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Patient perspectives are now widely recognized as a key element in the evaluation of health interventions. Therefore, the provision of specific and validated Patient Reported Outcome Measures that emphasize the lived experience of patients suffering from specific diseases is very important. In the field of sarcopenia, the only validated specific health-related quality of life (HRQoL) instrument available is the Sarcopenia Quality of Life questionnaire (SarQoL). This self-administrated HRQoL questionnaire, developed in 2015, consists of 55 items arranged into 22 questions and has currently been translated into 35 languages. Nineteen validation studies performed on SarQoL have consensually confirmed the capacity of SarQoL to detect difference in HRQoL between older people with and without sarcopenia, its reliability and its validity. Two further observational studies have also indicated its responsiveness to change. A short form SarQoL, including only 14 items has further been developed and validated to reduce the potential burden of administration. Research on the psychometric properties of SarQoL questionnaire is still encouraged as the responsiveness to change of SarQoL has not yet been measured in the context of interventional studies, as limited prospective data currently exist and as there is still not cut-off score to define a low HRQoL. In addition, SarQoL has mainly been used in community-dwelling older individuals with sarcopenia and would benefit to be studied in other types of populations. This review aims to provide to researchers, clinicians, regulators, pharmaceutical industries and other stakeholders a clear summary of comprehensive evidence on the SarQoL questionnaire published up to January 2023Query.

Vitamin D purportedly protects against cognitive decline and dementia based on observational data using circulating 25-hydroxyvitamin D (25(OH)D). Little is known about vitamin D in the human brain and the association with dementia or neuropathology.Decedents of the Rush Memory and Aging Project (n = 290) had vitamin D concentrations measured in four brain regions. Associations with cognitive and neuropathological outcomes were estimated using linear and logistic regression.The main form of vitamin D in all brain regions measured was 25(OH)DHigher brain 25(OH)D

© 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

Background: This paper reports results from the 5th International Conference “Controversies in Vitamin D” that was held in Stresa, Italy, 15–18 September 2021. The conference is part of this series that started in 2017 and has been conducted annually since. The objective of these conferences is to identify timely and controversial topics related to Vitamin D. Dissemination of the results of the conference through publications in peer-reviewed journals is an important means by which the most up to date information can be shared with physicians, investigators, and other health care professionals. Vitamin D and aging, the subject of this paper was featured at the conference. Methods: Participants were selected to review available literature on assigned topics related to vitamin D and aging and to present their findings with illustrative material, the intent of which was to stimulate discussion and to arrive at a consensus. The presentations were directed towards the following areas: impact of aging on vitamin D production and levels; skeletal effects of vitamin D deficiency in the older population; falls and vitamin D in the aging; potential extra skeletal effects of vitamin D; and strategies to prevent vitamin D deficiency. A final topic was related to how vitamin D might influence the efficacy of vaccines for Covid-19. Results: Hypovitaminosis D can lead to several skeletal and extra-skeletal outcomes. Older adults are at risk for vitamin D deficiency as both production and metabolism of vitamin D change with aging due to factors, such as reduced sun exposure and reduced production capacity of the skin. Skeletal consequences of these age-related changes can include reduced bone mineral density, osteomalacia and fractures. Potential extra-skeletal effects can include added risks for falls, reduced muscle strength, diabetes, cancer, and cardiovascular disease. Strategies to avoid these vitamin D deficiency-related negative outcomes include sun exposure, food fortification, and supplementation. While aging does not diminish sufficient reserve capacity for cutaneous vitamin D production, concerns about skin cancers and practical matters for the institutionalized elderly limit this option. Supplementation with vitamin D is the best option either pharmacologically or through food fortification. Regardless of treatment strategies, interventions to restore sufficient vitamin D status will show positive results only in those who are truly deficient. Thus, treatment goals should focus on avoiding 25(OH)D serum levels 50 nmol/l. Conclusions: The results of this conference has led to consensus on several issues. Vitamin D supplementation should be combined with calcium to reduce fractures in the older population. The goal for adequate Vitamin D status should be to reach a serum level of 25(OH)D >50 nmol/l. It appears that daily low-dose vitamin D regimens reduce the risk of falling, especially in the elderly, compared with infrequent, large bolus doses that may increase it. The role of Vitamin D supplementation on muscle strength remains to be clarified. On the other hand, supplementation decreases the risk of progression to T2D from prediabetes among those who are Vitamin Ddeficient. Of three possible strategies to establish vitamin D sufficiency – sunshine exposure, food fortification, and supplementation – the latter seems to be the most effective and practical in the aging population.

This study sought to examine the effect of vitamin DIt was conducted on a subset of the VDBaseline mean ± SD age was 61 ± 4 years and serum 25-hydroxyvitamin D (25OHD) level was 55.1 ± 22.8 nmol/L. Baseline characteristics did not differ significantly by group. Six-month mean ± SD 25OHD levels were 138.7 ± 22.2 nmol/L (VDThis study demonstrated no significant change in intramyonuclear VDR in response to either form of vitamin D vs. placebo. Type I FCSA significantly increased with VDNCT02527668.

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

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.

Objective Fasting plasma glucose (FPG), 2-hour plasma glucose (2hPG) from a 75-g oral glucose tolerance test (OGTT) and glycated hemoglobin (HbA1c) can lead to different results when diagnosing prediabetes and diabetes. The Hemoglobin Glycation Index (HGI) quantifies the interindividual variation in glycation resulting in discrepancies between FPG and HbA1c. We used data from the Vitamin D and Type 2 Diabetes (D2d) study to calculate HGI, to identify HGI-associated variables, and to determine how HGI affects prediabetes and diabetes diagnosis. Measurements A linear regression equation [HbA1c (%) = 0.0164 × FPG (mg/dL) + 4.2] was derived using the screening cohort (n = 6829) and applied to calculate predicted HbA1c. This was subtracted from the observed HbA1c to determine HGI in the baseline cohort with 2hPG data (n = 3945). Baseline variables plus prediabetes and diabetes diagnosis by FPG, HbA1c, and 2hPG were compared among low, moderate, and high HGI subgroups. Results The proportion of women and Black/African American individuals increased from low to high HGI subgroups. Mean FPG decreased and mean HbA1c increased from low to high HGI subgroups, consistent with the HGI calculation; however, mean 2hPG was not significantly different among HGI subgroups. Conclusions High HGI was associated with Black race and female sex as reported previously. The observation that 2hPG was not different across HGI subgroups suggests that variation in postprandial glucose is not a significant source of population variation in HGI. Exclusive use of HbA1c for diagnosis will classify more Black individuals and women as having prediabetes compared with using FPG or 2hPG.

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.

In this review we summarize the impact of bolus versus daily dosing of vitamin D on 25(OH)D and 1,25(OH)2D levels, as well as on key countervailing factors that block vitamin D functions at the cellular level. Further, we discuss the role of bolus versus daily dosing of vitamin D for several health outcomes, including respiratory infections and coronavirus disease 2019 (COVID‐19), rickets, falls and fractures, any cancer, and cancer‐related mortality. This discussion appears timely because bolus doses continue to be tested for various disease outcomes despite a growing amount of evidence suggesting lack of efficacy or even detrimental effects of bolus dosing of vitamin D for outcomes where daily dosing at modest levels was effective in the vitamin D deficient. As a result, these discordant results may bias health recommendations for vitamin D if the recommendations are based on meta‐analyses combining both daily and bolus dosing trials. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

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

Background: Individual randomized clinical trials have not shown conclusively that taking vitamin D can prevent type 2 diabetes. Methods: We conducted a systematic review and meta-analysis of individual participant-level data to determine whether vitamin D supplementation lowers the risk of diabetes in people with prediabetes. Trials published through February 12, 2021, that compared oral vitamin D supplementation (alone) with placebo over a minimum 2-year follow up, and had new-onset diabetes as a primary outcome were included. Proportional hazards models were used to analyze individual participant data, with pre-specified intention-to-treat (ITT) and per-protocol analyses, without and after adjustment for baseline age, gender, BMI, race and hemoglobin A1c. Safety was also assessed. Results: Three trials were eligible (testing D3 20,000 IU/week [Tromsø], D3 4,000 IU/day [D2d], and eldecalcitol 0.75 μg/day [DPVD] vs. matching placebos) and contributed data from 4190 randomized participants (mean age 60.4 years, 44.2% women). After a median 3.0 years of follow-up, new-onset diabetes occurred in 475/2097 participants assigned to vitamin D and 524/2093 assigned to placebo (8.42 and 9.50 events per 100 person-years, respectively). The unadjusted hazard ratio (95% CI) for vitamin D was 0.88 (0.77 to 0.99) in the ITT and 0.85 (0.75 to 0.97) in the per-protocol analyses. Adjusted hazard ratios were 0.85 (0.75 to 0.96) in the ITT and 0.83 (0.73 to 0.94) in the per-protocol analyses. There was no evidence of heterogeneity of treatment effect among the three trials. The incidence of hypercalcemia, hypercalciuria, or kidney stones did not differ between the vitamin D and placebo groups. Conclusion: In adult patients with prediabetes, vitamin D supplementation is safe and effective for lowering the risk of diabetes by about 15%. Disclosure A. G. Pittas: None. T. Kawahara: None. R. Jorde: None. J. P. Nelson: None. E. Angellotti: None. E. Vickery: None. B. Dawson-hughes: None. T. Trikalinos: None. E. M. Balk: None. Funding American Diabetes Association (1-14-D2D-01 to A.G.P.); National Institutes of Health (U01DK098245)

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).

To test the effects of vitamin D intervention and a simple home exercise program (HE) on health-related quality of life (HRQL) in the first 12 months after hip fracture. HRQL was reported in 173 acute hip fracture patients (mean age 84 years, 79% females, 77% community dwelling) who were enrolled in the 12-month 2 × 2 factorial Zurich Hip Fracture Trial. Pre-fracture HRQL was assessed at baseline (4.2 ± 2.2 days post-surgery) and then again at 6 and 12 months after hip fracture surgery by the EuroQol EQ-5D-3L index value (EQ-5D-3L questionnaire). The effects of vitamin D intervention (2000 vs. 800 IU vitamin D3) and exercise (HE vs. no HE) or of the combined interventions on HRQL were assessed using multivariable-adjusted repeated-measures linear mixed-effects regression models. The EQ-5D-3L index value significantly worsened from 0.71 pre-fracture to 0.57 over 12 months, but the degree of worsening did not differ between individual or combined interventions. However, regarding only the late recovery between 6 and 12 months, the group receiving neither intervention (800 IU/day and no HE) experienced a significant further decline in the EQ-5D-3L index value (adjusted mean change = 0.08 [95% CI 0.009, 0.15], p = 0.03) while all other groups remained stable. Hip fractures have a long-lasting negative effect on HRQL up to 12 months after hip fracture. However, HE and/or 2000 IU vitamin D per day may help prevent a further decline in HRQL after the first 6 months following the acute hip fracture event.

OBJECTIVES To test the effect of monthly high-dose vitamin D supplementation on mental health in pre-frail older adults. DESIGN Ancillary study of a 1-year double-blind randomized clinical trial conducted in Zurich, Switzerland. SETTING AND PARTICIPANTS 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 D3 (considered standard of care), 60 000 IU vitamin D3 , or 24 000 IU vitamin D3 plus 300 μg calcifediol per month. MEASURES The 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). RESULTS Participants' mean age was 78 years (67% women), and 58% were vitamin D deficient (

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.

The Third International Conference on Controversies in Vitamin D was held in Gubbio, Italy, September 10-13, 2019. The conference was held as a follow-up to previous meetings held in 2017 and 2018 to address topics of controversy in vitamin D research. The specific topics were selected by the steering committee of the conference and based upon areas that remain controversial from the preceding conferences. Other topics were selected anew that reflect specific topics that have surfaced since the last international conference. Consensus was achieved after formal presentations and open discussions among experts. As will be detailed in this article, consensus was achieved with regard to the following: the importance and prevalence of nutritional rickets, amounts of vitamin D that are typically generated by sun exposure, worldwide prevalence of vitamin D deficiency, the importance of circulating concentrations of 25OHD as the best index of vitamin D stores, definitions and thresholds of vitamin D deficiency, and efficacy of vitamin D analogues in the treatment of psoriasis. Areas of uncertainly and controversy include the following: daily doses of vitamin D needed to maintain a normal level of 25OHD in the general population, recommendations for supplementation in patients with metabolic bone diseases, cutaneous production of vitamin D by UVB exposure, hepatic regulation of 25OHD metabolites, definition of vitamin D excess, vitamin D deficiency in acute illness, vitamin D requirements during reproduction, potential for a broad spectrum of cellular and organ activities under the influence of the vitamin D receptor, and potential links between vitamin D and major human diseases. With specific regard to the latter area, the proceedings of the conference led to recommendations for areas in need of further investigation through appropriately designed intervention trials. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research. ispartof: JBMR PLUS vol:4 issue:12 ispartof: location:England status: published

OBJECTIVES: Vitamins D and K are present in human brain tissue, and evidence is emerging that these nutrients may have a role in neurodegenerative disease. Given the increasing interest in conducting analyses of archived brain samples, it is important to evaluate the stability of these nutrients in brain tissue over long-term storage. Therefore, we evaluated the influence of freezer storage time on vitamin D and vitamin K concentrations in human brain samples. METHODS: Post-mortem brain samples were obtained from 500 participants in the Rush Memory and Aging Project (mean age 91 yrs, 71% female). At autopsy and brain dissection, the tissues were immediately frozen on brass plates atop dry ice then stored at −80(o) C until analysis. Storage time was categorized in 1-year increments. Vitamin D [25(OH)D] and vitamin K [menaquinone-4 (MK4)] concentrations were measured in four regions (mid-temporal cortex, mid-frontal cortex, cerebellum, anterior watershed white matter) using LC/MS/MS and HPLC, respectively. We calculated the mean 25(OH)D and MK4 concentrations across the four regions and then applied a natural-log transformation to the means to improve normality. Analysis of variance was used to determine if the geometric mean ± SEM 25(OH)D and MK4 concentrations differed according to storage time. The samples stored ≤1.0 year served as the reference group. RESULTS: The mean 25(OH)D concentration in brains stored >6.0 years (n = 203; 0.8 ± 0.05 pmol/g), was significantly lower than the concentration in brains stored ≤1.0 year (n = 79; 1.2 ± 0.09 pmol/g, P ≤ 0.004). The 25(OH)D in the brains stored ≤1.0 year did not differ from the concentration in brains stored for 1.1–6.0 years (n = 212; 1.2 ± 0.05 pmol/g, P ≥ 0.37). The mean MK4 concentration in the brains stored ≥9.0 years (n = 81; 0.7 ± 0.6 pmol/g) was significantly lower than that in the brains stored ≤1.0 year (1.2 ± 1.3 pmol/g; P ≤ 0.01). The MK4 in brains stored ≤1.0 year did not differ from the concentration in brains stored for 1.1–9.0 years (n = 339; 1.3 ± 0.8 pmol/g; P ≥ 0.11). CONCLUSIONS: 25(OH)D and MK4 appear to be stable in brain tissue stored at −80 °C for up to 6 and 9 years, respectively, but not longer. This should be considered in the design and interpretation of studies linking brain concentrations of these nutrients to neurodegenerative diseases. FUNDING SOURCES: Supported by the National Institute of Aging.

Vitamin D deficiency has been associated with many acute and chronic diseases of immense importance. This chapter briefly considers data relating vitamin D status to immune function, cancer, muscle function and falls, and cardiovascular disease. Despite extensive in vitro, animal, and human studies, the role of vitamin D deficiency in these, and potentially multiple other nonskeletal diseases, remains unclear. This uncertainty is in no small part the result of inadequate standardization of 25-hydroxyvitamin D measurement and suboptimal clinical trial design. Improvements in the laboratory definition of vitamin D deficiency and advances in randomized trials of vitamin D supplementation are needed, as it is imperative that any role of vitamin D deficiency in a multitude of diseases be clarified.

The article 'Algorithm for the management of patients at low, high and very high risk of osteoporotic fractures',written by J. A. Kanis, was originally published Online First without Open Access. After publication in volume [#], issue [#] and page [#-#], the author decided to opt for Open Choice and to make the article an Open Access publication.

Context Over the last decade, vitamin D has emerged as a risk determinant for type 2 diabetes and vitamin D supplementation has been hypothesized as a potential intervention to lower diabetes risk. Recently, several trials have reported on the effect of vitamin D supplementation on diabetes prevention in people with prediabetes. Evidence Acquisition A comprehensive literature review was performed using PubMed, Embase, and ClinicalTrials.gov to identify: (1) recent meta-analyses of longitudinal observational studies that report on the association between blood 25-hydroxyvitamin D (25[OH]D) level and incident diabetes, and (2) clinical trials of adults with prediabetes that have reported on the effect of vitamin D supplementation on incident diabetes. Evidence Synthesis Longitudinal observational studies report highly consistent associations between higher blood 25(OH)D levels and a lower risk of incident diabetes in diverse populations, including populations with prediabetes. Trials in persons with prediabetes show risk reduction in incident diabetes with vitamin D supplementation. In the 3 large trials that were specifically designed and conducted for the prevention of diabetes, vitamin D supplementation, when compared with placebo, reduced the risk of developing diabetes by 10% to 13% in persons with prediabetes not selected for vitamin D deficiency. Conclusions Results from recent trials are congruent with a large body of evidence from observational studies indicating that vitamin D has a role in modulating diabetes risk. Participant-level meta-analysis of the 3 largest trials should provide a more refined estimate of risk reduction and identify patient populations that are likely to benefit the most from vitamin D supplementation.