The Study of Muscle, Mobility and Aging (SOMMA): A Unique Cohort Study About the Cellular Biology of Aging and Age-related Loss of Mobility.

BACKGROUND: The Study of Muscle, Mobility and Aging (SOMMA) aims to understand the biological basis of many facets of human aging, with a focus on mobility decline, by creating a unique platform of data, tissues, and images. METHODS: The multidisciplinary SOMMA team includes 2 clinical centers (University of Pittsburgh and Wake Forest University), a biorepository (Translational Research Institute at Advent Health), and the San Francisco Coordinating Center (California Pacific Medical Center Research Institute). Enrollees were age ≥70 years, able to walk ≥0.6 m/s (4 m); able to complete 400 m walk, free of life-threatening disease, and had no contraindications to magnetic resonance or tissue collection. Participants are followed with 6-month phone contacts and annual in-person exams. At baseline, SOMMA collected biospecimens (muscle and adipose tissue, blood, urine, fecal samples); a variety of questionnaires; physical and cognitive assessments; whole-body imaging (magnetic resonance and computed tomography); accelerometry; and cardiopulmonary exercise testing. Primary outcomes include change in walking speed, change in fitness, and objective mobility disability (able to walk 400 m in 15 minutes and change in 400 m speed). Incident events, including hospitalizations, cancer diagnoses, fractures, and mortality are collected and centrally adjudicated by study physicians. RESULTS: SOMMA exceeded its goals by enrolling 879 participants, despite being slowed by the COVID-19 pandemic: 59.2% women; mean age 76.3 ± 5.0 years (range 70-94); mean walking speed 1.04 ± 0.20 m/s; 15.8% identify as other than Non-Hispanic White. Over 97% had data for key measurements. CONCLUSIONS: SOMMA will provide the foundation for discoveries in the biology of human aging and mobility.

Association of 3D Geometric Measures Derived From Quantitative Computed Tomography With Hip Fracture Risk in Older Men.

We investigated the associations of 3D geometric measures and volumetric bone mineral density (vBMD) of the proximal femur assessed by quantitative computed tomography (QCT) with hip fracture risk among elderly men. This study was a prospective case-cohort design nested within the Osteoporotic Fractures in Men Study (MrOS) cohort. QCT scans of 230 men (65 with confirmed hip fractures) were evaluated with Mindways' QCTPRO-BIT software. Measures that are indicative of bone strength for the femoral neck (FN) and for the trochanteric region (TR) were defined. Bending strength measures were estimated by minimum section modulus, buckling strength by buckling ratio, and a local thinning index (LTI). Integral and trabecular vBMD measures were also derived. Areal BMD (aBMD) of the total proximal femur from dual-energy X-ray absorptiometry (DXA) is presented for comparison. Associations of skeletal measures with incident hip fracture were estimated with hazard ratios (HR) per standard deviation and their 95% confidence intervals (CI) from Cox proportional hazard regression models with adjustment for age, body mass index (BMI), site, and aBMD. Men with hip fractures were older than men without fracture (77.1 ± 6.0 years versus 73.3 ± 5.7 years, p < 0.01). Age, BMI, and site-adjusted HRs were significant for all measures except TR_LTI. Total femural BMD by DXA (HR = 4.9, 95% CI 2.5-9.9) and QCT (HR = 5.5, 95% CI 2.5-11.7) showed the strongest association followed by QCT FN integral vBMD (HR = 3.6, 95% CI 1.8-6.9). In models that additionally included aBMD, FN buckling ratio (HR = 1.9, 95% CI 1.1-3.2) and trabecular vBMD of the TR (HR = 2.0, 95% CI 1.2-3.4) remained associated with hip fracture risk, independent of aBMD. QCT-derived 3D geometric indices of instability of the proximal femur were significantly associated with incident hip fractures, independent of DXA aBMD. Buckling of the FN is a relevant failure mode not entirely captured by DXA. Further research to study these relationships in women is warranted. © 2016 American Society for Bone and Mineral Research.

Hip Fractures Risk in Older Men and Women Associated With DXA-Derived Measures of Thigh Subcutaneous Fat Thickness, Cross-Sectional Muscle Area, and Muscle Density.

Mid-thigh cross-sectional muscle area (CSA), muscle attenuation, and greater trochanter soft tissue thickness have been shown to be independent risk factors of hip fracture. Our aim was to determine whether muscle and adipose tissue measures derived from dual-energy X-ray absorptiometry (DXA) scans would have a similar risk association as those measured using other imaging methods. Using a case-cohort study design, we identified 169 incident hip fracture cases over an average of 13.5 years among participants from the Health ABC Study, a prospective study of 3075 individuals initially aged 70 to 79 years. We modeled the thigh 3D geometry and compared DXA and computed tomography (CT) measures. DXA-derived thigh CSA, muscle attenuation, and subcutaneous fat thickness were found to be highly correlated to their CT counterparts (Pearson's r = 0.82, 0.45, and 0.91, respectively; p < 0.05). The fracture risk of men and women were calculated separately. We found that decreased subcutaneous fat, CT thigh muscle attenuation, and appendicular lean mass by height squared (ALM/Ht(2)) were associated with fracture risk in men; hazard ratios (HR) = 1.44 (1.02, 2.02), 1.40 (1.05, 1.85), and 0.58 (0.36, 0.91), respectively, after adjusting for age, race, clinical site, body mass index (BMI), chronic disease, hip bone mineral density (BMD), self-reported health, alcohol use, smoking status, education, physical activity, and cognitive function. In a similar model for women, only decreases in subcutaneous fat and DXA CSA were associated with hip fracture risk; HR = 1.39 (1.07, 1.82) and 0.78 (0.62, 0.97), respectively. Men with a high ALM/Ht(2) and low subcutaneous fat thickness had greater than 8 times higher risk for hip fracture compared with those with low ALM/Ht(2) and high subcutaneous fat. In women, ALM/Ht(2) did not improve the model when subcutaneous fat was included. We conclude that the DXA-derived subcutaneous fat thickness is a strong marker for hip fracture risk in both men and women, especially in men with high ALM/Ht(2).

Objective assessment of activity, energy expenditure, and functional limitations in older men: the Osteoporotic Fractures in Men study.

BACKGROUND: The relationship between objectively assessed activity, energy expenditure, and the development of functional limitations is unknown. METHODS: Energy expenditure and activity levels were measured objectively using the multisensor SenseWear Pro Armband worn for greater than or equal to 5 days in 1,983 MrOS men (aged ≥ 78.3 years) free of functional limitations. Validated algorithms calculated energy expenditure; standard cut points defined moderate or greater activity (≥ 3.0 METS); and sedentary behavior (time awake ≤ 1.5 METS). Self-reported functional limitation was determined at the activity assessment and 2.0 years later as inability to perform instrumental activities of daily living (managing money, managing medications, shopping, housework, and meal preparation) and activities of daily living (climb stairs, walk two to three blocks, transfer, or bathe). RESULTS: Each standard deviation decrease in total energy expenditure (420.6 kcal/day) increased the likelihood of inability to perform an instrumental activity of daily living (multivariate odds ratio [mOR]: 1.61, 95% CI: 1.30-2.00) or activity of daily living (mOR: 1.35, 95% CI: 1.12-1.63). Each standard deviation decrease in moderate or greater activity (61.1 minutes/day) increased the likelihood of inability to perform an instrumental activity of daily living (mOR: 1.47, 95% CI: 1.22-1.78) or activity of daily living (mOR: 1.36, 95% CI: 1.14-1.61). Each standard deviation increase in minutes of sedentary behavior (105.2 minutes/day) increased the likelihood of inability to perform an instrumental activity of daily living (mOR: 1.20, 95% CI: 1.03-1.40) or activity of daily living (mOR: 1.17, 95% CI: 1.01-1.35). CONCLUSION: Older men with lower total energy expenditure, lower moderate activity, or greater sedentary time were more likely to develop a functional limitation.