Role of the Microbiome in Regulating Bone Metabolism and Susceptibility to Osteoporosis.

The human microbiota functions at the interface between diet, medication-use, lifestyle, host immune development and health. It is therefore closely aligned with many of the recognised modifiable factors that influence bone mass accrual in the young, and bone maintenance and skeletal decline in older populations. While understanding of the relationship between micro-organisms and bone health is still in its infancy, two decades of broader microbiome research and discovery supports a role of the human gut microbiome in the regulation of bone metabolism and pathogenesis of osteoporosis as well as its prevention and treatment. Pre-clinical research has demonstrated biological interactions between the microbiome and bone metabolism. Furthermore, observational studies and randomized clinical trials have indicated that therapeutic manipulation of the microbiota by oral administration of probiotics may influence bone turnover and prevent bone loss in humans. In this paper, we summarize the content, discussion and conclusions of a workshop held by the Osteoporosis and Bone Research Academy of the Royal Osteoporosis Society in October, 2020. We provide a detailed review of the literature examining the relationship between the microbiota and bone health in animal models and in humans, as well as formulating the agenda for key research priorities required to advance this field. We also underscore the potential pitfalls in this research field that should be avoided and provide methodological recommendations to facilitate bridging the gap from promising concept to a potential cause and intervention target for osteoporosis.

Implementation strategies for improving vitamin D status and increasing vitamin D intake in the UK: current controversies and future perspectives: proceedings of the 2nd Rank Prize Funds Forum on vitamin D.

A multi-disciplinary expert group met to discuss vitamin D deficiency in the UK and strategies for improving population intakes and status. Changes to UK Government advice since the 1st Rank Forum on Vitamin D (2009) were discussed, including rationale for setting a reference nutrient intake (10 µg/d; 400 IU/d) for adults and children (4+ years). Current UK data show inadequate intakes among all age groups and high prevalence of low vitamin D status among specific groups (e.g. pregnant women and adolescent males/females). Evidence of widespread deficiency within some minority ethnic groups, resulting in nutritional rickets (particularly among Black and South Asian infants), raised particular concern. Latest data indicate that UK population vitamin D intakes and status reamain relatively unchanged since Government recommendations changed in 2016. Vitamin D food fortification was discussed as a potential strategy to increase population intakes. Data from dose-response and dietary modelling studies indicate dairy products, bread, hens' eggs and some meats as potential fortification vehicles. Vitamin D3 appears more effective than vitamin D2 for raising serum 25-hydroxyvitamin D concentration, which has implications for choice of fortificant. Other considerations for successful fortification strategies include: (i) need for 'real-world' cost information for use in modelling work; (ii) supportive food legislation; (iii) improved consumer and health professional understanding of vitamin D's importance; (iv) clinical consequences of inadequate vitamin D status and (v) consistent communication of Government advice across health/social care professions, and via the food industry. These areas urgently require further research to enable universal improvement in vitamin D intakes and status in the UK population.

Individual participant data (IPD)-level meta-analysis of randomised controlled trials to estimate the vitamin D dietary requirements in dark-skinned individuals resident at high latitude.

CONTEXT AND PURPOSE: There is an urgent need to develop vitamin D dietary recommendations for dark-skinned populations resident at high latitude. Using data from randomised controlled trials (RCTs) with vitamin D3-supplements/fortified foods, we undertook an individual participant data-level meta-regression (IPD) analysis of the response of wintertime serum 25-hydroxyvitamin (25(OH)D) to total vitamin D intake among dark-skinned children and adults residing at ≥ 40° N and derived dietary requirement values for vitamin D. METHODS: IPD analysis using data from 677 dark-skinned participants (of Black or South Asian descent; ages 5-86 years) in 10 RCTs with vitamin D supplements/fortified foods identified via a systematic review and predefined eligibility criteria. Outcome measures were vitamin D intake estimates across a range of 25(OH)D thresholds. RESULTS: To maintain serum 25(OH)D concentrations ≥ 25 and 30 nmol/L in 97.5% of individuals, 23.9 and 27.3 µg/day of vitamin D, respectively, were required among South Asian and 24.1 and 33.2 µg/day, respectively, among Black participants. Overall, our age-stratified intake estimates did not exceed age-specific Tolerable Upper Intake Levels for vitamin D. The vitamin D intake required by dark-skinned individuals to maintain 97.5% of winter 25(OH)D concentrations ≥ 50 nmol/L was 66.8 µg/day. This intake predicted that the upper 2.5% of individuals could potentially achieve serum 25(OH)D concentrations ≥ 158 nmol/L, which has been linked to potential adverse effects in older adults in supplementation studies. CONCLUSIONS: Our IPD-derived vitamin D intakes required to maintain 97.5% of winter 25(OH)D concentrations ≥ 25, 30 and 50 nmol/L are substantially higher than the equivalent estimates for White individuals. These requirement estimates are also higher than those currently recommended internationally by several agencies, which are based predominantly on data from Whites and derived from standard meta-regression based on aggregate data. Much more work is needed in dark-skinned populations both in the dose-response relationship and risk characterisation for health outcomes. TRAIL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews (Registration Number: CRD42018097260).

Vitamin D Supplementation and Sunlight Exposure on Serum Vitamin D Concentrations in 2 Parallel, Double-Blind, Randomized, Placebo-Controlled Trials.

BACKGROUND: Vitamin D concentrations are a function of sunlight exposure and dietary intake. However, current dietary vitamin D recommendations do not consider differences in country-specific sunlight availability or spontaneous individual exposure. OBJECTIVES: We aimed to investigate the effects of vitamin D supplementation and sunlight exposure on vitamin D concentrations in Brazilian women living in high compared with low latitudes. METHODS: In 2 parallel, double-blind, randomized placebo-controlled trials, Brazilian women living in England (51°N) composed "without ultraviolet B (UVB) exposure" groups and those living in Brazil (16°S) composed the "with UVB exposure" groups (mean age, 31.39 ± 8.7 years). Participants received 15 µg cholecalciferol or placebo daily for 12 weeks during wintertime. Serum 25-hydroxyvitamin D [25(OH)D] concentrations, the primary outcome, were assessed by HPLC-MS/MS, vitamin D intakes were assessed by 4-day diet diaries, and sunlight exposure was assessed by UVB dosimeters. The effects of supplementation and UVB exposure were tested by the intention to treat with a linear mixed model. RESULTS: The 25(OH)D concentrations increased in both supplemented groups [from 75.1 ± 22.0 to 84.8 ± 21.0 nmol/L (P = 0.004) in the group with UVB exposure; from 38.1 ± 15.9 to 55.1 ± 12.2 nmol/L (P < 0.001) in the group without UVB exposure], with no significant changes in either placebo group. Concentrations in both supplemented groups were higher than those in the placebo group without UVB exposure (P = 0.0002 in the group with UVB exposure; P = 0.0035 in the group without UVB exposure). Postintervention 25(OH)D concentrations were significantly affected by serum 25(OH)D concentrations at baseline (P < 0.0001) and by intervention (placebo or supplement; P > 0.0001), with a large effect size (Cohen's D = 0.768), but were not affected by UVB exposure (with or without; P = 0.1386), nor by the interaction between the intervention (placebo or supplement) and UVB exposure (with or without; P = 0.9845). CONCLUSIONS: Moderate supplementation of 15 ug/d cholecalciferol, in accordance with current recommendations, supports an adequate vitamin D status in adult women, irrespective of latitude, and might concomitantly prevent an increase in parathyroid hormone. The Interaction Between Vitamin D Supplementation and Sunlight Exposure in Women Living in Opposite Latitudes (D-SOL) study was registered at clinicaltrials.gov as NCT03318029.

Very high prevalence of 25-hydroxyvitamin D deficiency in 6433 UK South Asian adults: analysis of the UK Biobank Cohort.

Little research has assessed serum 25-hydroxyvitamin D (25(OH)D) concentration and its predictors in Western-dwelling South Asians in a relatively large sample size. This observational, cross-sectional analysis assessed baseline prevalence of 25(OH)D deficiency in UK-dwelling South Asians (aged 40-69 years, 2006-2010) from the UK Biobank Cohort. Serum 25(OH)D measurements were undertaken using the DiaSorin Liaison XL assay. Of 6433 South Asians with a 25(OH)D measurement, using commonly used cut-off thresholds, 55 % (n 3538) had 25(OH)D < 25 nmol/l (severe deficiency) and 92 % (n 5918) had 25(OH)D < 50 nmol/l (insufficiency). Of the participants with a measurement, 20 % (n 1287) had 25(OH)D concentration <15 nmol/l (very severe deficiency). When 824 participants with undetectable (<10 nmol/l) 25(OH)D measurements were included (total n 7257), 29 % (n 2105) had 25(OH)D < 15 nmol/l, 60 % (n 4354) had 25(OH)D < 25 nmol/l and 93 % (n 6749) had 25(OH)D < 50 nmol/l. Logistic regression predictors of 25(OH)D < 25 nmol/l included the following characteristics: being male; Pakistani; higher BMI; 40-59 years old; never consuming oily fish; summer sun exposure <5 h/d, not using a vitamin D-containing supplement, measurement in winter or spring and vegetarianism. In terms of region, median 25(OH)D concentration was 19-20 nmol/l in Scotland, Northern England, the Midlands and Wales. Across Southern England and London, it was slightly higher at 24-25 nmol/l. Our analyses suggest the need for increased awareness of vitamin D deficiency in South Asians as well as urgent public health interventions to prevent and treat vitamin D deficiency in this group.

Individual participant data (IPD)-level meta-analysis of randomised controlled trials with vitamin D-fortified foods to estimate Dietary Reference Values for vitamin D.

CONTEXT AND PURPOSE: Individual participant data-level meta-regression (IPD) analysis is superior to meta-regression based on aggregate data in determining Dietary Reference Values (DRV) for vitamin D. Using data from randomized controlled trials (RCTs) with vitamin D3-fortified foods, we undertook an IPD analysis of the response of winter serum 25-hydroxyvitamin (25(OH)D) to total vitamin D intake among children and adults and derived DRV for vitamin D. METHODS: IPD analysis using data from 1429 participants (ages 2-89 years) in 11 RCTs with vitamin D-fortified foods identified via a systematic review and predefined eligibility criteria. Outcome measures were vitamin D DRV estimates across a range of serum 25(OH)D thresholds using unadjusted and adjusted models. RESULTS: Our IPD-derived estimates of vitamin D intakes required to maintain 97.5% of winter 25(OH)D concentrations ≥ 25 and ≥ 30 nmol/L are 6 and 12 µg/day, respectively (unadjusted model). The intake estimates to maintain 90%, 95% and 97.5% of concentrations ≥ 50 nmol/L are 33.4, 57.5 and 92.3 µg/day, respectively (unadjusted) and 17.0, 28.1 and 43.6 µg/day, respectively (adjusted for mean values for baseline serum 25(OH)D, age and BMI). CONCLUSIONS: IPD-derived vitamin D intakes required to maintain 90%, 95% and 97.5% of winter 25(OH)D concentrations ≥ 50 nmol/L are much higher than those derived from standard meta-regression based on aggregate data, due to the inability of the latter to capture between person-variability. Our IPD provides further evidence that using food-based approaches to achieve an intake of 12 µg/day could prevent vitamin D deficiency (i.e., serum 25(OH)D < 30 nmol/L) in the general population.

Serum 25-hydroxyvitamin D fluctuations in military personnel during 6-month summer operational deployments in Afghanistan.

Soldier operational performance is determined by their fitness, nutritional status, quality of rest/recovery, and remaining injury/illness free. Understanding large fluctuations in nutritional status during operations is critical to safeguarding health and well-being. There are limited data world-wide describing the effect of extreme climate change on nutrient profiles. This study investigated the effect of hot-dry deployments on vitamin D status (assessed from 25-hydroxyvitamin D (25(OH)D) concentration) of young, male, military volunteers. Two data sets are presented (pilot study, n 37; main study, n 98), examining serum 25(OH)D concentrations before and during 6-month summer operational deployments to Afghanistan (March to October/November). Body mass, percentage of body fat, dietary intake and serum 25(OH)D concentrations were measured. In addition, parathyroid hormone (PTH), adjusted Ca and albumin concentrations were measured in the main study to better understand 25(OH)D fluctuations. Body mass and fat mass (FM) losses were greater for early (pre- to mid-) deployment compared with late (mid- to post-) deployment (P<0·05). Dietary intake was well-maintained despite high rates of energy expenditure. A pronounced increase in 25(OH)D was observed between pre- (March) and mid-deployment (June) (pilot study: 51 (sd 20) v. 212 (sd 85) nmol/l, P<0·05; main study: 55 (sd 22) v. 167 (sd 71) nmol/l, P<0·05) and remained elevated post-deployment (October/November). In contrast, PTH was highest pre-deployment, decreasing thereafter (main study: 4·45 (sd 2·20) v. 3·79 (sd 1·50) pmol/l, P<0·05). The typical seasonal cycling of vitamin D appeared exaggerated in this active male population undertaking an arduous summer deployment. Further research is warranted, where such large seasonal vitamin D fluctuations may be detrimental to bone health in the longer-term.

Winter Cholecalciferol Supplementation at 51°N Has No Effect on Markers of Cardiometabolic Risk in Healthy Adolescents Aged 14-18 Years.

Background: Epidemiologic studies have supported inverse associations between low serum 25-hydroxyvitamin D [25(OH)D] and cardiometabolic risk markers, but few randomized trials have investigated the effect of vitamin D supplementation on these markers in adolescents. Objective: The objective of this study was to investigate the effect of winter-time cholecalciferol (vitamin D3) supplementation on cardiometabolic risk markers in white, healthy 14- to 18-y-old adolescents in the UK (51°N) as part of the ODIN Project. Methods: In a dose-response trial, 110 adolescents (mean ± SD age: 15.9 ± 1.4 y; 43% male; 81% normal weight) were randomly assigned to receive 0, 10 or 20 µg/d vitamin D3 for 20 wk (October-March). Cardiometabolic risk markers including BMI-for-age z score (BMIz), waist circumference, systolic and diastolic blood pressure, fasting plasma triglycerides, cholesterol (total, HDL, LDL, and total:HDL), and glucose were measured at baseline and endpoint as secondary outcomes, together with serum 25(OH)D. Intervention effects were evaluated in linear regression models as between-group differences at endpoint, adjusted for the baseline value of the outcome variable and additionally for age, sex, Tanner stage, BMIz, and baseline serum 25(OH)D. Results: Mean ± SD baseline serum 25(OH)D was 49.1 ± 12.3 nmol/L and differed between groups at endpoint with concentrations of 30.7 ± 8.6, 56.6 ± 12.4, and 63.9 ± 10.6 nmol/L in the 0, 10, and 20 µg/d groups, respectively (P ≤ 0.001). Vitamin D3 supplementation had no effect on any of the cardiometabolic risk markers (all P > 0.05), except for lower HDL (-0.12 mmol/L; 95% CI: -0.21, 0.04 mmol/L; P = 0.003) and total cholesterol (-0.21 mmol/L; 95% CI: -0.42, 0.00 mmol/L; P = 0.05) in the 20 µg/d than in the 10 µg/d group, which disappeared in the fully adjusted analysis (P = 0.27 and P = 0.30, respectively). Conclusions: Supplementation with vitamin D3 at 10 and 20 µg/d, which increased serum 25(OH)D concentrations during the winter-time, had no effect on markers of cardiometabolic risk in healthy 14- to 18-y-old adolescents. This trial was registered at clinicaltrials.gov as NCT02150122.

Winter Cholecalciferol Supplementation at 55°N Has No Effect on Markers of Cardiometabolic Risk in Healthy Children Aged 4-8 Years.

Background: Low serum 25-hydroxyvitamin D [25(OH)D] has been associated with unfavorable cardiometabolic risk profiles in many observational studies in children, but very few randomized controlled trials have investigated this. Objective: We explored the effect of winter-time cholecalciferol (vitamin D3) supplementation on cardiometabolic risk markers in young, white, 4- to 8-y-old healthy Danish children (55°N) as part of the pan-European ODIN project. Methods: In the ODIN Junior double-blind, placebo-controlled, dose-response trial, 119 children (mean ± SD age: 6.7 ± 1.5 y; 36% male; 82% normal weight) were randomly allocated to 0, 10 or 20 µg/d of vitamin D3 for 20 wk (October-March). Cardiometabolic risk markers including BMI-for-age z score (BMIz), waist circumference, systolic and diastolic blood pressure, serum triglycerides and cholesterol (total, LDL, HDL, and total:HDL), plasma glucose and insulin, and whole-blood glycated hemoglobin were measured at baseline and endpoint as secondary outcomes together with serum 25(OH)D. Intervention effects were evaluated in linear regression models as between-group differences at endpoint adjusted for baseline value of the outcome, and additionally for age, sex, baseline serum 25(OH)D, BMIz, time since breakfast, and breakfast content. Results: Mean ± SD serum 25(OH)D was 56.7 ± 12.3 nmol/L at baseline and differed between groups at endpoint with concentrations of 31.1 ± 7.5, 61.8 ± 10.6, and 75.8 ± 11.5 nmol/L in the 0-, 10-, and 20 µg/d groups, respectively (P < 0.0001). Vitamin D3 supplementation had no effect on any of the cardiometabolic risk markers in analyses adjusted for baseline value of the outcome (all P ≥ 0.05), and additional covariate adjustment did not change the results notably. Conclusions: Preventing the winter decline in serum 25(OH)D with daily vitamin D3 supplementation of 10 or 20 µg had no cardiometabolic effects in healthy 4- to 8-y-old Danish children. This trial was registered at www.clinicaltrials.gov as NCT02145195.

Vitamin D supplement use and associated demographic, dietary and lifestyle factors in 8024 South Asians aged 40-69 years: analysis of the UK Biobank cohort.

OBJECTIVE: Vitamin D deficiency (serum 25-hydroxyvitamin D<25nmol/L) is extremely common in western-dwelling South Asians but evidence regarding vitamin D supplement usage in this group is very limited. This work identifies demographic, dietary and lifestyle predictors associated with vitamin D supplement use. DESIGN: Cross-sectional analysis of baseline vitamin D supplement use data. SETTING: UK Biobank cohort. SUBJECTS: In total, n 8024 South Asians (Bangladeshi, Indian, Pakistani), aged 40-69 years. RESULTS: Twenty-three % of men and 39% of women (P<0.001) [22% of Bangladeshis, 32% of Indians, 25% of Pakistanis (P<0.001)] took a vitamin D containing supplement. Median vitamin D intakes from diet were low at 1.0-3.0 micrograms per day, being highest in Bangladeshis and lowest in Indians (P<0.001). Logistic regression modelling showed that females had a higher odds of vitamin D supplement use than males (odds ratio (OR) = 2.02; 95% confidence interval (CI) 1.79 to 2.28). A lower supplement usage was seen in younger persons (40-60 years) (OR=0.75; 95% CI 0.65 to 0.86 reference= >60 years), and those living outside of Greater London (OR=0.53 to 0.77), with borderline trends for a lower body mass index, higher oily fish intake and higher household income associated with increased odds of vitamin D supplement use. CONCLUSIONS: Vitamin D supplements were not used by most South Asians and intakes from diet alone are likely to be insufficient to maintain adequate vitamin D status. Public health strategies are now urgently required to promote the use of vitamin D supplements in these specific UK South Asian subgroups.

Association between maternal vitamin D status in pregnancy and neurodevelopmental outcomes in childhood: results from the Avon Longitudinal Study of Parents and Children (ALSPAC).

Seafood intake in pregnancy has been positively associated with childhood cognitive outcomes which could potentially relate to the high vitamin D content of oily fish. However, whether higher maternal vitamin D status (serum 25-hydroxyvitamin D (25(OH)D)) in pregnancy is associated with a reduced risk of offspring suboptimal neurodevelopmental outcomes is unclear. A total of 7065 mother-child pairs were studied from the Avon Longitudinal Study of Parents and Children cohort who had data for both serum total 25(OH)D concentration in pregnancy and at least one measure of offspring neurodevelopment (pre-school development at 6-42 months; 'Strengths and Difficulties Questionnaire' scores at 7 years; intelligence quotient (IQ) at 8 years; reading ability at 9 years). After adjustment for confounders, children of vitamin D-deficient mothers (<50·0 nmol/l) were more likely to have scores in the lowest quartile for gross-motor development at 30 months (OR 1·20; 95 % CI 1·03, 1·40), fine-motor development at 30 months (OR 1·23; 95 % CI 1·05, 1·44) and social development at 42 months (OR 1·20; 95 % CI 1·01, 1·41) than vitamin D-sufficient mothers (≥50·0 nmol/l). No associations were found with neurodevelopmental outcomes, including IQ, measured at older ages. However, our results suggest that deficient maternal vitamin D status in pregnancy may have adverse effects on some measures of motor and social development in children under 4 years. Prevention of vitamin D deficiency may be important for preventing suboptimal development in the first 4 years of life.

Energy expenditure, nutritional status, body composition and physical fitness of Royal Marines during a 6-month operational deployment in Afghanistan.

Understanding the nutritional demands on serving military personnel is critical to inform training schedules and dietary provision. Troops deployed to Afghanistan face austere living and working environments. Observations from the military and those reported in the British and US media indicated possible physical degradation of personnel deployed to Afghanistan. Therefore, the present study aimed to investigate the changes in body composition and nutritional status of military personnel deployed to Afghanistan and how these were related to physical fitness. In a cohort of British Royal Marines (n 249) deployed to Afghanistan for 6 months, body size and body composition were estimated from body mass, height, girth and skinfold measurements. Energy intake (EI) was estimated from food diaries and energy expenditure measured using the doubly labelled water method in a representative subgroup. Strength and aerobic fitness were assessed. The mean body mass of volunteers decreased over the first half of the deployment ( - 4·6 (sd 3·7) %), predominately reflecting fat loss. Body mass partially recovered (mean +2·2 (sd 2·9) %) between the mid- and post-deployment periods (P< 0·05). Daily EI (mean 10 590 (sd 3339) kJ) was significantly lower than the estimated daily energy expenditure (mean 15 167 (sd 1883) kJ) measured in a subgroup of volunteers. However, despite the body mass loss, aerobic fitness and strength were well maintained. Nutritional provision for British military personnel in Afghanistan appeared sufficient to maintain physical capability and micronutrient status, but providing appropriate nutrition in harsh operational environments must remain a priority.

Comparison of the Effect of Daily Vitamin D2 and Vitamin D3 Supplementation on Serum 25-Hydroxyvitamin D Concentration (Total 25(OH)D, 25(OH)D2, and 25(OH)D3) and Importance of Body Mass Index: A Systematic Review and Meta-Analysis.

BACKGROUND: Two previous meta-analyses showed smaller differences between vitamin D3 and vitamin D2 in raising serum 25-hydroxyvitamin D [25(OH)D] and a consistently high heterogeneity when only including daily dosing studies. OBJECTIVE: This study aimed to compare more frequently dosed vitamin D2 and vitamin D3 in improving total 25(OH)D and determine the concomitant effect of response modifiers on heterogeneity, and secondly, to compare the vitamin D2-associated change in 25(OH)D2 with the vitamin D3-associated change in 25(OH)D3. METHODS: PubMed, EMBASE, Cochrane, and the Web of Science Core collection were searched for randomized controlled trials of vitamin D2 compared with vitamin D3, daily or once/twice weekly dosed. After screening for eligibility, relevant data were extracted for meta-analyses to determine the standardized mean difference when different methods of 25(OH)D analyses were used. Otherwise, the weighted mean difference (WMD) was determined. RESULTS: Overall, the results based on 20 comparative studies showed vitamin D3 to be superior to vitamin D2 in raising total 25(OH)D concentrations, but vitamin D2 and vitamin D3 had a similar positive impact on their corresponding 25(OH)D hydroxylated forms. The WMD in change in total 25(OH)D based on 12 daily dosed vitamin D2-vitamin D3 comparisons, analyzed using liquid chromatography-tandem mass spectrometry, was 10.39 nmol/L (40%) lower for the vitamin D2 group compared with the vitamin D3 group (95% confidence interval: -14.62, -6.16; I2 = 64%; P < 00001). Body mass index (BMI) appeared to be the strongest response modifier, reducing heterogeneity to 0% in both subgroups. The vitamin D2- and vitamin D3-induced change in total 25(OH)D lost significance predominantly in subjects with a BMI >25 kg/m2 (P = 0.99). However, information on BMI was only available in 13/17 daily dosed comparisons. CONCLUSIONS: Vitamin D3 leads to a greater increase of 25(OH)D than vitamin D2, even if limited to daily dose studies, but vitamin D2 and vitamin D3 had similar positive impacts on their corresponding 25(OH)D hydroxylated forms. Next to baseline 25(OH)D concentration, BMI should be considered when comparing the effect of daily vitamin D2 and vitamin D3 supplementation on total 25(OH)D concentration. This study was registered in PROSPERO as CRD42021272674.

Determinant factors of bone health after long-term of Roux-en-Y gastric bypass surgery: A cross-sectional study.

OBJECTIVES: The aim of this study was to evaluate bone health and the potential influencing factors of bone metabolism disorders in adults ≥5 y after Roux-en-Y gastric bypass (RYGB) surgery. METHODS: In this cross-sectional study, patients who were ≥5 y post-RYGB were invited. Bone health considered as bone mineral content (BMC) and bone mineral density (BMD) in this study was assessed by dual x-ray absorptiometry. We also assessed 25-hydroxy-vitamin D concentrations, individual ultraviolet B radiation levels, serum ionized calcium, alkaline phosphatase, parathyroid, anthropometric, and body composition. RESULTS: The study evaluated 104 adults (90% women; 49.6 ± 9.1 y old; postoperative period 8.7 ± 2.2 y). Lumbar and femoral BMC and BMD were positively correlated to body mass index (BMI), appendicular lean mass (ALM), and negatively to %excess of weight loss (EWL). Femoral BMD was negatively correlated to age, and both femoral BMD and BMC were positively correlated to weekly exposed body part score. Sex, age, BMI, ALM, and weekly exposed body part score explained 35% and 54% of the total variance of femoral BMD and BMC, respectively. CONCLUSIONS: The present findings suggested that older age, lower BMI, higher %EWL, lower ALM, and lower weekly body part exposure score are important determinants in lowering BMD and BMC parameters in long-term post-bariatric surgery individuals, rather than serum 25-hydroxy-vitamin D and parathyroid.

The Food4Years Ageing Network: Improving foods and diets as a strategy for supporting quality of life, independence and healthspan in older adults.

By 2050, it is predicted that one in four people in the United Kingdom will be aged 65 years and over. Increases in lifespan are not always translated into years spent in good health. Incidence rates for chronic diseases are increasing, with treatments allowing people to live longer with their disease. There is good evidence to support changes to lifestyle to maintain or improve body composition, cognitive health, musculoskeletal health, immune function and vascular health in older adults. Much research has been done in this area, which has produced significant support for foods and nutrients that contribute to improved healthspan. Yet two major barriers remain: firstly, older adult consumers are not meeting current UK recommendations for macro- and micronutrients that could benefit health and quality of life and secondly, the UK-specific recommendations may not be sufficient to support the ageing population, particularly for nutrients with key physiological roles. More work is needed to improve intakes of specific foods, diets and nutrients by older adults, through a variety of mechanisms including (i) development of specific food products; (ii) improved clarity of information and (iii) appropriate marketing, and policy changes to enable incentives. The Food4Years Ageing Network aims to build a wide-reaching and multidisciplinary community that is committed to the development, integration and communication of healthy, affordable foods and specific diets for all older adults across the UK food landscape. The Network will identify evidence-based strategies for improving food intake and nutrition in older adults, paving the way to "living well while living longer."

Differences in vitamin D status and calcium metabolism in Saudi Arabian boys and girls aged 6 to 18 years: effects of age, gender, extent of veiling and physical activity with concomitant implications for bone health.

OBJECTIVE: Few data exist looking at vitamin D status and bone health in school-aged boys and girls from Saudi Arabia. The present study aimed to determine the extent of poor vitamin D status in school boys and girls aged 6-18 years and to examine if there was any difference in status with age, physical activity and veiling and concomitant effects on bone. DESIGN: Cross-sectional study. SETTING: Jeddah, Kingdom of Saudi Arabia. SUBJECTS: A total of 150 boys (7-16 years) and 150 girls (6-18 years) from local schools were divided into age categories: 6-9 years (elementary school); 10-12 years (secondary school); 13-14 years (middle years); 15-18 years (high school). RESULTS: Vitamin D status was significantly lower in girls than boys in all age groups (P < 0.01), with the 15-18-year-old girls having the lowest level (22.0 (SD 9.4) nmol/l) in comparison to the 15-18-year-old boys (39.3 (SD 14.0) nmol/l) and the 6-9-year-old girls (41.2 (SD 9.3) nmol/l). Parathyroid hormone status was highest in the 15-18-year-old girls in comparison to boys of the same age. A total of 64 % of 15-18-year-old girls had 25-hydroxyvitamin D (25OHD) status <25 nmol/l in comparison to 31 % in the 13-14 years age category, 26 % in the 10-12 years category and 2.5 % in the 6-9 years category. No boys had 25OHD status <25 nmol/l. Fully veiled girls had lower 25OHD status than partly veiled or unveiled girls (P < 0.05). Low 25OHD and high parathyroid hormone was associated with lower bone mass in the 6-9 years and 13-14 years age groups (P < 0.05). CONCLUSIONS: These data suggest significant hypovitaminosis D in older adolescent females, which is a cause for concern given that there is currently no public health policy for vitamin D in the Kingdom of Saudi Arabia.

Modifiable risk factors for bone health & fragility fractures.

Osteoporosis is an ageing disorder characterised by poor microstructural architecture of the bone and an increase in the risk of fragility fractures, which often leads to hospitalisation and eventually a loss of mobility and independence. By 2050, it is estimated that more than 30 million people in Europe will be affected by bone diseases, and European hospitalisation alone can approximately cost up to 3.5 billion euros each year [1]. Although inherited variation in bone mineral density (BMD) is pre-determined by up to 85% [2], there is a window of opportunity to optimise BMD and reduce fracture risk through key modifiable lifestyle factors during the life course. An optimal diet rich in micronutrients, such as calcium, vitamin D, and potassium, has long been considered an important modifiable component of bone health, which is attributed to their direct roles within bone metabolism. Recently, there has been emerging evidence to suggest that protein and even an adequate intake of fruit and vegetables may also play an important role in improving BMD [3,4]. Maintaining a physically active lifestyle is not only protective from non-communicable diseases such as cardiovascular disease but it also has been shown to lessen the risk of fractures later in life, thereby making it an imperative modifiable factor for bone health, particularly as it also supports peak bone mass attainment during childhood/adolescence and can facilitate the maintenance of bone mass throughout adulthood [5]. Other key lifestyle factors that could be potentially modified to reduce the risk of osteoporosis or osteoporotic fractures later in life include smoking status, alcohol intake, and body composition [6]. Therefore, the principle aim of this review is to highlight the recent evidence pertaining to modifiable lifestyle factors that contribute to optimal bone health and the prevention of fragility fractures in later life.

Lack of significant seasonal association between serum 25(OH)D concentration, muscle mass and strength in postmenopausal women from the D-FINES longitudinal study.

The aim of the present study was to assess the seasonal relationship between serum 25(OH)D concentration, lean mass and muscle strength. This was a secondary data analysis of a subgroup of 102 postmenopausal women participating in the 2006-2007 D-FINES (Vitamin D, Food Intake, Nutrition and Exposure to Sunlight in Southern England) study. The cohort was assessed as two age subgroups: <65 years (n=80) and ≥65 years (n=22). Outcome measures included lean mass (DXA), muscle strength (handgrip dynamometry) and serum 25(OH)D concentration (enzymeimmunoassay). Derived outcomes included appendicular skeletal muscle mass (ASM) and relative appendicular skeletal muscle index (RASM). Sarcopenia status was assessed using the European Working Group on Sarcopenia in Older People 2018 criteria. Non-parametric partial correlation using BMI as a covariate was used to evaluate the study aims. There were no statistically significant associations between total lean mass, ASM or RASM and 25(OH)D in any group at any season. There was a trend for handgrip strength to be positively associated with serum 25(OH)D concentration. There was a trend showing a higher prevalence of sarcopenia in women ≥65 years. Sarcopenia status appeared transient for five women. In conclusion, the present study found no significant association between vitamin D status and functional indicators of musculoskeletal health, which were additionally not affected by season.

Frequency of Vitamin D Deficiency and Associated Factors in Long-term Bariatric Surgery Patients: a Cross-sectional Study.

BACKGROUND: Vitamin D deficiency is a common consequence of bariatric surgery (BS). However, few studies have evaluated influential factors and to date there are no studies investigating individual ultraviolet B (UVB) radiation levels in BS patients. This study aimed to evaluate vitamin D deficiency and its associated factors, including UVB radiation, in Roux-Y gastric bypass (RYGB) patients. METHODS: This study included 104 adults (90.4% female) at least 5 years after RYGB. Patients underwent surgery in private hospitals (Private; n = 47) or in two public hospitals, one with ongoing outpatient care (Active; n = 17), and the other with discontinued service for BS (Discontinued; n = 40). 25-hydroxyvitamin D (25(OH)D) concentrations were analyzed by chemiluminescence, individual UVB radiation levels by dosimeter badges. Vitamin D intake, anthropometric, skin phototype, sociodemographic and lifestyle patterns were also assessed. RESULTS: Mean age was 49.6 ± 9.1 years and post-operative period 8.7 ± 2.2 years. The prevalence of 25(OH)D deficiency and insufficiency was 25.0% and 51.9% respectively. 25(OH)D concentration differed among the hospitals (private = 26.2 ± 8.5; active = 28.7 ± 11.4; discontinued = 23.5 ± 6.5 ng/mL; p = 0.038). A total of 26.2% of the variance observed in 25(OH)D concentrations was explained by daily UVB radiation levels (ß = 0.224; p = 0.032) and vitamin D intake (ß = 0.431; p < 0.001), controlling for age and BMI. CONCLUSION: A quarter of the evaluated patients presented vitamin D deficiency, which was associated with the discontinuation of the health care, higher BMI, lower vitamin D intake, and lower individual UVB radiation levels.