Yahtyng Sheu

Bone strength measured by peripheral quantitative computed tomography and the risk of nonvertebral fractures: The osteoporotic fractures in men (MrOS) study

Many fractures occur in individuals without osteoporosis defined by areal bone mineral density (aBMD). Inclusion of other aspects of skeletal strength may be useful in identifying at‐risk subjects. We used surrogate measures of bone strength at the radius and tibia measured by peripheral quantitative computed tomography (pQCT) to evaluate their relationships with nonvertebral fracture risk. Femoral neck (FN) aBMD, measured by dual‐energy X‐ray absorptiometry (DXA), also was included. The study population consisted of 1143 white men aged 69+ years with pQCT measures at the radius and tibia from the Minneapolis and Pittsburgh centers of the Osteoporotic Fractures in Men (MrOS) study. Principal‐components analysis and Cox proportional‐hazards modeling were used to identify 21 of 58 pQCT variables with a major contribution to nonvertebral incident fractures. After a mean 2.9 years of follow‐up, 39 fractures occurred. Men without incident fractures had significantly greater bone mineral content, cross‐sectional area, and indices of bone strength than those with fractures by pQCT. Every SD decrease in the 18 of 21 pQCT parameters was significantly associated with increased fracture risk (hazard ration ranged from 1.4 to 2.2) independent of age, study site, body mass index (BMI), and FN aBMD. Using area under the receiver operation characteristics curve (AUC), the combination of FN aBMD and three radius strength parameters individually increased fracture prediction over FN aBMD alone (AUC increased from 0.73 to 0.80). Peripheral bone strength measures are associated with fracture risk and may improve our ability to identify older men at high risk of fracture.

The role of bone marrow and visceral fat on bone metabolism.

The protective effect of total fat mass on bone mineral density (BMD) has been challenged with studies showing no or negative association after adjusting for weight. Subsequently, more studies have evaluated the relationship of regional adiposity with BMD, and findings were inconsistent for central obesity. Advancements in imaging techniques enable us to directly and noninvasively study the role of adiposity on skeletal health. Visceral adiposity measured by computed tomography (CT) has consistently been shown to have negative effects on bone. Availability of magnetic resonance spectroscopy (MRS) also allows us to noninvasively quantify bone marrow fat (BMF), which has been known to be associated with osteoporosis from histomorphometric studies. Using MRS along with dual energy x-ray absorptiometry, studies have reported a detrimental role of BMF on BMD. With the increase in aging and obesity of the population, it is important to continue this effort in identifying the contribution of adipose tissues to bone quality and fracture.

Greater adipose tissue infiltration in skeletal muscle among older men of African ancestry

CONTEXT There is substantial variability across ethnic groups in the predisposition to obesity and associated metabolic abnormalities. Skeletal muscle fat has been identified as an important depot that increases with aging and may contribute to the development of diabetes. OBJECTIVE We tested whether men of African ancestry have greater calf intermuscular adipose tissue (IMAT), compared to Caucasian men, and whether IMAT is associated with type 2 diabetes (T2D). DESIGN We measured fasting serum glucose, body mass index, total body fat by dual-energy x-ray absorptiometry, and calf skeletal muscle composition by quantitative computed tomography in 1105 Caucasian and 518 Afro-Caribbean men aged 65+. RESULTS Compared to Caucasian men, we found greater IMAT and lower sc adipose tissue in Afro-Caribbean men at all levels of total adiposity (P < 0.0001), including the subset of men matched on age and dual-energy x-ray absorptiometry total body fat percentage (P < 0.001). In addition, IMAT was 29 and 23% greater, whereas sc adipose tissue was 6 and 8% lower among Caucasian and Afro-Caribbean men with T2D, respectively, compared to men without T2D (P < 0.01). Observed differences in intermuscular and sc fat, both ethnic and between men with and without T2D, were independent of age, height, calf skeletal muscle and total adipose tissue, and lifestyle factors. CONCLUSIONS Our analyses suggest that despite lower total adiposity, skeletal muscle fat infiltration is greater among African than among Caucasian ancestry men and is associated with T2D in both ethnic groups. Additional studies are needed to determine the mechanisms contributing to ethnic differences in skeletal muscle adiposity and to define the metabolic and health implications of this fat depot.

Abdominal myosteatosis is independently associated with hyperinsulinemia and insulin resistance among older men without diabetes

Skeletal muscle adipose tissue (AT) infiltration (myosteatosis) increases with aging and may contribute to the development of Type 2 diabetes mellitus (T2DM). It remains unclear if myosteatosis is associated to glucose and insulin homeostasis independent of total and central adiposity.

Adipose Tissue and Volumetric Bone Mineral Density of Older Afro-Caribbean Men

Although low body weight is a risk factor for osteoporosis‐related fractures, conflicting data exist for the association between adiposity and bone mineral density (BMD). Studies examining these relationships have measured body fat and BMD with dual‐energy X‐ray absorptiometry (DXA), which cannot distinguish subcutaneous adipose tissue area (SAT) from total adiposity or trabecular from cortical bone. To investigate the relationship between adiposity and BMD further, we analyzed body composition and adipose tissue distribution by quantitative computed tomography (QCT) in 1829 Afro‐Caribbean men aged 40 years and older from a population‐based sample. Cortical volumetric BMD, muscle cross‐sectional area, total adipose tissue area (TAT), and percentage SAT were measured at the proximal tibia. Trabecular volumetric BMD was measured at the distal tibia. We used analysis of covariance to test for associations between quartile of the adipose tissue measures and BMD, adjusting for anthropometric, health, and lifestyle factors. Higher TAT was associated with lower cortical BMD in both unadjusted and adjusted models (p < .001). Men with a higher percentage SAT had greater cortical BMD (p < .001). Similar associations were seen between percent SAT and trabecular BMD at the distal tibia. These results indicate that total adiposity is a potentially important correlate of bone mass in older men and that different fat depots may have opposing associations with bone mass. Additional research is needed to better understand the mechanisms underlying the relationship between body fat distribution and bone mass.

Correlates of trabecular and cortical volumetric BMD in men of African ancestry.

QCT provides a measure of volumetric BMD (vBMD) and distinguishes trabecular from cortical bone. Few studies have determined the factors related to vBMD in men, especially among men of African heritage. This study evaluated the relationship of anthropometric, medical, and behavioral factors and vBMD in a population‐based cohort of men of African ancestry (n = 1901) ≥40 yr of age who had undergone screening for prostate cancer for the first time. Trabecular and cortical vBMD were measured at the radius and tibia by pQCT. Multiple linear regression analysis identified age, height, body weight, cigarette smoking, history of diabetes, fracture, and prostate cancer as the independent correlates of vBMD. However, associations with several variables differed between cortical and trabecular vBMD and between the radius and tibia. Longitudinal studies are needed to gain a better understanding of the mechanisms underlying these differential associations that may show new insight into the etiology of trabecular and cortical bone loss in men.

Patterns and correlates of grip strength change with age in Afro-Caribbean men

BACKGROUND muscle strength is essential for physical functions and an indicator of morbidity and mortality in older adults. Among the factors associated with muscle strength loss with age, ethnicity has been shown to play an important role. OBJECTIVE to examine the patterns and correlates of muscle strength change with age in a population-based cohort of middle-aged and older Afro-Caribbean men. METHODS handgrip strength and body composition were measured in 1,710 Afro-Caribbean men. Data were also collected for demographic variables, medical history and lifestyle behaviours. RESULTS the age range of the study population was 29-89 years. Grip strength increased below age 50 years, and decreased after age 50 years over 4.5-year follow-up. The average loss in grip strength was 2.2% (0.49% per year) for ages 50 years or older and 3.8% (0.64% per year) for ages 65 years or older. The significant independent predictors of grip strength loss included older age, a greater body mass index, lower initial arm lean mass and greater loss of arm lean mass. CONCLUSION Afro-Caribbean men experience a significant decline in muscle strength with advanced age. The major independent factors associated with strength loss were similar to other ethnic groups, including age, body weight and lean mass.

Calciotropic hormones and the risk of hip and nonspine fractures in older adults: The health ABC study

The effects of vitamin D and parathyroid hormone (PTH) levels on incident fracture remain uncertain. To test the hypothesis that increasing serum 25‐hydroxyvitamin D [25(OH)D] and decreasing PTH levels are associated with decreased risk of hip and any nonspine fracture, we conducted a prospective cohort study among 2614 community‐dwelling white and black participants, aged ≥70 years, from the Health, Aging and Body Composition (Health ABC) Study. Serum and plasma samples were drawn at year 2, which formed the baseline for this analysis. Serum 25(OH)D and intact PTH (1‐84) were measured using radioimmunoassay with DiaSorin reagents and EDTA plasma with a two‐site immunoradiometric assay kit, respectively. Incident fractures (hip and any nonspine) were assessed after year 2, every 6 months, by self‐report and validated by radiology reports. The median (interquartile range) follow‐up times for hip and any nonspine fractures were 6.4 (6.1–6.5) and 6.4 (5.5–6.5) years, respectively. Cox proportional hazards regression was used to estimate the hazard ratios (HR) with 95% confidence intervals (CI) for fracture. There were 84 hip and 247 nonspine fractures that occurred over the follow‐up period. The multivariable adjusted HRs (95% CIs) of hip fracture for participants in the lowest (≤17.78 ng/mL), second (17.79 to 24.36 ng/mL), and third quartiles (24.37 to 31.94 ng/mL) of 25(OH)D were 1.92 (0.97 to 3.83), 0.75 (0.32 to 1.72) and 1.86 (1.00 to 3.45), respectively, compared with participants in the highest 25(OH)D quartile (>31.94 ng/mL) (p trend = 0.217). Additional adjustment for IL‐6 (p = 0.107), PTH (p = 0.124), and hip areal bone mineral density (p = 0.137) attenuated HRs of hip fracture in the lowest quartile by 16.3%, 17.4%, and 26.1%, respectively. There was no evidence of an association between 25(OH)D and any nonspine fractures, or between PTH and hip or any nonspine fractures. We found limited evidence to support an association between calciotropic hormones and hip and nonspine fractures in older men and women.

Skeletal Muscle Adiposity is associated with Serum Lipid and Lipoprotein Levels in Afro-Caribbean Men

Objective: When compared with other ethnic groups, African ancestry individuals have lower triglycerides and higher High‐density lipoprotein cholesterol (HDL‐C) levels, although the mechanisms for these differences remain unclear. A comprehensive array of factors potentially related to fasting serum lipid and lipoprotein levels in African ancestry men was evaluated.

Natural History and Correlates of Hip BMD Loss With Aging in Men of African Ancestry: The Tobago Bone Health Study

Little is known about the magnitude, pattern, and determinants of bone loss with advancing age among men, particularly among those of African descent. We examined the rate of decline in hip BMD and identified factors associated with BMD loss among 1478 Afro‐Caribbean men ≥40 yr of age. BMD was measured at baseline and after an average of 4.4 yr by DXA. The rate of decline in femoral neck BMD was 0.29 ± 0.81%/yr in the total sample (p < 0.0001). However, a U‐shaped relationship between advancing age and the rate of decline in BMD was observed. The rate of decline in BMD at the femoral neck was −0.38 ± 0.77%/yr among men 40–44 yr of age, decelerated to −0.15 ± 0.81%/yr among men 50–54 yr of age, and then accelerated to −0.52 ± 0.90%/yr among those 75+ yr of age (all p < 0.003). Men who lost ≥5% of their body weight during follow‐up had significantly greater BMD loss than those who remained weight stable or gained weight (p < 0.0001). The relationship between weight loss and BMD loss was more pronounced among men who were older and leaner at study entry (p < 0.03). We also observed a strong impact of advanced prostate cancer and its treatment with androgen deprivation on BMD loss. Men of African ancestry experience substantial BMD loss with advancing age that seems to be comparable to the rate of loss among white men in other studies. Additional studies are needed to better define the natural history and factors underlying bone loss with aging in men of African ancestry.