Performance of FRAX in older adults with frailty: the Framingham Heart Study.

We compared the performance of FRAX according to frailty status in 3554 individuals from the Framingham Study. During 10-year follow-up, 6.9% and 3.0% of participants with and without frailty experienced MOF. Discrimination profiles were lower in participants with frailty compared to those without, but they improved when FRAX included BMD. INTRODUCTION: Frailty increases fracture risk. FRAX was developed to predict fractures but never validated in individuals with frailty. We aimed to compare the predictive performance of FRAX (v4.3) in individuals with and without frailty. METHODS: We conducted a cohort study using the Framingham Heart Study. Frailty was defined by the Fried phenotype. Major osteoporotic fractures (MOF) were ascertained from medical records during 10-year follow-up. To evaluate discrimination and calibration of FRAX, we calculated the area-under-the-receiver-operating characteristics curves (AUC) using logistic regression models and observed-to-predicted fracture probabilities. Analyses were stratified by frailty status. RESULTS: Frailty was present in 550/3554 (15.5%) of participants. Participants with frailty were older (81.1 vs. 67.6 years), female (68.6% vs. 55.1%), and had greater mean FRAX scores (MOF: 15.9% vs. 10.1%) than participants without frailty. During follow-up, 38 participants with frailty (6.9%) and 91 without (3.0%) had MOFs. The AUC for FRAX (without BMD) was lower in participants with frailty (0.584; 95% CI 0.504-0.663) compared to those without (0.695; 95% CI 0.649-0.741); p value = 0.02. Among participants with frailty, the AUC improved when FRAX included BMD (AUC 0.658, p value < 0.01). FRAX overestimated MOF risk, with larger overestimations in individuals without frailty. Performance of FRAX for hip fracture was similar. CONCLUSION: FRAX may have been less able to identify frail individuals at risk for fracture, as compared with individuals without frailty, unless information on BMD is available. This suggests that BMD captures features important for fracture prediction in frail persons. Future fracture prediction models should be developed among persons with frailty.

Higher abdominal adiposity is associated with higher lean muscle mass but lower muscle quality in middle-aged and older men and women: the Framingham Heart Study.

BACKGROUND: The objective was to determine if abdominal fat is related to poor muscle health. METHODS: This cross-sectional study included 428 males and 534 females with appendicular lean mass (ALM, kg) from dual-energy X-ray absorptiometry (DXA), grip strength (kg), and upper extremity muscle "quality" (grip strength/arm lean mass) measured (1996-2001) in the Framingham Offspring Study. Sex-specific linear regressions associated adiposity measures [waist circumference (WC, cm) and visceral adipose tissue (VAT, cm3), and subcutaneous adipose tissue (SAT, cm3)] as Z-scores with each measure of muscle, adjusting for covariates. Models were further stratified by body mass index (BMI, < 30, ≥ 30 kg/m2). RESULTS: Mean (± SD) age was 60 ± 9 years and BMI was 28.9 ± 4.6 kg/m2 (men) and 27.7 ± 5.8 kg/m2, (women). In men, the BMI-stratified analyses showed higher WC was associated with higher ALM (P < 0.0001 each) but with lower muscle quality (P < 0.02) in both BMI groups. Higher SAT was also associated with higher ALM (P = 0.0002) and lower muscle quality (P = 0.0002) in men with BMI < 30, but not in obese men. In women, higher WC, SAT, and VAT were each associated with higher ALM but lower muscle quality, particularly in obese women. Higher SAT (P = 0.05) and VAT (P = 0.04) were associated with higher quadriceps strength in women with BMI < 30 kg/m2 but not in obese women. CONCLUSIONS: Higher abdominal fat may be associated with greater lean mass but poorer muscle quality, particularly in obese women. This suggests that adipose tissue may have endocrine influences on muscle, which should be confirmed in longitudinal studies.

Dairy food intake is not associated with spinal trabecular bone score in men and women: the Framingham Osteoporosis Study.

BACKGROUND: Previous studies reported that dairy foods are associated with higher areal bone mineral density (BMD) in older adults. However, data on bone texture are lacking. We determined the association of dairy food intake (milk, yogurt, cheese, milk + yogurt and milk + yogurt + cheese) with spinal trabecular bone score (TBS). METHODS: In this cross-sectional study, a validated semi-quantitative food frequency questionnaire was used to assess dairy food intake (servings/wk). TBS, an analysis of bone texture, was calculated from dual energy X-ray absorptiometry (DXA) scans. Sex-specific multivariable linear regression was used to estimate the association of dairy food intake (energy adjusted via residual methods) with each bone measure adjusting for covariates. RESULTS: Mean age of 4,740 participants was 49 (SD: 13) years and mean milk + yogurt + cheese intake was 10.1 (SD: 8.4) servings/week in men and 10.9 (SD: 8.0) servings/week in women. There were no associations between dairy food intake and spinal TBS in adjusted models. CONCLUSIONS: In this cohort of primarily healthy adults, dairy intake was not associated with bone texture.

Association of dietary fiber and risk of hip fracture in men from the Framingham Osteoporosis Study and the Concord Health and Ageing in Men Project.

BACKGROUND: Data in the Offspring Framingham Osteoporosis Study (FOS) suggested that higher intake of dietary fiber was modestly protective against loss of bone mineral density at the femoral neck in men but not in women. AIM: To examine the relationship of fiber intake with risk of hip fractures in men. METHODS: We included 367 men from the FOS Original cohort, 1730 men from the FOS Offspring cohort, and 782 men from the Concord Health and Ageing in Men Project (CHAMP) in the analysis. Incident fractures were defined as medically confirmed first occurrence of osteoporotic fractures at the proximal femur. Fiber intake was estimated via a validated food frequency questionnaire (FFQ) or diet history. Cox proportional hazards models were applied to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). A random-effects model was used to estimate the pooled relative risk in meta-analysis. RESULTS: Seventy-two incident hip fractures were identified, of which 24 occurred in the FOS Original cohort [mean (SD): age 75.3 (5.1) years; follow-up time: 8.5 (6.2) years; dietary fiber: 19 (8) (g/d)], 19 in the FOS Offspring cohort [58.8 (9.8) years; 11.0 (5.9) years; 19 (8) (g/d)], and 29 in CHAMP [81.4 (4.5) years; 5.2 (1.5) years; 28 (10) (g/d)]. We did not find significant associations within each cohort between fiber intake and risk of hip fractures. The pooled HR (95% CI) was 0.80 (0.39, 1.66) comparing energy-adjusted dietary fiber at tertile 3 vs. tertile 1 (I2 = 0, p = 0.56). CONCLUSION: These data suggested that dietary fiber was not associated with risk of incident hip fractures in men.

Dairy intake and bone health across the lifespan: a systematic review and expert narrative.

Over the past 30-years, the U.S. Dietary Guidelines for Americans have included recommendations around dairy consumption, largely based on meeting recommendations for calcium intake with the intended purpose of osteoporosis prevention. Although dairy products provide more bone-beneficial nutrients (e.g., calcium, magnesium, potassium, zinc, phosphorus, and protein) per unit of energy than any other food group, the relevance of dairy products for long-term bone health and fracture prevention has resurged as some observational studies have suggested consumption to be associated with a greater risk of fractures. Given this controversy, we sought to synthesize the evidence on dairy consumption and bone health across the lifespan. We searched the PubMed, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials databases for English-language publications through June 2, 2020. Case-controlled, cross-sectional, prospective cohort or nestled case-control (or case cohort), and clinical trials reporting the effect of dairy products on bone mineral density, bone mineral content, and/or fractures were included in the systematic review. Two reviewers independently performed data extractions. Data from 91 publications, including 30 RCTs, 28 prospective cohorts, 23 cross-sectional studies, and 10 case-control studies were included in the systematic review. We assigned a "D" grade or "insufficient evidence" for the effect of dairy in infants and toddlers (0- to <36-months), children (3- to <10-years), and young adults (19- to <50-years). A "C" grade or "limited evidence" was assigned for the effect of dairy in adolescents (10- to <19-years). A "B" grade or "moderate" evidence was assigned for the effect of dairy in middle aged to older adults (≥50-years). Research on bone mass in adults between the ages of 20- to 50-years and individuals from other ethnic groups apart from Chinese females and Caucasians is greatly needed. Daily intake of low or nonfat dairy products as part of a healthy habitual dietary pattern may be associated with improved BMD of the total body and at some sites and associated with fewer fractures in older adults.

Higher Dairy Intakes Are Associated with Higher Bone Mineral Density among Adults with Sufficient Vitamin D Status: Results from the Boston Puerto Rican Osteoporosis Study.

Background: Dairy foods have been shown to improve bone mineral density (BMD) in non-Hispanic whites. Puerto Rican adults have a higher prevalence of osteoporosis and vitamin D deficiency than non-Hispanic whites. However, there is little understanding of lifestyle influences on bone in this population. Objective: The aim of this study was to examine associations of dairy intakes with BMD among adults from the Boston Puerto Rican Osteoporosis Study with and without adequate serum vitamin D status. Methods: A total of 904 participants in this cross-sectional analysis provided dietary intakes with a culturally tailored food-frequency questionnaire. Dairy food groups were calculated [total dairy, modified dairy (without cream or dairy desserts), fluid dairy (milk + yogurt), cheese, yogurt, and cream and desserts]. BMD (grams per centimeter squared) was measured using dual-energy X-ray absorptiometry. Vitamin D status was defined as sufficient (serum 25-hydroxyvitamin D [25(OH)D] ≥20 ng/mL) or insufficient (<20 ng/mL). General linear models were used to examine associations between dairy intake and BMD, stratified by vitamin D status. Results: Of the total sample, 73% were women, of whom 87% were postmenopausal. Mean ± SD age was 60.0 ± 7.6 y and mean ± SD body mass index (kg/m2) was 32.3 ± 6.6. Mean serum 25(OH)D (range: 4-48 ng/mL) was 14.3 ± 3.6 ng/mL in insufficient individuals and 26.0 ± 5.5 ng/mL in sufficient individuals. In the full sample, higher intakes of modified dairy foods (ß = 0.0015, P = 0.02) and milk (ß = 0.0018, P = 0.04) were associated with higher femoral neck (FN) BMD. Among those who were vitamin D sufficient, higher intakes of total dairy (P = 0.03-0.07), fluid dairy (P = 0.01-0.05), and milk (P = 0.02-0.09) were significantly related to higher FN and lumbar spine BMD, respectively. Among vitamin D-insufficient participants, dairy intakes were not associated with BMD (P-range = 0.11-0.94). Conclusions: Dairy food intakes were associated with higher BMD among adults, particularly those with sufficient vitamin D status. Future studies should confirm findings longitudinally and assess culturally acceptable lifestyle interventions to improve bone health among Hispanic adults. This trial was registered at clinicaltrials.gov as NCT01231958.

Dairy Intake Is Protective against Bone Loss in Older Vitamin D Supplement Users: The Framingham Study.

Background: Previous studies showed beneficial effects of specific dairy foods on bone health in middle-aged adults.Objective: We examined the association of milk, yogurt, cheese, cream, fluid dairy (milk + yogurt), and milk + yogurt + cheese intakes with bone mineral density (BMD) and 4-y percentage of change in BMD [▵%BMD; femoral neck, trochanter, and lumbar spine (LS)]. We further assessed whether these associations were modified by vitamin D supplement use in this cohort of older adults.Methods: Food-frequency questionnaire responses, baseline BMD (hip and spine, n = 862 in 1988-1989), and follow-up BMD (n = 628 in 1992-1993) were measured in the Framingham study, a prospective cohort study of older Caucasian men and women aged 67-93 y. Outcomes included baseline BMD and ▵%BMD. Dairy-food intakes (servings per week) were converted to energy-adjusted residuals, and linear regression was used, adjusting for covariates. These associations were further examined by vitamin D supplement use.Results: The mean age of the participants was 75 y. In the full sample, dairy-food items were not associated with BMD (P = 0.11-0.99) or with ▵%BMD (P = 0.29-0.96). Among vitamin D supplement users, but not among nonusers, higher milk, fluid dairy, and milk + yogurt + cheese intakes were associated with higher LS BMD (P = 0.011-0.009). Among vitamin D supplement users, but not among nonusers, higher milk + yogurt + cheese intakes were protective against trochanter BMD loss (P = 0.009).Conclusions: In this population of older adults, higher intakes of milk, fluid dairy, and milk + yogurt + cheese were associated with higher LS BMD, and a higher intake of milk + yogurt + cheese was protective against trochanter BMD loss among vitamin D supplement users but not among nonusers. These findings underscore that the benefits of dairy intake on the skeleton may be dependent on vitamin D intake.

Higher Protein Intake Is Associated with Higher Lean Mass and Quadriceps Muscle Strength in Adult Men and Women.

BACKGROUND: The impact of dietary protein intake on lower extremity lean mass and strength in community-dwelling adult Americans is not fully understood. OBJECTIVES: The objective was to determine the associations between total protein (TP), animal protein (AP), and plant protein (PP) intakes and lean mass of the legs and quadriceps muscle strength. We further examined whether the associations with quadriceps strength may be explained by lean mass of the legs. METHODS: This cross-sectional study included men (n = 1166) and women (n = 1509) from the Framingham Offspring Cohort in Massachusetts. Protein intake in grams per day was measured in either 1995-1998 or 1998-2001. Leg lean mass and isometric quadriceps strength, both in kilograms, were measured in 1996-2001. Multilinear regression models estimated adjusted least squares means of each of the muscle measures by quartile categories of protein intake, adjusting for relevant confounders and covariates. RESULTS: Mean age was 59 ± 9 y (range: 29-86 y) and TP intake was 80 ± 27 g/d in men and 76 ± 26 g/d in women. In men and women, leg lean mass was higher in participants in the highest quartiles of TP and AP intake compared with those in the lowest quartiles of intake [least squares means (kg): TP-17.6 vs. 17.1 in men, P-trend: 0.005, and 11.7 vs. 11.4 in women, P-trend: 0.006; AP-17.6 vs. 17.1 in men, P-trend: 0.002, and 11.7 vs. 11.4 in women, P-trend: 0.003]. PP intake was not associated with lean mass in either sex. In men and women, quadriceps strength was higher in participants in the highest quartile of PP intake compared with those in the lowest quartile [least squares means (kg): 22.9 vs. 21.7 in men, P-trend: 0.01, and 19.0 vs. 18.2 in women, P-trend: 0.01]; this association was no longer significant after adjustment for fruit and vegetable intake (P-trend: 0.06 in men and 0.10 in women). Although no significant association was observed for AP intake in either sex, nonsignificant protective trends were observed for TP intake (P-trend: 0.08 in men and 0.10 in women). CONCLUSIONS: Our findings suggest that maintaining adequate protein intake with age may help preserve muscle mass and strength in adult men and women. Dietary protein types may differentially affect muscle mass and strength. Whether PP is a marker of dietary quality or has a direct effect on muscle strength (independent of lean mass) needs to be further clarified.

Dietary Approaches for Bone Health: Lessons from the Framingham Osteoporosis Study.

Osteoporosis is characterized by systemic impairment of bone mass, strength, and microarchitecture, resulting in increased risk for fragility fracture, disability, loss of independence, and even death. Adequate nutrition is important in achieving and maintaining optimal bone mass, as well as preventing this debilitating disease. It is widely accepted that adequate calcium and vitamin D intake are necessary for good bone health; however, nutritional benefits to bone go beyond these two nutrients. This review article will provide updated information on all nutrients and foods now understood to alter bone health. Specifically, this paper will focus on related research from the Framingham Osteoporosis Study, an ancillary study of the Framingham Heart Study, with data on more than 5000 adult men and women.

Dietary protein is beneficial to bone health under conditions of adequate calcium intake: an update on clinical research.

PURPOSE OF REVIEW: To underscore recent clinical studies, which evaluate the association between dietary protein and bone health. RECENT FINDINGS: Epidemiologic studies show greater protein intake to be beneficial to bone health in adults. In addition, randomized controlled trials show that protein's positive effect on bone health is augmented by increased calcium intake. The relation between dietary protein and fracture risk is unclear. Dietary protein may positively impact bone health by increasing muscle mass, increasing calcium absorption, suppressing parathyroid hormone, and augmenting insulin-like growth factor 1 production; but the effects of other factors that contribute to this association, such as dietary protein dose and timing response, require further research. SUMMARY: The positive effects of protein intake on bone health may only be beneficial under conditions of adequate calcium intake. Dietary protein's relation with fracture risk requires further investigation.

Association of total protein intake with bone mineral density and bone loss in men and women from the Framingham Offspring Study.

OBJECTIVE: To examine (i) the association of percentage of total energy intake from protein (protein intake %) with bone mineral density (BMD, g/cm2) and bone loss at the femoral neck, trochanter and lumbar spine (L2-L4) and (ii) Ca as an effect modifier. SETTING: The Framingham Offspring Study. SUBJECTS: Men (n 1280) and women (n 1639) completed an FFQ in 1992-1995 or 1995-1998 and underwent baseline BMD measurement by dual-energy X-ray absorptiometry in 1996-2000. Men (n 495) and women (n 680) had follow-up BMD measured in 2002-2005. DESIGN: Cohort study using multivariable regression to examine the association of protein intake % with each BMD, adjusting for covariates. Statistical interaction between protein intake % and Ca (total, dietary, supplemental) intake was examined. RESULTS: The mean age at baseline was 61 (sd 9) years. In the cross-sectional analyses, protein intake % was positively associated with all BMD sites (P range: 0·02-0·04) in women but not in men. Significant interactions were observed with total Ca intake (<800 mg/d v. ≥800 mg/d) in women at all bone sites (P range: 0·002-0·02). Upon stratification, protein intake % was positively associated with all BMD sites (P range: 0·04-0·10) in women with low Ca intakes but not in those with high Ca intakes. In the longitudinal analyses, in men, higher protein intake % was associated with more bone loss at the trochanter (P = 0·01) while no associations were seen in women, regardless of Ca intake. CONCLUSIONS: This suggests that greater protein intake benefits women especially those with lower Ca intakes. However, protein effects are not significant for short-term changes in bone density. Contrastingly, in men, higher protein intakes lead to greater bone loss at the trochanter. Longer follow-up is required to examine the impact of protein on bone loss.

Polyunsaturated fatty acids and their relation with bone and muscle health in adults.

Age-related bone and muscle loss are major public health problems. Investigational therapies to reduce these losses include anti-inflammatory dietary supplementations, such as polyunsaturated fatty acids (PUFA). Surprisingly, this topic has received little attention in the osteoporosis community. Recent research highlights the role of PUFA in inflammatory regulation of bone remodeling via cellular pathways. Emerging research suggests significant roles for PUFA in reducing bone and muscle loss with aging; however, findings are conflicted for PUFA and fracture risk. Limited studies suggest a relation between higher omega-3 FA and better muscle/bone in older adults. This review highlights new research since 2008 and synthesizes our current understanding of PUFA in relation to bone and muscle. Across study designs, evidence indicates that PUFA has positive effects upon bone. As data are sparse, future clinical trials and prospective studies are important to determine the long term benefits of PUFA supplementation upon bone and muscle outcomes.

Association of Proinflammatory Diet With Frailty Onset Among Adults With and Without Depressive Symptoms: Results From the Framingham Offspring Study.

BACKGROUND: Dietary inflammation is associated with increased risk of frailty. Those with depressive symptoms may be at higher risk of frailty onset because they typically have higher levels of inflammation. The study objective was to determine the association between a proinflammatory diet and frailty onset in those with and without clinically relevant depressive symptoms. METHODS: This prospective study included 1 701 nonfrail individuals with self-reported baseline (1998-2001) data available for the evaluation of energy-adjusted dietary inflammatory index (E-DIITM; calculated from food frequency questionnaires), depressive symptoms (from the Center for Epidemiologic Studies Depression; CES-D), and follow-up frailty measurements (2011-2014). Frailty was defined as fulfilling ≥3 Fried frailty criteria (i.e., slow gait, weak grip strength, unintentional weightloss, low physical activity, and self-reported exhaustion). Results are presented by baseline CES-D scores <16 or ≥16 points, which denotes the absence or presence of clinically relevant depressive symptoms, respectively. Logistic regression estimated odds ratios (OR) and 95% confidence intervals (95% CI) between E-DII and frailty onset, adjusting for confounders. RESULTS: In all study participants, mean (SD) age was 58(8) years and E-DII was -1.95 (2.20; range: -6.71 to +5.40, higher scores denote a more proinflammatory diet), and 45% were male. In those without clinically relevant depressive symptoms, 1-unit higher E-DII score was associated with 14% increased odds (95% CI: 1.05-1.24) of frailty. In those with depressive symptoms, 1-unit higher E-DII score was associated with 55% increased odds of frailty (95% CI: 1.13-2.13). CONCLUSIONS: The association between inflammatory diet and increased odds of frailty appeared somewhat stronger among those with depressive symptoms. This preliminary finding warrants further investigation.

Dairy Food Intake Is Not Associated With Frailty in Adults From the Framingham Heart Study.

BACKGROUND: Nutrients, including protein, calcium, and fat may be associated with risk of frailty, yet specific contributions from whole dairy foods rich in these nutrients remain understudied. OBJECTIVE: To determine associations between dairy intake (milk, yogurt, cheese, total (milk + yogurt + cheese), low-fat and high-fat dairy, and servings per week) and frailty onset and frailty phenotype components. DESIGN: Prospective cohort study. All dairy intake exposures (servings per week) were assessed via a food frequency questionnaire. PARTICIPANTS AND SETTING: Participants (aged 33 to 86 years) from the Framingham Offspring Study who were not frail at baseline (1998-2001) completed a food frequency questionnaire and had 1 or 2 follow-up frailty assessments (2005-2008 and 2011-2014) were included. MAIN OUTCOME MEASURES: Frailty was defined as the presence of ≥3 Fried frailty phenotype components: unintentional weight-loss, exhaustion, slowness (gait speed), weakness (grip strength), and low physical activity. Individuals with zero to two components were considered nonfrail. STATISTICAL ANALYSES PERFORMED: Repeated measures logistic regression estimated odds ratios and 95% CIs for frailty onset. Logistic (exhaustion and weight loss) and linear regression (gait speed, grip strength, and physical activity) estimated the association between baseline dairy intake and each frailty component at follow-up, adjusting for baseline values for age, sex, energy intake (residual analysis), current smoking, and multivitamin use. Models were further adjusted for health status in a secondary analysis. RESULTS: Mean baseline age ± SD was 61 ± 9 years (range = 33 to 87 years), and 54% were women. Of 2,550 nonfrail individuals at baseline, 8.8% (2005-2008) and 13.5% (2011-2014) became frail. Higher yogurt intake was associated with decreased odds of frailty (odds ratio 0.96, 95% CI 0.93 to 0.99; P = 0.02). Each additional serving of yogurt (ß ± SE) .004 ± .001; P < 0.01) and low-fat dairy (ß ± SE) .001 ± .0006; P = 0.04) was associated with significantly faster follow-up gait speed. Dietary intakes of high-fat dairy were associated with increased odds of frailty (odds ratio 1.02, 95% CI 1.00 to 1.04; P = 0.05), but the P value was of borderline significance. No associations were observed for other dairy foods. After adjusting for health status, the associations of high-fat dairy and yogurt with frailty became nonsignificant, although the magnitudes of the associations did not change. The association between yogurt and gait speed decreased in magnitude after adjusting for health status (ß ± SE) .002 ± .001; P = 0.01). CONCLUSIONS: Dietary intakes of yogurt were modestly associated with reduced frailty onset and dietary intakes of high-fat dairy had a borderline association with increased odds of frailty, but other dairy food intakes showed no association in this study of healthy adults. Some dairy food intakes were modestly associated with follow-up gait speed. However, effect sizes were small, and the clinical importance of these associations remains undetermined.

Higher intake of dietary flavonols, specifically dietary quercetin, is associated with lower odds of frailty onset over 12 years of follow-up among adults in the Framingham Heart Study.

BACKGROUND: Polyphenolic antioxidants derived from plant foods may reduce oxidative stress and frailty, but the effect of the polyphenol subclass of dietary flavonoids and their subclasses on frailty is uncertain. OBJECTIVES: To determine the association between dietary flavonoids, their subclasses, quercetin (a specific flavonol), and frailty onset in adults. METHODS: This prospective cohort study included individuals from the Framingham Heart Study with no frailty at baseline. Intake of total flavonoids, subclasses of flavonoids (flavonols, flavan-3-ols, flavonones, flavones, anthocyanins, and polymeric flavonoids), and quercetin were estimated via semi-quantitative FFQ along with frailty (Fried phenotype), and covariates at baseline (1998-2001). Frailty was re-evaluated in 2011-2014. Logistic regression estimated OR and 95% CIs for each flavonoid variable and frailty onset. RESULTS: Mean age was 58.4 y (SD ± 8.3, n = 1701; 55.5% women). The mean total flavonoid intake was 309 mg/d (SD ± 266). After 12.4 (SD ± 0.8) y, 224 (13.2%) individuals developed frailty. Although total flavonoid intake was not statistically associated with frailty onset (adjusted OR: 1.00; 95% CI: 0.99-1.01), each 10 mg/d of higher flavonol intake was linked with 20% lower odds of frailty onset (OR: 0.80; 95% CI: 0.67-0.96). Other subclasses showed no association (P values range: 0.12-0.99), but every 10 mg/d of higher quercetin intake was associated with 35% lower odds of frailty onset (OR: 0.65; 95% CI: 0.48-0.88). CONCLUSIONS: Although no association was observed between total flavonoid intake and frailty onset in adults, a higher intake of flavonols was associated with lower odds of frailty onset, with a particularly strong association for quercetin. This hypothesis-generating study highlights the importance of assessing specific subclasses of flavonoids and the potential of dietary flavonols and quercetin as a strategy to prevent the development of frailty.

Association of Vascular Health Measures and Physical Function: A Prospective Analysis in the Framingham Heart Study.

BACKGROUND: Dysfunction in blood vessel dynamics may contribute to changes in muscle measures. Therefore, we examined associations of vascular health measures with grip strength and gait speed in adults from the Framingham Heart Study. METHODS: The cross-sectional study (1998-2001) included participants with 1 measure of grip strength (kg, dynamometer) or gait speed (4-m walk, m/s) and at least 1 measure of aortic stiffness (carotid-femoral pulse wave velocity, brachial pulse pressure, and brachial flow pulsatility index) or brachial artery structure and function (resting flow velocity, resting brachial artery diameter, flow-mediated dilation %, hyperemic brachial blood flow velocity, and mean arterial pressure [MAP]) assessed by tonometry and brachial artery ultrasound. The longitudinal study included participants with ≥1 follow-up measurement of gait speed or grip strength. Multivariable linear regression estimated the association of 1 standard deviation (SD) higher level of each vascular measure with annualized percent change in grip strength and gait speed, adjusting for covariates. RESULTS: In cross-sectional analyses (n = 2 498, age 61 ± 10 years; 56% women), higher resting brachial artery diameter (ß ± standard error [SE] per 1 SD: 0.59 ± 0.24, p = .01) and MAP (ß ± SE: 0.39 ± 0.17, p = .02) were associated with higher grip strength. Higher brachial pulse pressure (ß ± SE: -0.02 ± 0.01, p = .07) was marginally associated with slower gait speed. In longitudinal analyses (n = 2 157), higher brachial pulse pressure (ß ± SE: -0.19 ± 0.07, p = .005), was associated with slowing of gait speed but not with grip strength. CONCLUSIONS: Higher brachial artery pulse pressure (measure of aortic stiffness) was associated with loss of physical function over ~11 years, although we found no evidence that microvascular function contributed to the relation.

A two-cohort study on the association between the gut microbiota and bone density, microarchitecture, and strength.

The gut microbiome affects the inflammatory environment through effects on T-cells, which influence the production of immune mediators and inflammatory cytokines that stimulate osteoclastogenesis and bone loss in mice. However, there are few large human studies of the gut microbiome and skeletal health. We investigated the association between the human gut microbiome and high resolution peripheral quantitative computed tomography (HR-pQCT) scans of the radius and tibia in two large cohorts; Framingham Heart Study (FHS [n=1227, age range: 32 - 89]), and the Osteoporosis in Men Study (MrOS [n=836, age range: 78 - 98]). Stool samples from study participants underwent amplification and sequencing of the V4 hypervariable region of the 16S rRNA gene. The resulting 16S rRNA sequencing data were processed separately for each cohort, with the DADA2 pipeline incorporated in the16S bioBakery workflow. Resulting amplicon sequence variants were assigned taxonomies using the SILVA reference database. Controlling for multiple covariates, we tested for associations between microbial taxa abundances and HR-pQCT measures using general linear models as implemented in microbiome multivariable association with linear model (MaAslin2). Abundance of 37 microbial genera in FHS, and 4 genera in MrOS, were associated with various skeletal measures (false discovery rate [FDR] ≤ 0.1) including the association of DTU089 with bone measures, which was independently replicated in the two cohorts. A meta-analysis of the taxa-bone associations further revealed (FDR ≤ 0.25) that greater abundances of the genera; Akkermansia and DTU089, were associated with lower radius total vBMD, and tibia cortical vBMD respectively. Conversely, higher abundances of the genera; Lachnospiraceae NK4A136 group, and Faecalibacterium were associated with greater tibia cortical vBMD. We also investigated functional capabilities of microbial taxa by testing for associations between predicted (based on 16S rRNA amplicon sequence data) metabolic pathways abundance and bone phenotypes in each cohort. While there were no concordant functional associations observed in both cohorts, a meta-analysis revealed 8 pathways including the super-pathway of histidine, purine, and pyrimidine biosynthesis, associated with bone measures of the tibia cortical compartment. In conclusion, our findings suggest that there is a link between the gut microbiome and skeletal metabolism.

Adherence to the Mediterranean-style diet and high intake of total carotenoids reduces the odds of frailty over 11 years in older adults: Results from the Framingham Offspring Study.

BACKGROUND: The benefit of a Mediterranean-style diet in reducing frailty is not well established in older Americans. OBJECTIVES: We sought to determine associations of a Mediterranean-style dietary pattern and related antioxidants with frailty onset and worsening of the Fried phenotype in adults. METHODS: This prospective study included 2384 nonfrail adults from the Framingham Offspring Study with a Mediterranean-style dietary pattern score (MSDPS) and data on antioxidant intakes (vitamin C, E, and total carotenoids) estimated from an FFQ at the index examination (1998-2001) and 1 prior examination (if available), as well as a frailty assessment at the index examination and at least 1 follow-up. Frailty onset was defined as ≥3 of 5 Fried frailty phenotype criteria at follow-up and the worsening of the Fried frailty phenotype was defined as an increased number of frailty criteria over follow-up (yes or no). Logistic regression with generalized estimating equations estimated ORs and 95% CIs, adjusting for confounders. Analyses were stratified by age (<60 and ≥60 years) for significant interactions. RESULTS: The mean ± SD age was 60 ± 9 years (range, 33-86 years) and 55% were female. In adjusted models, a 1-unit higher MSDPS reduced the odds of frailty by 3% (OR, 0.97; 95% CI: 0.96-0.99). Each 10-mg higher total carotenoid and vitamin E intake reduced the odds of frailty by 16% (OR, 0.84; 95% CI: 0.73-0.98) and 1% (OR, 0.99; 95% CI: 0.98-1.00), respectively. No association with vitamin C (P = 0.36) was observed. The associations among participants aged <60 years of age were stronger for each 1-unit higher MSDPS (OR, 0.93; 95% CI: 0.89-0.96) and total carotenoid intake (OR, 0.59; 95% CI: 0.41-0.82) than those observed in older individuals [ORs, 0.98 (95% CI: 0.97-1.00) and 0.92 (95% CI: 0.79-1.08), respectively]. CONCLUSIONS: Our findings suggest that adherence to a Mediterranean-style diet and higher total carotenoid intake are associated with frailty prevention over time, particularly in adults <60 years.

Serum 25-Hydroxyvitamin D is Associated With Bone Microarchitecture and Strength in a Multiracial Cohort of Young Adults.

PURPOSE: To determine whether 25-hydroxyvitamin D (25-OH D) levels are associated with bone outcomes in a multiracial cohort of young adults. METHODS: This cross-sectional study included 165 participants (83 men, 82 women, 18-30 years of age) who self-identified as Asian, Black, or White. We measured bone microarchitecture and strength of the distal radius and tibia using high-resolution peripheral quantitative computed tomography. We used linear regression to estimate the association between 25-OH D (ng/mL) and bone measurements, adjusting for race, sex, age, weight, height, calcium intake, physical activity, and season. RESULTS: A total of 43.6% of participants were 25-OH D deficient (<20 ng/mL) with greater prevalence in Asian (38.9%) and Black (43.1%) compared with White (18.0%) participants (P < 0.001). At the distal radius, 25-OH D was positively associated with cortical area, trabecular density, cortical thickness, cortical porosity, and failure load (P < 0.05 for all). At the distal tibia, higher 25-OH D was associated with higher cortical area, trabecular density, trabecular number, failure load, and lower trabecular separation and cortical density (P < 0.05 for all). After multivariable adjustment, those with 25-OH D deficiency had generally worse bone microarchitecture than those with 25-OH D sufficiency. Black individuals had largely more favorable bone outcomes than Asian and White individuals, despite higher prevalence of 25-OH D deficiency. CONCLUSIONS: We found a high prevalence of 25-OH D deficiency in a multiracial cohort of young adults. Lower 25-OH D was associated with worse bone outcomes at the distal radius and tibia at the time of peak bone mass, warranting further attention to vitamin D status in young adults.