessary to reach premenopausal %carbOC levels. A stimulatory effect of calcium and/or vitamin D on %carbOC cannot be excluded. European Journal of Clinical Nutrition (2000) 54, 626-631.     

Seasonal changes in vitamin D status and bone turnover in healthy Irish postmenopausal women

OBJECTIVES: To examine the effect of season on biochemical markers of bone turnover in 51-to 75-year-old Irish women and to investigate whether such changes are related to vitamin D status. DESIGN: Longitudinal observational study. SETTING: Cork, Ireland (52 degrees N). SUBJECTS: 76 apparently healthy, free-living postmenopausal women (aged 51-75 years), not taking any medication and free from any condition likely to affect vitamin D status or calcium/bone metabolism. RESULTS: Serum 25-hydroxyvitamin D [S-25(OH)D] showed a clear seasonal variation with significantly higher (p < 0.001) values during late summer than late winter. Both urinary pyridinoline (Ur-Pyr) (p < 0.01) and deoxypyridinoline (Ur-Dpyr) (p < 0.001), but not serum parathyroid hormone or osteocalcin, showed a marked seasonal variation with lowest values during late-summer. Stratifying women into those with S-25(OH)D levels > or = or <50 nmol/L (vitamin D adequate and inadequate, respectively) during late-winter, showed that Ur-Pyr and Ur-Dpyr in both groups were significantly (p < 0.05) lower during late summer, and the magnitude of the reduction from winter to summer was similar in both groups. CONCLUSION: Seasonal changes in bone resorption markers appeared to be linked to seasonal changes in vitamin D status. Further research is needed to investigate the impact of these changes on risk of bone loss and fracture.     

Relationship between nutrient intake and vitamin D status in osteoporotic women

Vitamin D is essential for maintaining calcium homeostasis and optimizing bone health. Its inadequacy is related to many factors including dietary intake. The aim of the present study was to evaluate serum 25(OH)D and its relationship with nutrient intakes in postmenopausal Brazilian women with osteoporosis. This cross-sectional study comprised 45 free-living and assisted elderly at S?o Paulo Hospital. Three-day dietary records were used to assess dietary intakes. Bone mineral density was measured with a dual-energy X-ray absorptiometer (DXA). Blood and urine sample were collected for analysis of biochemical markers of bone and mineral metabolism. Insufficiency of vitamin D was observed in 24.4% of the women and optimal levels (> or = 50 nmol/L) were observed in 75.6%. Parathyroid hormone was above the reference range in 51% of the participants. The mean calcium (724 mg/day) and vitamin D (4.2 microg/day) intakes were lower than the value proposed by The Food and Nutrition Board and sodium intake was more than two-fold above the recommendation. Higher levels of serum 25(OH)D were inversely associated with sodium intake. Dietary strategies to improve serum vitamin D must focus on increasing vitamin D intake and should take a reduction of sodium intake into consideration.     

Bone density,calcium intake and vitamin D status in South Asian women living in Auckland,New Zealand

Aim: To investigate the bone health and associated risk factors of a group of South Asian women living in New Zealand. Studies on the Indian subcontinent suggest a high incidence of low bone mineral density in women with poor vitamin D status and low dietary calcium intake. Methods: Subjects were women of South Asian origin (n = 91) living in Auckland, New Zealand. Subjects were stratified by menopausal status. They completed a 4-day food diary, and provided a fasting blood sample. Bone mineral density was measured in the lumbar spine and proximal femur using dual X-ray densitometry. Results: Mean age of premenopausal (n = 71) and postmenopausal (n = 20) women was 39.8 ± 7.8 and 55.3 ± 5.4 years, respectively. Osteoporosis (T-score ≤−2.5) was present in 32% of postmenopausal and 3% of premenopausal subjects, but only in the lumbar spine. Adequate 25(OH)D levels (>50 nmol/L) were found in only 22% of premenopausal, and 26% of postmenopausal women. A body mass index in the overweight or obese category was found in 61% of premenopausal and 75% of postmenopausal women. Conclusion: The high incidence of osteoporosis in the postmenopausal group could be associated with the early age of oophorectomy or menopause together with low vitamin D status.     

Urbanization of black South African women may increase risk of low bone mass due to low vitamin D status, low calcium intake, and high bone turnover

Globally, rural to urban migration is accompanied by changes in dietary patterns and lifestyle that have serious health implications, including development of low bone mass. We hypothesized that serum 25 (OH) vitamin D3 (25[OH]D3) levels will be lower, bone turnover higher, and nutrition inadequate in urban postmenopausal black women, increasing risk for low bone mass. We aimed to assess the prevalence of risk factors for low bone mass in 1261 black women from rural and urban areas in the North West Province of South Africa (Prospective Urban and Rural Epidemiology-South Africa project). Fasting blood samples were taken; and participants were interviewed to complete questionnaires on self-reported diseases, fractures, and dietary intakes. Bone health markers were assessed in a subgroup of 658 women older than 45 years. Specific lifestyle risk factors identified were inactivity, smoking, injectable progestin contraception use, and high alcohol consumption. Dietary risk factors identified were low calcium and high animal protein, phosphorous, and sodium intakes. The 25(OH)D3 and C-terminal telopeptide (CTX) levels were significantly higher in the rural vs the urban women older than 50 years. Parathyroid hormone (PTH) levels increased with age in both groups. The 25(OH)D levels were inversely correlated with CTX and PTH in rural women. In urban women, PTH and CTX were correlated while dietary calcium was inversely correlated with CTX and PTH with 25(OH)D3. The combination of low dietary calcium (<230 mg/d), marginally insufficient 25(OH)D3 status, and raised PTH may result in increased bone resorption. Further research is required to assess bone health and fracture risk in black African women.     

维生素D和骨形态发生蛋白-2水平与生长激素缺乏症儿童成骨细胞功能的相关性研究

目的 研究维生素D及骨形态发生蛋白-2(BMP-2)与生长激素缺乏症(GHD)患儿成骨细胞功能的相关性,以期为矮小症的辅助治疗提供理论依据。方法 收集2012年3月—2013年12月确诊为GHD患儿83例作为病例组,同期随机选取健康儿童40例作为对照组,按年龄及Turner分期分为青春期前组和青春期组。测定其身高、身高标准差得分(HtSDS) 、骨龄等一般指标。用酶联法分别检测并比较病例组及对照组儿童血清25(OH)D₃、BMP-2、骨钙素(OC)、Ⅰ型前胶原氨基端前肽(PINP)水平。用Pearson相关性分析法分析25(OH)D₃、BMP-2与OC、PINP、HtSDS、生长激素(GH)峰值、骨龄与年龄差值的相关性。结果 青春期前GHD组和青春期 GHD组患儿血清25(OH)D₃、BMP-2、OC、PINP均显著低于对照组水平(t=4.282、7.162、3.940、4.832,P＜0.05);经Pearson相关性分析,病例组25(OH)D₃与OC(r=0.481)、PINP(r=0.473)、BMP-2(r=0.324)及GH峰值(r=0.545)存在显著正相关性(P<0.05);BMP-2与OC(r=0.322)、PINP(r=0.415)及GH峰值(r=0.619)存在显著正相关性(P<0.05);25(OH)D₃、BMP-2与HtSDS及骨龄和年龄的差值之间无相关性(P>0.05)。结论 GHD患儿骨形成处于低水平状态。GHD患儿骨形成标志物OC、PINP水平降低与其体内低维生素D、BMP-2水平密切相关。GH的分泌状态影响维生素D、BMP-2的水平。     

植物异黄酮对更年期妇女骨密度和骨代谢血清生化指标的影响

目的:研究植物异黄酮(葛根异黄酮和大豆异黄酮)对更年期妇女骨密度和骨代谢生化指标的影响。方法:将96例身体健康的更年期女性随机分为5组,安慰剂组、钙儿奇-D组、葛根异黄酮组、大豆异黄酮组和钙儿奇-D+大豆异黄酮组。服药3个月后,比较各处理组用药前后血清钙(Ca)、血清碱性磷酸酶(ALP)、骨钙素(BGP)和骨密度(BMD)等指标的变化情况。结果:服药后血清Ca有升高的趋势,其中钙儿奇-D和葛根异黄酮组的血清Ca比服药前显著升高(P<0.05);服药后血清ALP葛根异黄酮和大豆异黄酮组有上升趋势;服药后血清BGP(除了安慰剂组)各组有增加的趋势,其中钙儿奇-D组的血清BGP明显增加。结论:植物异黄酮可以使更年期妇女血清Ca升高,使血清ALP和BGP处于较活跃的水平。     

Long-term effects of nutrient intervention on markers of bone remodeling and calciotropic hormones in late-postmenopausal women

BACKGROUND: Adequate intakes of calcium and vitamin D reduce bone loss and fracture risk in the elderly. Other nutrients also affect bone health, and adequate intakes may influence bone turnover and balance. OBJECTIVE: We compared the long-term effects on bone turnover markers and calciotropic hormones of a multinutrient supplement, a calcium and vitamin D supplement, and dietary instruction aimed at increasing calcium intake through foods. DESIGN: Ninety-nine healthy postmenopausal women participated in a 3-y, randomized trial, receiving either 1) supplemental calcium (1450 mg/d) and vitamin D [10 microg (400 IU)/d], 2) calcium, vitamin D, and other nutrients (multinutrient supplement), or 3) dietary instruction (dietary control group). Data are from 83 subjects who completed the trial. RESULTS: Increases over baseline in calcium intakes and serum 25-hydroxyvitamin D concentrations were sustained over 3 y in all treatment groups. Circulating parathyroid hormone concentrations were reduced at year 1 in all treatment groups but trended toward baseline thereafter. Bone turnover markers followed a similar pattern, and none of the changes in biochemical concentrations differed significantly between groups. CONCLUSIONS: All 3 interventions offer long-term feasibility for increasing calcium intake and serum 25-hydroxyvitamin D concentrations. The dietary addition of micronutrients implicated in skeletal physiology confers no obvious bone-sparing effect in healthy postmenopausal women beyond that of calcium and vitamin D alone. The attenuation over time in suppression of parathyroid hormone and bone turnover might help explain why nutrient intervention tends to have less of a bone-sparing effect than do skeletally active medications such as estrogen or bisphosphonates.     

The influence of smoking on vitamin D status and calcium metabolism

OBJECTIVE: To assess the influence of smoking on serum parathyroid hormone (PTH), serum vitamin D metabolites, serum ionized calcium, serum phosphate, and biochemical markers of bone turnover in a cohort of 510 healthy Danish perimenopausal women. DESIGN: A cross-sectional study. SETTING: Copenhagen, Denmark. SUBJECTS: Five-hundred-and-ten healthy women aged 45-58 y, included 3-24 months after last menstrual bleeding. None were using hormone replacement therapy. METHODS: The women were grouped according to their current smoking status. The two groups were compared with regard to serum levels of 25-hydroxyvitamin D (25OHD) and 1, 25-dihydroxyvitamin D (1,25-(OH)2D), intact PTH, ionized calcium and phosphate, osteocalcin, as well as urine pyridinolines. Bone mineral density (BMD) was measured with DEXA-scans. Multiple regression analyses were performed to detect the effect of potentially confounding lifestyle factors, such as calcium and vitamin D intakes, alcohol and coffee consumption, sunbathing, and physical exercise. RESULTS: Fifty percent were current smokers. Smokers had significantly reduced levels of serum 25OHD (P=0.02), 1,25(OH)2D (P=0.001), and PTH (P<0.001). There was no difference in serum ionized calcium between smokers and non-smokers. We found a negative effect of smoking on serum osteocalcin (P=0.01), while urinary pyridinolines were similar in the two groups. The small differences in lifestyle between the two groups could not explain these findings. Smokers had small but significant reductions in bone mineral density. CONCLUSIONS: Smoking has a significant effect on calcium and vitamin D metabolism, which is not likely to be explained by other confounding lifestyle factors. The depression of the vitamin D-PTH system seen among smokers may represent another potential mechanism for the deleterious effects of smoking on the skeleton, and may contribute to the reported risk of osteoporosis among smokers. Sponsorship: Grants from the Karen Elise Jensens Foundation.     

补充钙及维生素D对2～3岁幼儿身长的影响

目的 分析钙与维生素D(VitD)的营养情况与2～3岁幼儿身长发育的相关性,为体格发育偏离干预提供一定理论依据。方法 回顾性分析在2019年9月—2021年6月西北妇女儿童医院儿童保健科常规体检的204例幼儿(年龄2～3岁)的临床资料。对这些幼儿进行标准体格测量和对其既往钙和维生素D的补充情况以问卷形式进行回顾性调查,同时检测儿童的血清25-(OH)D和骨密度。对体格发育情况与钙和VitD的营养状况采用了Spearman相关及Logistic多因素回归分析等方法进行统计学分析。结果 每日平均补充VitD剂量的中位数为569.5 U,204例幼儿血清25-(OH)D的中位数为35.60 ng/dl。VitD缺乏检出率1.96%、不足检出率0.98%、充足检出率97.06%,无VitD过量;骨密度中位数为P64.0;单因素Spearman秩相关分析显示,每日平均补充VitD的剂量和每日平均补充钙剂量均与身长呈正相关(r=0.172、0.213,P<0.05);骨密度与身长呈负相关(r=-0.138,P<0.05);多因素Logistics回归分析显示,每日平均补充钙剂量与身长呈...     

Effect of age on calcium absorption in postmenopausal women

BACKGROUND: It is assumed that calcium absorption decreases with age, but this is not well documented. We report a study that addresses this issue. OBJECTIVE: The aim was to establish the extent and timing of any age-related change in calcium absorption in postmenopausal women. DESIGN: We measured radiocalcium absorption (alpha) in 262 healthy postmenopausal women aged 40-87 y. We also measured the serum vitamin D metabolites, parathyroid hormone (PTH), and other biochemical variables. RESULTS: Radiocalcium absorption decreased with age (P = 0.018); it was 28% lower in the 25 women aged >75 y than in the rest (P < 0.001). It was significantly related to serum 1,25-dihydroxyvitamin D [1,25(OH)(2)D] in the whole set and in both the younger and older subsets, but it was not related to either 25-dihydroxyvitamin D [25(OH)D] or PTH or to any other measured variable. No decrease in 1,25(OH)(2)D was seen with age to account for the decrease in calcium absorption, so radiocalcium absorption corrected for serum 1,25(OH)(2)D decreased significantly after age 75 y. On multivariate analysis, the serum 1,25(OH)(2)D concentration was a positive function of 25(OH)D (P < 0.001), albumin (P = 0.010), and PTH (P = 0.012) and a negative function of serum creatinine (P = 0.003). PTH was a negative function of calculated ionized calcium (P = 0.004) and 25(OH)D (P = 0.009) and a positive function of weight (P = 0.011) and age (P = 0.028). CONCLUSIONS: A late age-related decrease in calcium absorption is seen in postmenopausal women in addition to the decline that occurs at menopause. This decrease could be due to a decline in either the active calcium transport or diffusion component of the calcium absorption system.     

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: effects on parathyroid hormone and 1, 25-dihydroxyvitamin D in postmenopausal women

BACKGROUND: Low serum 25-hydroxyvitamin D ?25(OH)D concentrations are commonly found in the elderly and are associated with hip fracture. Treatment with vitamin D and calcium can reduce the risk of fracture. The relation between the rise in parathyroid hormone (PTH) with age and the decrease in 25(OH)D is not clear. Neither is there any consensus on the serum concentration of 25(OH)D required for bone health. OBJECTIVE: Our objective was to study the relations between serum PTH, serum vitamin D metabolites, and other calcium-related variables in postmenopausal women. DESIGN: This was a cross-sectional study of 496 postmenopausal women without vertebral fractures attending our menopausal osteoporosis clinics. RESULTS: PTH was significantly positively related to age and serum 1, 25-dihydroxyvitamin D ?1,25(OH)(2)D and inversely related to 25(OH)D and plasma ionized calcium. There was a step-like increase in PTH as serum 25(OH)D fell below 40 nmol/L. In women with 25(OH)D concentrations >40 nmol/L, 1,25(OH)(2)D was positively related to 25(OH)D; in women with 25(OH)D concentrations 40 nmol/L, 1,25(OH)(2)D was most closely (inversely) related to plasma creatinine. Therefore, with serum 25(OH)D concentrations increasingly <40 nmol/L, serum 1,25(OH)(2)D becomes critically dependent on rising concentrations of PTH. CONCLUSION: The data suggest that aging women should maintain 25(OH)D concentrations >40 nmol/L (which is the lower limit of our normal range for healthy young subjects) for optimal bone health.     

Effect of vitamin D and calcium supplementation on bone turnover in institutionalized adults with Down's Syndrome

OBJECTIVE: To assess the status of vitamin D and the effects of calcium and vitamin D3 supplementation on the bone metabolism in a group of adults with Down's syndrome (DS). DESIGN: Randomized, parallel, controlled and open clinical trial. SETTING: Institution for mentally handicapped: Fundación Uliazpi, Diputación Foral de Guipúzcoa, San Sebastián, Spain. SUBJECTS: A total of 23 persons with DS, residents at the Uliazpi Foundation were recruited and all completed the study. INTERVENTION: In all, 12 participants were randomly allocated to receive 1 g of calcium and 800 IU of vitamin D once daily for 1 year while 11 were assigned to the control group, receiving no supplementation. RESULTS: We found no differences between groups regarding serum calcium and phosphorous levels. The remaining parameters showed differences between the two groups consistent with a beneficial effect of the intervention: serum levels of parathyroid hormone, osteocalcin and crosslaps diminished while serum 25 OH vitamin D3 level increased. CONCLUSIONS: The results obtained allow to include people with DS as a risk group with regards to vitamin D deficit, which that can be corrected with vitamin D and calcium supplementation, and giving rise to an improvement of the biochemical markers related to the phospho-calcium metabolism and bone remodelling.     

Changes in Vitamin D Supplement Use and Baseline Plasma 25-Hydroxyvitamin D Concentration Predict 5-y Change in Concentration in Postmenopausal Women

Few studies have prospectively examined predictors of change in plasma concentrations of 25-hydroxyvitamin D [25(OH)D]. We sought to determine the predictors of 5-y change in 25(OH)D. Plasma 25(OH)D concentrations were assessed at baseline (1997-2000) and 5 y later (2002-2005) in 668 postmenopausal women enrolled in the Osteoporosis and Periodontal Disease Study. Baseline and changes in demographic, dietary, lifestyle, and health-related factors were tested as predictors of change in 25(OH)D concentrations by using multivariable linear regression. The mean 5-y change in 25(OH)D (mean ± SD) was 7.7 ± 0.7 nmol/L (P < 0.001). In our predictive model (n = 643), predictors explained 31% of the variance in change in 25(OH)D concentrations and included baseline 25(OH)D, baseline and change in vitamin D supplementation and physical activity, change in season of blood draw, BMI, whole-body T score, and baseline hormone therapy use. Baseline 25(OH)D and change in vitamin D supplementation explained the most variation (25%) in 25(OH)D. Exploratory analyses showed a borderline significant interaction between tertiles of baseline 25(OH)D and change in vitamin D supplementation over time (P = 0.06). The greatest mean increase in 25(OH)D (22.9 ± 16.8 nmol/L), with adjustment for other statistically significant predictors, occurred in women whose baseline 25(OH)D concentration was ≤51.0 nmol/L (tertile 1) and who increased supplementation use over time. These results confirm the importance of supplementation in increasing 25(OH)D concentrations in aging women, even after other statistically significant predictors are controlled for. These data also suggest that this is especially true among aging women with inadequate 25(OH)D (e.g., <50 nmol/L).     

Bone and gastric bypass surgery: effects of dietary calcium and vitamin D

OBJECTIVE: To examine bone mass and metabolism in women who had previously undergone Roux-en-Y gastric bypass (RYGB) and determine the effect of supplementation with calcium (Ca) and vitamin D. RESEARCH METHODS AND PROCEDURES: Bone mineral density and bone mineral content (BMC) were examined in 44 RYGB women (> or = 3 years post-surgery; 31% weight loss; BMI, 34 kg/m(2)) and compared with age- and weight-matched control (CNT) women (n = 65). In a separate analysis, RYGB women who presented with low bone mass (n = 13) were supplemented to a total 1.2 g Ca/d and 8 microg vitamin D/d over 6 months and compared with an unsupplemented CNT group (n = 13). Bone mass and turnover and serum parathyroid hormone (PTH) and 25-hydroxyvitamin D were measured. RESULTS: Bone mass did not differ between premenopausal RYGB and CNT women (42 +/- 5 years), whereas postmenopausal RYGB women (55 +/- 7 years) had higher bone mineral density and BMC at the lumbar spine and lower BMC at the femoral neck. Before and after dietary supplementation, bone mass was similar, and serum PTH and markers of bone resorption were higher (p < 0.001) in RYGB compared with CNT women and did not change significantly after supplementation. DISCUSSION: Postmenopausal RYGB women show evidence of secondary hyperparathyroidism, elevated bone resorption, and patterns of bone loss (reduced femoral neck and higher lumbar spine) similar to other subjects with hyperparathyroidism. Although a modest increase in Ca or vitamin D does not suppress PTH or bone resorption, it is possible that greater dietary supplementation may be beneficial.     

Overview of the conference "Vitamin D and Health in the 21st Century: an Update"

We summarize the key findings, strength of the evidence, and research needs identified in the National Institutes of Health conference "Vitamin D and Health in the 21st Century: an Update," which was held in September 2007; a systematic evidence-based review; and a National Institutes of Health roundtable discussion held after the conference by scientists with relevant expertise. The evidence-based review addressed 5 questions on 25-hydroxyvitamin D [25(OH)D] and functional outcomes across the life cycle and response to exposure, bone health outcomes of supplementation, risks and benefits of sun exposure, and adverse outcomes. These questions also framed the conference and roundtable discussions. Researchers have made considerable progress in understanding the relation of 25(OH)D to bone health outcomes in the elderly and in postmenopausal women, but we know less about its impact on other stages of the life cycle and in racial and ethnic groups. Limitations of the existing data include the failure of many studies to control for important confounders [baseline 25(OH)D concentration, skin pigmentation, body mass index, compliance, etc], sparse data on key vulnerable populations (dark-skinned persons, reproducing women, infants, children, and adolescents), problems of accuracy and excessive variability in measuring 25(OH)D, lack of established relation of 25(OH)D with functional outcomes except in the elderly, and limited information on the effects of vitamin D independent of calcium, magnesium, and phosphate. Future research should determine and validate across the life cycle relevant functional outcomes for bone and other health factors as well as adverse outcomes for the biomarker of exposure, 25(OH)D, to enable assessment of the role of vitamin D status in health maintenance and disease prevention.     

Applying Machine Learning to Determine 25(OH)D Threshold Levels Using Data from the AMATERASU Vitamin D Supplementation Trial in Patients with Digestive Tract Cancer

Some controversy remains on thresholds for deficiency or sufficiency of serum 25-hydroxyvitamin D (25(OH)D) levels. Moreover, 25(OH)D levels sufficient for bone health might differ from those required for cancer survival. This study aimed to explore these 25(OH)D threshold levels by applying the machine learning method of multivariable adaptive regression splines (MARS) in post hoc analyses using data from the AMATERASU trial, which randomly assigned Japanese patients with digestive tract cancer to receive vitamin D or placebo supplementation. Using MARS, threshold 25(OH)D levels were estimated as 17 ng/mL for calcium and 29 ng/mL for parathyroid hormone (PTH). Vitamin D supplementation increased calcium levels in patients with baseline 25(OH)D levels ≤17 ng/mL, suggesting deficiency for bone health, but not in those >17 ng/mL. Vitamin D supplementation improved 5-year relapse-free survival (RFS) compared with placebo in patients with intermediate 25(OH)D levels (18–28 ng/mL): vitamin D, 84% vs. placebo, 71%; hazard ratio, 0.49; 95% confidence interval, 0.25–0.96; p = 0.04. In contrast, vitamin D supplementation did not improve 5-year RFS among patients with low (≤17 ng/mL) or with high (≥29 ng/mL) 25(OH)D levels. MARS might be a reliable method with the potential to eliminate guesswork in the estimation of threshold values of biomarkers.     

Effect of vitamin D supplementation on vitamin D status and bone turnover markers in young adults

OBJECTIVE: To assess the vitamin D status of healthy young people living in Northern Ireland and the effect of vitamin D supplementation on vitamin D status and bone turnover. DESIGN: Double-blinded randomised controlled intervention study. SETTING: University of Ulster, Coleraine, Northern Ireland. SUBJECTS: In total, 30 apparently healthy students (15 male and 15 female subjects), aged 18-27 years, were recruited from the university, with 27 completing the intervention. INTERVENTIONS: Subjects were randomly assigned, to receive either 15 microg (600 IU) vitamin D(3) and 1,500 mg calcium/day (vitamin D group), or 1,500 mg calcium/day (control group) for 8 weeks between January and March. Vitamin D status, bone turnover markers, serum calcium and parathyroid hormone concentrations were measured at baseline and post intervention. RESULTS: At baseline, vitamin D status was low in both the vitamin D group (47.9 (s.d. 16.0)) and the control group (55.5 (s.d. 18.6) nmol/l 25(OH)D). Post intervention vitamin D status was significantly higher in the vitamin D-treated group (86.5 (s.d. 24.5)) compared to the control group (48.3 (s.d. 16.8) nmol/l) (P<0.0001). There was no significant effect of supplementation on bone turnover markers or PTH concentrations. CONCLUSIONS: This study suggests that young adults in Northern Ireland do not consume an adequate daily dietary intake of vitamin D to maintain plasma vitamin D concentrations in the wintertime. A daily supplement of 15 microg vitamin D(3) significantly increased vitamin D status in these individuals to levels of sufficiency. Achievement of an optimum vitamin D status among young adults may have future positive health implications.     

Early life influences on serum 1,25 (OH) vitamin D

There is increasing evidence to support the role of the intrauterine and early postnatal environment in determining adult bone mass and risk of fracture. The mechanisms by which this occurs are uncertain but include perturbations in several endocrine axes. Vitamin D is integrally involved in bone metabolism and is therefore an ideal candidate. This study assesses whether birthweight and weight at 1 year of age are associated with the calcium vitamin D axis in elderly women. Vitamin D metabolites, parathyroid hormone, bone mineral density and biochemical markers of bone turnover were measured in 129 healthy women (mean age 65.5 years) from the MRC Hertfordshire Cohort Study whose birthweight and weight at 1 year were available from records. Serum 1,25 (OH)2 vitamin D concentrations were reduced with increasing weight at 1 year (19.1% reduction between the lowest and highest tertiles, P <0.01). A similar, but weaker trend was seen for birthweight. These associations were not explained by serum levels of serum calcium, phosphate, PTH, creatinine or sex hormones. The association of serum calcium with 1,25 (OH)2 vitamin D was greatest in the lowest tertile with little association in the highest tertile suggesting an increased sensitivity of renal 1-alpha hydroxylase in the lowest tertile. Highest levels of 1,25 (OH)2 vitamin D were associated with low BMD and high levels of urinary N-telopeptide suggesting that vitamin D metabolism may mediate the intrauterine and early postnatal environmental effects on adult BMD.