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© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/., Vitamin D is a key component for optimal growth and for calcium-phosphate homeostasis. Skin photosynthesis is the main source of vitamin D. Limited sun exposure and insufficient dietary vitamin D supply justify vitamin D supplementation in certain age groups. In older adults, recommended doses for vitamin D supplementation vary between 200 and 2000 IU/day, to achieve a goal of circulating 25-hydroxyvitamin D (calcifediol) of at least 50 nmol/L. The target level depends on the population being supplemented, the assessed system, and the outcome. Several recent large randomized trials with oral vitamin D regimens varying between 2000 and 100,000 IU/month and mostly conducted in vitamin D-replete and healthy individuals have failed to detect any efficacy of these approaches for the prevention of fracture and falls. Considering the well-recognized major musculoskeletal disorders associated with severe vitamin D deficiency and taking into account a possible biphasic effects of vitamin D on fracture and fall risks, an European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) working group convened, carefully reviewed, and analyzed the meta-analyses of randomized controlled trials on the effects of vitamin D on fracture risk, falls or osteoarthritis, and came to the conclusion that 1000 IU daily should be recommended in patients at increased risk of vitamin D deficiency. The group also addressed the identification of patients possibly benefitting from a vitamin D loading dose to achieve early 25-hydroxyvitamin D therapeutic level or from calcifediol administration., Open access funding provided by University of Geneva

This position paper of the International Osteoporosis Foundation (IOF) and the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) addresses the rationale for separate diagnostic and intervention thresholds in osteoporosis. We conclude that the current BMD-based diagnostic criteria for osteoporosis be retained whilst clarity is brought to bear on the distinction between diagnostic and intervention thresholds.

Context Observational studies suggest that low vitamin D status may be a risk factor for cancer. Objective In a population with prediabetes and overweight/obesity that is at higher risk of cancer than the general population, we sought to determine if vitamin D supplementation lowers the risk of cancer and precancers. Methods The Vitamin D and type 2 diabetes (D2d) cancer outcomes study (D2dCA) is an ancillary study to the D2d study, which was conducted at 22 academic medical centers in the United States. Participants had prediabetes and overweight/obesity and were free of cancer for the previous 5 years. Participants were randomized to receive vitamin D3 4000 IU daily or placebo. At scheduled study visits (4 times/year), cancer and precancer events were identified by questionnaires. Clinical data were collected and adjudicated for all reported events. Cox proportional hazard models compared the hazard ratio (HR) of incident cancers and precancers between groups. Results Over a median follow-up period of 2.9 years, among 2385 participants (mean age 60 years and 25-hydroxyvitamin D 28 ng/mL), there were 89 cases of cancer. The HR of incident cancer for vitamin D vs placebo was 1.07 (95% CI 0.70, 1.62). Of 241 participants with incident precancers, 239 had colorectal adenomatous polyps. The HR for colorectal polyps for vitamin D vs placebo was 0.83 (95% CI 0.64, 1.07). Conclusion In the D2d population of participants with prediabetes and overweight/obesity, not selected for vitamin D insufficiency, vitamin D supplementation did not have a significant effect on risk of incident cancer or colorectal polyps.

BACKGROUND: Vitamins D and K, which are present in human brain, may have a role in neurodegenerative disease. OBJECTIVES: Given the interest in measuring nutrient concentrations in archived brain samples, it is important to evaluate whether freezer storage time affects these concentrations. Therefore, we evaluated differences in vitamin D and vitamin K concentrations in human brain samples stored for various lengths of time. METHODS: Postmortem brain samples were obtained from 499 participants in the Rush Memory and Aging Project (mean age 92 y, 72% female). Concentrations of vitamins D and K and their metabolites were measured in 4 regions (midtemporal cortex, midfrontal cortex, cerebellum, anterior watershed white matter) using LC-MS/MS and HPLC, respectively. The predominant forms were 25-hydroxycholecalciferol [25(OH)D(3)] and menaquinone-4 (MK4). ANOVA was used to determine if concentrations differed according to storage time. RESULTS: The geometric mean of the mean 25(OH)D(3) concentration (across 4 regions) in brains stored for 1.1 to 6.0 y did not differ from that in brains stored ≤1.0 y (all P ≥ 0.37), whereas 25(OH)D(3) in brains stored >6.0 y was 31–40% lower (P ≤ 0.003). MK4 had similar results, with the geometric mean MK4 concentration in the brains stored ≥9.0 y being 48–52% lower than those in brains stored ≤1.0 y (P ≤ 0.012). The 25(OH)D(3) and MK4 concentrations were positively correlated across all 4 regions (all Spearman ρ ≥ 0.79, P

OBJECTIVE Postrandomization biases may influence the estimate of efficacy of supplemental vitamin D in diabetes prevention trials. In the Vitamin D and Type 2 Diabetes (D2d) study, repeated measures of serum 25-hydroxyvitamin D [25(OH)D] level provided an opportunity to test whether intratrial vitamin D exposure affected diabetes risk and whether the effect was modified by trial assignment (vitamin D vs. placebo). RESEARCH DESIGN AND METHODS The D2d study compared the effect of daily supplementation with 100 μg (4,000 units) of vitamin D3 versus placebo on new-onset diabetes in adults with prediabetes. Intratrial vitamin D exposure was calculated as the cumulative rolling mean of annual serum 25(OH)D measurements. Hazard ratios for diabetes among participants who had intratrial 25(OH)D levels of RESULTS There was an interaction of trial assignment with intratrial 25(OH)D level in predicting diabetes risk (interaction P = 0.018). The hazard ratio for diabetes for an increase of 25 nmol/L in intratrial 25(OH)D level was 0.75 (95% CI 0.68–0.82) among those assigned to vitamin D and 0.90 (0.80–1.02) among those assigned to placebo. The hazard ratios for diabetes among participants treated with vitamin D who maintained intratrial 25(OH)D levels of 100–124 and ≥125 nmol/L were 0.48 (0.29–0.80) and 0.29 (0.17–0.50), respectively, compared with those who maintained a level of 50–74 nmol/L. CONCLUSIONS Daily vitamin D supplementation to maintain a serum 25(OH)D level ≥100 nmol/L is a promising approach to reducing the risk of diabetes in adults with prediabetes.

Background Observational studies report higher blood pressure (BP) among individuals with lower 25-hydroxyvitamin D concentration. Whether dosage of vitamin D supplementation has a differential effect on BP control remains unclear. Objective The study aimed to determine if daily vitamin D supplementation with 2000 IU is more effective than 800 IU for BP control among older adults. Methods This randomized, double-blind, ancillary trial of the Zurich Multiple Endpoint Vitamin D Trial in Knee Osteoarthritis enrolled adults aged ≥60 y who underwent elective surgery due to severe knee osteoarthritis. Participants were randomly assigned to receive high dose (2000 IU) or standard dose (800 IU) daily vitamin D3 for 24 mo. Outcomes included daytime and 24-h mean systolic BP. BP variability and serum 25-hydroxyvitamin D concentration were examined in a post hoc and observational analysis. Results Of the 273 participants randomly assigned, 250 participants completed a follow-up 24-h ambulatory BP monitoring (mean age: 70.4 ± 6.4 y; 47.2% men). The difference in daytime mean systolic BP reduction between the 2000 IU (n = 123) and 800 IU (n = 127) groups was not statistically significant (-2.75 mm Hg vs. -3.94 mm Hg; difference: 1.18 mm Hg; 95% CI: -0.68, 3.05; P = 0.21), consistent with 24-h mean systolic BP. However, systolic BP variability was significantly reduced with 2000 IU (average real variability: -0.37 mm Hg) compared to 800 IU vitamin D3 (0.11 mm Hg; difference: -0.48 mm Hg; 95% CI: -0.94, -0.01; P = 0.045). Independent of group allocation, maximal reductions in mean BP were observed at 28.7 ng/mL of achieved serum 25-hydroxyvitamin D concentrations. Conclusions While daily 2000 IU and 800 IU vitamin D3 reduced mean systolic BP over 2 y to a small and similar extent, 2000 IU reduced mean systolic BP variability significantly more compared with 800 IU. However, without a placebo control group we cannot ascertain whether vitamin D supplementation effectively reduces BP.This trial was registered at www.clinicaltrials.gov as NCT00599807.

Western diets are net acid-producing, based on their general characteristics of containing excessive amounts of grains in relation to their content of fruits and vegetables. The continuous consumption of acid-producing diets is countered by the renal excretion of the excess acid. However, when renal excretion is not adequate, as is the case in many older adults with mildly and moderately impaired renal function, other adaptations are employed to preserve neutrality. In adults who are unable to excrete the daily dietary acid load, the excess acid is buffered by bone. The mechanisms by which hydrogen ions affect bone have been well defined. Current evidence also indicates a role for muscle in preserving neutrality; however, the mechanism(s) by which this occurs have not been directly demonstrated. The evidence supporting the role of bone and muscle in defending against the development of frank metabolic acidosis are reviewed herein. This evidence stems from observational studies and randomized, controlled clinical trials. Gaps in the evidence that would be useful to fill are also indicated.

Context Supplementation with vitamin D has the potential to both reduce and increase risk of falling, and parathyroid hormone (PTH) may contribute to fall risk. Objective To assess the associations of intra-trial mean circulating levels of 25-hydroxyvitamin D [25(OH)D] and PTH on incident falls in healthy older adults. Design Observational within a clinical trial. Setting The Bone Metabolism Laboratory at the USDA Nutrition Center at Tufts University. Participants 410 men and women age ≥65 years who participated in the 3-year Boston STOP IT trial to determine the effect of supplementation with 700 IU of vitamin D3 plus calcium on incident falls (secondary endpoint). Intra-trial exposures of 25(OH)D and PTH were calculated as the mean of biannual measures up to and including the first fall. Main outcome measures Incidence of first fall. Results Intra-trial mean 25(OH)D was significantly associated with risk of falling in a U-shaped pattern; the range associated with minimal risk of falling was approximately 20 to 40 ng/mL. PTH was not significantly associated with risk of falling. Conclusions The findings highlight the importance of maintaining the circulating 25(OH)D level between 20 and 40 ng/mL, the range that is also recommended for bone health. At PTH levels within the normal range, there was no detectible independent association of PTH with fall risk.

BACKGROUND: Vitamin C may benefit bone as an antioxidant. OBJECTIVES: This cross-sectional study evaluated associations between dietary, supplemental, and plasma vitamin C with bone mineral density (BMD) among Puerto Rican adults. METHODS: Diet was assessed by food-frequency questionnaire (n = 902); plasma vitamin C, measured in fasting blood (n = 809), was categorized as sufficient (≥50 μmol/L), insufficient (20–49 μmol/L), or low (

Context COVID-19 is a major health problem because of saturation of intensive care units (ICU) and mortality. Vitamin D has emerged as a potential treatment able to reduce the disease severity. Objective To elucidate the effect of calcifediol [25OHD3] treatment on COVID-19-related outcomes. Design Observational cohort study from March to May, 2020. Setting Patients admitted to COVID-19 wards of Hospital del Mar, Barcelona, Spain. Patients A total of 930 patients with COVID-19 were included. Ninety-two were excluded due to previous calcifediol intake. Intervention Of the remaining 838, a total of 447 received calcifediol (532ug on day one plus 266ug on day 3, 7, 15, and 30) whereas 391 were not treated at the time of hospital admission (Intention-to-Treat). Of the latter, 53 patients were treated later during ICU admission and were allocated in the treated group in a second analysis. In healthy subjects, calcifediol is about 3.2-fold more potent on a weight basis than cholecalciferol. Main Outcome Measures ICU admission and mortality. Results ICU assistance was required by 102 (12.2%) participants. Out of 447 patients treated with calcifediol at admission, 20 (4.5%) required ICU, compared to 82 (21%) out of 391 non-treated (p-value

This cross-sectional study assessed cortical bone properties via impact microindentation in adults with normoglycemia, prediabetes, and early-stage T2D. Bone material strength index was stable across the glycemia categories in whites but it declined in blacks. Blacks may be more susceptible than whites to impaired cortical bone properties in early diabetes. Individuals with long-standing type 2 diabetes (T2D) have altered cortical bone material properties as determined by impact microindentation. This cross-sectional study was done to determine whether altered cortical bone material properties could be detected in adults with prediabetes or early-stage T2D. Men and postmenopausal women aged ≥ 50 years with no diabetes (50 white, 6 black), prediabetes (75 white, 13 black), and T2D of ≤ 5 years duration (24 white and 16 black) had assessments of bone material strength index (BMSi) by impact microindentation, trabecular bone score (TBS), and bone mineral density (BMD) by DXA and the advanced glycation end product, urine pentosidine. The association between glycemia category and BMSi differed by race (interaction p = 0.037). In the whites, BMSi did not differ across the glycemia categories, after adjustment for age, sex, and BMI (no diabetes 76.3 ± 1.6 (SEM), prediabetes 77.2 ± 1.3, T2D 76.2 ± 2.5, ANCOVA p = 0.887). In contrast, in the blacks, BMSi differed (ANCOVA p = 0.020) and was significantly lower in subjects with T2D than in those with prediabetes (p

The etiology of endemic rickets was discovered a century ago. Vitamin D is the precursor of 25-hydroxyvitamin D and other metabolites, including 1,25(OH)2D, the ligand for the vitamin D receptor (VDR). The effects of the vitamin D endocrine system on bone and its growth plate are primarily indirect and mediated by its effect on intestinal calcium transport and serum calcium and phosphate homeostasis. Rickets and osteomalacia can be prevented by daily supplements of 400 IU of vitamin D. Vitamin D deficiency (serum 25-hydroxyvitamin D

It is well recognized that poor muscle function and poor physical performance are strong predictors of clinically relevant adverse events in older people. Given the large number of approaches to measure muscle function and physical performance, clinicians often struggle to choose a tool that is appropriate and validated for the population of older people they deal with. In this paper, an overview of different methods available and applicable in clinical settings is proposed. This paper is based on literature reviews performed by members of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) working group on frailty and sarcopenia. Face-to-face meetings were organized afterwards where the whole group could amend and discuss the recommendations further. Several characteristics should be considered when choosing a tool: (1) purpose of the assessment (intervention, screening, diagnosis); (2) patient characteristics (population, settings, functional ability, etc.); (3) psychometric properties of the tool (test–retest reliability, inter-rater reliability, responsiveness, floor and ceiling effects, etc.); (4) applicability of the tool in clinical settings (overall cost, time required for the examination, level of training, equipment, patient acceptance, etc.); (5) prognostic reliability for relevant clinical outcomes. Based on these criteria and the available evidence, the expert group advises the use of grip strength to measure muscle strength and the use of 4-m gait speed or the Short Physical Performance Battery test to measure physical performance in daily practice. The tools proposed are relevant for the assessment of muscle weakness and physical performance. Subjects with low values should receive additional diagnostic workups to achieve a full diagnosis of the underlying condition responsible (sarcopenia, frailty or other).

Because of its low prevalence and the need for physical tests to establish a diagnosis, recruiting sarcopenic people for clinical studies can be a resource-intensive process.We investigated whether the SarQoLWe performed a secondary analysis of data from older, community-dwelling participants of the SarcoPhAge study, evaluated for sarcopenia according to the EWGSOP2 criteria, and who completed the SarQoLThe analysis of 309 participants provided an optimal threshold value of ≤ 52.4 points for identifying people with sarcopenia with the SarQoLThe SarQoLThis exploratory study showed that the SarQoL

We thank Rinkoo Dalan for the comments on our paper (1, 2). We agree that although the reduction in diabetes risk with vitamin D supplementation among people at high risk for diabetes appears to be moderate (~ 12% relative risk reduction compared to placebo) (3), certain individuals may derive a higher (or lower) benefit based on certain characteristics. For example, in the simplest demonstration of such heterogeneity, vitamin D supplementation reduced diabetes risk by 62% among participants in the Vitamin D and Type 2 Diabetes (D2d) study who had a baseline serum 25-hydroxyvitamin D (25[OH]D) level of less than 12 ng/mL (30 mmol/L) (2). Consistent with the focus of the scientific community on precision nutrition, we agree that we need to better understand responsiveness to vitamin D supplementation for specific outcomes of interest. The vitamin D response index is an interesting concept that reflects activation of the vitamin D receptor, and it is determined on the basis of measuring vitamin D–triggered changes in the expression of 24 target genes in peripheral blood mononuclear cells and 12 clinical and biochemical parameters (4). There are at least 2 limitations: 1) Although such an index may reflect vitamin D–induced changes in specific response parameters, these changes may not necessarily translate to clinically meaningful outcomes, such as lowering diabetes risk. 2) Low-, mid-, and high-responders are determined with statistical means within a specific cohort but that can be calculated only retrospectively; specific cutoffs to define degree of response need to be established for use in real time in research or in the clinical setting. The author also suggests that daily, steady exposure to vitamin D is preferred over intermittent exposure for optimal benefit, and we agree. In a secondary analysis from the D2d study, we reported that participants who received the active intervention (100 mcg [4000 units] of vitamin D3 daily) and maintained high 25(OH)D levels that were stable throughout the trial period had the lowest risk of diabetes, whereas participants in the placebo group who maintained similar overall 25(OH)D levels that fluctuated during follow-up did not derive significant benefit (5).

We performed this study to enable a reliable transition for clinical study participants and patients from a GE Lunar Prodigy to a Hologic Horizon A dual-energy X-ray absorptiometry (DXA) scanner and to assess the reproducibility of measurements made on the new DXA scanner. Forty-five older adults had one spine, hip, and total body scan on a Prodigy dual-energy X-ray absorptiometry (DXA) scanner and 2 spine, hip, and total body scans, with repositioning, on a new Hologic Horizon A DXA scanner. Linear regression models were used to derive cross calibration equations for each measure on the 2 scanners. Precision (group root-mean-square average coefficient of variation) of bone mineral density (BMD) of the total hip, femoral neck, and lumbar spine (L1-L4), and total body fat, bone, and lean mass, appendicular lean mass, and trabecular bone score (TBS) was assessed using the International Society of Clinical Densitometry's (ISCD's) Advanced Precision Calculation Tool. Correlation coefficients for the BMD and body composition measures on the 2 scanners ranged from 0.94 to 0.99 (p

IMPORTANCE: The benefits of vitamin D, omega-3 fatty acids, and exercise in disease prevention remain unclear. OBJECTIVE: To test whether vitamin D, omega-3s, and a strength-training exercise program, alone or in combination, improved 6 health outcomes among older adults. DESIGN, SETTING, AND PARTICIPANTS: Double-blind, placebo-controlled, 2 × 2 × 2 factorial randomized clinical trial among 2157 adults aged 70 years or older who had no major health events in the 5 years prior to enrollment and had sufficient mobility and good cognitive status. Patients were recruited between December 2012 and November 2014, and final follow-up was in November 2017. INTERVENTIONS: Participants were randomized to 3 years of intervention in 1 of the following 8 groups: 2000 IU/d of vitamin D(3), 1 g/d of omega-3s, and a strength-training exercise program (n = 264); vitamin D(3) and omega-3s (n = 265); vitamin D(3) and exercise (n = 275); vitamin D(3) alone (n = 272); omega-3s and exercise (n = 275); omega-3s alone (n = 269); exercise alone (n = 267); or placebo (n = 270). MAIN OUTCOMES AND MEASURES: The 6 primary outcomes were change in systolic and diastolic blood pressure (BP), Short Physical Performance Battery (SPPB), Montreal Cognitive Assessment (MoCA), and incidence rates (IRs) of nonvertebral fractures and infections over 3 years. Based on multiple comparisons of 6 primary end points, 99% confidence intervals are presented and P

A recent article from the New England Journal of Medicine questioned the use of race or ethnicity in assessment algorithms [1]. In the case of osteoporosis, the authors noted that the US FRAX calculator returns a lower fracture risk for women who are Black (by a factor of 0.43), Asian (0.50) or Hispanic (0.53). They conclude that the lower risk for Black, Asian and minority ethnic (BAME) women may delay intervention with osteoporosis therapy. The New York Times goes further in stating that with FRAX (sic) black women end up having a score that makes them less likely to be prescribed osteoporosis medication than white women who are similar in all other respects [2]. In the case of osteoporosis and FRAX, the authors do not appear to have grasped the reality of fracture epidemiology and risk assessment. In this editorial, we set out the key messages from the epidemiology of fracture globally, key considerations in building risk assessment tools, the specific contribution of race/ethnicity and practical considerations related to any move to alter race/ethnicity categorisation or remove them entirely.

There is no consensus on the most reliable method of ascertaining falls among the elderly. Therefore, we investigated which method captured the most falls among prefrail and frail seniors from 2 randomized controlled trials conducted in Zurich, Switzerland: an 18-month trial (2009-2010) including 200 community-dwelling prefrail seniors with a prior fall and a 12-month trial (2005-2008) including 173 frail seniors with acute hip fracture. Both trials included the same methods of fall ascertainment: monthly active asking, daily self-report diary entries, and a call-in hotline. We compared numbers of falls reported and estimated overall and positive percent agreement between methods. Prefrail seniors reported 499 falls (fall rate = 2.5/year) and frail seniors reported 205 falls (fall rate = 1.4/year). Most falls (81% of falls in prefrail seniors and 78% in frail seniors) were reported via active asking. Among prefrail seniors, diaries captured an additional 19% of falls, while the hotline added none. Among frail seniors, the hotline added 16% of falls, while diaries added 6%. The positive percent agreement between active asking and diary entries was 100% among prefrail seniors and 88% among frail seniors. While monthly active asking captures most falls in both groups, this method alone missed 19% of falls in prefrail seniors and 22% in frail seniors. Thus, a combination of active asking and diaries for prefrail seniors and a combination of active asking and a hotline for frail seniors is warranted.

ObjectiveTo increase understanding of the biological mechanisms underlying the association, we investigated the individual relations to cognitive decline of the primary nutrients and bioactives in green leafy vegetables, including vitamin K (phylloquinone), lutein, β-carotene, nitrate, folate, kaempferol, and α-tocopherol.MethodsThis was a prospective study of 960 participants of the Memory and Aging Project, ages 58–99 years, who completed a food frequency questionnaire and had ≥2 cognitive assessments over a mean 4.7 years.ResultsIn a linear mixed model adjusted for age, sex, education, participation in cognitive activities, physical activities, smoking, and seafood and alcohol consumption, consumption of green leafy vegetables was associated with slower cognitive decline; the decline rate for those in the highest quintile of intake (median 1.3 servings/d) was slower by β = 0.05 standardized units (p = 0.0001) or the equivalent of being 11 years younger in age. Higher intakes of each of the nutrients and bioactives except β-carotene were individually associated with slower cognitive decline. In the adjusted models, the rates for the highest vs the lowest quintiles of intake were β = 0.02, p = 0.002 for phylloquinone; β = 0.04, p = 0.002 for lutein; β = 0.05, p < 0.001 for folate; β = 0.03, p = 0.02 for α-tocopherol; β = 0.04, p = 0.002 for nitrate; β = 0.04, p = 0.003 for kaempferol; and β = 0.02, p = 0.08 for β-carotene.ConclusionsConsumption of approximately 1 serving per day of green leafy vegetables and foods rich in phylloquinone, lutein, nitrate, folate, α-tocopherol, and kaempferol may help to slow cognitive decline with aging.

We evaluated the prevalence of osteoporosis using the osteoporosis diagnostic criteria developed by the National Bone Health Alliance (NBHA), which includes qualified fractures, FRAX score in addition to bone mineral density (BMD). The expanded definition increases the prevalence compared to BMD alone definitions; however, it may better identify those at elevated fracture risk. The purpose of this paper is to estimate the prevalence of osteoporosis in US adults ≥50 years using the NBHA osteoporosis diagnostic criteria. Utilizing 2005–2008 data of the National Health and Nutrition Examination Survey (NHANES), we identified participants with osteoporosis with any one of the following: (1) femoral neck or lumbar spine T-score ≤ −2.5; (2) low trauma hip fracture irrespective of BMD or clinical vertebral, proximal humerus, pelvis, or distal forearm fracture with a T-score >−2.5

Summary Guidance is provided in an international setting on the assessment and specific treatment of postmenopausal women at low, high and very high risk of fragility fractures. Introduction The International Osteoporosis Foundation and European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis published guidance for the diagnosis and management of osteoporosis in 2019. This manuscript seeks to apply this in an international setting, taking additional account of further categorisation of increased risk of fracture, which may inform choice of therapeutic approach. Methods Clinical perspective and updated literature search. Results The following areas are reviewed: categorisation of fracture risk and general pharmacological management of osteoporosis. Conclusions A platform is provided on which specific guidelines can be developed for national use to characterise fracture risk and direct interventions.

BACKGROUND: Conflicting results on associations between dietary quality and bone have been noted across populations, and this has been understudied in Puerto Ricans, a population at higher risk of osteoporosis than previously appreciated. OBJECTIVE: To compare cross-sectional associations between 3 dietary quality indices [Dietary Approaches to Stop Hypertension (DASH), Alternative Health Eating Index (AHEI-2010), and Mediterranean Diet Score (MeDS)] with bone outcomes. METHOD: Participants (n = 865–896) from the Boston Puerto Rican Osteoporosis Study (BPROS) with complete bone and dietary data were included. Indices were calculated from validated food frequency data. Bone mineral density (BMD) was measured using DXA. Associations between dietary indices (z-scores) and their individual components with BMD and osteoporosis were tested with ANCOVA and logistic regression, respectively, at the lumbar spine and femoral neck, stratified by male, premenopausal women, and postmenopausal women. RESULTS: Participants were 59.9 y ± 7.6 y and mostly female (71%). Among postmenopausal women not taking estrogen, DASH (score: 11–38) was associated with higher trochanter (0.026 ± 0.006 g/cm(2), P

PURPOSE: The purpose of this paper was to review the available approaches for bone strength assessment, osteoporosis diagnosis and fracture risk prediction, and to provide insights into radiofrequency echographic multi spectrometry (REMS), a non-ionizing axial skeleton technique. METHODS: A working group convened by the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis met to review the current image-based methods for bone strength assessment and fracture risk estimation, and to discuss the clinical perspectives of REMS. RESULTS: Areal bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) is the consolidated indicator for osteoporosis diagnosis and fracture risk assessment. A more reliable fracture risk estimation would actually require an improved assessment of bone strength, integrating also bone quality information. Several different approaches have been proposed, including additional DXA-based parameters, quantitative computed tomography, and quantitative ultrasound. Although each of them showed a somewhat improved clinical performance, none satisfied all the requirements for a widespread routine employment, which was typically hindered by unclear clinical usefulness, radiation doses, limited accessibility, or inapplicability to spine and hip, therefore leaving several clinical needs still unmet. REMS is a clinically available technology for osteoporosis diagnosis and fracture risk assessment through the estimation of BMD on the axial skeleton reference sites. Its automatic processing of unfiltered ultrasound signals provides accurate BMD values in view of fracture risk assessment. CONCLUSIONS: New approaches for improved bone strength and fracture risk estimations are needed for a better management of osteoporotic patients. In this context, REMS represents a valuable approach for osteoporosis diagnosis and fracture risk prediction.

BACKGROUND: Observational studies support an association between a low blood 25-hydroxyvitamin D level and the risk of type 2 diabetes. However, whether vitamin D supplementation lowers the risk of diabetes is unknown. METHODS: We randomly assigned adults who met at least two of three glycemic criteria for prediabetes (fasting plasma glucose level, 100 to 125 mg per deciliter; plasma glucose level 2 hours after a 75-g oral glucose load, 140 to 199 mg per deciliter; and glycated hemoglobin level, 5.7 to 6.4%) and no diagnostic criteria for diabetes to receive 4000 IU per day of vitamin D(3) or placebo, regardless of the baseline serum 25-hydroxyvitamin D level. The primary outcome in this time-to-event analysis was new-onset diabetes, and the trial design was event-driven, with a target number of diabetes events of 508. RESULTS: A total of 2423 participants underwent randomization (1211 to the vitamin D group and 1212 to the placebo group). By month 24, the mean serum 25-hydroxyvitamin D level in the vitamin D group was 54.3 ng per milliliter (from 27.7 ng per milliliter at baseline), as compared with 28.8 ng per milliliter in the placebo group (from 28.2 ng per milliliter at baseline). After a median follow-up of 2.5 years, the primary outcome of diabetes occurred in 293 participants in the vitamin D group and 323 in the placebo group (9.39 and 10.66 events per 100 person-years, respectively). The hazard ratio for vitamin D as compared with placebo was 0.88 (95% confidence interval, 0.75 to 1.04; P = 0.12). The incidence of adverse events did not differ significantly between the two groups. CONCLUSIONS: Among persons at high risk for type 2 diabetes not selected for vitamin D insufficiency, vitamin D(3) supplementation at a dose of 4000 IU per day did not result in a significantly lower risk of diabetes than placebo. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; D2d ClinicalTrials.gov number, .)

Progressive age-related reductions in muscle mass and strength (sarcopenia) can cause substantial morbidity. This narrative review summarizes evidence of nutritional interventions for maintaining muscle mass and strength from midlife through old age. PubMed and Cochrane databases were searched to identify studies of dietary intake and nutritional interventions for sustaining muscle mass and strength. The benefits of progressive resistance training with and without dietary interventions are well documented. Protein and amino acid (particularly leucine) intake should be considered, and supplementation may be warranted for those not meeting recommended intakes. Vitamin D receptors are expressed in muscle tissue; meta-analyses have shown that vitamin D benefits muscle strength. Data suggest that milk and other dairy products containing different bioactive compounds (i.e. protein, leucine) can enhance muscle protein synthesis, particularly when combined with resistance exercise. Omega-3 s can improve muscle mass and strength by mediating cell signaling and inflammation-related oxidative damage; no studies were specifically conducted in sarcopenia. Low-dose antioxidants (e.g. vitamins C and E) can protect muscle tissue from oxidative damage, but relevant studies are limited. Magnesium is involved with muscle contraction processes, and data have shown benefits to muscle strength. Acidogenic diets increase muscle protein breakdown, which is exacerbated by aging. Alkalizing compounds (e.g. bicarbonates) can promote muscle strength. Small studies of probiotics and plant extracts have generated interest, but few large studies have been conducted. Based on available data, dietary and supplemental interventions may add to the benefits of exercise on muscle mass and strength; effects independent of exercise have not been consistently shown.

Summary: In this study of acute hip fracture patients, we show that hip fracture rates differ by gender between community-dwelling seniors and seniors residing in nursing homes. While women have a significantly higher rate of hip fracture among the community-dwelling seniors, men have a significantly higher rate among nursing home residents. Introduction: Differences in gender-specific hip fracture risk between community-dwelling and institutionalized seniors have not been well established, and seasonality of hip fracture risk has been controversial. Methods: We analyzed detailed data from 1,084 hip fracture patients age 65years and older admitted to one large hospital center in Zurich, Switzerland. In a sensitivity analysis, we extend to de-personalized data from 1,265 hip fracture patients from the other two large hospital centers in Zurich within the same time frame (total n = 2,349). The denominators were person-times accumulated by the Zurich population in the corresponding age/gender/type of dwelling stratum in each calendar season for the period of the study. Results: In the primary analysis of 1,084 hip fracture patients (mean age 85.1years; 78% women): Among community-dwelling seniors, the risk of hip fracture was twofold higher among women compared with men (RR = 2.16; 95% CI, 1.74-2.69) independent of age, season, number of comorbidities, and cognitive function; among institutionalized seniors, the risk of hip fracture was 26% lower among women compared with men (RR = 0.77; 95% CI: 0.63-0.95) adjusting for the same confounders. In the sensitivity analysis of 2,349 hip fracture patients (mean age 85.0years, 76% women), this pattern remained largely unchanged. There is no seasonal swing in hip fracture incidence. Conclusion: We confirm for seniors living in the community that women have a higher risk of hip fracture than men. However, among institutionalized seniors, men are at higher risk for hip fracture.

Objectives To evaluate 2 simple strategies, vitamin D3 and a home exercise program, in functional recovery during the first year after hip fracture. Design Secondary analysis of a factorial clinical trial. Patients were randomly allocated to 800 IU (standard of care) or 2000 IU vitamin D3 and a daily instruction of a simple home exercise program (SHEP) or standard physiotherapy alone during acute care. Setting and participants Acute hip fracture patients aged ≥65 years, after hip fracture surgery, admitted to a large hospital in Zurich, Switzerland. Measures Three objective measures of lower extremity function were assessed at baseline and 6 and 12 months, with the Timed Up and Go test (TUG) as the primary endpoint, and knee flexor and extensor strength, and a self-reported physical function score (PF-10) as secondary endpoints. Linear mixed model regression analyses were based on intention to treat, adjusting for baseline function, time, age, sex, and baseline 25-hydroxyvitamin D level. Results We enrolled 173 patients (79.2% women; mean age 84 years; 77.5% living at home). A significant interaction was found between vitamin D3 dose and SHEP for TUG (P = .045). Thus, findings compared the standard of care reference arm with 800 IU vitamin D3 without SHEP to 3 interventions arms (800 IU vitamin D3+SHEP; 2000 IU vitamin D3 without SHEP; 2000 IU vitamin D3+SHEP). For TUG, over 12 months the 800 IU vitamin D3+SHEP group performed significantly better than the standard-of-care group (13.8 vs 19.5 seconds; P = .01). Findings for knee flexor strength were in line with TUG results and approached significance (P = .07), whereas knee extensor strength and PF-10 did not differ by treatments. Conclusions/Implications For functional recovery after hip fracture, combining home exercise with 800 IU vitamin D3 is superior to no home exercise or 2000 IU vitamin D3. None of the interventions improved subjective physical functioning.

SUMMARY: Few studies have examined knowledge and perceptions of osteoporosis among Caribbean Latino adults. Confusion regarding the term osteoporosis was noted. Doctors were viewed as trusted sources of health information, although descriptions of a paradoxical relationship emerged. This study can be used to inform culturally tailored interventions for osteoporosis prevention. PURPOSE: The overall goal of this study was to assess knowledge, attitudes, and beliefs of bone health and osteoporosis among Caribbean Latino adults aged ≥ 50 years. METHODS: This triangulated mixed methods study included completion of a quantitative questionnaire and participation in one of four focus groups to obtain information on (1) general health, (2) knowledge about bone health and osteoporosis, (3) sources of information about bone health, and (4) prevention knowledge and personal responsibility. Quantitative data were analyzed using SAS, and qualitative data were analyzed using descriptive and structural coding by two independent research members. RESULTS: The majority of participants were female (73%), Dominican (84%), and low income (82% < $20,000) with a mean age of 68.4 (± 8.5) years. Most participants had heard of osteoporosis (90%); however, the majority were not able to accurately describe this chronic condition. Health care providers were viewed as most trusted sources of health information, despite feelings of being rushed during their visits, with limited communication about preventative care. Most participants felt that nutrition and exercise were important for overall health. CONCLUSIONS: Caribbean Hispanic adults in this study reported knowledge of osteoporosis and nutritional factors associated with prevention of this chronic condition. However, qualitatively, there was confusion between osteoporosis and other bone and joint conditions. Culturally specific interventions to promote prevention of osteoporosis are urgently needed for this underserved, high-risk population.

Background The impact of nutrition on the metabolic profile of osteoporosis (OS) is unknown. Objective Identify biochemical factors driving the association of fruit and vegetable (FV) intakes with OS prevalence using an untargeted metabolomics approach. Design Cross-sectional dietary, anthropometric and plasma metabolite data were examined from the Boston Puerto Rican Osteoporosis Study, n = 600 (46–79 yr). Methods Bone mineral density was assessed by DXA. OS was defined by clinical standards. A culturally adapted FFQ assessed usual dietary intake. Principal components analysis (PCA) of 42 FV items created 6 factors. Metabolomic profiles derived from plasma samples were assessed on a commercial platform. Differences in levels of 525 plasma metabolites between disease groups (OS vs no-OS) were compared using logistic regression; and associations with FV intakes by multivariable linear regression, adjusted for covariates. Metabolites significantly associated with OS status or with total FV intake were analyzed for enrichment in various biological pathways using Mbrole 2.0, MetaboAnalyst, and Reactome, using FDR correction of P-values. Correlation coefficients were calculated as Spearman's rho rank correlations, followed by hierarchical clustering of the resulting correlation coefficients using PCA FV factors and sex-specific sets of OS-associated metabolites. Results High FV intake was inversely related to OS prevalence (Odds Ratio = 0.73; 95% CI = 0.57, 0.94; P = 0.01). Several biological processes affiliated with the FV-associating metabolites, including caffeine metabolism, carnitines and fatty acids, and glycerophospholipids. Important processes identified with OS-associated metabolites were steroid hormone biosynthesis in women and branched-chain amino acid metabolism in men. Factors derived from PCA were correlated with the OS-associated metabolites, with high intake of dark leafy greens and berries/melons appearing protective in both sexes. Conclusions These data warrant investigation into whether increasing intakes of dark leafy greens, berries and melons causally affect bone turnover and BMD among middle-aged and older adults at risk for osteoporosis via sex-specific metabolic pathways, and how gene-diet interactions alter these sex-specific metabolomic-osteoporosis links. ClinicalTrials.gov Identifier: NCT01231958 .

BACKGROUND/OBJECTIVES Acid-producing diets have been associated with adverse health conditions. Dietary acid load can be estimated from dietary intake data, but the available methods require a full dietary assessment. We sought to identify a simpler means to estimate 24-h urinary net acid excretion (NAE), a robust measure of net endogenous acid production, using self-reported intakes of fruits, vegetables (acid-neutralizing foods), grain and/or protein (acid-producing foods) acquired by two different methods in community-dwelling older adults. Identifying food groups associated with NAE by using a method not requiring a full diet assessment could have a broad clinical application. SUBJECTS/METHODS Fruit, vegetable, protein and grain servings/day were estimated with a widely used food frequency questionnaire (study A, n=162, 63±8 years). Differences in their intakes across NAE categories (

Obesity and sarcopenia are major causes of morbidity and mortality among seniors. Vitamin D deficiency is very common especially among seniors and has been associated with both muscle health and obesity. This study investigated if 25-hydroxyvitamin D (25(OH)D) status is associated with body composition and insulin resistance using baseline data of a completed RCT among relatively healthy community-dwelling seniors (271 seniors age 60+ years undergoing elective surgery for unilateral total knee replacement due to osteoarthritis). Cross-sectional analysis compared appendicular lean mass index (ALMI: lean mass kg/height m2) and fat mass index (FMI: fat mass kg/height m2) assessed by DXA and insulin resistance between quartiles of serum 25(OH)D concentration using multivariable linear regression adjusted for age, sex, smoking status, physical activity, and body mass index (BMI). Participants in the lowest serum 25(OH)D quartile (4.7&ndash, 17.5 ng/mL) had a higher fat mass (9.3 kg/m2) compared with participants in the third (8.40 kg/m2, Q3 = 26.1&ndash, 34.8 ng/mL) and highest (8.37 kg/m2, Q4 = 34.9&ndash, 62.5 ng/mL) quartile (poverall = 0.03). Higher serum 25(OH)D quartile status was associated with higher insulin sensitivity (poverall = 0.03) and better beta cell function (p = 0.004). Prevalence of insulin resistance tended to be higher in the second compared with the highest serum 25(OH)D quartile (14.6% vs. 4.8%, p = 0.06). Our findings suggest that lower serum 25(OH)D status may be associated with greater fat mass and impaired glucose metabolism, independent of BMI and other risk factors for diabetes.

To test the effect of monthly high-dose vitamin D supplementation on mental health in pre-frail older adults.Ancillary study of a 1-year double-blind randomized clinical trial conducted in Zurich, Switzerland.A total of 200 community-dwelling adults 70 years and older with a prior fall event in the last year. Participants were randomized to receive 24 000 IU vitamin DThe primary end point was the Mental Component Summary (MCS) of the SF-36. Secondary end points were the SF-36 Mental Health (MH) subscale and the Geriatric Depression Scale (GDS-15).Participants' mean age was 78 years (67% women), and 58% were vitamin D deficient (20 ng/mL). Over time, primary and secondary end points did not differ significantly among the three treatment groups or in subgroups by vitamin D status at baseline. Given the lack of a true placebo group, we explored in a predefined observational analysis the change in mental health scales by achieved 25(OH)D levels at 12 months. After adjusting for confounders, participants achieving the highest 25(OH)D quartile (Q) at 12 months (44.7-98.9 ng/mL) had the greatest improvements in MCS (Q4 = 0.79 vs Q1 = -2.9; p = .03) and MH scales (Q4 = 2.54 vs Q1 = -3.07; p = .03); these associations were strongest among participants who were vitamin D deficient at baseline. No association was found for GDS (p = .89).For mental health, our study suggests no benefit of higher monthly doses of vitamin D

The effect of vitamin D supplementation on muscle function in older adults has been tested in randomized trials with mixed results, which may be due to differences in the study participant characteristics, including baseline vitamin D status. The results of 2 meta-analyses of randomized trials suggested a beneficial effect of vitamin D supplementation on muscle function in older adults with low baseline serum 25-hydroxyvitamin D [25(OH)D].We aimed to test the effect of 12 mo of vitamin D supplementation on lower-extremity power and function in older community-dwelling adults screened for low serum 25(OH)D.This was a single-center, double-blind, randomized, placebo-controlled trial that included 100 community-dwelling men and women ≥60 y old who had serum 25(OH)D ≤20 ng/mL at screening and a mean ± SD serum 25(OH)D of 20.2 ± 6.7 ng/mL at baseline. Participants were randomly assigned to 800 IU vitamin D3/d (intervention) or placebo. Those in the intervention group whose serum 25(OH)D was28 ng/mL after 4 mo were given an additional 800 IU vitamin D3/d, whereas all other participants received placebo as an additional pill.After 12 mo, the mean ± SD serum 25(OH)D was 32.5 ± 5.1 ng/mL in the intervention group and 19.8 ± 7.3 ng/mL in the control group (treatment × time P 0.001). The change in leg press power, function, and strength did not differ between the 2 groups over 12 mo (all treatment × time P ≥ 0.60), nor did the change in lean mass (treatment × time P ≥ 0.89).Increasing serum 25(OH)D to32 ng/mL (on average) over 12 mo did not affect lower-extremity power, strength, or lean mass in older community-dwelling adults. This trial was registered at clinicaltrials.gov as NCT02293187.

There are no large community-based studies examining the association of body size vs. body fat with vitamin D status. Association of serum 25-hydroxyvitamin D (25OHD) with body weight and subcategories of body weight defined by fat mass were evaluated in a large, free living population. Out of a total of 29,235 subjects from the 2008&ndash, 2010 Korean National Health and Nutrition Examination Survey, the relevant data included 6458 subjects over 50 years of age who were analyzed cross-sectionally. Serum 25OHD concentrations were compared in men (n = 3164) and in women (n = 3294) by tertiles of body weight and body fat mass, as measured by Dual-energy X-ray Absorptiometry (DXA) within sex-specific tertiles of body weight. Serum 25OHD was weakly inversely correlated with body weight in the men and the women after adjustment for age (r = &minus, 0.075 and &minus, 0.073, respectively, p &lt, 0.001 for both). Within each tertile of body weight, serum 25OHD decreased progressively as fat mass increased in men. This pattern was similar in the women but not consistently significant. Whereas body weight predicted a small decrease in serum 25OHD in the men and the women, greater adiposity, for any given weight, predicted larger decreases in the men, but not consistently in women.

Objective With advancing age, the prevalence of vitamin D deficiency and musculoskeletal pain increases. However, published data on the effectiveness of vitamin D supplementation in reducing chronic pain are inconclusive. The purpose of this study was to test the effect of 3 different monthly doses of vitamin D on chronic pain in seniors 70 years and older with a prior fall event. Design 1-year, double-blind randomized clinical trial. Setting The trial was conducted in Zurich, Switzerland. Participants were 200 community-dwelling men and women 70 years and older with a prior fall. Intervention Three study groups with monthly treatments were randomized to either a low-dose control group of vitamin D (24,000 IU vitamin D3/mo), a high dose of vitamin D3 (60,000 IU vitamin D3/mo), or a combination of calcifediol and vitamin D3 (24,000 IU vitamin D3 plus 300 μg calcifediol/mo). Measurements The primary endpoint was the change in the mean number of painful areas using the McGill Pain map over 12 months of follow-up. All analyses were adjusted for age, sex, body mass index, 25-hydroxyvitamin (OH)D3 levels, and pain scores at baseline. A predefined subgroup analysis was performed by baseline 25(OH)D status ( Results The mean age of the participants was 78 years, 67.0% (134 of 200) were female, and 58.0% (116 of 200) were vitamin D deficient ( Conclusion Our results suggest that both starting level of 25(OH)D3 and monthly treatment dose of vitamin D may be important with respect to chronic pain reduction—with the only benefit seen among vitamin D–replete seniors treated with a monthly dose of 24,000 IU vitamin D3.

Low calcium intake may adversely affect bone health in adults. Recognizing the presence of low calcium intake is necessary to develop national strategies to optimize intake. To highlight regions where calcium intake should be improved, we systematically searched for the most representative national dietary calcium intake data in adults from the general population in all countries. We searched 13 electronic databases and requested data from domain experts. Studies were double-screened for eligibility. Data were extracted into a standard form. We developed an interactive global map, categorizing countries based on average calcium intake and summarized differences in intake based on sex, age, and socioeconomic status. Searches yielded 9780 abstracts. Across the 74 countries with data, average national dietary calcium intake ranges from 175 to 1233 mg/day. Many countries in Asia have average dietary calcium intake less than 500 mg/day. Countries in Africa and South America mostly have low calcium intake between about 400 and 700 mg/day. Only Northern European countries have national calcium intake greater than 1000 mg/day. Survey data for three quarters of available countries were not nationally representative. Average calcium intake is generally lower in women than men, but there are no clear patterns across countries regarding relative calcium intake by age, sex, or socioeconomic status. The global calcium map reveals that many countries have low average calcium intake. But recent, nationally representative data are mostly lacking. This review draws attention to regions where measures to increase calcium intake are likely to have skeletal benefits.

After a hip fracture, 50% of senior patients are left with permanent functional decline and 30% lose their autonomy. The aim of this prospective study was to evaluate whether seniors who are in a caregiver role have better functional recovery after hip fracture compared with noncaregivers.Prospective observational study.A total of 107 Swiss patients with acute hip fracture age 65 years and older (84% women; 83.0 ± 6.9 years; 87% community-dwelling).At baseline, participants were asked if they were caregivers for a person, a pet, or a plant. Lower-extremity mobility was measured using the Timed Up and Go (TUG) test at baseline during acute care (day 1-12 after hip fracture surgery) and at 6 and 12 months follow-up. Subjective physical functioning (SPF) was rated for prefracture values and at 6 and 12 months follow-up using the Short Form 36 Health Survey questionnaire. Differences in TUG performance or SPF between caregivers and noncaregivers at 6 and 12 months were assessed using multivariable repeated-measures analysis adjusted for age, sex, body mass index, Charlson comorbidity index, Mini-Mental State Examination, living condition, baseline TUG, and treatment (vitamin D, home exercise program as part of the original trial).At baseline, adjusted TUG performance was better in caregivers of any kind compared with noncaregivers (40.9 vs 84.4 seconds, P .0001). At 6 months, and after adjustment for baseline TUG performance and other covariates, TUG was better in caregivers of any kind (-6.4 seconds, P = .007) and caregivers of plants (-6.6 seconds, P = .003) compared with noncaregivers. At 12 months, only caregivers of persons had better TUG performance compared with noncaregivers (-7.3 seconds, P = .009). Moreover, at 12 months, SPF was better in caregivers of persons (58.9 vs 45.6, P = .01) and caregivers of any kind (50.8 vs 39.3, P = .02) compared with noncaregivers.Senior hip fracture patients who have a caregiver role of any kind, and especially of plants, had better short-term recovery after hip fracture assessed with the TUG. For long-term recovery, senior hip fracture patients who are caregivers for other persons appeared to have a significant benefit. These benefits were independent of baseline function and all other covariates.

Context Elevated urine net acid excretion (NAE), indicative of subclinical metabolic acidosis, has been associated with higher bone turnover. Urine citrate, which is a common clinical measure, changes in response to acid-base status but its association with bone turnover is uncertain. Objective We evaluated the association between change in urine citrate and change in bone turnover and calcium excretion. Design, Intervention, and Participants A total of 233 healthy men and women ≥60 years old were randomly assigned to 1.0 mmol/kg/d potassium bicarbonate (KHCO3), 1.5 mmol/kg/d KHCO3, or placebo for 84 days. Outcome Measures Urine citrate, NAE, N-telopeptide of collagen type-I (NTX), calcium excretion, and serum amino-terminal propeptide of type 1 procollagen (P1NP) were measured before and after intervention. Results Urine citrate increased dose dependently after KHCO3 supplementation (P trend < 0.001). The urine citrate change was significantly inversely associated with P1NP change (P = 0.021) but not with change in NTX (P = 0.051) or calcium excretion (P = 0.652). The NAE change was positively associated with change in NTX and calcium excretion (P ≤ 0.003) but not with change in P1NP (P = 0.051). When the urine citrate change and NAE change were included in the same model, the urine citrate change was not associated with change in NTX, calcium excretion, or serum P1NP (P ≥ 0.086), whereas change in NAE remained associated with change in NTX and calcium excretion (P ≤ 0.003). Conclusion Urine citrate may not be a suitable alternative to NAE when assessing acid-base status in relation to bone turnover in older adults.

We examined associations between body weight and plasma 25-hydroxyvitamin D concentration (25OHD) in prediabetes and sought to estimate the impact of adiposity on these associations. The study was conducted in the placebo (n = 1082) and intensive lifestyle (n = 1079) groups of the Diabetes Prevention Program (DPP), a multicenter trial to prevent type 2 diabetes in adults with prediabetes. Weight and 25OHD were measured at baseline, month 6, years 1 and 2. In a subset (n = 584), visceral (VAT) and subcutaneous (SAT) adiposity were assessed by computed tomography at baseline and year 1. In cross-sectional analyses, baseline body weight, total fat, VAT, and SAT were inversely associated with plasma 25OHD concentration after multivariable adjustment. VAT accounted for 40 % [95 % CI 11, 69] of the association of body weight with plasma 25OHD concentration. There was no significant contribution by total fat or SAT. Two-year changes in plasma 25OHD concentration varied inversely with changes in body weight (p

The aim of this study was to determine whether calcium supplementation, compared with placebo, increases urine calcium concentrations to levels indicative of increased renal stone risk, and the role that fluid intake, as indicated by urine volume, may play in mitigating this risk.This is a secondary analysis of data from a randomized placebo-controlled trial of 500 mg/d calcium supplementation to prevent bone loss. Subjects were 240 white postmenopausal women age 40 to 70 years in good general health. Effects of supplementation on 1-year changes in 24h urine calcium concentration and urine volume were examined.Both treatment group and urine volume were strong independent predictors of urine calcium concentration (p0.001). Among subjects with urine volume under 2 L/24 h, more than half of placebo subjects were at lowest risk for renal stones compared with less than 35% of calcium-supplemented subjects. Among those with higher urine volumes, all placebo subjects and more than 80% of calcium supplemented subjects were at lowest risk.The increased risk of renal stones with calcium supplement use may be largely eliminated with adequate fluid intake, but older adults may not spontaneously consume adequate fluids to minimize this risk and should be counseled to do so.

Background The plasma 25-hydroxyvitamin D response to supplementation with vitamin D varies widely, but vitamin D absorption differences based on diet composition is poorly understood. Objectives We tested the hypotheses that absorption of vitamin D-3 is greater when the supplement is taken with a meal containing fat than with a fat-free meal and that absorption is greater when the fat in the meal has a higher monounsaturated-to-polyunsaturated fatty acid ratio (MUFA:PUFA). Design Open, three-group, single-dose vitamin D-3 comparative absorption experiment. Participants/setting Our 1-day study was conducted in 50 healthy older men and women who were randomly assigned to one of three meal groups: fat-free meal, and a meal with 30% of calories as fat with a low (1:4) and one with a high (4:1) MUFA:PUFA. After a 12-hour fast, all subjects took a single 50,000 IU vitamin D-3 supplement with their test breakfast meal. Main outcome measures Plasma vitamin D-3 was measured by liquid chromatography–mass spectrometry before and 10, 12 (the expected peak), and 14 hours after the dose. Statistical analyses performed Means were compared with two-tailed t tests for independent samples. Group differences in vitamin D-3 absorption across the measurement time points were examined by analysis of variance with the repeated measures subcommand of the general linear models procedure. Results The mean peak (12-hour) plasma vitamin D-3 level after the dose was 32% (95% CI 11% to 52%) greater in subjects consuming fat-containing compared with fat-free meals ( P =0.003). Absorption did not differ significantly at any time point in the high and low MUFA and PUFA groups. Conclusions The presence of fat in a meal with which a vitamin D-3 supplement is taken significantly enhances absorption of the supplement, but the MUFA:PUFA of the fat in that meal does not influence its absorption.

Historically, osteoporosis has not been considered a public health priority for the Hispanic population. However, recent data indicate that Mexican Americans are at increased risk for this chronic condition. Although it is well established that there is heterogeneity in social, lifestyle, and health-related factors among Hispanic subgroups, there are currently few studies on bone health among Hispanic subgroups other than Mexican Americans. The current study aimed to determine the prevalence of osteoporosis and low bone mass (LBM) among 953 Puerto Rican adults, aged 47 to 79 years and living on the US mainland, using data from one of the largest cohorts on bone health in this population: The Boston Puerto Rican Osteoporosis Study (BPROS). Participants completed an interview to assess demographic and lifestyle characteristics and bone mineral density measures. To facilitate comparisons with national data, we calculated age-adjusted estimates for osteoporosis and LBM for Mexican American, non-Hispanic white, and non-Hispanic black adults, aged ≥50 years, from the National Health and Nutrition Examination Survey (NHANES). The overall prevalence of osteoporosis and LBM were 10.5% and 43.3% for participants in the BPROS, respectively. For men, the highest prevalence of osteoporosis was among those aged 50 to 59 years (11%) and lowest for men ≥70 years (3.7%). The age-adjusted prevalence of osteoporosis for Puerto Rican men was 8.6%, compared with 2.3% for non-Hispanic white, and 3.9% for Mexican American men. There were no statistically significant differences between age-adjusted estimates for Puerto Rican women (10.7%), non-Hispanic white women (10.1%), or Mexican American women (16%). There is a need to understand specific factors contributing to osteoporosis in Puerto Rican adults, particularly younger men. This will provide important information to guide the development of culturally and linguistically tailored interventions to improve bone health in this understudied and high-risk population. © 2017 American Society for Bone and Mineral Research.

We examined whether escalating doses of potassium bicarbonate (KHCO3) supplements alter urinary nitrogen excretion expressed as a ratio to same day nitrogen intake (measure of muscle-protein breakdown). The ratio declined significantly from placebo to low to high dose of KHCO3 supplementation in older adults over 3 months, suggesting muscle-sparing. Neutralization of dietary acid load with alkali supplementation (i.e., KHCO3) has been hypothesized to have muscle protein-sparing effects. In controlled feeding studies with fixed nitrogen (N) intake/day, 24-h urinary N excretion is a good marker of muscle breakdown. However, in studies with self-selected diets, changes in 24-h urinary N excretion can be influenced by shifts in N intake. We evaluated changes in 24-h total urinary N excretion as a ratio of N excretion to concurrent N intake in 233 older men and women who participated in an 84-day KHCO3 supplementation randomized placebo-controlled trial. After adjustment for relevant cofactors, escalating doses of KHCO3 (1 mmol/kg/day [low] or 1.5 mmol/kg/day [high]) resulted in a progressive decline in urinary N excretion/N intake compared to placebo (overall P for trend = 0.042). The 84-day change in urinary N excretion/N intake in the high-dose KHCO3 group was statistically significantly lower compared to placebo (P = 0.012) but not compared to the low-dose KHCO3 group (P = 0.276). The 84-day change in urinary N excretion/N intake in the low-dose KHCO3 group did not differ significantly from placebo (P = 0.145). Urinary N excretion expressed as ratio to same day N intake declined steadily with increasing doses of KHCO3 supplementation from low 1 mmol/kg/day to high 1.5 mmol/kg/day, suggesting a nitrogen-sparing effect. Compared to urinary N excretion alone, this ratio could be a more reasonable measure of muscle protein metabolism in large-scale long-term human studies. Trial registration: Clinicaltrials.gov NCT1475214

Objectives To determine whether statin use alters response of 25-hydroxyvitamin D (25(OH)D) level to vitamin D treatment. Design Pooled analysis. Setting Three double-blind randomized controlled trials that tested different doses of vitamin D. Participants Participants of three trials (N = 646; mean age 76.3 ± 8.4, 65% female). Measurements In all three trials, 25(OH)D status and statin use were assessed repeatedly over time (baseline, 6 and 12 months). Repeated-measures analysis was used to compare 25(OH)D response to vitamin D treatment at baseline and 6 and 12 months of statin users and nonusers, controlling for age, sex, body mass index, Charlson Comorbidity Index, vitamin D dose, trial, and season. Results At baseline, 17.5% were statin users, and 65% were vitamin D deficient (25(OH)D

Diet-related mild metabolic acidosis may play a role in the development of sarcopenia. We investigated the relationship between dietary acid load and total lean body mass in male and female seniors age ≥ 60 years. We found that a more alkaline diet was associated with a higher %TLM only among senior women. The aim of this study was to determine if dietary acid load is associated with total lean body mass in male and female seniors age ≥ 60 years. We investigated 243 seniors (mean age 70.3 ± 6.3; 53% women) age ≥ 60 years who participated in the baseline assessment of a clinical trial on vitamin D treatment and rehabilitation after unilateral knee replacement due to severe knee osteoarthritis. The potential renal acid load (PRAL) was assessed based on individual nutrient intakes derived from a food frequency questionnaire. Body composition including percentage of total lean body mass (%TLM) was determined using dual-energy X-ray absorptiometry. Cross-sectional analyses were performed for men and women separately using multivariable regression models controlling for age, physical activity, smoking status, protein intake (g/kg BW per day), energy intake (kcal), and serum 25-hydroxyvitamin D concentration. We included a pre-defined subgroup analysis by protein intake ( 1 g/kg BW day) and by age group (

The place of calcium supplementation, with or without concomitant vitamin D supplementation, has been much debated in terms of both efficacy and safety. There have been numerous trials and meta-analyses of supplementation for fracture reduction, and associations with risk of myocardial infarction have been suggested in recent years. In this report, the product of an expert consensus meeting of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) and the International Foundation for Osteoporosis (IOF), we review the evidence for the value of calcium supplementation, with or without vitamin D supplementation, for healthy musculoskeletal ageing. We conclude that (1) calcium and vitamin D supplementation leads to a modest reduction in fracture risk, although population-level intervention has not been shown to be an effective public health strategy; (2) supplementation with calcium alone for fracture reduction is not supported by the literature; (3) side effects of calcium supplementation include renal stones and gastrointestinal symptoms; (4) vitamin D supplementation, rather than calcium supplementation, may reduce falls risk; and (5) assertions of increased cardiovascular risk consequent to calcium supplementation are not convincingly supported by current evidence. In conclusion, we recommend, on the basis of the current evidence, that calcium supplementation, with concomitant vitamin D supplementation, is supported for patients at high risk of calcium and vitamin D insufficiency, and in those who are receiving treatment for osteoporosis.

OBJECTIVE Observational studies suggest that vitamin D may lower the risk of type 2 diabetes. However, data from long-term trials are lacking. The Vitamin D and Type 2 Diabetes (D2d) study is a randomized clinical trial designed to examine whether a causal relationship exists between vitamin D supplementation and the development of diabetes in people at high risk for type 2 diabetes. RESEARCH DESIGN AND METHODS D2d was designed with support from a U34 planning grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The final protocol was approved by the D2d Research Group, the data and safety monitoring board, and NIDDK. Key eligibility criteria are age ≥30 years, BMI of 24 (22.5 for Asian Americans) to 42 kg/m2, increased risk for diabetes (defined as meeting two of three glycemic criteria for prediabetes established by the American Diabetes Association [fasting glucose 100–125 mg/dL (5.5–6.9 mmol/L), 2-h postload glucose after 75-g glucose load 140–199 mg/dL (7.7–11.0 mmol/L), hemoglobin A1c 5.7–6.4% (39–46 mmol/mol)]), and no hyperparathyroidism, nephrolithiasis, or hypercalcemia. D2d participants are randomized to once-daily vitamin D3 (cholecalciferol 4,000 IU) or placebo and followed for an average of 3 years. The primary end point is time to incident diabetes as assessed by laboratory criteria during the study or by adjudication if diagnosed outside of D2d. Recruitment was initiated at the end of 2013. CONCLUSIONS D2d will test whether vitamin D supplementation is safe and effective at lowering the risk of progression to diabetes in people at high risk for type 2 diabetes.