Background/Objectives: Previous research demonstrates higher sodium retention with increasing levels of dietary salt in some populations. Our objective was to determine whole-body sodium retention and sodium distribution on high and low salt diets using rodent models. Methods: Whole body retention of orally dosed Na-22, a gamma emitter, was measured in female growing and adult Sprague-Dawley rats on high (3.1% by wt. of diet) and low salt (0.13% by wt. of diet) diets. In a second study, whole-body sodium retention was compared between destructive inductively coupled plasma optical emission spectroscopy (ICP-OES) and neutron activation analysis (NAA) in adult male and female C57BL/6 mice. Results: Whole body retention of Na-22 was not different due to the age of rats on a high salt diet, but rats fed the high salt diet excreted Na-22 much more rapidly than rats fed a low salt diet. In mice, neither sodium retention nor tissue distribution was affected by dietary salt. Bland-Altman analysis indicated overall agreement between NAA and ICP-OES measurements, with observed systematic positive bias. Conclusions: Dietary salt had little effect on retention in normotensive rodents and should be studied in hypertensive models.

Despite the availability of multiple highly effective pharmacologic therapies for osteoporosis, fracture rates in the United States have plateaued or increased in recent years. At the same time, individuals with osteoporosis are exposed to an abundance of digital health information and frequently seek guidance on nutrition, exercise, and other lifestyle strategies to improve bone health. Many endocrinologists, however, may have limited time or expertise to address these questions comprehensively during routine clinical encounters. Current clinical practice guidelines provide valuable direction on selecting pharmacotherapy based on fracture risk, yet they offer limited guidance on how to personalize treatment plans by integrating patient values, beliefs, and preferences. The aim of this manuscript is to equip clinicians with practical, preference-sensitive strategies to address common concerns raised by postmenopausal women with osteoporosis, including evidence-based guidance on nutrition and on safe, effective resistance, impact, and balance-focused exercises for bone health and fall prevention. We also outline suggested approaches for responding to common concerns among patients who are reluctant to initiate pharmacologic therapy. Through two illustrative cases, we highlight how clinicians can integrate pharmacologic options with evidence-based lifestyle guidance and engage patients in shared decision making to develop individualized, goal-concordant care plans. Our goal is to provide clinicians with tools that support more effective, patient-centered conversations and ultimately improve the quality of osteoporosis care.

The biology of nutrition is essential and inextricably involved in all aspects of human growth and development. Nutritional status is governed by an ecology consisting of internal (biology, genetics, metabolism, health status, developmental stage, and nutrient intake) and external (home, community, school, and physical environment) inputs. The application of an ecological perspective considers internal and external components that may influence the effect of nutrition on growth and development. These interactions will differ across various stages of human development. The importance of diet and nutritional status and health during the "first 1000 d," which is inclusive of pregnancy through 2 y of postnatal life, is well recognized. However, significant gaps exist in our understanding of the importance of nutrition during the "next 7000 d" through adolescence (2-21 y). The community expends substantial resources to ensure nutritional adequacy during this critical developmental period, but not on improved precision of assessment of the need for or impact of these efforts. The "Biomarkers of Nutrition for Development: Knowledge Indicating Dietary Sufficiency (BOND-KIDS)" Project applied an ecological approach to understand both the need for, and impact of, programs and interventions intended to address nutrition in school-aged children. This paper summarizes the findings of Working Group 1 of the BOND-KIDS Project, which focuses on the biological evidence underlying nutritional needs and responses to interventions. Specifically, based on a review of the role of nutrition in the development of key functional systems (the musculoskeletal system, brain, metabolic processes, and immune system in school-aged children), we examined the importance of nutrition and physical activity for body size and composition, bone health, neurobehavioral function, and risk of noncommunicable diseases both in childhood and in later life. This work provides the biological underpinning upon which the other 3 BOND-KIDS Working Groups built their reports.

Dietary bioactives, which are commonly found in food, beverages, and dietary supplements, include nonessential food components that can support health beyond preventing nutrient deficiencies. Despite their known health benefits and potential for adverse effects, there is limited guidance on appropriate intake levels, safety, and efficacy of these ingredients, particularly those present in dietary supplements. This lack of guidance can be challenging for individuals attempting to make informed decisions about products marketed for health benefits. A previously published perspective proposed a 4-step framework for developing quantitative intake recommendations for bioactive constituents in food. This framework addressed bioactive characterization, safety evaluation, efficacy assessment, and how to develop intake levels from foods. However, it did not account for the unique considerations of bioactives consumed in dietary supplement form. The current paper builds on the original framework by addressing the specific factors that must be considered when developing intake guidance for bioactive constituents found in dietary supplements. These include differences in dose, matrix, purity, bioavailability, and intended use. In doing so, this paper aims to advance the development of evidence-based recommendations for supplements, while also highlighting the fundamental distinctions between bioactive constituents delivered through food and diet compared with those delivered through dietary supplements.

BACKGROUND:Prebiotic fiber supplementation increases calcium absorption but its long-term effects on bone mass are mixed in children and adolescents. OBJECTIVES:This study aimed to determine the effect of 1-y soluble corn fiber (SCF) supplementation compared with that of placebo (maltodextrin; main comparison), with or without calcium (calcium gluconate; secondary comparison) on bone mineral content (BMC) and bone mineral density (BMD) in children and adolescents with low habitual calcium intake through a randomized clinical trial. We hypothesized that SCF supplementation would result in higher bone mass. METHODS:Healthy children and adolescents (9-14 y old) with usual low calcium intake were recruited and randomly assigned for 1 y to SCF (12 g/d) or placebo (12 mg/d), with or without calcium (600 mg/d). Bone mass was measured using dual-energy x-ray absorptiometry at baseline, 6 mo, and 12 mo. Results are shown as mean ± SD. Statistical analyses included linear mixed-effects and analysis of variance. RESULTS:Totally, 213 participants were recruited, of whom 177 were randomized. Most were White (41.3%), Hispanic (69.5%), and with healthy weight (74.0%). Girls had significantly higher Tanner score (3.10 ± 1.20) than boys (2.30 ± 1.20; P < 0.001) and a significantly higher body fat percentage (P < 0.05); therefore, results were stratified by sex. Among completers (n = 151), whole-body BMC and BMD significantly increased from baseline to 6 mo and to 12 mo. In girls, 1-y gain in whole-body BMC was higher with SCF (216.3 ± 138.3 g or 18.8%) than with placebo (139.9 ± 84.0 g, 12.9%) after adjusting for age, Tanner stage, height velocity, weight velocity, lean mass velocity, fat mass velocity, and compliance (P < 0.05). Similar results were found for BMD in girls. This was not observed in boys or when calcium supplementation was added. CONCLUSIONS:A 1-y supplementation with SCF results in higher whole-body BMC and BMD than placebo in girls only. This effect could have potential long-term benefits on bone mass acquisition in girls. This trial was registered at clinicaltrials.gov as NCT02916862 (https://clinicaltrials.gov/study/NCT02916862).

The essentiality of protein in the human diet is unequivocal. Yet researchers, clinicians, and lay people often believe numerous propositions about dietary protein despite insufficient supporting or refuting data in some instances. To address this disconnect, and to "pressure-test" current beliefs about dietary protein, the Indiana University School of Public Health-Bloomington convened a workshop in February 2025 titled "Human Dietary Protein Needs and Benefits: A Critical Assessment of Postulated Propositions." More than 20 international experts discussed (1) methodologic issues affecting data acquisition and interpretation; (2) "optimal" dietary protein intakes and effects on muscle protein synthesis rates, muscle protein accretion, muscle growth, and muscle repair; (3) protein needs during weight loss; (4) acute protein intake thresholds above and below which protein is no longer related to anabolism; and (5) dietary protein intakes above which protein may be detrimental to health. The experts rated each proposition on a scale from "existing evidence strongly supports the proposition" to "existing evidence seems sufficient to rule out the viability of the proposition." In most instances, the experts believed additional research was warranted. For many propositions the research base was insufficient in terms of quality (rigor), quantity (sample size, study duration), or pertinence (e.g., use of surrogate markers).

BACKGROUND:Calcium intake shortfalls are common worldwide, yet calcium adequacy is typically estimated from total calcium content without accounting for differences in bioavailability. As a result, the amount of calcium available for absorption across the global food supply remains unclear. OBJECTIVES:The objective of this study was to apply the Weaver et al. calcium bioavailability algorithm, which incorporates calcium load, phytate, and oxalate, to estimate bioavailable calcium in the global food supply, compare total and bioavailable calcium against recommended intakes, and identify regional differences in calcium adequacy. METHODS:Data from the Food and Agriculture Organization Food Balance Sheets were integrated with nutrient composition data from FoodData Central to estimate total and bioavailable calcium availability by country and region. Food Balance Sheets provide standardized national-level estimates of per capita food availability for human consumption; therefore, results reflect food supply availability rather than actual intake and do not account for dietary needs across life stages. Calcium, phytate, and oxalate values were mapped to food composition databases, adjusted for serving size, and used to calculate bioavailable calcium for individual foods. Country-level estimates were generated by summing daily per capita bioavailable calcium across foods. RESULTS:The Weaver et al. calcium bioavailability algorithm was successfully applied to global food supply data, yielding an estimated mean calcium bioavailability of 30.7%, consistent with the general estimate that ∼30% of dietary calcium is absorbed. Predicted bioavailable calcium was lower than total calcium across all food categories, reflecting reduced absorption associated with calcium load and the presence of phytate and oxalate in the food supply. The greatest shortfalls in bioavailable calcium supply were observed in Africa and Southeast Asia, where predicted bioavailability was below recommended intakes for healthy adults. CONCLUSIONS:These findings demonstrate that accounting for bioavailability can improve assessment of calcium adequacy and help identify regions where public health strategies are needed to improve access to bioavailable calcium.

The growing interest in personalized nutrition stems from a deeper understanding of subgroup differences in response to environmental factors, including diet. Preliminary evidence in Black and White adolescent girls showed that Black girls retain more calcium and excrete more sodium compared to White girls on a high sodium diet. However, little is known about calcium absorption efficiency across other races or age groups. This report outlines the rationale and design of a planned randomized controlled trial aimed at investigating calcium absorption and calcium and sodium excretion in response to diets high (typical Western diet) and low (recommended) in sodium in Black, White, Hispanic, and Asian adults. It is hypothesized that fractional calcium absorption and urinary sodium excretion will vary by subgroup, with Blacks predicted to have the highest rates and Whites the lowest, and intermediate responses in Hispanics and Asians. Participants will undergo two 2-day dietary intervention arms, with biospecimen collection following each arm. Primary outcomes include fractional calcium absorption and urinary calcium excretion, and secondary outcomes comprise urinary sodium excretion and blood pressure. Findings from this study could advance precision nutrition by informing strategies to alleviate osteoporosis and cardiovascular diseases risks across different race/ethnicity groups.

Objective.Sodium (Na) overconsumption has been associated with hypertension risk and progression. Human soft tissue and bone are recognized as quickly and slowly exchangeable compartments for sodium storage. How such a distribution regulates blood pressure remains unknown. This study performedin vivoNa measurements on human subjects who underwent dietary intervention, utilizing a compact neutron generator-based neutron activation analysis system. It aimed to evaluate the performance of this innovative system for body Na assessment.Approach. Participants were provided with low and high sodium diets. Baseline measurements were taken before each intervention feeding period, and follow-up measurements were conducted afterwards. The human hands were irradiated for 20 min, followed by 2 cycles of Na gamma ray collection. A biokinetic model was used to calculate sodium concentrations in soft tissue and bone, reflecting sodium accumulation in the two compartments.Main results. For soft tissue, Na levels after low Na diet decreased from baseline in half of the subjects, with reductions ranging from 8% to 55%. The other half of participants exhibited relatively stable Na content. Among participants consuming high Na diet, all participants had elevated Na in soft tissue compared to those on low Na diet. By contrast, Na in bone showed no significant changes from baseline and follow-up for either dietary intervention. Bone Na concentrations ranged from approximately 1000-2000 ppm.Significance. For the first time, Na in soft tissue and bone was measured in humans using neutron activation analysis in response to dietary interventions. This study demonstrates thatin vivoneutron activation analysis can be used to measure Na concentration in both soft tissue and bone. It successfully detects Na alteration in soft tissue and explores the biokinetics of Na retention following dietary interventions. Measuring soft tissue and bone sodium content is a potentially useful approach to study diet and disease links affected by sodium.

The food matrix which includes the physiochemical structure and interaction with chemical constituents is a focus of investigation that is revealing potentially important influences on diet and health. This paper, the first in an article collection titled, The Important Role of the Dairy Matrix in Diet and Health, serves as an introduction to the food matrix to put into context the subsequent articles specific to the matrix effects of dairy milk, cheese and yogurt on human health. This introductory article describes the effects of processing on the food matrix and implications for diet and health, examines the contribution of nutrients compared to whole foods and food patterns, and characterizes examples of the complexity of the food matrix including current controversies of dairy fat and ultra-processed foods. The gaps in knowledge and research identified in this overview may help guide researchers and funding entities moving forward. Current knowledge indicates that translating research on the food matrix to the consumer through recommendations for the intake of whole foods and food patterns is prudent at this time.

BACKGROUND:The relationship among dietary patterns, calcium bioavailability, and bone health in United States adults remains unclear. OBJECTIVES:This study aims to examine associations among dietary calcium, phytate, and oxalate intake and calcium bioavailability and bone health indicators, including bone mineral density (BMD), osteoporosis prevalence, and fracture incidence. METHODS:A serial cross-sectional analysis was conducted using National Health and Nutrition Examination Survey (NHANES) data (1999-2023) for adults aged 18-85. Serum calcium and BMD were measured in NHANES laboratories; dietary intake, osteoporosis, and fracture history were self-reported. Primary exposures included dietary calcium, phytate, and oxalate; outcomes included estimated calcium absorption, and changes in BMD, osteoporosis, and fractures. Survey-weighted regression models were used to assess temporal changes and associations across survey cycles. RESULTS:In 2017-2020, mean phytate intake was significantly higher than in 1999-2000 (834.1 ± 26.2 mg/d compared with 593.5±23.2 mg/d), and oxalate intake increased from 241.5 ± 6.6 mg/d to 280.5 ± 6.6 mg/d. Calcium intake peaked at 1025.3 ± 9.7 mg/d in 2009-2010 but lowered to 899.9 ± 15.7 mg/d by 2021-2023. Periods of lower calcium intake and higher phytate and oxalate concentrations corresponded with reduced calcium absorption. Milk consumption, a primary source of bioavailable calcium, decreased from 0.95 ± 0.03 cup-equivalents/d in 1999-2000 to 0.56 ± 0.02 in 2017-2020. Serum calcium concentrations lowered from 9.46 ± 0.02 mg/dL in 2009-2010 to 9.29 ± 0.01 mg/dL in 2017-2020. BMD at the femur dropped from 0.982 ± 0.004 to 0.934 ± 0.005 g/cm2, and at the femoral neck from 0.849 ± 0.003 to 0.775 ± 0.005 g/cm2 between 2009-2010 and 2017-2020. Osteoporosis prevalence increased, and fractures at the hip, wrist, and spine were more frequently reported in 2017-2020 compared with those in 2009-2010. CONCLUSIONS:Diets with greater phytate and oxalate and lower calcium and dairy intake may contribute to reduced calcium bioavailability and unfavorable bone health outcomes among United States adults.

Sodium (Na) is an essential mineral for human health regulation and in excess has been associated with many diseases. Its storage has been found in rapidly (soft tissue) and slowly exchangeable pools (bone) in human body. However, Na concentration and metabolism information in human bone and soft tissue cannot be determined using conventional biological urine and blood samples. The aim of this study was to apply a transportable neutron generator based in vivo neutron activation analysis technique to separately quantify Na in bone and soft tissue. Two pigs were fed with low and high Na diet to investigate the effects of dietary Na intake on Na storage and metabolism. The emitted gamma rays from Na activated by thermal neutron capture reaction in pig leg were collected using a high purity germanium detector. A biokinetic model based on internal dosimetry theorem was developed to obtain the bone and soft tissue Na concentration, as well as half-life of Na retention in the two compartments. The results show that soft tissue Na concentration was significantly higher in the pig that received a high Na diet (1057.08±43.62ppmvs704.46±45.60ppm,p=0.007). In contrast, the bone sodium concentration was not affected by dietary intervention (856.45±78.48ppmvs803.30±48.98ppm,p=0.107). The developed methodology is capable of effectively measuring altered Na levels resulting from dietary Na consumption, with great potential in exploring the association between Na intake and health outcomes such as hypertension.

Current nutrient intake recommendations, nutritional assessments, and food labeling rely on estimated total nutrient content in foods and dietary supplements. However, the adequacy of nutrient intake depends not only on the total amount consumed but also on the fraction absorbed and utilized by the body. Accurate assessments of nutrient bioavailability require predictive equations or algorithms. This paper outlines a 4-step framework designed to guide researchers in developing such equations. The framework includes: 1) identifying key factors that influence nutrient or bioactive compound bioavailability; 2) conducting a comprehensive literature review of high-quality human studies to inform the development of predictive equations; 3) constructing predictive equations based on these insights; and 4) validate the equation, when feasible, to potentiate translation. This structured approach aims to enhance the accuracy and precision of nutrient bioavailability estimates, address data limitations, and highlight evidence gaps to inform future research and policy on nutrients and bioactive compounds.

PURPOSE:Normative values of bone mass, bone turnover markers (BTMs) and muscle-bone unit (MBU) among healthy Asian children are needed to enable accurate skeletal assessment. This cross-sectional study characterizes the bone mineral density (BMD), bone mineral content (BMC), BTMs and MBU of 243 Malaysian preadolescent children aged 9-11 years. METHODS:The total body BMD (TBBMD), total body BMC (TBBMC), lumbar spine BMD, lumbar spine BMC, and body composition were assessed using dual-energy x-ray absorptiometry. Total and regional MBU were calculated by dividing BMC by lean body mass. Serum BTMs (c-terminal telopeptide 1, procollagen type 1 N propeptide, bone alkaline phosphate, osteocalcin) and serum intact parathyroid hormone were measured. RESULTS:Based on the Asian reference population, 97.5% of participants had TBBMD z-scores above -1 standard deviation (SD), 2.5% were at risk for low TBBMD for age (-1.9 to -1.0 SD) and no one had low TBBMD for age (&lt;-2.0 SD). Participants had lower TBBMD values compared to children of the same age according to published data of Asian children despite having higher body weights. There were sex-specific differences in the BTMs and regional MBU of study participants. CONCLUSION:This study provides a population-based dataset on bone mass, BTMs, and MBU of healthy preadolescent Malaysian children, which enables accurate skeletal assessment in this population.

Foods high in phenolics such as prunes have been shown to exert protective effects on bone mineral density (BMD), but only certain individuals experience these benefits. This post-hoc analysis of a 12-month randomized controlled trial aimed to identify the relationship among the gut microbiome, immune responses, and bone protective effects of prunes on postmenopausal women. Subjects who consumed 50–100 g prunes daily were divided into responders (n = 20) and non-responders (n = 32) based on percent change in total hip bone mineral density (BMD, ≥1% or ≤−1% change, respectively). DXA scans were used to determine body composition and BMD. Immune markers were measured using immunoassays and flow cytometry. Targeted phenolic metabolites were analyzed using ultra performance liquid chromatography-tandem mass spectrometry. The fecal microbiota was characterized through 16S rRNA gene PCR amplicon sequencing. After 12 months of prune consumption, anti-inflammatory markers showed responders had significantly lower levels of IL-1β and TNF-α. QIIME2 sequence analysis showed that microbiomes of responders and non-responders differed in alpha (Shannon and Faith PD, Kruskal-Wallis p < 0.05) and beta diversity (unweighted Unifrac, PERMANOVA p < 0.04) metrics both before and after prune treatment. Furthermore, responders had a higher abundance of bacterial families Oscillospiraceae and Lachnospiraceae (ANCOM-BC p < 0.05). These findings provide evidence that postmenopausal women with initial low BMD can benefit from prunes if they host certain gut microbes. These insights can guide precision nutrition strategies to improve BMD tailored to diet and microbiome composition.

BACKGROUND:Estrogen withdrawal during menopause is associated with an unfavorable cardiometabolic profile. Prunes (dried plums) represent an emerging functional food and have been previously demonstrated to improve bone health. However, our understanding of the effects of daily prune intake on cardiometabolic risk factors in postmenopausal women is limited. OBJECTIVES:We conducted an ancillary investigation of a randomized controlled trial (RCT), The Prune Study, to evaluate the effect of 12-mo prune supplementation on cardiometabolic health markers in postmenopausal women. METHODS:The Prune Study was a single-center, parallel-design, 12-mo RCT in which postmenopausal women were allocated to no-prune control, 50 g/d prune, or 100 g/d prune groups. Blood was collected at baseline, 6 mo, and 12 mo/post to measure markers of glycemic control and blood lipids. Body composition was assessed at baseline, 6 mo, and 12 mo/post using dual-energy X-ray absorptiometry. Linear mixed-effects models were used to evaluate the effect of time, treatment, and their interaction on cardiometabolic health markers, all quantified as exploratory outcomes. RESULTS:A total of 183 postmenopausal women (mean age, 62.1 ± 4.9 y) completed the entire 12-mo RCT: control (n = 70), 50 g/d prune (n = 67), and 100 g/d prune (n = 46). Prune supplementation at 50 g/d or 100 g/d did not alter markers of glycemic control and blood lipids after 12 mo compared with the control group (all P > 0.05). Furthermore, gynoid percent fat and visceral adipose tissue (VAT) indices did not significantly differ in women consuming 50 g/d or 100 g/d prunes compared with the control group after 12 mo of intervention. However, android total mass increased by 3.19% ± 5.5% from baseline in the control group, whereas the 100 g/d prune group experienced 0.02% ± 5.6% decrease in android total mass from baseline (P < 0.01). CONCLUSIONS:Prune supplementation at 50 g/d or 100 g/d for 12 mo does not improve glycemic control and may prevent adverse changes in central adiposity in postmenopausal women. This trial was registered at clinicaltrials.gov as NCT02822378.

Healthcare professionals are consistently bombarded with conflicting messages about the role of diet in bone health. Yet, few resources are available that compile the broad scope of dietary factors that influence bone health. This article evaluates the evidence on the association of diet and exercise with bone health, with the aim to provide a resource for healthcare professionals and researchers in the field. This review also highlights gaps in knowledge, provides dialogue around why some studies exhibit conflicting outcomes, and showcases why many remaining questions likely cannot be answered with the current evidence to date. The best evidence to date supports obtaining recommended dairy and calcium intakes for building bone in early life and mitigating bone loss with age. However, nutrients do not solely work in isolation, and there is growing evidence that many other nutrients and dietary bioactives play a synergistic role in supporting bone health. Large randomized controlled trials, particularly in traditionally underserved subpopulations (eg, people of color, transgender individuals, older adults, etc), are needed to fully elucidate the effects of diet and exercise on bone health across the lifespan.