Moderate consumption of freeze-dried blueberry powder increased net bone calcium retention compared with no treatment in healthy postmenopausal women: a randomized crossover trial.

BACKGROUND: Preclinical studies suggest that blueberry consumption is associated with improved bone health. OBJECTIVES: We conducted a blueberry dose-response study in ovariectomized (OVX)-rats that informed a study in postmenopausal women using the urinary appearance of calcium (Ca) tracers from prelabeled bone to reflect changes in bone balance. We hypothesized that blueberry consumption would reduce bone loss in a dose-dependent manner compared with no treatment. METHODS: OVX rats were fed 4 doses of blueberry powder (2.5%, 5%, 10%, and 15%) in randomized order to determine bone 45Ca retention. Fourteen healthy, nonosteoporotic women ≥4 y past menopause were dosed with 50 nCi of 41Ca, a long-lived radioisotope, and equilibrated for 5 mo to allow 41Ca deposition in bone. Following a 6-wk baseline period, participants were assigned to a random sequence of 3 6-wk interventions, a low (17.5 g/d), medium (35 g/d), or high (70 g/d) dose of freeze-dried blueberry powder equivalent to 0.75, 1.5, or 3 cups of fresh blueberries incorporated into food and beverage products. Urinary 41Ca:Ca ratio was measured by accelerator mass spectrometry. Serum bone resorption biomarkers and urinary polyphenols were measured at the end of each control and intervention period. Data were analyzed using a linear mixed model and repeated measures analysis of variance. RESULTS: In both OVX rats and postmenopausal women, blueberry interventions benefited net bone calcium balance at lower but not at higher doses. In women, net bone calcium retention increased by 6% with the low (95% CI: 2.50, 8.60; P < 0.01) and 4% with the medium (95% CI: 0.96, 7.90; P < 0.05) dose compared with no treatment. Urinary excretion of hippuric acid increased dose-dependently with blueberry consumption. No significant relationships were found between bone resorption biomarkers, 25-hydroxyvitamin D, and interventions. CONCLUSIONS: Moderate consumption (<1 cup/d) of blueberries may be an effective strategy to attenuate bone loss in healthy postmenopausal women. This trial was registered at clinicaltrials.gov as NCT02630797.

Skeletal Protection and Promotion of Microbiome Diversity by Dietary Boosting of the Endogenous Antioxidant Response.

There is an unmet need for interventions with better compliance that prevent the adverse effects of sex steroid deficiency on the musculoskeletal system. We identified a blueberry cultivar (Montgomerym [Mont]) that added to the diet protects female mice from musculoskeletal loss and body weight changes induced by ovariectomy. Mont, but not other blueberries, increased the endogenous antioxidant response by bypassing the traditional antioxidant transcription factor Nrf2 and without activating estrogen receptor canonical signaling. Remarkably, Mont did not protect the male skeleton from androgen-induced bone loss. Moreover, Mont increased the variety of bacterial communities in the gut microbiome (α-diversity) more in female than in male mice; shifted the phylogenetic relatedness of bacterial communities (ß-diversity) further in females than males; and increased the prevalence of the taxon Ruminococcus1 in females but not males. Therefore, this nonpharmacologic intervention (i) protects from estrogen but not androgen deficiency; (ii) preserves bone, skeletal muscle, and body composition; (iii) elicits antioxidant defense responses independently of classical antioxidant/estrogenic signaling; and (iv) increases gut microbiome diversity toward a healthier signature. These findings highlight the impact of nutrition on musculoskeletal and gut microbiome homeostasis and support the precision medicine principle of tailoring dietary interventions to patient individualities, like sex. © 2020 American Society for Bone and Mineral Research (ASBMR).

Adiposity, Insulin Resistance, and Bone Mass in Children and Adolescents.

Context: Insulin resistance is an adverse health outcome that accompanies obesity. Fat mass is negatively associated with the bone mass after adjustment for confounders. Insulin resistance might be an intermediary in this relationship. Objective: To determine whether insulin resistance is an intermediary in the relationship between adiposity and bone mass in adolescents. Design: Cross-sectional secondary analysis of baseline data from a previous randomized trial. Setting: University research facility. Participants: A total of 240 adolescents (68% female), aged 7 to 15 years. Main Outcome Measures: Using dual energy x-ray absorptiometry, bone mineral content (BMC), areal bone mineral density, lean mass, and fat mass were measured. Skeletal sites of interest included the total body and lumbar spine (LS). Waist circumference was measured using an anthropometric tape measure. Insulin and glucose were measured in fasting sera, and the homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Path analysis was performed to determine whether the relationship between adiposity and bone was mediated through insulin resistance. Results: Fat mass (r = 0.467; P < 0.001) and waist circumference (r = 0.487; P < 0.001) correlated positively with HOMA-IR. Controlling for race, sex, maturation, lean mass, and height, fat mass, waist circumference, and HOMA-IR were negatively associated with LS BMC and total body areal bone mineral density (P < 0.05 for all). Additionally, path models for fat mass (95% CI, -5.893 to -0.956) and waist circumference (95% CI, -15.473 to -2.124) showed a negative relationship with LS BMC via HOMA-IR. Conclusions: These results support an intermediary role of insulin resistance in the relationship between adiposity and LS bone mass.

Mineral Intake Ratios Are a Weak but Significant Factor in Blood Pressure Variability in US Adults.

Background: Hypertension contributes substantially to chronic disease and mortality. Mineral intakes can modify blood pressure. Objective: Individual minerals and their intake ratios in US adults and their association with blood pressure were examined. Methods: Regression models were used to examine the associations of sodium, potassium, and calcium intakes and their ratios from food and supplements with blood pressure in 8777 US adults without impaired renal function from the 2011-2014 NHANES. We evaluated men (n = 4395) and women (n = 4382) separately. Models for predicting blood pressure were developed using age, blood pressure medication, race, body mass index (BMI), and smoking as explanatory variables. Results: Few adults met the recommended intake ratios for sodium:potassium (1.2% and 1.5%), sodium:calcium (12.8% and 17.67%), and sodium:magnesium (13.7% and 7.3%) for men and women, respectively. Approximately half of adults (55.2% of men and 54.8% of women) met calcium:magnesium intake ratio recommendations. In our regression models, the factors that explained the largest amount of variability in blood pressure were age, blood pressure medication, race/ethnicity, BMI, and smoking status. Together, these factors explained 31% and 15% of the variability in systolic blood pressure in women and men, respectively. The sodium:potassium (men and women), sodium:magnesium (women), and sodium:calcium (men) intake ratios were positively associated with systolic blood pressure, whereas calcium intake was inversely associated with systolic blood pressure in men only. When mineral intake ratios were added individually to our regression models, they improved the percentage of variability in blood pressure explained by the model by 0.13-0.21%. Conclusions: Strategies to lower blood pressure are needed. Lower sodium:potassium intake ratios provide a small benefit for protection against hypertension in US adults.

Twenty-Four-Hour Urine Phosphorus as a Biomarker of Dietary Phosphorus Intake and Absorption in CKD: A Secondary Analysis from a Controlled Diet Balance Study.

BACKGROUND AND OBJECTIVES: Twenty-four-hour urine phosphorus is commonly used as a surrogate measure for phosphorus intake and absorption in research studies, but its reliability and accuracy are unproven in health or CKD. This secondary analysis sought to determine the reliability and accuracy of 24-hour urine phosphorus as a biomarker of phosphorus intake and absorption in moderate CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Eight patients with stage 3-4 CKD participated in 2-week balance studies with tightly controlled phosphorus and calcium intakes. Thirteen 24-hour urine collections per patient were analyzed for variability and reliability of 24-hour urine phosphorus and phosphorus-to-creatinine ratio. The accuracy of 24-hour urine phosphorus to predict phosphorus intake was determined using a published equation. The relationships of 24-hour urine phosphorus with phosphorus intake, net absorption, and retention were determined. RESULTS: There was wide day-to-day variation in 24-hour urine phosphorus within and among subjects (coefficient of variation of 30% and 37%, respectively). Two 24-hour urine measures were needed to achieve ≥75% reliability. Estimating dietary phosphorus intake from a single 24-hour urine resulted in underestimation up to 98% in some patients and overestimation up to 79% in others. Twenty-four-hour urine phosphorus negatively correlated with whole-body retention but was not related to net absorption. CONCLUSIONS: From a sample of eight patients with moderate CKD on a tightly controlled dietary intake, 24-hour urine phosphorus was highly variable and did not relate to dietary phosphorus intake or absorption, rather it inversely related to phosphorus retention.

Behavioral Intervention in Adolescents Improves Bone Mass, Yet Lactose Maldigestion Is a Barrier.

Calcium intake during adolescence is important for attainment of peak bone mass. Lactose maldigestion is an autosomal recessive trait, leading to lower calcium intake. The Adequate Calcium Today study aimed to determine if a school-based targeted behavioral intervention over one year could improve calcium intake and bone mass in early adolescent girls. The school-randomized intervention was conducted at middle schools in six states over one school year. A total of 473 girls aged 10-13 years were recruited for outcome assessments. Bone mineral content (BMC) was determined by dual energy X-ray absorptiometry. Dietary calcium intake was assessed with a semi-quantitative food frequency questionnaire. Baseline calcium intake and BMC were not significantly different between groups. After the intervention period, there were no differences in changes in calcium intake and BMC at any site between groups. An unanticipated outcome was a greater increase in spinal BMC among lactose digesters than lactose maldigesters in the intervention schools only (12 months) (6.9 ± 0.3 g vs. 6.0 ± 0.4 g, p = 0.03) and considering the entire study period (18 months) (9.9 ± 0.4 vs. 8.7 ± 0.5 g, p < 0.01). Overall, no significant differences between the intervention and control schools were observed. However, lactose digesters who received the intervention program increased bone mass to a greater extent than lactose maldigesters.

The effect of dairy intake on bone mass and body composition in early pubertal girls and boys: a randomized controlled trial.

Background: Calcium retention increases with increasing body mass index (BMI) on recommended calcium intakes. Dairy foods are an excellent source of essential nutrients that are needed to increase bone mineral content (BMC) and potentially decrease fracture.Objective: We compared children who were overweight with children who were healthy weight for the accrual of bone mass in response to an extra 3 servings dairy/d compared with usual intake.Design: Participants were 240 healthy boys and girls (64%), aged 8-15.9 y (mean ± SD age: 11.8 ± 1.5 y), who consumed low amounts of dairy (<800 mg Ca/d). A total of 181 subjects completed the trial-61% were black, 35% were white, and 4% were other; 50% of subjects were healthy weight [5th through 70th BMI percentiles for age (percentile)], and 50% of subjects were overweight (≥85th percentile). Participants were randomly assigned within BMI categories to receive an 18-mo dairy intervention (3 servings/d equivalent to ∼900 mg Ca/d) or control. Main outcome measures assessed every 6 mo included the total-body bone mineral content and density, cortical and trabecular bone mineral density (BMD), BMC, and bone area at the 4% tibia and anthropometric measures.Results: No significant differences in the change of BMD, BMC, or bone area for the total-body radius, lumbar spine, and total hip were observed between subjects who received the dairy intervention (achieved consumption of 1500 mg Ca/d) and subjects who did not (achieved 1000 mg Ca/d, which represented ∼2 cups milk or other dairy as part of the diet) with the exception of a tibial BMC gain, which was greater in the group who were given dairy (P = 0.02). Body fat was not influenced by the diet assignment.Conclusions: Dairy food interventions generally had no effect on bone mineral acquisition or body composition either within or between weight groups. This study suggests that 2 cups milk or the dairy equivalent is adequate for normal bone gain between ages 8 and 16 y. This trial was registered at clinicaltrials.gov as NCT00635583.

Associations among osteocalcin, leptin and metabolic health in children ages 9-13 years in the United States.

BACKGROUND: This study aimed to investigate the relationships among osteocalcin, leptin and metabolic health outcomes in children ages 9-13 years. METHODS: This was a cross-sectional analysis of baseline data from 161 boys and 157 girls (ages 9-13 years) who previously participated in a double-blinded randomized placebo controlled trial of vitamin D supplementation. Relationships among fasting serum total osteocalcin (tOC), undercarboxylated osteocalcin (ucOC), leptin, and metabolic health outcomes were analyzed. RESULTS: Approximately 52% of study participants were obese based on percent body fat cutoffs (>25% for boys and >32% for girls) and about 5% had fasting serum glucose within the prediabetic range (i.e. 100 to 125 mg/dL). Serum tOC was not correlated with leptin, glucose, insulin, HOMA-IR, or HOMA-ß after adjusting for percent body fat. However, serum ucOC negatively correlated with leptin (partial r = -0.16; p = 0.04) and glucose (partial r = -0.16; p = 0.04) after adjustment for percent body fat. Leptin was a positive predictor of insulin, glucose, HOMA-IR, and HOMA-ß after adjusting for age, sex and percent body fat (all p < 0.001). CONCLUSIONS: These data depict an inverse relationship between leptin and various metabolic health outcomes in children. However, the notion that tOC or ucOC link fat with energy metabolism in healthy children was not supported. CLINICAL TRIAL REGISTRATION NUMBER: NCT00931580.

Nrf2 regulates mass accrual and the antioxidant endogenous response in bone differently depending on the sex and age.

Accumulation of reactive oxygen species (ROS) is an important pathogenic mechanism underling the loss of bone mass and strength with aging and other conditions leading to osteoporosis. The transcription factor erythroid 2-related factor2 (Nrf2) plays a central role in activating the cellular response to ROS. Here, we examined the endogenous response of bone regulated by Nrf2, and its relationship with bone mass and architecture in the male and female murine skeleton. Young (3 month-old) and old (15 month-old) Nrf2 knockout (KO) mice of either sex exhibited the expected reduction in Nrf2 mRNA expression compared to wild type (WT) littermates. Nrf2 deletion did not lead to compensatory increase in Nrf1 or Nrf3, other members of this transcription factor family; and instead, Nrf1 expression was lower in KO mice. Compared to the respective WT littermate controls, female KO mice, young and old, exhibited lower expression of both detoxifying and antioxidant enzymes; young male KO mice, displayed lower expression of detoxifying enzymes but not antioxidant enzymes; and old male KO mice showed no differences in either detoxifying or antioxidant enzymes. Moreover, old male WT mice exhibited lower Nrf2 levels, and consequently lower expression of both detoxifying and antioxidant enzymes, compared to old female WT mice. These endogenous antioxidant responses lead to delayed rate of bone acquisition in female KO mice and higher bone acquisition in male KO mice as quantified by DXA and µCT, demonstrating that Nrf2 is required for full bone accrual in the female skeleton but unnecessary and even detrimental in the male skeleton. Therefore, Nrf2 regulates the antioxidant endogenous response and bone accrual differently depending on sex and age. These findings suggest that therapeutic interventions that target Nrf2 could be developed to enhance the endogenous antioxidant response in a sex- and age-selective manner.

Bioavailability of potassium from potatoes and potassium gluconate: a randomized dose response trial.

BACKGROUND: The bioavailability of potassium should be considered in setting requirements, but to our knowledge, the bioavailability from individual foods has not been determined. Potatoes provide 19-20% of potassium in the American diet. OBJECTIVE: We compared the bioavailability and dose response of potassium from nonfried white potatoes with skin [targeted at 20, 40, and 60 milliequivalents (mEq) K] and French fries (40 mEq K) with potassium gluconate at the same doses when added to a basal diet that contained ∼60 mEq K. DESIGN: Thirty-five healthy, normotensive men and women with a mean ± SD age of 29.7 ± 11.2 y and body mass index (in kg/m(2)) of 24.3 ± 4.4 were enrolled in a single-blind, crossover, randomized controlled trial. Participants were partially randomly assigned to the order of testing for nine 5-d interventions of additional potassium as follows: 0 (control; repeated at phases 1 and 5), 20, 40, and 60 mEq K/d consumed as a potassium gluconate supplement or as unfried potato or 40 mEq K from French fries completed at phase 9. The bioavailability of potassium was determined from the area under the curve (AUC) of serial blood draws and cumulative urinary excretion during a 24-h period and from a kinetic analysis. The effects of the potassium source and dose on the change in blood pressure and augmentation index (AIx) were determined. RESULTS: The serum potassium AUC increased with the dose (P < 0.0001) and did not differ because of the source (P = 0.53). Cumulative 24-h urinary potassium also increased with the dose (P < 0.0001) and was greater with the potato than with the supplement (P < 0.0001). The kinetic analysis showed the absorption efficiency was high across all interventions (>94% ± 12%). There were no significant differences in the change in blood pressure or AIx with the treatment source or dose. CONCLUSIONS: The bioavailability of potassium is as high from potatoes as from potassium gluconate supplements. Future studies that measure the effect of dietary potassium on blood pressure will need to evaluate the effect of various dietary sources on potassium retention and in both normal and hypertensive populations. This trial was registered at clinicaltrials.gov as NCT01881295.

Soluble corn fiber increases bone calcium retention in postmenopausal women in a dose-dependent manner: a randomized crossover trial.

BACKGROUND: Dietary soluble corn fiber (SCF) significantly improves calcium absorption in adolescents and the bone strength and architecture in rodent models. OBJECTIVE: In this study, we aimed to determine the skeletal benefits of SCF in postmenopausal women. DESIGN: We used our novel technology of determining bone calcium retention by following the urinary appearance of (41)Ca, a rare long-lived radioisotope, from prelabeled bone to rapidly and sensitively evaluate the effectiveness of SCF in reducing bone loss. A randomized-order, crossover, double-blinded trial was performed in 14 healthy postmenopausal women to compare doses of 0, 10, and 20 g fiber from SCF/d for 50 d. RESULTS: A dose-response effect was shown with 10 and 20 g fiber from SCF/d, whereby bone calcium retention was improved by 4.8% (P < 0.05) and 7% (P < 0.04), respectively. The bone turnover biomarkers N-terminal telopeptide and osteocalcin were not changed by the interventions; however, a significant increase in bone-specific alkaline phosphatase, which is a bone-formation marker, was detected between 0 and 20 g fiber from SCF/d (8%; P = 0.035). CONCLUSION: Daily SCF consumption significantly increased bone calcium retention in postmenopausal women, which improved the bone calcium balance by an estimated 50 mg/d. This study was registered at clinicaltrials.gov as NCT02416947.

Soluble Corn Fiber Increases Calcium Absorption Associated with Shifts in the Gut Microbiome: A Randomized Dose-Response Trial in Free-Living Pubertal Females.

BACKGROUND: Soluble corn fiber (SCF; 12 g fiber/d) is shown to increase calcium absorption efficiency, associated with shifts in the gut microbiota in adolescent males and females who participated in a controlled feeding study. OBJECTIVE: We evaluated the dose response of 0, 10, and 20 g fiber/d delivered by PROMITOR SCF 85 (85% fiber) on calcium absorption, biochemical bone properties, and the fecal microbiome in free-living adolescents. METHODS: Healthy adolescent females (n = 28; aged 11-14 y) randomly assigned into a 3-phase, double-blind, crossover study consumed SCF for 4 wk at each dose (0, 10, and 20 g fiber/d from SCF) alongside their habitual diet and were followed by 3-d clinical visits and 3-wk washout periods. Stable isotope ((44)Ca and (43)Ca) enrichment in pooled urine was measured by inductively coupled plasma mass spectrometry. Fecal microbial community composition was assessed by high-throughput sequencing (Illumina) of polymerase chain reaction-amplified 16S rRNA genes. Mixed model ANOVA and Friedman analysis were used to determine effects of SCF on calcium absorption and to compare mean microbial proportions, respectively. RESULTS: Calcium absorption increased significantly with 10 (13.3% ± 5.3%; P = 0.042) and 20 g fiber/d (12.9% ± 3.6%; P = 0.026) from SCF relative to control. Significant differences in fecal microbial community diversity were found after consuming SCF (operational taxonomic unit measures of 601.4 ± 83.5, 634.5 ± 83.8, and 649.6 ± 75.5 for 0, 10, and 20 g fiber/d, respectively; P < 0.05). Proportions of the genus Parabacteroides significantly increased with SCF dose (1.1% ± 0.8%, 2.1% ± 1.6%, and 3.0% ± 2.0% for 0, 10, and 20 g fiber/d from SCF, respectively; P < 0.05). Increases in calcium absorption positively correlated with increases in Clostridium (r = 0.44, P = 0.023) and unclassified Clostridiaceae (r = 0.40, P = 0.040). CONCLUSIONS: SCF, a nondigestible carbohydrate, increased calcium absorption in free-living adolescent females. Two groups of bacteria may be involved, one directly fermenting SCF and the second fermenting SCF metabolites further, thereby promoting increased calcium absorption. This trial was registered at clinicaltrials.gov as NCT01660503.

Individual variation in urinary sodium excretion among adolescent girls on a fixed intake.

BACKGROUND: According to traditional understanding of sodium homeostasis, nearly all of daily sodium intake is excreted in urine, with intraindividual variability attributed to variability in dietary sodium intake and urine collection errors. OBJECTIVE: To analyze the variability of urinary sodium in excretion from a balance study with fixed sodium intakes. METHODS: Daily 24-h urine collections were assessed for sodium, potassium, and creatinine in 22 black and 13 white adolescent girls (11-15 year, BMI 15-29 kg/m) in a randomized, crossover design with controlled diets containing either low (57 mmol/day) or high (167 mmol/day) sodium, each fed for 3 weeks. RESULTS: Coefficient of variation analysis indicated higher variation in urinary sodium excretion about the mean on low (vs high) sodium (40 vs 32%, P = 0.02) and in black (vs white) girls (42 vs 30%, P < 0.001). A mixed model showed no sodium intake × race interaction. Urinary sodium excretion was not correlated with urinary potassium or creatinine excretion. Excretion of 65 mmol/day (adequate intake) or less was documented on 16% on the days during the high-sodium diet. Reliability of the mean of several urine sodium samples varied from 23% for one sample to 75% for 10 samples for the high-sodium diet. CONCLUSION: The high intraindividual variability in urinary sodium excretion on a fixed diet highlights the potential for substantial error in (a) using a single 24-h urine collection to estimate an individual's usual sodium intake and (b) relating sodium excretion from a single 24-h collection with outcomes. Further research is warranted to understand the causes of such variation.

Effect of Hesperidin With and Without a Calcium (Calcilock) Supplement on Bone Health in Postmenopausal Women.

CONTEXT: Citrus fruits contain unique flavanones. One of the most abundant of the flavanones, hesperidin, has been shown to prevent bone loss in ovariectomized rats. OBJECTIVE: The objective of the study was to measure the effect of hesperidin with or without calcium supplementation on bone calcium retention in postmenopausal women. DESIGN: The study was a double-blind, placebo-controlled, randomized-order crossover design of 500 g hesperidin with or without 500 mg calcium supplement in 12 healthy postmenopausal women. Bone calcium retention was determined from urinary excretion of the rare isotope, (41)Ca, from bone. RESULTS: Calcium plus hesperidin, but not hesperidin alone, improved bone calcium retention by 5.5% (P < .04). CONCLUSION: Calcium supplementation (Calcilock), in combination with hesperidin, is effective at preserving bone in postmenopausal women.

Impact of equol-producing capacity and soy-isoflavone profiles of supplements on bone calcium retention in postmenopausal women: a randomized crossover trial.

BACKGROUND: Postmenopausal estrogen depletion is a major contributing factor to bone loss. Soy isoflavones have variable effects on the prevention of postmenopausal bone loss, which is possibly related to the specific isoflavone content or the variable equol-producing capacity of individuals. OBJECTIVE: We aimed to determine the effects of the content of isoflavones in a soy supplement and the equol-producing ability of the individual on postmenopausal bone calcium retention. DESIGN: The study was a blinded, randomized, crossover intervention trial in 24 postmenopausal women who were prescreened for their ability to convert daidzein to equol. Women were equilibrated with (41)Ca before the intervention. Interventions were 5 soy isoflavone oral supplements (2 doses of a genistein-rich soy supplement and 3 doses of mixed isoflavones in various proportions) and a bisphosphonate (risedronate). Each intervention was given sequentially for 50 d followed by a 50-d washout period. The percentage of bone calcium retention was determined from the change in urinary (41)Ca:calcium. RESULTS: Interventions that ranged from 52 to 220 mg total isoflavones/d increased bone calcium retention between 3.4% and 7.6% (P < 0.05), which was a moderate effect compared with that of risedronate at 15.3% (95% CI: 7.1%, 22.7%; P = 0.0014). The most-effective soy intervention delivered 105.23 mg total isoflavones/d as genistein, daidzein, and glycitein in their natural ratios and increased bone calcium retention by 7.6% (95% CI: 4.9%, 10.2%; P < 0.0001). Genistein, at 52.85 mg/d, increased bone calcium retention by 3.4% (95% CI: 0.5%, 6.2%; P = 0.029); but there was no benefit at higher amounts (113.52 mg/d). There was no difference (P = 0.5) in bone calcium retention between equol producers and nonproducers. CONCLUSION: Soy isoflavones, although not as potent as risedronate, are effective bone-preserving agents in postmenopausal women regardless of their equol-producing status, and mixed isoflavones in their natural ratios are more effective than enriched genistein. This trial was registered at clinicaltrials.gov as NCT00244907.

Dietary calcium requirements do not differ between Mexican-American boys and girls.

Mexican Americans are an understudied ethnic group for determinants of bone health, although the risk of age-related osteoporosis is high in this rapidly growing sector of the U.S. population. Thus, the objective of the present study was to establish the dietary calcium requirements for bone health in Mexican-American adolescents by measuring calcium retention calculated from balance in response to a range of dietary calcium intakes and to determine predictors of skeletal calcium retention. Adolescents aged 12-15 y were studied twice on paired calcium intakes ranging from 600 to 2300 mg/d using randomized-order, crossover 3-wk balance studies. Skeletal calcium retention was calculated as dietary calcium intake minus calcium excreted in feces and urine over the last 2 wk of balance. A linear model was developed to explain the variation in calcium retention. Boys (n = 20) were taller and had higher lean mass, usual dietary calcium intake, bone mineral content, and serum alkaline phosphatase compared with girls, whereas girls (n = 20) had higher Tanner scores and greater fat mass. Calcium retention increased with calcium intake (P < 0.0001) and did not differ by sex (P = 0.66). In boys and girls considered together, calcium intake explained 33% of the variation in calcium retention. Serum alkaline phosphatase explained an additional 11% of the variation in calcium retention. Other variables measured, including the urine N-telopeptide of type I collagen/creatinine ratio, Tanner score, serum parathyroid hormone and 25-hydroxyvitamin D, weight, height, and body mass index, did not contribute to the variance in calcium retention. In adolescence, calcium retention in both Mexican-American boys and girls was higher than determined previously in adolescent nonHispanic white girls. This trial was registered at clinicaltrials.gov as NCT01277185.

Soluble maize fibre affects short-term calcium absorption in adolescent boys and girls: a randomised controlled trial using dual stable isotopic tracers.

Soluble maize fibre (SCF) has been found to significantly improve bone mineral density and strength in growing rats compared with several other novel prebiotic fibres. The objective of the present study was to investigate the effect of SCF on Ca absorption and retention in pubertal children by studying the potential absorption mechanisms of the intestinal microbiota. A total of twenty-four adolescent boys and girls (12-15 years) participated in two 3-week metabolic balance studies testing 0 g/d SCF (control (CON) treatment) and 12 g/d SCF (SCF treatment) in a random order by inclusion in a low-Ca diet (600 mg/d). Fractional Ca absorption was measured at the end of the two intervention periods using a dual-stable isotope method. Diet composites and faecal and urine samples were collected daily and analysed for Ca content. Ca retention was calculated as dietary Ca intake minus Ca excretion in faeces and urine over the last 2 weeks. Microbial community composition in the faecal samples collected at the beginning and end of each session was determined by 454 pyrosequencing of the PCR-amplified 16S ribosomal RNA gene. Fractional Ca absorption was 12 % higher (41 mg/d) after the SCF treatment compared with that after the CON treatment (0·664 (sd 0·129) and 0·595 (sd 0·142), respectively; P= 0·02), but Ca retention was unaffected. The average proportion of bacteria of the phylum Bacteroidetes was significantly greater in the participants after the SCF treatment than after the CON treatment. These results suggest that moderate daily intake of SCF, a well-tolerated prebiotic fibre, increases short-term Ca absorption in adolescents consuming less than the recommended amounts of Ca.

Current estimate of Down Syndrome population prevalence in the United States.

OBJECTIVE: To calculate a reliable estimate of the population prevalence of Down syndrome in the US. STUDY DESIGN: The annual number of births of infants with Down syndrome were estimated by applying published birth prevalence rates of Down syndrome by maternal age to US data from the Centers for Disease Control and Prevention for the years for which births by maternal age were available (1940-2008). Death certificate data for persons with Down syndrome were available for the years 1968-2007. We estimated the number of people with Down syndrome on January 1, 2008, using a life table approach based on proportions of deaths by age. Monte Carlo sampling was used to create 90% uncertainty intervals (UIs) for our estimates. RESULTS: We estimated the January 1, 2008, population prevalence of Down syndrome as approximately 250700 (90% UI, 185900-321700) based on proportions of deaths by age from the most recent 2 years (2006-2007) of death certificate data. This estimate corresponds to a prevalence of 8.27 people with Down syndrome per 10000 population (90% UI, 6.14-10.62). CONCLUSION: Our estimate of Down syndrome prevalence is roughly 25%-40% lower than estimates based solely on current birth prevalence. The results presented here can be considered a starting point for facilitating policy and services planning for persons with Down syndrome.

Magnesium retention from metabolic-balance studies in female adolescents: impact of race, dietary salt, and calcium.

BACKGROUND: Previously, we showed that black girls retained more calcium than white girls did and that salt loading negatively affected calcium retention. Racial differences likely exist in other bone minerals also, such as magnesium, in response to salt loading during growth. OBJECTIVE: We studied racial differences in magnesium metabolism in response to dietary sodium and calcium during rapid bone growth. DESIGN: Twenty-seven white and 40 black girls (11-15 y old) were studied for 3 wk while they consumed low-sodium (1.3 g/d) and high-sodium (3.8 g/d) diets by using a randomized-order, crossover metabolic study with 3 dietary calcium intakes; the magnesium dietary intake was fixed at 230 mg/d. Urine and feces were collected during each 3-wk period in 24-h pools and analyzed for magnesium. A mixed-model ANOVA was used to determine the effect of race and dietary sodium with calcium intake as a covariate. RESULTS: Salt loading or calcium intake had no significant effect on urinary magnesium excretion. Blacks excreted significantly less urinary magnesium (mean ± SD: 83.8 ± 25.6 mg/d) than did whites (94.9 ± 27.3 mg/d; P < 0.05). No effects were observed in fecal magnesium excretion. Magnesium retention was higher with the low-sodium diet (50.1 ± 44.0 mg/d) than with the high-sodium diet (39.3 ± 49.8 mg/d) (P < 0.05), with no effects of race or calcium intake. Salt loading had no effect on biomarkers. Whites had higher 25-hydroxyvitamin D and insulin-like growth factor binding protein 3 but lower 1,25-dihydroxyvitamin D and parathyroid hormone concentrations. CONCLUSIONS: Blacks excreted less urinary magnesium than did whites. Magnesium retention was similar between races but higher with the low-sodium diet. Kinetic studies are needed to fully explain magnesium homeostasis. This trial was registered at clinicaltrials.gov as NCT01564238.

Down syndrome and personalized medicine: changing paradigms from genotype to phenotype to treatment.

Personalized Medicine represents a paradigm shift in the conceptual framework of research and clinical care. This shift argues that Down syndrome is a treatable condition, and therefore we must invest in research to improve outcomes. Individuals with Down syndrome have varying levels of increased risk for a number of co-morbidities, including infantile spasms and early onset Alzheimer's disease. We will review research in these associated conditions to show how investigators are attempting to identify biomarkers, including genomic, epigenomic, proteomic and metabolomic "signatures" that will predict who may be at risk to develop a specific co-morbidity prior to onset and will provide novel targets for therapeutic development. This Personalized Medicine approach will permit predictive and preventive approaches for individuals at increased risk for co-morbidities. The support for clinical trials among individuals with Down syndrome is beginning to overcome the "culture of intractability" that has surrounded this disorder.