Low Protein Intake Irrespective of Source is Associated with Higher Mortality Among Older Community-dwelling Men.

OBJECTIVES: Our aim was to determine the association between protein intake (overall and by source) and all-cause and cause-specific mortality among older men. DESIGN: Prospective cohort study. SETTING: 5790 ambulatory community-dwelling older men from multicenter Osteoporotic Fractures in Men (MrOS) study. MEASUREMENTS: Total energy and protein intake, and protein intake by source (dairy, non-dairy animal, plant) were assessed using a 69-item food frequency questionnaire. We included up to 10-year follow-up with adjudicated cardiovascular, cancer and other mortality outcomes. We used time-to-event analysis with protein exposures, mortality outcome, and adjusted for possible confounders including age, center, education, race, smoking, alcohol use, physical activity, weight, total energy intake (TEI), and comorbidities. Hazard ratios were expressed per each unit=2.9% TEI decrement for all protein intake variables. RESULTS: The mean (SD) baseline age of 5790 men was 73.6 (5.8) y. There were 1611 deaths and 211 drop-outs prior to 10 years, and 3868 men who were alive at the 10-year follow-up. The mean (SD) total protein intake was 64.7 (25.8) g/d, while the mean (SD) intake expressed as percent of total energy intake (%TEI) was 16.1 (2.9) %TEI. Lower protein intake was associated with an increased risk of death, with unadjusted HR=1.11 (95% CI: 1.06, 1.17) and adjusted HR=1.09 (95% CI: 1.04, 1.14) and the associations for protein intake by source were similar. The adjusted HR for cancer mortality was HR=1.13 (95% CI: 1.03, 1.25) while the association for CVD mortality was HR=1.08 (95% CI: 0.99, 1.18). CONCLUSIONS: Low protein intake, irrespective of source, was associated with a modest increase in risk of all-cause and cause-specific mortality among older men. Special consideration should be given to level of protein intake among older adults.

Investigation of the Diet-Gut-Muscle Axis in the Osteoporotic Fractures in Men Study.

OBJECTIVES: To investigate the association between dietary fiber density (grams of fiber consumed per 100 kcal) with the gut-muscle axis in older adult men. DESIGN: Cross-sectional study. SETTING: Osteoporotic Fractures in Men (MrOS) cohort participants at Visit 4 (2014-16). PARTICIPANTS: Older adult men (average age, 85y) from the MrOS study. MEASUREMENTS: Men who were in the highest tertiles for dietary fiber density and the percentage of whole body lean mass were defined as T3T3 (n=42), whereas men who were in the lowest and intermediate tertiles for these variables were defined as T1T1 (n=32), T1T3 (n=24), and T3T1 (n=13), respectively. Additionally, measures of physical function, including the short physical performance battery (SPPB) score and grip strength were higher in T3T3 when compared with T1T1. Gut bacterial abundance was quantified with use of 16S v4 rRNA sequencing, and the bacterial functional potential was derived from the 16S data with PICRUSt. Chao1, ACE, Shannon, Simpson, and Fisher indices were used as measures of α-diversity. Weighted and unweighted Unifrac, and Bray-Curtis were used as measures of ß-diversity. Age, physical activity score, smoking, and number of medications-adjusted DESeq2 models were used to identify bacteria and functions that were different when comparing T3T3 with T1T1, but that were not also different when comparing T3T3 with T1T3 or T3T1. RESULTS: α-diversity was not different, but significant differences for ß-diversity (unweighted UniFrac, Bray-Curtis) were identified when comparing T3T3 with T1T1. Known butyrate-producing bacteria, including Ruminococcus, Lachnospira, and Clostridia, and gene counts for butyrate production (KEGG IDs: K01034, K01035) were higher in T3T3, when compared with T1T1. CONCLUSION: These data suggest that a high-fiber diet may positively impact butyrate-producing genera and gene counts, which collectively may be involved in mechanisms related to the percentage of whole body lean mass and physical functioning in older adult men. Future studies aimed at testing the causative role of this hypothesis are of interest.

The Association between Objectively Measured Physical Activity and the Gut Microbiome among Older Community Dwelling Men.

OBJECTIVES: To determine the relationship between objectively measured physical activity (PA) and the gut microbiome among community-dwelling older men. DESIGN: Cross-sectional study. SETTING: Osteoporotic Fractures in Men (MrOS) cohort participants at Visit 4 (2014-16). PARTICIPANTS: Eligible men (n=373, mean age 84 y) included participants with 5-day activity assessment with at least 90% wear time and analyzed stool samples. MEASUREMENTS: PA was measured with the SenseWear Pro3 Armband and stool samples analyzed for 16S v4 rRNA marker genes using Illumina MiSeq technology. Armband data together with sex, height, and weight were used to estimate total steps, total energy expenditure, and level of activity. 16S data was analyzed using standard UPARSE workflow. Shannon and Inverse Simpson indices were measures of (within-participant) α-diversity. Weighted and unweighted Unifrac were measures of (between-participant) ß-diversity. We used linear regression analysis, principal coordinate analysis, zero-inflated Gaussian models to assess association between PA and α-diversity, ß-diversity, and specific taxa, respectively, with adjustments for age, race, BMI, clinical center, library size, and number of chronic conditions. RESULTS: PA was not associated with α-diversity. There was a slight association between PA and ß-diversity (in particular the second principal coordinate). Compared to those who were less active, those who had higher step counts had higher relative abundance of Cetobacterium and lower relative abundance of taxa from the genera Coprobacillus, Adlercreutzia, Erysipelotrichaceae CC-115 after multivariable adjustment including age, BMI, and chronic conditions. There was no consistent pattern by phylum. CONCLUSION: There was a modest association between levels of PA and specific gut microbes among community-dwelling older men. The observed associations are consistent with the hypothesis that underlying health status and composition of the host microbiome are related.

Dietary patterns and longitudinal change in hip bone mineral density among older men.

Studying dietary patterns is often more informative than individual nutrients or foods. We found that a Prudent dietary pattern (rich in vegetables and fish) was associated with reduced loss of total hip BMD in older men. A Prudent dietary pattern may be a potential lifestyle strategy for minimizing bone loss. INTRODUCTION: This study aimed to identify baseline dietary patterns using factor analysis in a cohort of older men and to evaluate whether the dietary patterns were associated with bone mineral density change (%ΔBMD) at the total hip and femoral neck over time. METHODS: Participants (n = 4379; mean age 72.9 ± 5.5 years) were from the Osteoporotic Fractures in Men (MrOS) prospective cohort study and had dietary data collected at baseline (March 2000-April 2002) and BMD measured at baseline and Visit 2 (March 2005-May 2006). Dietary intake was assessed with a brief Block food frequency questionnaire (FFQ); factor analysis was used to derive dietary patterns. BMD was measured by dual-energy x-ray absorptiometry (DXA); %ΔBMD was calculated from baseline to Visit 2. We used generalized linear regression to estimate least square (LS) means of %ΔBMD in quartiles of the dietary pattern scores adjusted for potential confounding factors. RESULTS: Two major dietary patterns were derived: Prudent (abundant in vegetables, salad, and non-fried fish) and Western (rich in hamburger, fries, processed meats, cheese, and sweets/desserts). There was an inverse association between adherence to the Prudent pattern and total hip %ΔBMD (p-trend = 0.028 after adjusting for age and clinical site; p-trend = 0.033 after further adjustment for smoking, calcium supplement use, diabetes, hypertension, and total energy intake). No other consistent associations between dietary patterns and %ΔBMD were observed. CONCLUSIONS: Greater adherence to a Prudent dietary pattern may attenuate total hip BMD loss (%ΔBMD) in older men.

Low magnesium intake is associated with increased knee pain in subjects with radiographic knee osteoarthritis: data from the Osteoarthritis Initiative.

OBJECTIVE: As magnesium mediates bone and muscle metabolism, inflammation, and pain signaling, we aimed to evaluate whether magnesium intake is associated with knee pain and function in radiographic knee osteoarthritis (OA). METHODS: We investigated the associations between knee pain/function metrics and magnesium intake from food and supplements in 2548 Osteoarthritis Initiative cohort participants with prevalent radiographic knee OA (Kellgren-Lawrence score ≥2). Magnesium intake was assessed by Food Frequency Questionnaire (FFQ) at baseline. WOMAC and Knee Injury and Osteoarthritis Outcome Score (KOOS) scores were reported annually with total follow up of 48 months. Analyses used linear mixed models. RESULTS: Among participants with baseline radiographic knee OA the mean total magnesium intake was 309.9 mg/day (SD 132.6) for men, and 287.9 mg/day (SD 118.1) for women, with 68% of men and 44% of women below the estimated average requirement. Subjects with lower magnesium intake had worse knee OA pain and function scores, throughout the 48 months (P < 0.001). After adjustment for age, sex, race, body mass index (BMI), calorie intake, fiber intake, pain medication use, physical activity, renal insufficiency, smoking, and alcohol use, lower magnesium intake remained associated with worse pain and function outcomes (1.4 points higher WOMAC and 1.5 points lower KOOS scores for every 50 mg of daily magnesium intake, P < 0.05). Fiber intake was an effect modifier (P for interaction <0.05). The association between magnesium intake and knee pain and function scores was strongest among subjects with low fiber intake. CONCLUSION: Lower magnesium intake was associated with worse pain and function in knee OA, especially among individuals with low fiber intake.

High dairy protein intake is associated with greater bone strength parameters at the distal radius and tibia in older men: a cross-sectional study.

Dairy protein but not plant protein was associated with bone strength of the radius and tibia in older men. These results are consistent with previous results in women and support similar findings related to fracture outcomes. Bone strength differences were largely due to thickness and area of the bone cortex. INTRODUCTION: Our objective was to determine the association of protein intake by source (dairy, non-dairy animal, plant) with bone strength and bone microarchitecture among older men. METHODS: We used data from 1016 men (mean 84.3 years) who attended the Year 14 exam of the Osteoporotic Fractures in Men (MrOS) study, completed a food frequency questionnaire (500-5000 kcal/day), were not taking androgen or androgen agonists, and had high-resolution peripheral quantitative computed tomography (HR-pQCT) scans of the distal radius and distal or diaphyseal tibia. Protein was expressed as percentage of total energy intake (TEI); mean ± SD for TEI = 1548 ± 607 kcal/day and for total protein = 16.2 ± 2.9%TEI. We used linear regression with standardized HR-pQCT parameters as dependent variables and adjusted for age, limb length, center, education, race/ethnicity, marital status, smoking, alcohol intake, physical activity level, corticosteroids use, supplement use (calcium and vitamin D), and osteoporosis medications. RESULTS: Higher dairy protein intake was associated with higher estimated failure load at the distal radius and distal tibia [radius effect size = 0.17 (95% CI 0.07, 0.27), tibia effect size = 0.13 (95% CI 0.03, 0.23)], while higher non-dairy animal protein was associated with higher failure load at only the distal radius. Plant protein intake was not associated with failure load at any site. CONCLUSION: The association between protein intake and bone strength varied by source of protein. These results support a link between dairy protein intake and skeletal health, but an intervention study is needed to evaluate causality.

Physical activity, body mass index and bone mineral density-associations in a prospective population-based cohort of women and men: the Canadian Multicentre Osteoporosis Study (CaMos).

BACKGROUND: Physical activity (PA) is an important modifiable risk factor for both bone mineral density (BMD) and body mass index (BMI). However, BMI is itself strongly predictive of BMD. Our aim was to determine the association between PA and BMD, with consideration of BMI as a potential mediating factor. METHODS: The Canadian Multicentre Osteoporosis Study (CaMos) is a population-based prospective cohort study of Canadian women and men. PA was determined from interviewer-administered questionnaires at baseline and Year 5 and summarized as daily energy expenditure in total metabolic equivalents of the task multiplied by minutes/day (MET*m/d). Height, weight, and total hip and lumbar spine BMD were measured at baseline and Year 5. General linear models assessed relationships between PA and BMD, both cross-sectionally (baseline PA with baseline BMD) and longitudinally (average PA and change in PA with change in BMD). BMI was considered as a mediating factor. Potential confounders included age, center, education, caffeine intake, alcohol exposure, smoking history, history of weight-cycling, age at menarche, past use of oral contraceptives, history of >3 months missed menstruation, menopausal status, and antiresorptive use, as relevant. RESULTS: The study included 2855 men and 6442 women. PA was inversely associated with BMI at baseline, and an increase in PA between baseline and Year 5 was associated with a decrease in BMI, with 0.41 (95% CI: 0.22, 0.60) kg/m(2) loss per 1000 MET*m/d increase (in men) and 0.40 (95% CI: 0.23, 0.57) kg/m(2) loss per 1000 MET*m/d increase (in women). BMI was strongly associated with BMD, both cross-sectionally and longitudinally. However, increased PA was associated with a small increase in total hip BMD, 0.004 (95% CI: 0.000-0.008) g/cm(2) per 1000 MET*m/d (in men) and 0.003 (95% CI: 0.000-0.007) g/cm(2) per 1000 MET*m/d (in women). Average PA was associated with an increase in lumbar spine BMD in women, but not in men; it was not associated with change in total hip BMD in either sex. CONCLUSION: Increased PA is associated with an increase in BMD and a concomitant decrease in BMI. These findings suggest that population-level interventions to increase PA would favorably impact bone and other health outcomes.