Meryl E. Wastney

Bone markers, calcium metabolism, and calcium kinetics during extended-duration space flight on the Mir Space Station

Bone loss is a current limitation for long‐term space exploration. Bone markers, calcitropic hormones, and calcium kinetics of crew members on space missions of 4–6 months were evaluated. Spaceflight‐induced bone loss was associated with increased bone resorption and decreased calcium absorption.

Galacto-oligosaccharides increase calcium absorption and gut bifidobacteria in young girls: a double-blind cross-over trial

Adolescence is a time for rapid growth that represents an opportunity to influence peak bone mass. Prebiotic agents, such as galacto-oligosaccharides (GOS), increase Ca absorption in animal models and postmenopausal women. The objectives of the present study were to investigate the dose-response relationship of GOS supplementation on Ca absorption during growth and to assess changes in colonic microbiota to better understand the mechanism by which GOS is acting. A total of thirty-one healthy adolescent girls aged 10-13 years consumed smoothie drinks twice daily with 0, 2·5 or 5 g GOS for three 3-week periods in a random order. Fractional Ca absorption was determined from urinary Ca excretion over 48 h at the end of each 3-week period using a dual stable isotope method. Faecal microbiota and bifidobacteria were assessed by PCR-denaturing gradient gel electrophoresis and quantitative PCR. Fractional Ca absorption after the 48 h treatment with control, 5 and 10 g GOS/d was 0·393 (SD 0·092), 0·444 (SD 0·086) and 0·419 (SD 0·099), respectively. Significant improvements in Ca absorption were seen with both low and high doses of GOS compared with the control (P,0·02), but itwas not a dose-response relationship. The increase in absorption was greatest in the urine collected after 24 h, which is consistent with lower gut absorption. Faecal bifidobacteria increased (control 10·89 (SD 13·86), 5 g GOS 22·80 (SD 15·74) and 10 g GOS 11·54 (SD 14·20)) with the GOS treatment (P,0·03). The results suggest that daily consumption of 5 g GOS increases Ca absorption, which may be mediated by the gut microbiota, specifically bifidobacteria.

Comparative effect of soy protein, soy isoflavones, and 17β-estradiol on bone metabolism in adult ovariectomized rats

This study provided a comprehensive investigation on the effect of soy protein and soy isoflavones on both calcium and bone metabolism in virgin adult rats. The measurements included bone histology, calcium kinetic modeling, calcium balance, bone densitometry, and whole body densitometry. Results confirmed the bone‐preserving effect of estrogen but did not support a bone‐sparing role of soy isoflavones.

Calcium requirements and metabolism in Chinese-American boys and girls

Calcium requirements of North American adolescents were set at 1300u2009mg/day based on data from white girls. Calcium requirements for Asian‐American adolescents have not been studied. Using metabolic balance protocols and a range in calcium intakes, skeletal calcium retention was determined in Chinese‐American adolescents. A sample of 29 adolescents, 15 boys aged 12 to 15 years and 14 girls aged 11 to 15 years, was studied twice on paired calcium intakes ranging between 629 to 1835u2009mg/day using a randomized‐order crossover design. Calcium absorption and bone turnover rates using double‐stable calcium isotope kinetic analysis on two calcium intakes per subject were measured and compared in boys and girls. Girls and boys had low habitual mean calcium intakes of 648 and 666u2009mg/day, respectively, and low mean serum 25‐hydroxyvitamin D concentrations of 19.1 and 22.2u2009ng/mL, respectively. True fractional calcium absorption varied inversely with calcium load. Boys had significantly higher bone turnover rate than girls at the same calcium intake. Calcium retention increased with calcium intake; calcium intakes to achieve maximal calcium retention were 1100u2009mg/day in boys and 970u2009mg/day in girls. Recommendations for calcium requirements should be lowered for Chinese‐American adolescents.

A Human Model of Selenium that Integrates Metabolism from Selenite and Selenomethionine

Selenium (Se) metabolism is affected by its chemical form in foods and by its incorporation (specific vs. nonspecific) into multiple proteins. Modeling Se kinetics may clarify the impact of form on metabolism. Although the kinetics of Se forms have been compared in different participants, or the same participants at different times, direct comparisons of their respective metabolism in the same participants have not been made. The aim of this study was to simultaneously compare kinetics of absorbed Se from inorganic selenite (Sel) and organic selenomethionine (SeMet) in healthy participants (n = 31). After oral administration of stable isotopic tracers of each form, urine and feces were collected for 12 d and blood was sampled over 4 mo. Tracer enrichment was determined by isotope-dilution-GC-MS. Using WinSAAM, a compartmental model was fitted to the data. Within 30 min of ingestion, Se from both forms entered a common pool, and metabolism was similar for several days before diverging. Slowly turning-over pools were required in tissues and plasma for Se derived from SeMet to account for its 3-times-higher incorporation into RBC compared with Se from Sel; these presumably represent nonspecific incorporation of SeMet into proteins. Pool sizes and transport rates were determined and compared by form and gender. The final model consisted of 11 plasma pools, 2 pools and a delay in RBC, and extravascular pools for recycling of Se back into plasma. This model will be used to evaluate changes in Se metabolism following long-term (2 y) Se supplementation.

Interpretation of 41Ca data using compartmental modeling in post-menopausal women.

Calcium-41 (t1/2u2009=u2009105xa0years) can be used after a single dose to follow calcium metabolism over a subjects lifetime. The aims of this study were to expand a 41Ca kinetic model and estimate bone resorption in women with stable bone loss, compare the rates with those calculated with classical isotope studies, and to use the model to simulate dynamic changes in urinary 41Ca:Ca ratios and bone balance for the design and interpretation of 41Ca studies. Forty-two women >5xa0years post-menopause were given 41Ca intravenously. Bone mineral content and bone mineral density of total body were measured by dual-energy X-ray absorptiometry at the beginning of the study. Urine collections were made periodically for up to ∼5xa0years while subjects were free living. Urinary 41Ca:Ca ratios were measured using accelerator mass spectrometry. The isotope data were analyzed by compartmental modeling. Four compartments were necessary to fit the urinary tracer data and total bone calcium. The final model included pathways for absorption, distribution, urinary excretion, and endogenous excretion and was used to calculate rates of bone turnover. Estimates of bone resorption in a subset of the women (nu2009=u200913), studied previously in a 3-week balance and full kinetic study with 45Ca, agreed with those using 41Ca methodology. Thus, rates of bone resorption can be estimated from 41Ca urinary data in stable post-menopausal women. The model was used to simulate dynamic changes in urinary 41Ca:Ca ratios and bone balance, as a result of interventions that perturb calcium metabolism to aid in study design and interpretation.

Calcium bioavailability and kinetics of calcium ascorbate and calcium acetate in rats.

The objective was to investigate the bioavailability and mechanism of calcium absorption of calcium ascorbate (ASC) and calcium acetate (AC). A series of studies was performed in adult Sprague-Dawley male rats. In the first study, each group of rats (n = 10/group) was assigned to one of the five test meals labeled with 45Ca: (i) 25 mg calcium as heated ASC or (ii) unheated ASC, (iii) 25 mg calcium as unheated AC, (iv) 3.6 mg Ca as unheated ASC, or (v) unheated AC. Femur uptake indicated better calcium bioavailability from ASC than AC t both calcium loads. A 5-min heat treatment partly reduced bioavailability of ASC. Kinetic studies were performed to further investigate the mechanism of superior calcium bioavailability from ASC. Two groups of rats (n = 10/group) received oral doses of 25 mg Ca as ASC or AC. Each dose contained 20 μCi 45Ca. Two additional groups of rats (n = 10/group) received an intravenous injection (iv) of 10 μCi 45Ca after receiving an unlabeled oral dose of 25 mg calcium as ASC or AC. Sequential blood samples were collected over 48 hrs. Urine and fecal samples were collected every 12 hrs for 48 hrs and were analyzed for total calcium and 45Ca content. Total calcium and 45Ca from serum, urine, and feces were fitted by a compartment kinetics model with saturable and nonsaturable absorption pathways by WinSAAM (Windows-based Simulation Analysis and Modeling). The difference in calcium bioavailability between the two salts was due to differences in saturable rather than passive intestinal absorption and not to endogenous secretion or calcium deposition rate. The higher bioavailability of calcium ascorbate was due to a longer transit time in the small intestine compared with ASC.

Acute versus chronic effects of whey proteins on calcium absorption in growing rats.

The acute and chronic effects of whey proteins on calcium metabolism and bone were evaluated. In acute studies, 8-week-old male rats were gavaged with 50 mg whey protein concentrate (WPC) and 25 mg calcium. 45Ca was administered intravenously or orally. Kinetic studies were performed, and femurs were harvested. Four of seven WPCs significantly increased femur uptake of 45Ca compared with controls. One WPC at 50 mg enhanced calcium absorption over a range of calcium Intakes from 35.1 ± 9.4% to 42.4 ± 14.0% (P < 0.01). Three of the most effective WPCs were tested further in a chronic feeding study. One hundred 3-week-old rats were randomly divided into four adequate dietary calcium (ADC; 0.4% Ca) groups (control of 20% casein and three WPC groups with 1% substitution of casein with each of three WPCs) and two low calcium (LC; 0.2% Ca) groups (control of 20% casein and one WPC group with 1% substitution of casein with one WPC). After 8 weeks, there was no effect of WPCs on femur uptake of 45Ca among ADC groups and there was no effect of WPCs on calcium retention, femur breaking force, femur bone mineral density, or total femur calcium at either dietary calcium intake. However, whole body bone mineral content (BMC) was significantly higher (P < 0.05) in the three whey protein concentrate ADC groups compared with the ADC control group. Total BMC at the proximal tibia in whey protein ADC groups was increased, as shown by peripheral quantitative computed tomography. Our results indicate that the acute calcium absorption–enhancing effect of whey proteins did not persist through long-term feeding in rats. However, the initial enhancement of calcium absorption by whey protein was sufficient to Increase BMC.

Effect of High‐Calcium Diet on Coronary Artery Disease in Ossabaw Miniature Swine With Metabolic Syndrome

Background Calcium is a shortfall essential nutrient that has been a mainstay of osteoporosis management. Recent and limited findings have prompted concern about the contribution of calcium supplementation to cardiovascular risk. A proposed mechanism is through the acceleration of coronary artery calcification. Determining causality between calcium intake and coronary artery calcification has been hindered by a lack of sensitive methodology to monitor early vascular calcium accumulation. The primary study aim was to assess the impact of high calcium intake on coronary artery calcification using innovative calcium tracer kinetic modeling in Ossabaw swine with diet-induced metabolic syndrome. Secondary end points (in vitro wire myography, histopathology, intravascular ultrasound) assessed coronary disease. Methods and Results Pigs (n =24; aged ≈15 months) were fed an atherogenic diet with adequate calcium (0.33% by weight) or high calcium (1.90% from calcium carbonate or dairy) for 6 months. Following 5 months of feeding, all pigs were dosed intravenously with 41Ca, a rare isotope that can be measured in serum and tissues at a sensitivity of 10−18 mol/L by accelerator mass spectrometry. Kinetic modeling evaluated early coronary artery calcification using 41Ca values measured in serial blood samples (collected over 27 days) and coronary artery samples obtained at sacrifice. Serum disappearance of 41Ca and total coronary artery 41Ca accumulation did not differ among groups. Secondary end points demonstrated no treatment differences in coronary artery disease or function. Conclusion There was no detectable effect of high calcium diets (from dairy or calcium carbonate) on coronary artery calcium deposition in metabolic syndrome swine.

Soft tissue calcification in the Ossabaw miniature pig: experimental and kinetic modeling studies

SummaryCalcium (Ca) deposition into vascular tissue was measured in Ossabaw miniature pigs with and without metabolic syndrome (MetS) using Ca tracer kinetics and coronary atherosclerosis measured with intravascular ultrasound. Pigs with MetS had higher Ca uptake into coronary arteries than lean pigs.IntroductionCa deposition into arteries is a common disease in humans. The Ossabaw pig develops MetS when fed an atherogenic diet. The aim of this study was to measure Ca deposition into arteries of lean vs. MetS pigs.MethodsMale pigs were fed for 5xa0months with chow diet (healthy, lean; nu2009=u20097) or atherogenic diet (nu2009=u20098) consisting of chow supplemented with 2xa0% cholesterol, 43xa0% kcal from fat, and 20xa0% kcal from fructose. Pigs were verified to have MetS by obesity, insulin resistance, impaired glucose tolerance, dyslipidemia, and hypertension. Two pigs received 50xa0nCi of 41Ca i.v. and blood was drawn frequently for 24xa0h, and 2, 3, 6, 8, 10, 15, 20, and at sacrifice at 28xa0days after injection. Peripheral arteries were biopsied four times per pig over the 28th day and coronary artery sampled at sacrifice. Tissues were analyzed for 41Ca:Ca. A compartmental model was used to estimate rates of Ca deposition into the arteries.ResultsThe MetS swine had higher 41Ca and atherosclerosis in coronary arteries than lean pigs.ConclusionsThis pig model is a suitable model for studying vascular calcification in humans.