3T-MRI-based age, sex and site-specific markers of musculoskeletal health in healthy children and young adults.

Objective: The aim of this study is to investigate the role of 3T-MRI in assessing musculoskeletal health in children and young people. Design: Bone, muscle and bone marrow imaging was performed in 161 healthy participants with a median age of 15.0 years (range, 8.0, 30.0). Methods: Detailed assessment of bone microarchitecture (constructive interference in the steady state (CISS) sequence, voxel size 0.2 × 0.2 × 0.4 mm3), bone geometry (T1-weighted turbo spin echo (TSE) sequence, voxel size 0.4 × 0.4 × 2 mm3) and bone marrow (1H-MRS, point resolved spectroscopy sequence (PRESS) (single voxel size 20 × 20 × 20 mm3) size and muscle adiposity (Dixon, voxel size 1.1 × 1.1 × 2 mm3). Results: There was an inverse association of apparent bone volume/total volume (appBV/TV) with age (r = -0.5, P < 0.0005). Cortical area, endosteal and periosteal circumferences and muscle cross-sectional area showed a positive association to age (r > 0.49, P < 0.0001). In those over 17 years of age, these parameters were also higher in males than females (P < 0.05). This sex difference was also evident for appBV/TV and bone marrow adiposity (BMA) in the older participants (P < 0.05). AppBV/TV showed a negative correlation with BMA (r = -0.22, P = 0.01) which also showed an association with muscle adiposity (r = 0.24, P = 0.04). Cortical geometric parameters were highly correlated with muscle area (r > 0.57, P < 0.01). Conclusions: In addition to providing deep insight into the normal relationships between bone, fat and muscle in young people, these novel data emphasize the role of MRI as a non-invasive method for performing a comprehensive and integrated assessment of musculoskeletal health in the growing skeleton.

Pathogenesis of Musculoskeletal Deficits in Children and Adults with Inflammatory Bowel Disease.

Musculoskeletal deficits are among the most commonly reported extra-intestinal manifestations and complications of inflammatory bowel disease (IBD), especially in those with Crohn's disease. The adverse effects of IBD on bone and muscle are multifactorial, including the direct effects of underlying inflammatory disease processes, nutritional deficits, and therapeutic effects. These factors also indirectly impact bone and muscle by interfering with regulatory pathways. Resultantly, individuals with IBD are at increased risk of osteoporosis and sarcopenia and associated musculoskeletal morbidity. In paediatric IBD, these factors may contribute to suboptimal bone and muscle accrual. This review evaluates the main pathogenic factors associated with musculoskeletal deficits in children and adults with IBD and summarises the current literature and understanding of the musculoskeletal phenotype in these patients.

Muscle deficits with normal bone microarchitecture and geometry in young adults with well-controlled childhood-onset Crohn's disease.

BACKGROUND: Muscle-bone deficits are common in pediatric Crohn's disease; however, few studies have assessed long-term musculoskeletal outcomes in adults with childhood-onset Crohn's disease. This study assessed the prevalence of musculoskeletal deficits in young adults with childhood-onset Crohn's disease compared with healthy controls. METHODS: High-resolution MRI and MR spectroscopy were used to assess bone microarchitecture, cortical geometry and muscle area, and adiposity at distal femur and bone marrow adiposity (BMA) at lumbar spine. Muscle function and biomarkers of the muscle-bone unit were also assessed. RESULTS: Twenty-seven adults with Crohn's disease with median (range) age 23.2 years (18.0, 36.1) and 27 age and sex-matched controls were recruited. Trabecular microarchitecture, cortical geometry and BMA were not different between Crohn's disease and controls (P > 0.05 for all). Muscle area was lower (P = 0.01) and muscle fat fraction was higher (P = 0.04) at the distal femur in Crohn's disease compared to controls. Crohn's disease participants had lower grip strength [-4.3 kg (95% confidence interval (CI), -6.8 to -1.8), P = 0.001] and relative muscle power [-5.0 W/kg (95% CI, -8.8 to -1.2), P = 0.01]. Crohn's disease activity scores negatively associated with trabecular bone volume (r = -0.40, P = 0.04) and muscle area (r = -0.41, P = 0.03). CONCLUSION: Young adults with well-controlled Crohn's disease managed with contemporary therapies did not display abnormal bone microarchitecture or geometry at the distal femur but exhibited muscle deficits. The observed muscle deficits may predispose to musculoskeletal morbidity in future and interventions to improve muscle mass and function warrant investigation.

Dose-response associations of cardiorespiratory fitness with all-cause mortality and incidence and mortality of cancer and cardiovascular and respiratory diseases: the UK Biobank cohort study.

OBJECTIVE: To investigate the association of cardiorespiratory fitness with all-cause mortality, and cardiovascular disease (CVD), respiratory disease, chronic obstructive pulmonary disease (COPD) and cancer mortality and incidence. DESIGN: Prospective population-based study. SETTING: UK Biobank. PARTICIPANTS: Of the 5 02 628 (5.5% response rate) participants recruited by UK Biobank, we included 73 259 (14.6%) participants with available data in this analysis. Of these, 1374 participants died and 4210 developed circulatory diseases, 1293 respiratory diseases and 4281 cancer, over a median of 5.0 years (IQR 4.3-5.7) follow-up. MAIN OUTCOME MEASURES: All-cause mortality and circulatory disease, respiratory disease, COPD and cancer (such as colorectal, lung, breast and prostate) mortality/incidence. Fitness was estimated using a submaximal cycle ergometer test. RESULTS: The HR for all-cause mortality for each metabolic equivalent of task (MET) higher fitness was 0.96 (95% CI 0.93 to 0.98). Similar results were observed for incident circulatory disease (HR 0.96 [0.95 to 0.97]), respiratory disease (HR 0.96 [0.94 to 0.98]), COPD (HR 0.90 [0.86 to 0.95) and colorectal cancer (HR 0.96 [0.92 to 1.00]). Nonlinear analysis revealed that a high level of fitness (>10METs) was associated with a greater incidence of atrial fibrillation (HR 1.24 [1.07 to 1.44]) and prostate cancer (HR 1.16 [1.02 to 1.32]) compared with average fitness. All results were adjusted for sociodemographic, lifestyle and dietary factors, body composition, and morbidity at baseline and excluded events in the first 2 years of follow-up. CONCLUSIONS: Higher cardiorespiratory fitness was associated with lower risk of premature mortality and incidence of CVD, respiratory disease and colorectal cancer.

Associations of Dietary Protein Intake With Fat-Free Mass and Grip Strength: A Cross-Sectional Study in 146,816 UK Biobank Participants.

Adequate dietary protein intake is important for the maintenance of fat-free mass (FFM) and muscle strength, but optimal requirements remain unknown. Our aim in the current study was to explore the associations of protein intake with FFM and grip strength. We used baseline data from the UK Biobank (a study of 146,816 participants aged 40-69 years with data collected across the United Kingdom in 2007-2010) to examine the associations of protein intake with FFM and grip strength. Protein intake was positively associated with FFM (men: 5.1% (95% confidence interval (CI): 5.0, 5.2); women: 7.7% (95% CI: 7.7, 7.8)) and grip strength (men: 0.076 kg/kg (95% CI: 0.074, 0.078); women: 0.074 kg/kg (95% CI: 0.073, 0.076)) per 0.5-g/kg/day (grams per kg of body mass per day) increment in protein intake. FFM and grip strength were higher with higher intakes across the full range of intakes (i.e., highest in persons who reported consuming ≥2.00 g/kg/day) independently of sociodemographic factors, other dietary measures, physical activity, and comorbidity. FFM and grip strength were lower with age, but this association did not differ by category of protein intake (P > 0.05). The current recommendation for all adults (ages 40-69 years) to maintain a protein intake of 0.8 g/kg/day may need to be increased to optimize FFM and grip strength.

Associations of discretionary screen time with mortality, cardiovascular disease and cancer are attenuated by strength, fitness and physical activity: findings from the UK Biobank study.

BACKGROUND: Discretionary screen time (time spent viewing a television or computer screen during leisure time) is an important contributor to total sedentary behaviour, which is associated with increased risk of mortality and cardiovascular disease (CVD). The aim of this study was to determine whether the associations of screen time with cardiovascular disease and all-cause mortality were modified by levels of cardiorespiratory fitness, grip strength or physical activity. METHODS: In total, 390,089 participants (54% women) from the UK Biobank were included in this study. All-cause mortality, CVD and cancer incidence and mortality were the main outcomes. Discretionary television (TV) viewing, personal computer (PC) screen time and overall screen time (TV + PC time) were the exposure variables. Grip strength, fitness and physical activity were treated as potential effect modifiers. RESULTS: Altogether, 7420 participants died, and there were 22,210 CVD events, over a median of 5.0 years follow-up (interquartile range 4.3 to 5.7; after exclusion of the first 2 years from baseline in the landmark analysis). All discretionary screen-time exposures were significantly associated with all health outcomes. The associations of overall discretionary screen time with all-cause mortality and incidence of CVD and cancer were strongest amongst participants in the lowest tertile for grip strength (all-cause mortality hazard ratio per 2-h increase in screen time (1.31 [95% confidence interval: 1.22-1.43], p < 0.0001; CVD 1.21 [1.13-1.30], p = 0.0001; cancer incidence 1.14 [1.10-1.19], p < 0.0001) and weakest amongst those in the highest grip-strength tertile (all-cause mortality 1.04 [0.95-1.14], p = 0.198; CVD 1.05 [0.99-1.11], p = 0.070; cancer 0.98 [0.93-1.05], p = 0.771). Similar trends were found for fitness (lowest fitness tertile: all-cause mortality 1.23 [1.13-1.34], p = 0.002 and CVD 1.10 [1.02-1.22], p = 0.010; highest fitness tertile: all-cause mortality 1.12 [0.96-1.28], p = 0.848 and CVD 1.01 [0.96-1.07], p = 0.570). Similar findings were found for physical activity for all-cause mortality and cancer incidence. CONCLUSIONS: The associations between discretionary screen time and adverse health outcomes were strongest in those with low grip strength, fitness and physical activity and markedly attenuated in those with the highest levels of grip strength, fitness and physical activity. Thus, if these associations are causal, the greatest benefits from health promotion interventions to reduce discretionary screen time may be seen in those with low levels of strength, fitness and physical activity.

Associations of grip strength with cardiovascular, respiratory, and cancer outcomes and all cause mortality: prospective cohort study of half a million UK Biobank participants.

OBJECTIVE: To investigate the association of grip strength with disease specific incidence and mortality and whether grip strength enhances the prediction ability of an established office based risk score. DESIGN: Prospective population based study. SETTING: UK Biobank. PARTICIPANTS: 502 293 participants (54% women) aged 40-69 years. MAIN OUTCOME MEASURES: All cause mortality as well as incidence of and mortality from cardiovascular disease, respiratory disease, chronic obstructive pulmonary disease, and cancer (all cancer, colorectal, lung, breast, and prostate). RESULTS: Of the participants included in analyses, 13 322 (2.7%) died over a mean of 7.1 (range 5.3-9.9) years' follow-up. In women and men, respectively, hazard ratios per 5 kg lower grip strength were higher (all at P<0.05) for all cause mortality (1.20, 95% confidence interval 1.17 to 1.23, and 1.16, 1.15 to 1.17) and cause specific mortality from cardiovascular disease (1.19, 1.13 to 1.25, and 1.22, 1.18 to 1.26), all respiratory disease (1.31, 1.22 to 1.40, and 1.24, 1.20 to 1.28), chronic obstructive pulmonary disease (1.24, 1.05 to 1.47, and 1.19, 1.09 to 1.30), all cancer (1.17, 1.13 to 1.21, 1.10, 1.07 to 1.13), colorectal cancer (1.17, 1.04 to 1.32, and 1.18, 1.09 to 1.27), lung cancer (1.17, 1.07 to 1.27, and 1.08, 1.03 to 1.13), and breast cancer (1.24, 1.10 to 1.39) but not prostate cancer (1.05, 0.96 to 1.15). Several of these relations had higher hazard ratios in the younger age group. Muscle weakness (defined as grip strength <26 kg for men and <16 kg for women) was associated with a higher hazard for all health outcomes, except colon cancer in women and prostate cancer and lung cancer in both men and women. The addition of handgrip strength improved the prediction ability, based on C index change, of an office based risk score (age, sex, diabetes diagnosed, body mass index, systolic blood pressure, and smoking) for all cause (0.013) and cardiovascular mortality (0.012) and incidence of cardiovascular disease (0.009). CONCLUSION: Higher grip strength was associated with a range of health outcomes and improved prediction of an office based risk score. Further work on the use of grip strength in risk scores or risk screening is needed to establish its potential clinical utility.

Joint effect of physical activity and sedentary behaviour on cardiovascular risk factors in Chilean adults.

Background: To investigate the associations between combined categories of moderate-to-vigorous physical activity (MVPA) and sedentary behaviour (SB) with markers of adiposity and cardiovascular risk in adults. Methods: Overall, 5040 participants (mean age 46.4 years and 59.3% women) from the cross-sectional Chilean National Health Survey 2009-2010 were included in this study. MVPA and SB were measured using the Global Physical Activity questionnaire. Four categories were computed using MVPA- and SB-specific cut-offs ('High-SB & Active', 'Low-SB & Active', 'High-SB & Inactive' and 'Low-SB & Inactive'). Results: Compared to the reference group ('High-SB & Inactive'), those in 'High-SB & Active' and 'Low-SB & Active' were less likely to have an obese BMI (OR: 0.67 [0.54; 0.85], P = 0.0001 and 0.74 [0.59; 0.92] P = 0.0007, respectively) and less likely to have metabolic syndrome (OR: 0.63 [0.49; 0.82], P < 0.0001 and 0.72 [0.57; 0.91], P = 0.007), central obesity (OR: 0.79 [0.65; 0.96], P = 0.016 and 0.71 [0.59; 0.84], P < 0.0001), diabetes (OR: 0.45 [0.35; 0.59], P < 0.0001 and 0.44 [0.34; 0.56], P < 0.0001) and hypertension (OR: 0.52 [0.43; 0.63], P < 0.0001 and 0.60 [0.50; 0.72], P < 0.0001), respectively. Conclusions: Being physically active and spending less time in SBs was associated with lower adiposity and improvements in cardiovascular risk factors.

Active commuting is associated with a lower risk of obesity, diabetes and metabolic syndrome in Chilean adults.

Background: There is limited evidence on how active commuting is associated with health benefits in developing countries. The aim of this study therefore was to investigate the associations between active commuting and markers of adiposity and cardiometabolic risk in the Chilean adult population. Methods: In total, 5157 participants from the Chilean National Health Survey 2009-10 were included in this cross-sectional study. Active commuting was measured using the Global Physical Activity Questionnaire (GPAQ v2). Body mass index (BMI) and waist circumference (WC) were measured and used to define obesity and central obesity. Type 2 diabetes (T2D) and metabolic syndrome were determined using WHO and updated ATPIII-NCEP criteria, respectively. Results: The main finding of this study is that a 30 min increase in active commuting is associated with lower odds for BMI > 25.0 kg m-2 (0.93 [95% CI: 0.88-0.98, P = 0.010]). Similarly, the odds for central obesity was 0.87 [0.82-0.92, P < 0.0001]. Similar associations were found for T2D (0.81 [0.75-0.88], P < 0.0001) and metabolic syndrome (OR: 0.86 [0.80-0.92], P < 0.0001). Conclusion: Our findings show that active commuting is associated with lower adiposity and a healthier metabolic profile including lower risk for obesity, diabetes and metabolic syndrome.

Higher levels of self-reported sitting time is associated with higher risk of type 2 diabetes independent of physical activity in Chile.

Background: Sitting behaviours have increased markedly during the last two decades in Chile. However, their associations with health outcomes such as diabetes have not been reported. Therefore, the aim of this study was to investigate the independent association of self-reported sitting time with diabetes-related markers and diabetes prevalence in Chile. Methods: This cross-sectional study included participants (aged ≥18 years) from the Chilean National Health Survey 2009-10 (n = 4457). Fasting glucose and haemoglobin A1c (HbA1c) were measured by standardized protocols. The prevalence of type 2 diabetes (T2D) was determined using WHO criteria. Physical activity (PA) and time spent sitting were determined using the Global Physical Activity Questionnaire (GPAQ). Results: The odds ratio for T2D was 1.10 [95% CI: 1.04-1.16, P = 0.002] and 1.08 [1.02-1.14, P = 0.002] per 1 h increase in sitting time in men and women, respectively, independent of age, education, smoking, BMI and total PA. Overall, prevalence of T2D was 10.2 and 17.2% in individuals classified in the lowest and highest categories of sitting time, respectively. No significant associations were found between sitting time and glucose or HbA1c. Conclusions: Sitting time is positively associated with diabetes risk, independent of socio-demographic, obesity and PA levels, in the Chilean population.

Association between active commuting and incident cardiovascular disease, cancer, and mortality: prospective cohort study.

Objective To investigate the association between active commuting and incident cardiovascular disease (CVD), cancer, and all cause mortality.Design Prospective population based study. Setting UK Biobank.Participants 263 450 participants (106 674 (52%) women; mean age 52.6), recruited from 22 sites across the UK. The exposure variable was the mode of transport used (walking, cycling, mixed mode v non-active (car or public transport)) to commute to and from work on a typical day.Main outcome measures Incident (fatal and non-fatal) CVD and cancer, and deaths from CVD, cancer, or any causes.Results 2430 participants died (496 were related to CVD and 1126 to cancer) over a median of 5.0 years (interquartile range 4.3-5.5) follow-up. There were 3748 cancer and 1110 CVD events. In maximally adjusted models, commuting by cycle and by mixed mode including cycling were associated with lower risk of all cause mortality (cycling hazard ratio 0.59, 95% confidence interval 0.42 to 0.83, P=0.002; mixed mode cycling 0.76, 0.58 to 1.00, P<0.05), cancer incidence (cycling 0.55, 0.44 to 0.69, P<0.001; mixed mode cycling 0.64, 0.45 to 0.91, P=0.01), and cancer mortality (cycling 0.60, 0.40 to 0.90, P=0.01; mixed mode cycling 0.68, 0.57 to 0.81, P<0.001). Commuting by cycling and walking were associated with a lower risk of CVD incidence (cycling 0.54, 0.33 to 0.88, P=0.01; walking 0.73, 0.54 to 0.99, P=0.04) and CVD mortality (cycling 0.48, 0.25 to 0.92, P=0.03; walking 0.64, 0.45 to 0.91, P=0.01). No statistically significant associations were observed for walking commuting and all cause mortality or cancer outcomes. Mixed mode commuting including walking was not noticeably associated with any of the measured outcomes.Conclusions Cycle commuting was associated with a lower risk of CVD, cancer, and all cause mortality. Walking commuting was associated with a lower risk of CVD independent of major measured confounding factors. Initiatives to encourage and support active commuting could reduce risk of death and the burden of important chronic conditions.

Sleep characteristics modify the association of genetic predisposition with obesity and anthropometric measurements in 119,679 UK Biobank participants.

Background: Obesity is a multifactorial condition influenced by genetics, lifestyle, and environment.Objective: We investigated whether the association of a validated genetic profile risk score for obesity (GPRS-obesity) with body mass index (BMI) and waist circumference (WC) was modified by sleep characteristics.Design: This study included cross-sectional data from 119,859 white European adults, aged 37-73 y, participating in the UK Biobank. Interactions of GPRS-obesity and sleep characteristics (sleep duration, chronotype, day napping, and shift work) with their effects on BMI and WC were investigated. Results: ß Values are expressed as the change in BMI (in kg/m2) or WC per 1-SD increase in GPRS-obesity. The GPRS-obesity was associated with BMI (ß: 0.57; 95% CI: 0.55, 0.60; P = 6.3 × 10-207) and WC (1.21 cm; 95% CI: 1.15, 1.28 cm; P = 4.2 × 10-289). There were significant interactions of GPRS-obesity and a variety of sleep characteristics with their relation with BMI (P-interaction < 0.05). In participants who slept <7 or >9 h daily, the effect of GPRS-obesity on BMI was stronger (ß: 0.60; 95% CI: 0.54, 0.65 and ß: 0.73; 95% CI: 0.49, 0.97, respectively) than in normal-length sleepers (7-9 h; ß: 0.52; 95% CI: 0.49, 0.55). A similar pattern was observed for shift workers (ß: 0.68; 95% CI: 0.59, 0.77 compared with ß: 0.54; 95% CI: 0.51, 0.58 for non-shift workers) and for night-shift workers (ß: 0.69; 95% CI: 0.56, 0.82 compared with ß: 0.55; 95% CI: 0.51, 0.58 for non-night-shift workers), for those taking naps during the day (ß: 0.65; 95% CI: 0.52, 0.78 compared with ß: 0.51; 95% CI: 0.48, 0.55 for those who never or rarely had naps), and for those with a self-reported evening chronotype (ß: 0.72; 95% CI: 0.61, 0.82 compared with ß: 0.52; 95% CI: 0.47, 0.57 for morning chronotype). Similar findings were obtained by using WC as the outcome.Conclusion: This study shows that the association between genetic risk for obesity and phenotypic adiposity measures is exacerbated by adverse sleeping characteristics.