Vertebral bone marrow fat, bone mineral density and diabetes: The Osteoporotic Fractures in Men (MrOS) study.

Elevated vertebral bone marrow fat (BMF) among individuals with osteoporosis has been established in histomorphometric studies. Several studies have found a negative correlation between BMF and bone mineral density (BMD) at the spine in men and women across different age groups. Animal studies have also observed bone loss with increased BMF in mice with induced diabetes. Our study objective was to test the hypothesis that the association between BMF and BMD varies by diabetic status. We performed a cross-sectional study of 156 men aged 74-96years from the Osteoporotic Fractures in Men study at the Pittsburgh clinical site. All men had spine BMF scans using proton magnetic resonance spectroscopy and spine and hip BMD scans by dual-energy X-ray absorptiometry. BMF was expressed as lipid to "lipid+water" ratio (%). Men were considered diabetic if they self-reported a physician diagnosis of diabetes, diabetes medication or had a fasting glucose ≥126mg/dl. Men with diabetes (n=38) had a significantly higher spine BMF (58.9 vs. 54.6%, p=0.0035), spine BMD (1.20 vs. 1.10g/cm2, P=0.007) and total hip BMD (1.00 vs. 0.94g/cm2, p=0.04) than those without, while no differences were observed for body weight, body mass index or waist circumference. Pearson correlation tests showed no significant correlation of spine BMF with age or BMD in non-diabetics. Significant inverse correlations were observed between BMF and BMD (-0.30 for femoral neck and -0.39 for total hip) among diabetic men. In conclusion, men with diabetes had a higher BMF compared to non-diabetic men. The correlation between BMF and BMD differed by diabetes status. Further investigation of the association of diabetes with BMF and BMD may provide a better understanding of the high fracture rates among individuals with diabetes despite their higher BMD.

Sports- and Recreation-related Injury Episodes in the United States, 2011-2014.

Objective-Much of the research on sports- and recreation-related injuries focuses on a specific population, activity, or type of injury, and national estimates of the total burden of sports- and recreation-related injuries are limited. This study provides national estimates of the injury burden and examines the distribution of sports- and recreation-related injuries across demographic groups, activities, and injury circumstances. Methods-Information on medically attended injury episodes for persons aged 5 years and over were obtained from the 2011-2014 National Health Interview Survey. Sports- and recreation-related injuries are categorized by the associated activity using a classification scheme based on the International Classification of External Causes of Injury. Results-An average annual estimate of 8.6 million sports- and recreation-related injury episodes was reported, with an age-adjusted rate of 34.1 per 1,000 population. Males (61.3%) and persons aged 5-24 years (64.9%) accounted for more than one-half of injury episodes. Injury rates were higher among males, children aged 5-14 years, and non-Hispanic white persons than for their counterparts. One-half of the sports- and recreation-related injury episodes (50.0%) resulted in treatment at a doctor's office or other health clinic without an emergency department visit or hospitalization. Overall, general exercise was the most frequently mentioned activity associated with sports- and recreation-related injuries, but types of activities varied across sex and age groups. Body regions injured while engaging in sports and recreation activities included the lower extremity (42.0%), upper extremity (30.3%), and head and neck (16.4%). Conclusion-As the nation continues to recognize the importance of physical activity to maintain health, more research efforts are needed to examine sport and recreation injury across various activities, demographic groups, and health care settings, especially settings other than emergency departments and hospitals.

Increases in Medically Attended Nonfatal Injury Episodes Among Females in the United States.

KEY FINDINGS: Data from the National Health Interview Survey •From 2005-2008 to 2011-2014, the nonfatal injury rate increased for females but remained unchanged for males. •In 2005-2008, males had a higher nonfatal injury rate than females; however, in 2011-2014, the rates for males and females were similar. •From 2005-2008 to 2011-2014, the nonfatal injury rate increased significantly for women aged 45-64 and for non-Hispanic white females. •The increase in the nonfatal injury rate among females over time could not be attributed to a specific cause or place of injury occurrence.

Rates of and risk factors for trabecular and cortical BMD loss in middle-aged and elderly African-ancestry men.

Low trabecular (Tb) and cortical (Ct) volumetric BMD (vBMD) are related to increased fracture risk, but little is known about the patterns and correlates of Tb and Ct vBMD loss with aging. We examined the rates of change in total, Tb.vBMD, and Ct.vBMD at the radius and tibia, and identified factors associated with vBMD loss among 1569 men of African descent aged 40 years and older. Quantitative computed tomography was used to measure vBMD 6 years apart. The annualized rate of loss in Tb.vBMD was significant at the radius (-0.047%/yr, p = 0.016) but not at the tibia. At the radius, a significant loss of Tb.vBMD was observed in men aged 40 to 49 years that appeared to be attenuated and not statistically significant among older age men. In contrast, the decline in Ct.vBMD was similar at both skeletal sites (-0.254 to -0.264%/yr, p < 0.0001) and was consistent across all age groups. Positive associations were found for vBMD changes with body weight (all but radius Ct.vBMD) and diabetes (Ct.vBMD only), whereas negative associations were found with hypertension (all but radius Tb.vBMD), smoking (Ct.vBMD only), and androgen deprivation therapy (cortical vBMD only). Trabecular and cortical vBMD loss appears to follow different patterns among middle- and older-aged men of African ancestry. Factors associated with the decline in vBMD also varied by compartment and anatomical site. Additional studies are needed to better understand the physiological mechanisms underlying early BMD loss among African-ancestry men.

Risk factors for fracture in middle-age and older-age men of African descent.

Although fracture rates are lower in individuals of African descent compared to individuals of European ancestry, morbidity and mortality following a fracture may be greater in individuals of African ancestry. However, fracture risk and associated clinical risk factors have not been well-defined among African ancestry populations, especially among men of African ancestry. We used data collected from the Tobago Bone Health Study to examine potential clinical risk factors for incident fractures, including demographic information, anthropometric measurements, medical history, lifestyle factors, bone mineral density (BMD), and hip structural geometry. Among 1933 Afro-Caribbean men aged ≥40 years at study entry (mean age: 57.2 ± 11.0 years), 65 reported at least one new fracture during 10 years of subsequent follow-up. Younger age, mixed Afro-Caribbean ancestry, prior fracture history, BMD, and hip structural geometry were statistically significant risk factors for incident fractures. A 1-SD change in several skeletal parameters (hip BMD, cross-sectional area, outer diameter, cortical thickness, and buckling ratio) were each associated with a 35% to 56% increase in incident fracture risk after adjusting for age. Men with a prior fracture history were three times more likely to experience a new fracture during follow-up, and the association remained strong after adjusting for age, mixed Afro-Caribbean ancestry, and skeletal parameters (hazard ratios ranged from 2.72 to 2.82). Our findings suggest that except for age, risk factors for fracture in men of African ancestry are similar to established risk factors in white populations. Prior fracture history is a powerful and independent risk factor for incident fractures among men of African ancestry and could easily be incorporated into clinical risk evaluation.

Sclerostin and bone strength in women in their 10th decade of life.

Sclerostin is a potent inhibitor of bone formation but has been shown to correlate positively with areal bone mineral density (aBMD). Little is known about its relationship to parameters of bone strength and volumetric BMD (vBMD) as measured by peripheral quantitative computed tomography (pQCT). We measured both serum sclerostin and parameters of tibial bone size and strength by pQCT to characterize this relationship. Our study population consisted of 223 white and 35 African American women (mean age 87 years) from the Study of Osteoporotic Fractures (SOF) cohort, who had usable pQCT scans of the tibia at sites 4% (T4%), 33% (T33%), and 66% (T66%) from the ankle. Analysis of covariance was used to test for differences in age-adjusted means of aBMD, pQCT variables, and serum biomarkers across sclerostin quartiles. African American women had significantly lower median sclerostin (34.3 pmol/L) than white women (48.5 pmol/L) (p = 0.05). Women in the highest sclerostin quartile had 7% to 14.5% higher hip aBMD and pQCT parameters of vBMD and bone size than those in the lowest quartile in multivariate models adjusting for age, race, weight, height, and diabetes status. The association of sclerostin with parameters of bone strength differed dramatically between T33% and T66% sites. At T66%, women in the highest sclerostin quartile had pQCT strength parameters 9.4% to 15.3% greater than the lowest quartile, whereas no trend was found for the T33% site. Our results suggest paradoxical associations between circulating sclerostin and bone size, density, and strength.

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

OBJECTIVE: 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. DESIGN AND METHODS: The association between intermuscular AT (IMAT) in the abdominal skeletal muscles (total, paraspinal, and psoas) and fasting serum glucose, insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) in 393 nondiabetic Caucasian men aged 65+ was evaluated. Abdominal IMAT, visceral AT (VAT), and subcutaneous AT (SAT) (cm(3) ) were measured by quantitative computed tomography at the L4-L5 intervertebral space. RESULTS: In age, study site, height, and muscle volume adjusted regression analyses, total abdominal and psoas (but not paraspinal) IMAT were positively associated with glucose, insulin, and HOMA-IR (all P < 0.003). The associations between total abdominal and psoas IMAT and insulin and HOMA-IR remained significant after further adjusting for lifestyle factors, as well as duel-energy x-ray absorptiometry (DXA) measured total body fat, VAT, or SAT in separate models (all P < 0.009). CONCLUSIONS: A previously unreported, independent association between abdominal myosteatosis and hyperinsulinemia and insulin resistance among older Caucasian men was indicated. These associations may be specific for particular abdominal muscle depots, illustrating the potential importance of separately studying specific muscle groups.

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.

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.

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.

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.

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.

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) >or=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.

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 >or=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 >or=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.

Nuclear receptor coactivator-3 alleles are associated with serum bioavailable testosterone, insulin-like growth factor-1, and vertebral bone mass in men.

CONTEXT: Nuclear receptor coactivator-3 (NCOA3) is a member of the steroid receptor coactivator family that interacts with nuclear hormone receptors to enhance their transcriptional activation function and may play a role in somatic growth. OBJECTIVE: The aim of this study was to examine the relationships between the CAG/CAA (glutamine) length variation at the NCOA3 locus, sex steroid hormone, and IGF-I levels and bone mineral density (BMD) in a cohort of older Caucasian men. DESIGN AND METHODS: We analyzed the association between potentially functional alleles at this locus, serum sex steroid hormone, and IGF-I levels and lumbar spine and proximal femur BMD (Hologic QDR) in 263 community-dwelling Caucasian men (age 66 +/- 7 yr, mean +/- sd; range 51-84 yr). Men were genotyped for a CAG/CAA repeat polymorphism in NCOA3, which encodes a polyglutamine tract of variable length in the C-terminal transcriptional activation domain of the protein. RESULTS: We found a significant monotonic decrease in lumbar spine, but not hip, BMD with increasing copies of the most common allele (29 repeats, 53%). For example, men with the 29/29 genotype had 6% or nearly 0.5 sd lower spine BMD than men without this genotype, and NCOA3 genotype explained 3.2% of the phenotypic variation in this trait. Serum levels of bioavailable testosterone and IGF-I paralleled genotype-related differences in lumbar spine BMD. CONCLUSION: Allelic variation at the NCOA3 locus may contribute to the genetic control of androgenic hormone and IGF levels and vertebral bone mass among older men.

Genetic epidemiology of osteoporosis: past, present, and future.

Research during the past several decades has unequivocally established a role of heredity in the etiology of osteoporosis. Major efforts are currently underway to identify the genes and allelic variants that confer genetic susceptibility to this common and disabling condition. Genome-wide linkage mapping in families, candidate gene association studies in unrelated individuals, and quantitative trait locus mapping in animal models are the primary strategies being used to search for the genetic contributors to osteoporosis. Genome-wide mapping efforts have identified the low-density lipoprotein receptor-related protein 5, bone morphogenetic protein 2, and 15-lipoxygenase as potential susceptibility genes for osteoporosis in the past few years, providing a rich new base for understanding bone biology. Candidate gene association analyses have also provided evidence for a modest role of allelic variants in several additional genes including collagen type Ialpha1, vitamin D receptor, and estrogen receptor-alpha. With the development of a high-density genome-wide polymorphism and haplotype map and continued improvements in high-throughput and cost-effective genotyping technologies, many more genetic contributors to osteoporosis will probably be identified in the near future. The results of this research should facilitate the development of new methods for diagnosing, preventing, and treating the growing clinical and public health problem of osteoporosis.

Relationships between perceived stress, coping behavior and cortisol secretion in women with high and low levels of internalized racism.

AIM: It is hypothesized that a chronic defeat response to social or environmental stressors increases the likelihood of dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis with dysregulation of cortisol, accumulation of abdominal fat and development of glucose intolerance. Recent studies show that African-Caribbean women who have a high level of internalized racism (INR) are at increased risk for abdominal obesity and glucose intolerance. The aim of the current study was to determine if African-Caribbean women with high and low INR differ in their levels of perceived stress and defeat coping style, and in the relationship of these factors to cortisol secretion. METHODS: On the island of Dominica, information on perceived stress and coping style was collected from age- and body mass index-matched samples of nondiabetic women aged 25-60 with high (n = 27) and low (n = 26) INR. Cortisol levels for each participant were determined from saliva specimens collected at 8:30 am and 10:30 pm. RESULTS: A higher mean perceived stress score (PSS) and greater tendency to use "restraint," "denial" and "behavioral disengagement" (defeated) coping (BDC) styles were found among women with high INR compared to those with low INR. In the combined sample, PSS and BDC were significantly correlated with an indicator of dysregulation of cortisol. However, in group-specific analyses, adjusting for age and education, these correlations remained significant only among women with high INR. CONCLUSION: These findings support the view that high perceived stress and defeated coping style may be factors that link high INR to dysregulation of cortisol and, perhaps, also to greater risk of metabolic abnormalities.