Short-term risk of fracture is increased by deficits in cortical and trabecular bone microarchitecture independent of DXA BMD and FRAX: Bone Microarchitecture International Consortium (BoMIC) prospective cohorts.

Identifying individuals at risk for short-term fracture is essential to offer prompt beneficial treatment, especially since many fractures occur in those without osteoporosis by DXA-aBMD. We evaluated whether deficits in bone microarchitecture and density predict short-term fracture risk independent of the clinical predictors, DXA-BMD and FRAX. We combined data from eight cohorts to conduct a prospective study of bone microarchitecture at the distal radius and tibia (by HR-pQCT) and 2-year incidence of fracture (non-traumatic and traumatic) in 7327 individuals (4824 women, 2503 men, mean 69 ± 9 years). We estimated sex-specific hazard ratios (HR) for associations between bone measures and 2-year fracture incidence, adjusted for age, cohort, height, and weight, and then additionally adjusted for FN aBMD or FRAX for major osteoporotic fracture. Only 7% of study participants had FN T-score ≤ -2.5, whereas 53% had T-scores between -1.0 and -2.5 and 37% had T-scores ≥-1.0. Two-year cumulative fracture incidence was 4% (296/7327). Each SD decrease in radius cortical bone measures increased fracture risk by 38%-76% for women and men. After additional adjustment for FN-aBMD, risks remained increased by 28%-61%. Radius trabecular measures were also associated with 2-year fracture risk independently of FN-aBMD in women (HRs range: 1.21 per SD for trabecular separation to 1.55 for total vBMD). Decreased failure load (FL) was associated with increased fracture risk in both women and men (FN-aBMD ranges of adjusted HR = 1.47-2.42). Tibia measurement results were similar to radius results. Findings were also similar when models were adjusted for FRAX. In older adults, FL and HR-pQCT measures of cortical and trabecular bone microarchitecture and density with strong associations to short-term fractures improved fracture prediction beyond aBMD and FRAX. Thus, HR-pQCT may be a useful adjunct to traditional assessment of short-term fracture risk in older adults, including those with T-scores above the osteoporosis range.

Identifying individuals at risk for short-term fractures (within 2 years) is essential to offer prompt treatment. We examined bone microarchitecture at arm and lower leg for prediction of short-term fractures in 7327 older adults, independent of the common clinical practice measures­DXA-BMD and FRAX. After adjusting for other factors, we found that measures of FL, cortical and trabecular bone microarchitecture, and density predicted short-term risk of fracture beyond the usual clinical measures of DXA and FRAX. These measures of bone that indicate deficits in microarchitecture may be a useful adjunct to traditional assessment of fracture risk in older adults.

Fracture risk based on high-resolution peripheral quantitative computed tomography measures does not vary with age in older adults-the bone microarchitecture international consortium prospective cohort study.

Fracture risk increases with lower areal bone mineral density (aBMD); however, aBMD-related estimate of risk may decrease with age. This may depend on technical limitations of 2-dimensional (2D) dual energy X-ray absorptiometry (DXA) which are reduced with 3D high-resolution peripheral quantitative computed tomography (HR-pQCT). Our aim was to examine whether the predictive utility of HR-pQCT measures with fracture varies with age. We analyzed associations of HR-pQCT measures at the distal radius and distal tibia with two outcomes: incident fractures and major osteoporotic fractures. We censored follow-up time at first fracture, death, last contact or 8 years after baseline. We estimated hazard ratios (HR) and 95%CI for the association between bone traits and fracture incidence across age quintiles. Among 6835 men and women (ages 40-96) with at least one valid baseline HR-pQCT scan who were followed prospectively for a median of 48.3 months, 681 sustained fractures. After adjustment for confounders, bone parameters at both the radius and tibia were associated with higher fracture risk. The estimated HRs for fracture did not vary significantly across age quintiles for any HR-pQCT parameter measured at either the radius or tibia. In this large cohort, the homogeneity of the associations between the HR-pQCT measures and fracture risk across age groups persisted for all fractures and for major osteoporotic fractures. The patterns were similar regardless of the HR-pQCT measure, the type of fracture, or the statistical models. The stability of the associations between HR-pQCT measures and fracture over a broad age range shows that bone deficits or low volumetric density remain major determinants of fracture risk regardless of age group. The lower risk for fractures across measures of aBMD in older adults in other studies may be related to factors which interfere with DXA but not with HR-pQCT measures.

Patients' perspectives on systemic sclerosis-related Raynaud's phenomenon in the feet: A qualitative study from the OMERACT Foot and Ankle Working Group.

OBJECTIVE: To explore, from patients' perspectives, the symptoms and impact of Raynaud's phenomenon (RP) on the feet of patients with systemic sclerosis (SSc-RP), and to identify which foot-related domains are important to patients. METHODS: Forty participants (34 women) with SSc-RP took part in one of six focus groups held in the United Kingdom or United States. Participants were purposively sampled to ensure diversity in disease type, duration, and ethnicity. The topic guide included questions on RP impact, self-management, and treatment expectations. Qualitative content analysis was employed to identify key concepts in the data relating to foot-specific symptoms and their impact. Themes were organized by corresponding domains of potential importance. RESULTS: Twenty-eight participants (70 %) reported experiencing RP in their feet. Five themes were identified corresponding to domains of potential importance: temperature changes, pain, cramping and stiffness, numbness, and color changes. These issues negatively affected participants' lives, impairing walking, driving, and socializing, and causing issues with footwear and hosiery. CONCLUSIONS: This large qualitative study exploring the experiences of patients with SSc-RP in the feet identified several key domains of high importance to patients. SSc-RP is common in the feet, presents in several patterns, and impacts multiple aspects of patients' lives. These findings indicate where future foot-specific interventions for RP could be targeted. Findings from this study improve understanding of what domains are important to patients with SSc-RP affecting the feet and will contribute to the development of a core outcome set for foot and ankle disorders in rheumatic and musculoskeletal diseases.

Association of Foot Symptoms With Decreased Time to All-Cause Mortality: The Johnston County Osteoarthritis Project.

OBJECTIVE: Adults with foot symptoms (ie, pain, aching, or stiffness) may be at increased risk of reduced time to all-cause mortality. The purpose of this study was to evaluate whether foot symptoms are independently associated with all-cause mortality in older adults. METHODS: We analyzed longitudinal data from 2613 participants from the Johnston County Osteoarthritis Project, a longitudinal population-based cohort of adults 45 years of age and older. Participants completed questionnaires at baseline to determine presence of foot symptoms and covariable status. Baseline walking speed was measured via an 8-foot walk test. To examine the association of foot symptoms with time to mortality, hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox regression models, adjusted for potential confounders. RESULTS: We observed 813 deaths over 4 to 14.5 years of follow-up. At baseline, 37% of participants had foot symptoms, mean age was 63 years, mean body mass index was approximately 31 kg/m2 , 65% were women, and 33% were Black. Moderate to severe foot symptoms were associated with reduced time to mortality after adjustment for demographics, comorbidities, physical activity, and knee and hip symptoms (HR = 1.30, 95% CI 1.09-1.54). Importantly, this association was not modified by walking speed or diabetes. CONCLUSION: Individuals with foot symptoms had an increased hazard of all-cause mortality compared with those with no foot symptoms. These effects were independent of key confounders and were not moderated by walking speed. Effective interventions to identify and manage at least moderate foot symptoms may reduce the risk of decreased time to mortality.

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.

Living with foot and ankle disorders in rheumatic and musculoskeletal diseases: A systematic review of qualitative studies to inform the work of the OMERACT Foot and Ankle Working Group.

OBJECTIVES: This study aimed to determine outcome domains of importance to patients living with foot and ankle disorders in rheumatic and musculoskeletal diseases (RMDs), by exploring the symptoms and impact of these disorders reported in existing qualitative studies. METHODS: Six databases were searched from inception to March 2022. Studies were included if they used qualitative interview or focus group methods, were published in English, and involved participants living with RMDs (inflammatory arthritis, osteoarthritis, crystal arthropathies, connective tissue diseases, and musculoskeletal conditions in the absence of systemic disease) who had experienced foot and ankle problems. Quality was assessed using the Critical Appraisal Skills Programme qualitative tool and confidence in the findings was assessed using the Grading of Recommendations Assessment, Development and Evaluation Confidence in the Evidence from Reviews of Qualitative research (GRADE-CERQual) approach. All data from the results section of included studies were extracted, coded and synthesised to develop themes. RESULTS: Of 1,443 records screened, 34 studies were included, with a total of 503 participants. Studies included participants with rheumatoid arthritis (n = 18), osteoarthritis (n = 5), gout (n = 3), psoriatic arthritis (n = 1), lupus (n = 1), posterior tibial tendon dysfunction (n = 1), plantar heel pain (n = 1), Achilles tendonitis (n = 1), and a mixed population (n = 3), who live with foot and ankle disorders. Seven descriptive themes were generated from the thematic synthesis: pain, change in appearance, activity limitations, social isolation, work disruption, financial burden and emotional impact. Descriptive themes were inductively analysed further to construct analytical themes relating to potential outcome domains of importance to patients. Foot or ankle pain was the predominant symptom experienced by patients across all RMDs explored in this review. Based on grading of the evidence, we had moderate confidence that most of the review findings represented the experiences of patients with foot and ankle disorders in RMDs. CONCLUSIONS: Findings indicate that foot and ankle disorders impact on multiple areas of patients' lives, and patients' experiences are similar regardless of the RMD. This study will inform the development of a core domain set for future foot and ankle research and are also useful for clinicians, helping to focus clinical appointments and measurement of outcomes within clinical practice.

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.

A Fracture Risk Assessment Tool for High Resolution Peripheral Quantitative Computed Tomography.

Most fracture risk assessment tools use clinical risk factors combined with bone mineral density (BMD) to improve assessment of osteoporosis; however, stratifying fracture risk remains challenging. This study developed a fracture risk assessment tool that uses information about volumetric bone density and three-dimensional structure, obtained using high-resolution peripheral quantitative compute tomography (HR-pQCT), to provide an alternative approach for patient-specific assessment of fracture risk. Using an international prospective cohort of older adults (n = 6802) we developed a tool to predict osteoporotic fracture risk, called µFRAC. The model was constructed using random survival forests, and input predictors included HR-pQCT parameters summarizing BMD and microarchitecture alongside clinical risk factors (sex, age, height, weight, and prior adulthood fracture) and femoral neck areal BMD (FN aBMD). The performance of µFRAC was compared to the Fracture Risk Assessment Tool (FRAX) and a reference model built using FN aBMD and clinical covariates. µFRAC was predictive of osteoporotic fracture (c-index = 0.673, p < 0.001), modestly outperforming FRAX and FN aBMD models (c-index = 0.617 and 0.636, respectively). Removal of FN aBMD and all clinical risk factors, except age, from µFRAC did not significantly impact its performance when estimating 5-year and 10-year fracture risk. The performance of µFRAC improved when only major osteoporotic fractures were considered (c-index = 0.733, p < 0.001). We developed a personalized fracture risk assessment tool based on HR-pQCT that may provide an alternative approach to current clinical methods by leveraging direct measures of bone density and structure. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Developing a core outcome set for foot and ankle disorders in rheumatic and musculoskeletal diseases: A scoping review and report from the OMERACT 2022 foot and ankle special interest group session.

OBJECTIVES: Foot and ankle involvement is common in rheumatic and musculoskeletal diseases, yet high-quality evidence assessing the effectiveness of treatments for these disorders is lacking. The Outcome Measures in Rheumatology (OMERACT) Foot and Ankle Working Group is developing a core outcome set for use in clinical trials and longitudinal observational studies in this area. METHODS: A scoping review was performed to identify outcome domains in the existing literature. Clinical trials and observational studies comparing pharmacological, conservative or surgical interventions involving adult participants with any foot or ankle disorder in the following rheumatic and musculoskeletal diseases (RMDs) were eligible for inclusion: rheumatoid arthritis (RA), osteoarthritis (OA), spondyloarthropathies, crystal arthropathies and connective tissue diseases. Outcome domains were categorised according to the OMERACT Filter 2.1. RESULTS: Outcome domains were extracted from 150 eligible studies. Most studies included participants with foot/ankle OA (63% of studies) or foot/ankle involvement in RA (29% of studies). Foot/ankle pain was the outcome domain most commonly measured (78% of studies), being the most frequently specified outcome domain across all RMDs. There was considerable heterogeneity in the other outcome domains measured, across core areas of manifestations (signs, symptoms, biomarkers), life impact, and societal/resource use. The group's progress to date, including findings from the scoping review, was presented and discussed during a virtual OMERACT Special Interest Group (SIG) in October 2022. During this meeting, feedback was sought amongst delegates regarding the scope of the core outcome set, and feedback was received on the next steps of the project, including focus group and Delphi methods. CONCLUSION: Findings from the scoping review and feedback from the SIG will contribute to the development of a core outcome set for foot and ankle disorders in RMDs. The next steps are to determine which outcome domains are important to patients, followed by a Delphi exercise with key stakeholders to prioritise outcome domains.

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.

Long-Term Consumption of Nuts (Including Peanuts, Peanut Butter, Walnuts, and Other Nuts) in Relation to Risk of Frailty in Older Women: Evidence from a Cohort Study.

BACKGROUND: Adherence to a healthy diet is inversely associated with frailty. However, the relationship between nuts, a key food group of Mediterranean diet, and frailty is unclear. OBJECTIVES: This study aimed to evaluate the association between nut consumption and frailty in an aging female population. METHODS: This population-based observational study included nonfrail women (≥60 y old) in the NHS from 11 states of the United States. Outcome was incident frailty, defined as having ≥3 of the FRAIL components (fatigue, lower strength, reduced aerobic capacity, multiple chronic conditions, and significant weight loss) and assessed every 4 y from 1992 to 2016. From 1990 to 2014, FFQs were used to assess the intakes of peanuts, peanut butter, walnuts (added in 1998), and other nuts at 4-y intervals. Exposure was total nut consumption, calculated as the sum of intakes of peanuts, peanut butter, walnuts, and other nuts and categorized into <1 serving/mo, 1-3 servings/mo, 1 serving/wk, 2-4 servings/wk, and ≥5 servings/wk. The relations of intakes of peanuts, peanut butter, and walnuts with frailty were also investigated separately. Cox proportional hazards models were used to assess the associations between nut consumption and frailty after adjusting for age, smoking, BMI, EI, diet quality, and medication use. RESULTS: Among 71,704 participants, 14,195 incident frailty cases occurred over 1,165,290 person-years. The adjusted HR (95% CI) for consuming ≥5 servings/wk of nuts was 0.80 (0.73, 0.87), as compared with <1 serving/mo. Higher intakes of peanuts and walnuts, but not peanut butter, were also inversely associated with frailty. CONCLUSIONS: This large prospective cohort study showed a strong and consistent inverse association between regular nut consumption and incident frailty. This suggests that nut consumption should be further tested as a convenient public health intervention for the preservation of health and well-being in older adults.

Developing an Outcome Measures in Rheumatology (OMERACT) Core set of Outcome Measures for FOot and ankle disorders in RheumaTic and musculoskeletal diseases (COMFORT): core domain set study protocol.

BACKGROUND: Foot and ankle involvement is common in rheumatic and musculoskeletal diseases (RMDs). High-quality evidence is lacking to determine the effectiveness of treatments for these disorders. Heterogeneity in the outcomes used across clinical trials and observational studies hinders the ability to compare findings, and some outcomes are not always meaningful to patients and end-users. The Core set of Outcome Measures for FOot and ankle disorders in RheumaTic and musculoskeletal diseases (COMFORT) study aims to develop a core outcome set (COS) for use in all trials of interventions for foot and ankle disorders in RMDs. This protocol addresses core outcome domains (what to measure) only. Future work will focus on core outcome measurement instruments (how to measure). METHODS: COMFORT: Core Domain Set is a mixed-methods study involving the following: (i) identification of important outcome domains through literature reviews, qualitative interviews and focus groups with patients and (ii) prioritisation of domains through an online, modified Delphi consensus study and subsequent consensus meeting with representation from all stakeholder groups. Findings will be disseminated widely to enhance uptake. CONCLUSIONS: This protocol details the development process and methodology to identify and prioritise domains for a COS in the novel area of foot and ankle disorders in RMDs. Future use of this standardised set of outcome domains, developed with all key stakeholders, will help address issues with outcome variability. This will facilitate comparing and combining study findings, thus improving the evidence base for treatments of these conditions. Future work will identify suitable outcome measurement instruments for each of the core domains. TRIAL REGISTRATION: This study is registered with the Core Outcome Measures in Effectiveness Trials (COMET) database, as of June 2022: https://www.comet-initiative.org/Studies/Details/2081.

Accumulation in Visceral Adipose Tissue Over 6 Years Is Associated With Lower Paraspinal Muscle Density.

CONTEXT: Visceral adipose tissue (VAT) has been recognized to be a metabolically active fat depot that may have paracrine effects on surrounding tissues, including muscle. Since many adults accumulate VAT as they age, the effect of changes in VAT on muscle is of interest. OBJECTIVE: We determined the association between 6-year changes in VAT and paraspinal muscle density, an indicator of fatty infiltration. METHODS: This study included 1145 participants from the Framingham Study third-generation cohort who had both quantitative computed tomography scans of the spine at baseline and 6-year's follow-up, on whom muscle density was measured along with VAT. We implemented multiple regression to determine the association of muscle density at follow-up as primary outcome measure with changes in VAT (follow-up minus baseline divided by 100), adjusting for VAT at baseline, age, sex, height, menopausal status, presence of diabetes, and physical activity. Analyses were performed in men and women separately. RESULTS: After adjustment for covariates, individuals with the greatest accumulation of VAT over 6 years had significantly lower paraspinal density at the follow-up with an estimated 0.302 (95% CI, -0.380 to -0.224) and 0.476 (95% CI: -0.598 to -0.354) lower muscle density (HU) per 100-cm3 increase in VAT (both P values < .001) in men and women, respectively. CONCLUSION: These results highlight that age-related accumulation of VAT in men and women is associated with lower muscle density. VAT may represent a modifiable risk factor for poor musculoskeletal outcomes with aging.

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.

Foot pain and inflammatory markers: a cross sectional study in older adults.

BACKGROUND: Foot disorders may limit independence and reduce quality of life for older adults. Obesity is a risk factor for foot conditions; both mechanical load and metabolic effects may contribute to these conditions. This study determined cross-sectional associations between inflammatory markers and foot disorders. METHODS: Participants were drawn from the Framingham Foot Study (2002-2008). C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) were each examined for associations with foot pain, forefoot pain, hindfoot pain, hallux valgus, hallux rigidus, and toe deformities (claw, hammer, or overlapping toes). Unadjusted and adjusted (age, body mass index, physical activity, smoking status) sex-specific logistic regression was performed. RESULTS: Of 909 participants, 54% were women (mean age 65 [Formula: see text] 9 years), 20% had foot pain, 29% had hallux valgus, 3% had hallux rigidus, and 27% had toe deformities. In unadjusted models, higher CRP (OR [95% CI] = 1.5 [1.1, 2.0]) and IL-6 (OR [95% CI] = 1.8 [1.2, 2.6]) were associated with foot pain among men; higher CRP was associated with foot pain (OR [95% CI] = 1.3 [1.0, 1.5]) among women. Higher CRP (OR [95% CI] = 1.9 [1.1, 3.2]) and IL-6 (OR [95% CI] = 2.4 [1.2, 4.7]) were associated with forefoot pain in men. Higher CRP was associated with hindfoot pain ([95% CI] = 1.8 [1.2, 2.6]) in women. After adjustment, CRP ([95% CI] = 1.5 [1.1, 2.0]) and IL-6 ([95% CI] = 1.8 [1.2, 2.6]) remained associated with foot pain in men, and IL-6 with forefoot pain ([95% CI] = 2.9 [1.4, 6.1]) in men. No associations with structural foot disorders were observed. CONCLUSIONS: Inflammation may impact foot pain. Future work assessing whether inflammation is part of the mechanism linking obesity to foot pain may identify areas for intervention and prevention.

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.

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.

Bone Microarchitecture Phenotypes Identified in Older Adults Are Associated With Different Levels of Osteoporotic Fracture Risk.

Prevalence of osteoporosis is more than 50% in older adults, yet current clinical methods for diagnosis that rely on areal bone mineral density (aBMD) fail to detect most individuals who have a fragility fracture. Bone fragility can manifest in different forms, and a "one-size-fits-all" approach to diagnosis and management of osteoporosis may not be suitable. High-resolution peripheral quantitative computed tomography (HR-pQCT) provides additive information by capturing information about volumetric density and microarchitecture, but interpretation is challenging because of the complex interactions between the numerous properties measured. In this study, we propose that there are common combinations of bone properties, referred to as phenotypes, that are predisposed to different levels of fracture risk. Using HR-pQCT data from a multinational cohort (n = 5873, 71% female) between 40 and 96 years of age, we employed fuzzy c-means clustering, an unsupervised machine-learning method, to identify phenotypes of bone microarchitecture. Three clusters were identified, and using partial correlation analysis of HR-pQCT parameters, we characterized the clusters as low density, low volume, and healthy bone phenotypes. Most males were associated with the healthy bone phenotype, whereas females were more often associated with the low volume or low density bone phenotypes. Each phenotype had a significantly different cumulative hazard of major osteoporotic fracture (MOF) and of any incident osteoporotic fracture (p < 0.05). After adjustment for covariates (cohort, sex, and age), the low density followed by the low volume phenotype had the highest association with MOF (hazard ratio = 2.96 and 2.35, respectively), and significant associations were maintained when additionally adjusted for femoral neck aBMD (hazard ratio = 1.69 and 1.90, respectively). Further, within each phenotype, different imaging biomarkers of fracture were identified. These findings suggest that osteoporotic fracture risk is associated with bone phenotypes that capture key features of bone deterioration that are not distinguishable by aBMD. © 2021 American Society for Bone and Mineral Research (ASBMR).

Social Isolation and Falls Risk: Lack of Social Contacts Decreases the Likelihood of Bathroom Modification Among Older Adults With Fear of Falling.

Fall prevention strategies exist, but little is known about factors that influence whether they are used. We assessed whether social isolation modifies the association between fear of falling (FOF) and bathroom environmental modification. Data were included from 2858 Medicare beneficiaries in the National Health and Aging Trends Study. FOF and social isolation were assessed at baseline (2011); new bathroom modifications were assessed 1-year post-baseline. Social network size was dichotomized as any versus no social contacts. Logistic regression assessed associations between FOF and bathroom modification. Effect modification between FOF and social isolation was assessed with multiplicative interaction terms. FOF was associated with increased odds of bathroom modification. We observed a statistically significant interaction between FOF and social isolation (p = 0.03). Among those with no social contacts, FOF was associated with reduced odds bathroom modification that did not reach statistical significance (OR 0.5, 95% CI 0.2-1.3).