Higher Appendicular Lean Mass Research Articles

Sarcopenia Is Associated with Neoplasm of Bone and Articular Cartilage: Findings from Mendelian Randomized Study.

Exploring the causal relationship between sarcopenia and neoplasm of bone and articular cartilage (NBAC) by bidirectional Mendelian randomization (MR). Genome-wide association study (GWAS) data on sarcopenia-associated traits including appendicular lean mass, low handgrip strength (including criteria from the European Working Group on Sarcopenia in Older People and the Foundation for the National Institutes of Health), and usual walking speeds were obtained from the UK Biobank. GWAS data for NBAC (benign and malignant) were provided by the Finnish Genetic Database. Three different methods of MR analysis, including inverse-variance weighted, Mendelian randomized Egger regression, and weighted median methods, were utilized. MR analysis showed that high appendicular lean mass was positively associated with the risk of developing benign NBAC (odds ratio and 95% confidence interval = 1.236 (1.026,1.489), p = 0.025). At the same time, there is no statistically significant association was found between traits related to sarcopenia and malignant neoplasm of bone and articular cartilage. There was also no reverse causal correlation between NBAC and traits related to sarcopenia. In European populations, better appendicular lean body mass is positively associated with the risk of benign neoplasm of bone and articular cartilage, representing the possibility that sarcopenia may be a protective factor against neoplasm of bone and articular cartilage.

Higher serum myostatin levels are associated with lower insulin sensitivity in adults with overweight/obesity.

Myostatin inhibition improves insulin sensitivity in preclinical and clinical models; however, studies investigating the relationship between serum myostatin levels and insulin sensitivity are discrepant. Sensitive and specific myostatin LC-MS/MS assays are now available to accurately assess serum myostatin level invivo. We sought to determine whether higher serum myostatin levels are independently associated with lower insulin sensitivity in adults with overweight/obesity. Participants included 74 adults, 20-65 years old, BMI ≥25 kg/m2 without type 2 diabetes. Appendicular lean mass (ALM) was measured by dual-energy x-ray absorptiometry; visceral adipose tissue (VAT) was measured by computed tomography. Main outcome measures were serum myostatin levels (LC-MS/MS) and insulin sensitivity (Matsuda index). Mean age was 48 ± 12 years, and BMI was 33.1 ± 5.6 kg/m2 (mean ± SD). Men had higher mean serum myostatin levels versus women (8.3 ± 1.9 vs. 7.2 ± 1.9 ng/mL, p = 0.01) and higher serum myostatin levels were associated with higher ALM (R = 0.34, p = 0.003). Higher serum myostatin levels were associated with lower Matsuda index (R = -0.44, p = 0.0004), which remained significant after controlling for BMI, VAT, ALM, and sex. In conclusion, higher serum myostatin levels are independently associated with lower insulin sensitivity in adults with overweight/obesity and may be a marker of or play a mechanistic role in the development of insulin resistance.

Cachexia-related consequences of glycemic metabolism: A multivariable and two-step Mendelian randomization study

BackgroundCachexia is a global burden that is caused by chronic diseases such as cancer. It is characterized by inflammation and progressive loss of muscle and adipose tissue, aggravating the patient’s health. Glycemic metabolism disorders exacerbate cachexia and mutually reinforce each other. Thus far, no research has established a connection between the two. Therefore, we aim to explore the influence of glucose metabolism on cachexia using Mendelian randomization (MR) and provide a theoretical basis for the early prediction of cachexia. MethodsWe used glycemic traits (type 2 diabetes (T2D), fasting glucose (FG), fasting insulin (FI), hemoglobin A1c (HbA1c), and 2-hour postprandial glucose (2hPG)) as exposures; and cachexia traits (hand grip strength (HGS), appendicular lean mass (ALM), and walking pace (WP)) as outcomes. 22 mediators were included for mediating effects. Multivariable and mediation MR were used to assess the impact of glycemic metabolism on cachexia. ResultsIn univariate MR, higher FI increased HGS (β = 0.113, 95% confidence interval (CI): 0.060–0.166) and WP (β = 0.066, 95% CI: 0.021–0.112). Higher HbA1c was associated with higher ALM (β = 0.067, 95% CI: 0.017–0.117). Higher 2hPG was associated with weaker HGS (β = −0.037, 95% CI: −0.054 to −0.021). In multivariable MR, only FI maintained a relationship with HGS after adjustments for T2D (β = 0.103, 95% CI: 0.026–0.181), FG (β = 0.101, 95% CI: 0.034–0.169), HbA1c (β = 0.115, 95% CI: 0.055–0.176), and 2hPG (β = 0.101, 95% CI: 0.033–0.169). In mediation MR, three mediators were found to be significant between FI and HGS: waist circumference (WC) (48.1%), lumbar spine bone mineral density (LSBMD) (21.3%) and insulin-like growth factor 1 (IGF-1) (6.7%). ConclusionsUsing multivariable and mediation MR, our finding suggests that higher FI increases HGS with an independent effect. WC, LSBMD, and IGF-1 mediate between FI and HGS. This study offers a theoretical framework for the early prediction and assessment of the prognosis of cachexia in cancer patients with glycemic metabolism disorders.

Association of lipid-lowering drugs with risk of sarcopenia: a drug target mendelian randomization study and meta-analysis

BackgroundLipid-lowering drugs are widely used among the elderly, with some studies suggesting links to muscle-related symptoms. However, the causality remains uncertain.MethodsUsing the Mendelian randomization (MR) approach, we assessed the causal effects of genetically proxied reduced low-density lipoprotein cholesterol (LDL-C) through inhibitions of hydroxy-methyl-glutaryl-CoA reductase (HMGCR), proprotein convertase subtilisin/kexin type 9 (PCSK9), and Niemann-Pick C1-like 1 (NPC1L1) on sarcopenia-related traits, including low hand grip strength, appendicular lean mass, and usual walking pace. A meta-analysis was conducted to combine the causal estimates from different consortiums.ResultsUsing LDL-C pooled data predominantly from UK Biobank, genetically proxied inhibition of HMGCR was associated with higher appendicular lean mass (beta = 0.087, P = 7.56 × 10− 5) and slower walking pace (OR = 0.918, P = 6.06 × 10− 9). In contrast, inhibition of PCSK9 may reduce appendicular lean mass (beta = -0.050, P = 1.40 × 10− 3), while inhibition of NPC1L1 showed no causal impact on sarcopenia-related traits. These results were validated using LDL-C data from Global Lipids Genetics Consortium, indicating that HMGCR inhibition may increase appendicular lean mass (beta = 0.066, P = 2.17 × 10− 3) and decelerate walking pace (OR = 0.932, P = 1.43 × 10− 6), whereas PCSK9 inhibition could decrease appendicular lean mass (beta = -0.048, P = 1.69 × 10− 6). Meta-analysis further supported the robustness of these causal associations.ConclusionsGenetically proxied HMGCR inhibition may increase muscle mass but compromise muscle function, PCSK9 inhibition could result in reduced muscle mass, while NPC1L1 inhibition is not associated with sarcopenia-related traits and this class of drugs may serve as viable alternatives to sarcopenia individuals or those at an elevated risk.

Sarcopenia-related Traits, Body Mass Index and Ovarian Cancer Risk: Investigation of Causal Relationships Through Multivariable Mendelian Randomization Analyses

Abstract Objective: This study was aimed at exploring the causal relationships of four sarcopenia-related traits (appendicular lean mass, usual walking pace, right hand grip strength, and levels of moderate to vigorous physical activity) with body mass index (BMI) and ovarian cancer risk, by using univariable and multivariable Mendelian randomization (MR) methods. Materials and Methods: Univariable and multivariable MR was performed to estimate causal relationships among sarcopenia-related traits, BMI, and ovarian cancer risk, in aggregated genome-wide association study (GWAS) data from the UK Biobank. Genetic variants associated with each variable (P < 5 × 10−8) were identified as instrumental variables. Three methods—inverse variance weighted (IVW) analysis, weighted median analysis, and MR-Egger regression—were used. Results: Univariable MR analyses revealed positive causal effects of high appendicular lean mass (P = 0.02) and high BMI (P = 0.001) on ovarian cancer occurrence. In contrast, a genetically predicted faster usual walking pace was associated with lower risk of ovarian cancer (P = 0.03). No evidence was found supporting roles of right hand grip strength and levels of moderate to vigorous physical activity in ovarian cancer development (P = 0.56 and P = 0.22, respectively). In multivariable MR analyses, the association between a genetically predicted faster usual walking pace and lower ovarian cancer risk remained significant (P = 0.047). Conclusions: Our study highlights a role of slower usual walking pace in the development of ovarian cancer. Further studies are required to validate our findings and understand the underlying mechanisms.

Increased Dietary Niacin Intake Improves Muscle Strength, Quality, and Glucose Homeostasis in Adults over 40 Years of Age.

Age-related loss of skeletal muscle mass and strength begins at 40 years of age, and limited evidence suggests that niacin supplementation increases levels of nicotinamide adenine dinucleotide in mouse muscle tissue. In addition, skeletal muscle has a key role in the body's processing of glucose. Therefore, this study aimed to investigate the relationship between dietary niacin and skeletal muscle mass, strength, and glucose homeostasis in people aged 40 years and older. This study was an American population-based cross-sectional analysis using data from the National Health and Nutrition Examination Survey (NHANES). Considering that some outcomes are only measured in specific survey cycles and subsamples, we established three data sets: a grip strength dataset (2011-2014, n=3772), a body mass components dataset (2011-2018, n=3279), and a glucose homeostasis dataset (1999-2018, n=9189). Dietary niacin and covariates were measured in all survey cycles. Linear regression or logistic regression models that adjusted for several main covariates, such as physical activity and diet, was used to evaluate the relationship between dietary niacin and grip strength, total lean mass, appendicular lean mass, total fat, trunk fat, total bone mineral content, homeostasis model assessment of insulin resistance (HOMA-IR), fasting blood glycose, fasting insulin and sarcopenia risk. Subgroup analyses, a trend test, an interaction test, and a restricted cubic spline were used for further exploration. Higher dietary niacin intake was significantly correlated with higher grip strength (β 0.275, 95% confidence intervals [CI] 0.192-0.357), higher total lean mass (β 0.060, 95% CI 0.045-0.074), higher appendicular lean mass (β 0.025, 95% CI 0.018-0.033), and higher total bone mineral content (β 0.005, 95% CI 0.004-0.007). By contrast, higher dietary niacin intake was significantly associated with lower total fat (β -0.061, 95% CI -0.076 to -0.046), lower trunk fat (β -0.041, 95% CI -0.050 to -0.032) and lower sarcopenia risk (OR 0.460, 95% CI 0.233 to 0.907). In addition, dietary niacin significantly reduced HOMA-IR, fasting blood glucose (in participants without diabetes), and fasting insulin (p <0.05). Niacin is associated with improved body composition (characterized by increased muscle mass and decreased fat content) and improved glucose homeostasis in dietary doses. Dietary niacin supplementation is a feasible way to alleviate age-related muscular loss.

Identification of three bacterial species associated with increased appendicular lean mass: the HUNT study

Appendicular lean mass (ALM) associates with mobility and bone mineral density (BMD). While associations between gut microbiota composition and ALM have been reported, previous studies rely on relatively small sample sizes. Here, we determine the associations between prevalent gut microbes and ALM in large discovery and replication cohorts with information on relevant confounders within the population-based Norwegian HUNT cohort (n = 5196, including women and men). We show that the presence of three bacterial species – Coprococcus comes, Dorea longicatena, and Eubacterium ventriosum – are reproducibly associated with higher ALM. When combined into an anabolic species count, participants with all three anabolic species have 0.80 kg higher ALM than those without any. In an exploratory analysis, the anabolic species count is positively associated with femoral neck and total hip BMD. We conclude that the anabolic species count may be used as a marker of ALM and BMD. The therapeutic potential of these anabolic species to prevent sarcopenia and osteoporosis needs to be determined.

Erythrocyte Linoleic Acid Is Associated With Higher Heart Rate Variability and Better Sleep Quality: A Possible Link to Reducing Risk for Cardiometabolic Diseases

ObjectivesCancer patients often experience poor sleep quality, an aspect of health that accelerates the risk for cardiovascular and metabolic diseases. Higher intake of linoleic acid (LA: 18:2n-6) is linked with reduced risk for cardiometabolic diseases. This study has two objectives: To identify whether erythrocyte LA content is associated with sleep quality in women who were newly diagnosed with breast cancer; 2) Measure the association of erythrocyte LA with metabolism and postprandial heart rate variability (HRV). MethodsIn this cross-sectional study, erythrocyte LA levels were quantified at the same visit as measurements of body composition, self-reported sleep quality, HRV, postprandial energy metabolism and cardiorespiratory fitness (VO2peak) in women (N = 150) newly diagnosed with breast cancer. At a separate visit, cardiometabolic fitness was also measured. ResultsErythrocyte LA was positively associated with higher appendicular lean mass (ALM/BMI) and higher pre-meal heart rate variability. In addition, higher erythrocyte LA was associated with better reported overall sleep quality. Postprandially, women with higher erythrocyte LA had a steeper decline of pulse and a less steep decline of glucose. ConclusionsThe positive relationship between LA with better sleep quality and higher heart rate variability supports the need to test whether fortifying the diet with LA-rich oils lowers cardiometabolic risk in cancer patients involving the autonomic nervous system. Funding SourcesFunding was provided by the National Cattleman’s Beef Association (MAB), NIH (JKG) CA186720, Ohio Agriculture Research and Development Center (MAB) and the Carol S. Kennedy Professorship (MAB).

Appendicular Lean Mass and Frailty among Geriatric Outpatients.

The objective of this observational study was to examine the association between appendicular lean mass and frailty in adults aged 60 years and older. This study was conducted in the Outpatient Department of the National Geriatric Hospital in Hanoi, Vietnam. Appendicular lean mass (kg) was assessed by using Dual energy X-ray absorptiometry scans. Frailty was defined according to Fried's frailty criteria. A total of 560 outpatients were included in the study, with a mean age of 70 years. The prevalence of frailty was 12.0%. Frail patients had significantly lower appendicular lean mass compared with non-frail outpatients (9.6 ± 2.0 kg vs. 11.7 ± 3.1 kg, p<0.001). On multivariable logistic regression models, higher appendicular lean mass was associated with significantly reduced odds for frailty (adjusted OR = 0.74, 95%CI 0.59 - 0.93). These findings suggest that the assessment of appendicular lean mass should be considered in older patients attending outpatient geriatric clinics.

Association of serum adiponectin and myostatin levels with skeletal muscle in patients with obesity: A cross-sectional study.

BackgroundAdiponectin has been reported to be associated with lower skeletal muscle mass and skeletal strength and may be involved in skeletal muscle regulation along with myostatin. This study aims to evaluate the association between serum adiponectin and myostatin levels and identify independent factors using body composition and metabolic parameters in patients with obesity.MethodsOverall, 148 patients (age, 45.9 ± 14.3 years, body mass index, 37.2 ± 8.0 kg/m2) who initially visited the outpatient clinic of obesity between November 2013 and November 2019 were included. Body composition was measured using InBody 720 and dual energy X-ray absorptiometry. In addition, muscle strength, vascular function, and metabolic parameters were measured. Serum levels of adiponectin, leptin, myostatin, and irisin were measured from blood samples.ResultsThe serum adiponectin level was 2.9 μg/mL (1.7–4.1 μg/mL), and the serum myostatin level was 2398.4 pg/mL (1,777.1–2952.5 pg/mL). The stepwise regression analysis revealed less leg strength, homeostasis model assessment of insulin resistance, and C-reactive protein as an independent predictor of serum adiponectin levels based on the significance of the univariate analysis (R2 = 0.190, P < 0.001). A high appendicular lean mass/body weight, reactive hyperemia index, and irisin were independent factors for serum myostatin levels (R2 = 0.260, P < 0.001)ConclusionThe serum adiponectin level was associated with less muscle strength. Although serum myostatin was associated with a high appendicular lean mass, it is possible that myostatin was regulated by the percentage of body weight from appendicular lean mass.

Introduction of Fall Risk Assessment (FRA) System and Cross-Sectional Validation Among Community-Dwelling Older Adults.

ObjectiveTo predict the risk of falls, Fall Risk Assessment (FRA) system has been newly developed to measure multi-systemic balance control among community-dwelling older adults. The aim of this study was to examine the association between FRA and fall-related physical performance tests.MethodsA total of 289 community-dwelling adults aged 65 years and older participated in this cross-sectional study. All participants underwent FRA test and physical performance tests such as Short Physical Performance Battery (SPPB), Berg Balance Scale (BBS), and Timed Up and Go Test (TUG).ResultsParticipants who were younger, male, highly educated, living with family members, having high body mass index, having high appendicular lean mass index, and having no irritative lower urinary tract syndrome were more likely to have higher FRA scores. SPPB (β=1.012), BBS (β=0.481), and TUG (β=-0.831) were significantly associated with FRA score after adjusting for the variables (all p<0.001).ConclusionFRA composite score was closely correlated with SPPB, BBS, and TUG, suggesting that FRA is a promising candidate as a screening tool to predict falls among community-dwelling elderly people.

What is the best adjustment of appendicular lean mass for predicting mortality or disability among Japanese community dwellers?

BackgroundAge-related declines in skeletal muscle mass and strength, representing “sarcopenia,” are a growing concern in aging societies. However, the prevalence of low muscle mass based on the height2-adjustment has been shown to be extremely low, and a more appropriate definition of low muscle mass is needed, particularly for Asian women. The aim of this study was to explore the most appropriate adjustment of appendicular lean mass (ALM) for predicting mortality or disability risk using ALM or any of 5 adjustments of ALM among community-dwelling Japanese.MethodsSubjects comprised 1026 men and 952 women between 40 and 79 years old at baseline (1997–2000) who participated in the National Institute for Longevity Sciences - Longitudinal Study of Aging, Japan. ALM (kg) and 5 adjusted indices of ALM (ALM/leg length, ALM/height, ALM/height2, ALM/weight, and ALM/body mass index [BMI]) were assessed at baseline. Disability was defined by long-term care insurance certification based on responses to a survey mailed in 2013, and death records were obtained as vital statistics until December 2014. Crude and adjusted Cox proportional hazard models were used to estimate hazard ratios for mortality or disability by sex-stratified quintiles of each ALM index (ALM and adjusted ALM) or sarcopenia-related indices. The area under the curve (AUC) was calculated with the multivariate-adjusted logistic regression model. Additionally, mixed-effects analyses were used to clarify the age-related ALM indices decline over 12 years (n = 1838).ResultsCrude Cox proportional hazard models and multivariate-adjusted logistic model (AUC) indicated that higher ALM and ALM/BMI in women, and higher ALM, ALM/leg length, ALM/height, and ALM/BMI in men were associated with lower risks for mortality or disability than ALM/height2. The mixed effect model indicated all ALM indices in men, and ALM, ALM/leg length, and ALM/height in women could better predict age-related lean muscle mass decline.ConclusionsUnadjusted ALM in women, and ALM/leg length, ALM/height, ALM/BMI, and ALM in men may be more appropriate for predicting future mortality or disability than ALM/height2. Considering the age-related muscle mass decline, unadjusted ALM would be the first variable to assess, regardless of sex, in this Japanese cohort study.

Musculoskeletal decline and mortality: prospective data from the Geelong Osteoporosis Study.

BackgroundWe aimed to examine the relationship between musculoskeletal deterioration and all‐cause mortality in a cohort of women studied prospectively over a decade.MethodsA cohort of 750 women aged 50–94 years was followed for a decade after femoral neck bone mineral density (BMD) and appendicular lean mass (ALM) were measured using dual energy X‐ray absorptiometry, in conjunction with comorbidities, health behaviour data, and other clinical measures. The outcome was all‐cause mortality identified from the Australian National Deaths Index. Using Cox proportional hazards models and age as the time variable, mortality risks were estimated according to BMD groups (ideal‐BMD, osteopenia, and osteoporosis) and ALM groups (T‐scores > −1.0 high, −2.0 to −1.0 medium, <−2.0 low).ResultsDuring 6712 person years of follow‐up, there were 190 deaths, the proportions increasing with diminishing BMD: 10.7% (23/215) ideal‐BMD, 23.5% (89/378) osteopenia, 49.7% (78/157) osteoporosis; and with diminishing ALM: 17.0% (59/345) high, 26.2% (79/301) medium, 50.0% (52/104) low. In multivariable models adjusted for smoking, polypharmacy, and mobility, compared with those with ideal BMD, mortality risk was greater for those with osteopenia [hazard ratio (HR) 1.77, 95% confidence interval (CI) 1.11–2.81] and osteoporosis (HR 2.61, 95%CI 1.60–4.24). Similarly, compared with those with high ALM, adjusted mortality risk was greater for medium ALM (HR 1.36, 95%CI 0.97–1.91) and low ALM (HR 1.65, 95%CI 1.11–2.45). When BMD and ALM groups were tested together in the model, BMD remained a predictor of mortality (HR 1.74, 95%CI 1.09–2.78; HR 2.82, 95%CI 1.70–4.70; respectively), and low ALM had borderline significance (HR 1.52, 95%CI 1.00–2.31), which was further attenuated after adjusting for smoking, polypharmacy, and mobility.ConclusionsPoor musculoskeletal health increased the risk for mortality independent of age. This appears to be driven mainly by a decline in bone mass. Low lean mass independently exacerbated mortality risk, and this appeared to operate through poor health exposures.

Appendicular Lean Mass and Mortality among Prefrail and Frail Older Adults.

Prefrail and frail older adults are a heterogeneous population. The measurement of appendicular lean mass (ALM) may distinguish those at higher versus lower risk of poor outcomes. We examined the relationship between ALM and mortality among prefrail and frail older adults. This was a population-based cohort study. The Third National Health and Nutrition Survey (NHANES III; 1988-1994). Older adults (age ≥65 years) with pre-frailty or frailty defined using the Fried criteria. ALM was quantified using bioimpedance analysis. Multivariable-adjusted Cox regression analysis examined the relationship between ALM and mortality. Logistic regression analysis was used to determine if ALM added to age and sex improved the predictive discrimination of five-year and ten-year mortality. At baseline, the average age was 74.9 years, 66.7% were female, 86.3% and 13.7% were prefrail and frail, respectively. The mean ALM was 18.9 kg [standard deviation (SD): 5.5]. During a median 8.9 years of follow-up, 1,307 of 1,487 study participants died (87.9%). Higher ALM was associated with a lower risk of mortality. In a multivariable-adjusted regression model that accounted for demographic, behavioral, clinical, physical function, and frailty characteristics, each SD increase in ALM was associated with an 50% lower risk of mortality [Hazard Ratio: 0.50 (95% CI: 0.27-0.92); P=0.026]. The addition of ALM to age and sex improved the predictive discrimination of five-year (P=0.027) and ten-year (P=0.016) mortality. ALM distinguishes the risk of mortality among prefrail and frail older adults. Additional research examining ALM as a therapeutic target is warranted.

Physical activity across adulthood in relation to fat and lean body mass in early old age: findings from the Medical Research Council National Survey of Health and Development, 1946-2010.

Fat and lean body mass have important implications for health and physical functioning in older age, and physical activity is purported to be an important modifiable determinant. However, our evidence-based understanding of its role is limited. We examined the associations of physical activity, assessed both by self-report (using data on leisure time physical activity (LTPA) collected on 4 occasions over a 28-year period) and objectively (using 5-day heart rate and movement monitoring), with fat and lean mass at ages 60–64 years in 1,162 British participants from the Medical Research Council National Survey of Health and Development in 1946–2010. Higher objectively assessed physical activity energy expenditure (PAEE) at ages 60–64 years was associated with lower fat mass and android (abdominal):gynoid (hip) fat ratio (mean differences in fat mass per 1–standard deviation increase in PAEE were −0.79 kg/m1.2 in men (95% confidence interval: −1.08, −0.50) and −1.79 kg/m1.2 (95% confidence interval: −2.15, −1.42) in women). After adjustment for fat mass, higher PAEE was associated with higher appendicular lean mass. Both light and moderate-to-vigorous intensities of activity were associated with fat mass, and the latter was associated with lean mass. More frequent LTPA across adulthood was associated with lower fat mass (in women only) and higher appendicular lean mass (in both sexes, after adjustment for fat mass). These results support the promotion of LTPA across adulthood, as well as both light and moderate-to-vigorous intensities of activity among older adults.

Relationships of appendicular LMI and total body LMI to bone mass and physical activity levels in a birth cohort of New Zealand five-year olds

The present study was undertaken to determine whether children with lower bone mass display lower muscle mass for their height than those with high bone mineral content (BMC) and whether appendicular lean mass (bone-free lean mass in arms plus legs) is associated with physical activity and/or BMC in preschool children. 158 children (59% male) from a New Zealand cohort born in 2001–2002 were studied close to their fifth birthday. Body composition was measured by dual energy X-ray absorptiometry (Lunar DPX-L). Lean mass index (LMI) was calculated as lean mass (kg) divided by height in metres squared. Physical activity was assessed objectively by accelerometry (Actical Mini-Mitter). Girls and boys had similar heights, weights and daily accelerometry counts but boys had lower fat mass, and higher lean mass and total body BMC than the girls ( P < 0.00l). In both sexes children with greater quantities of total and regional lean mass and higher LMI values had significantly higher bone mass. Appendicular LMI was more strongly associated with BMC than LMI. Accelerometry counts showed no associations with height but were positively associated with lean mass ( r = 0.23, P < 0.03), appendicular LMI ( r = 0.25 P < 0.01), total body BMC ( r = 0.24, P < 0.02) and total body less head BMC ( r = 0.27 P < 0.009) in the boys, but not in the girls. Greater time spent in more intense physical activity was also associated with higher appendicular lean mass and TBLH BMC only in the boys. We conclude that children with lower BMC values display not only lower lean mass but also lower total and appendicular lean mass for their height, than those with higher BMC values. The sex differences in associations of accelerometry counts to lean mass and BMC have been noted by others and require further investigation.