Appendicular Lean Body 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.

Growth and physical development of children at apparent risk of sarcopenia.

The consequences of sarcopenia on growth have received little attention. We analysed the potential risk resulting from the low lean mass for age expressed through the appendicular lean body mass index (aLBMI) and the ratio aLBM/trunk fat mass (trFM). The sample consisted of 580 participants 10-13 yrs evaluated twice in a 12-month interval: height, trFM, total and aLBM, whole-body bone mineral density less head (WBLH BMD), tibia and radius SOS, maturity and handgrip strength were measured. All variables except maturity and BMI were standardised according to sex and age group (Z-score) using the sample as a reference. A high risk of sarcopenia was identified for Z-scores ≤ -1 on aLBMI (Group B) or aLBM/trFM (Group C), while Z-scores > -1 on both markers were considered at low risk for sarcopenia (Group A). The ANCOVA adjusted for maturity was used to compare the three groups. Girls showed a more significant decrease in the total BMC/LBM ratio in Group B and a minor increase in WBLH BMD in Group C (p < 0.050); boys in Group B showed a tendency to gain less height (p = 0.053). The high risk of sarcopenia expressed through aLBMI or aLBM/trFM Z-score ≤ -1 compromises bone mineralisation in girls. The findings emphasise the necessity of implementing routine screening protocols for sarcopenia risk within clinical environments and educational institutions. Such screenings should extend beyond merely assessing body mass index to encompass broader body composition variables like lean body mass. By integrating these assessments into routine health evaluations, healthcare professionals and educators can proactively identify at-risk individuals and initiate timely interventions for suboptimal physical growth and development.

Causal relationship between sarcopenia with osteoarthritis and the mediating role of obesity: a univariate, multivariate, two-step Mendelian randomization study

BackgroundRecent genetic evidence supports a causal role for sarcopenia in osteoarthritis, which may be mediated by the occurrence of obesity or changes in circulating inflammatory protein levels. Here, we leveraged publicly available genome-wide association study data to investigate the intrinsic causal relationship between sarcopenia, obesity, circulating inflammatory protein levels, and osteoarthritis.MethodsIn this study, we used Mendelian randomization analyses to explore the causal relationship between sarcopenia phenotypes (Appendicular lean mass [ALM], Low hand-grip strength [LHG], and usual walking pace [UWP]) and osteoarthritis (Knee osteoarthritis [KOA], and Hip osteoarthritis [HOA]). Univariable Mendelian randomization (UVMR) analyses were performed using the inverse variance weighted (IVW) method, MR-Egger, weighted median method, simple mode, and weighted mode, with the IVW method being the primary analytical technique. Subsequently, the independent causal effects of sarcopenia phenotype on osteoarthritis were investigated using multivariate Mendelian randomization (MVMR) analysis. To further explore the mechanisms involved, obesity and circulating inflammatory proteins were introduced as the mediator variables, and a two-step Mendelian randomization analysis was used to explore the mediating effects of obesity and circulating inflammatory proteins between ALM and KOA as well as the mediating proportions.ResultsUVMR analysis showed a causal relationship between ALM, LHG, UWP and KOA [(OR = 1.151, 95% CI: 1.087–1.218, P = 1.19 × 10–6, PFDR = 7.14 × 10–6) (OR = 1.215, 95% CI: 1.004–1.470; P = 0.046, PFDR = 0.055) (OR = 0.503, 95% CI: 0.292–0.867; P = 0.013, PFDR = 0.027)], and a causal relationship between ALM, UWP and HOA [(OR = 1.181, 95% CI: 1.103–1.265, P = 2.05 × 10–6, PFDR = 6.15 × 10–6) (OR = 0.438, 95% CI: 0.226–0.849, P = 0.014, PFDR = 0.022)]. In the MVMR analyses adjusting for confounders (body mass index, insomnia, sedentary behavior, and bone density), causal relationships were observed between ALM, LHG, UWP and KOA [(ALM: OR = 1.323, 95%CI: 1.224- 1.431, P = 2.07 × 10–12), (LHG: OR = 1.161, 95%CI: 1.044- 1.292, P = 0.006), (UWP: OR = 0.511, 95%CI: 0.290- 0.899, P = 0.020)], and between ALM and HOA (ALM: OR = 1.245, 95%CI: 1.149- 1.348, P = 7.65 × 10–8). In a two-step MR analysis, obesity was identified to play a potential mediating role in ALM and KOA (proportion mediated: 5.9%).ConclusionsThe results of this study suggest that decreased appendicular lean mass, grip strength, and walking speed increase the risk of KOA and decreased appendicular lean mass increases the risk of HOA in patients with sarcopenia in a European population. Obesity plays a mediator role in the occurrence of KOA due to appendicular lean body mass reduction.

Interaction between fat- and muscle development in children and adolescents.

Background: Prevalence of obesity increased noticeably during the last decades. Little is known so far about the association between fat accumulation due to obesity and skeletal muscle mass. The aim of this study was to describe the association between fat mass and muscle mass after adjusting for relevant confounding factors in the National Health and Nutrition Examination Survey (NHANES) study population of children and adolescents. We postulated a negative correlation between fat mass and lean body mass. Methodology: A total of 849 whole body DXA-scans of the NHANES study population of children and adolescents aged eight to twenty years of the years 1999-2004 were eligible for statistical analysis. Appendicular lean body mass (appLBM) was used to evaluate muscle mass. Bivariate analysis (Pearson's correlation coefficient), multiple linear regression analysis and mediation analysis were performed. The multiple regression analysis and mediation analysis were adjusted for weight, age height, sex ethnicity and physical activity. Results: Fat mass correlates with appendicular lean body mass (Pearons's r 0.336, p < 0.001). In the multiple linear regression analysis the regression coefficient between appLBM and FM was positive (0.204; p < 0.001), when considering appendicular lean body mass, fat mass and body weight, the regression coefficient was negative (-0.517; p < 0.001). Conclusions: Study results indicate a negative association of fat mass and skeletal muscle mass in children and adolescents, when weight, age, height, sex ethnicity and physical activity are considered. Further investigations are needed to evaluate if there is a biochemical interaction between fat cells and muscle cells that could explain this effect.

Opposite causal effects of birthweight on myocardial infarction and atrial fibrillation and the distinct mediating pathways: a Mendelian randomization study

BackgroundPrevious observational studies have documented an inverse association of birthweight with myocardial infarction (MI) but a positive association with atrial fibrillation (AF). However, the causality of these associations and the underlying mediating pathways remain unclear. We aimed to investigate the causal effects of birthweight, incorporating both fetal and maternal genetic effects, on MI and AF, and identify potential mediators in their respective pathways.MethodsWe performed Mendelian randomization (MR) analyses using genome-wide association study summary statistics for birthweight (N = 297,356 for own birthweight and 210,248 for offspring birthweight), MI (Ncase=61,000, Ncontrol=577,000), AF (Ncase=60,620, Ncontrol=970,216), and 52 candidate mediators (N = 13,848-1,295,946). Two-step MR was employed to identify and assess the mediation proportion of potential mediators in the associations of birthweight with MI and AF, respectively. As a complement, we replicated analyses for fetal-specific birthweight and maternal-specific birthweight.ResultsGenetically determined each 1-SD lower birthweight was associated with a 40% (95% CI: 1.22–1.60) higher risk of MI, whereas each 1-SD higher birthweight was causally associated with a 29% (95% CI: 1.16–1.44) higher risk of AF. Cardiometabolic factors, including lipids and lipoproteins, glucose and insulin, blood pressure, and fatty acids, each mediated 4.09-23.71% of the total effect of birthweight on MI, followed by body composition and strength traits (i.e., appendicular lean mass, height, and grip strength) and socioeconomic indicators (i.e., education and household income), with the mediation proportion for each factor ranging from 8.08 to 16.80%. By contrast, appendicular lean mass, height, waist circumference, childhood obesity, and body mass index each mediated 15.03-45.12% of the total effect of birthweight on AF. Both fetal-specific birthweight and maternal-specific birthweight were inversely associated with MI, while only fetal-specific birthweight was positively associated with AF. Psychological well-being and lifestyle factors conferred no mediating effect in either association.ConclusionsCardiometabolic factors mainly mediated the association between lower birthweight and MI, while body composition and strength traits mediated the association between higher birthweight and AF. These findings provide novel evidence for the distinct pathogenesis of MI and AF and advocate adopting a life-course approach to improving fetal development and subsequent causal mediators to mitigate the prevalence and burden of cardiovascular diseases.

Resistance Training Muscle Adaptations Using D3-creatine Dilution In Older Adults: A Pilot Study

High intensity resistance training (RT) is well known to increase muscle mass in older adults. However, the degree to which is dependent on the measurement method. D3-creatine (D3Cr) dilution is a promising new method that provides a direct and accurate measurement of creatine pool size and whole-body skeletal muscle mass. There are a limited number of studies that compare intervention-based adaptations between D3Cr derived skeletal mass versus lean mass by dual energy x-ray absorptiometry (DXA) Purpose: To evaluate and compare D3Cr derived skeletal mass and DXA lean mass changes following whole body progressive RT in moderate to low functioning older adults. Methods: Twenty-four older adults who tested as moderate to low-functioning on a standardized performance battery were randomized to a whole-body RT or health education program. RT was performed 3 days per week for 14 weeks. It included upper and lower body exercises performed at ~70% of maximal strength in progressive manner. Health education workshops were conducted weekly as an attention “control”. D3Cr dilution and whole body DXA scans were performed prior to randomization and shortly after completion of the programs. Results: D3Cr derived whole body skeletal mass increased more in participants randomized to the RT group compared to the health education group (3.5 ± 2.0 vs. 1.2 ± 1.7 kg, p = 0.03). Mean differences between groups was lower with DXA appendicular lean (RT: 0.81 ± 0.67 vs Education: -0.23 ± 0.70 kg, p = 0.008) and DXA total lean body mass (RT: 1.1 ± 1.4 vs Education: -0.19 ± 0.70 kg, p = 0.06). Pearson correlation coefficients showed weak relationships between changes in D3Cr muscle and DEXA appendicular (0.19, p = 0.48) and total lean mass measures (0.41, p = 0.13). Conclusions: This pilot study demonstrates that D3Cr dilution method is sufficiently sensitive to detect whole body changes in skeletal muscle mass of older adults. The unexpected discordance between D3Cr dilution and traditional DXA based measures of lean mass requires further study.

The Combined Oral Stable Isotope Assessment of Muscle (COSIAM) reveals D-3 creatine derived muscle mass as a standout cross-sectional biomarker of muscle physiology vitality in older age

Validated diagnostics of skeletal muscle vitality could benefit clinical and basic science in terms of mechanistic insights and in determining the efficacy of interventions, e.g. exercise/pharmaceuticals/nutrients. We recently developed a Combined Oral Assessment of Muscle (COSIAM) that can be used to simultaneously quantify whole-body muscle mass (WBMM), muscle protein synthesis (MPS) and muscle protein breakdown (MPB). Here, we aimed to establish, in a cross-sectional fashion, links between COSIAM parameters and established aspects of muscle function. We recruited 37 healthy older adults (male (M):female (F) (21/16); 72 ± 5 y)) into a 3-day trial. Subjects consumed D3-creatine (D3-Cr dilution to assess WBMM), D2O (MPS by incorporation of alanine) and D3-3-methylhistidine (D3-MH dilution to assess MPB). A biopsy at day 3 was used to determine MPS, and blood/urine samples were collected to determine D3-Cr/D3-MH dilution for WBMM and MPB. Physiological measures of muscle mass (e.g. DXA/ultrasound) and function (e.g. handgrip strength, maximum voluntary contraction (MVC), one-repetition maximum (1-RM)) were ascertained. A stepwise linear regression approach was used to address links between facets of COSIAM (MPS, MPB, WBMM) and muscle physiology. Despite expected differences in muscle mass, there were no significant differences in MPS or MPB between sexes. WBMM as measured using D3-Cr positively correlated with DXA-derived lean body mass (LBM) and appendicular LBM (ABLM). Stepwise linear regression was used to assess which combination of MPS, MPB, D3-Cr and absolute synthesis rate (ASR) best predicted physiological measures of muscle health in these older adults. D3-Cr WBMM alone was the best predictor of handgrip, 1RM and MVC, and outperformed more traditional measures of muscle mass by DXA. The COSIAM approach substantiates D3-Cr as a robust biomarker of multiple muscle physiology health biomarkers. Future work using COSIAM should focus upon how and which parameters it can inform upon in relation to disease progression and the efficacy of interventions.

Ultrasound Evaluation of the Rectus Femoris for Sarcopenia in Patients with Early Subacute Stroke.

We investigated the ultrasound characteristics of the rectus femoris for sarcopenia detected by dual-energy X-ray absorptiometry (DEXA) in the early subacute stroke phase. Physical features (age, sex, body mass index, and circumference of thigh) and performances (modified Barthel index in Korean, functional ambulation categories, and mini-mental state examination in Korean) were measured. The thickness of the fat layer, the thickness of the rectus femoris (TRF), echo intensity (EI), EI to TRF ratio, and strain ratio of elastography (SRE) were measured by ultrasound in 30 patients with first-ever stroke (male: n = 20). Appendicular lean body mass was measured by DEXA. Sarcopenia was defined according to the Foundation for the National Institutes of Health Sarcopenia Project. In total, 14 patients were in the sarcopenia group, and 16 were in the non-sarcopenia group. Clinical characteristics were similar between the two groups. In the sarcopenia group, TRF was significantly decreased in the paretic (p < 0.026) and non-paretic sides (p < 0.01), and the EI to TRF ratio on the paretic side was significantly increased (p < 0.049). Multivariate binary logistic regression showed that TRF on the non-paretic side was independently and significantly associated with sarcopenia (OR = 0.616, 95% CI: 0.381–0.996). The EI and SRE were not significant between the two groups. In the early subacute stroke phase, TRF on the non-paretic side is a key factor for quantitative evaluation of sarcopenia, and the EI to TRF ratio on the paretic side is also a meaningful qualitative evaluation of sarcopenia.

The diagnostic value of the Short Physical Performance Battery for sarcopenia

BackgroundSarcopenia is defined as the age-related loss of muscle mass, strength, and physical performance. The original European Working Group on Sarcopenia in Older Persons (EWGSOP1) definition, and its revision (EWGSOP2), provide new cut-points and alternate measures for sarcopenia diagnosis. However, sarcopenia is rarely diagnosed in clinical settings owing to its labor-intensive diagnostic process. Given the Short Physical Performance Battery (SPPB) is a quick, easily administrable, and objective measure of muscle strength and physical performance, both of which are key components of sarcopenia, this study examined the diagnostic value of the SPPB for this muscle disease.MethodsA cross-sectional analysis of 294 community-dwelling older persons (≥65 years) was conducted. Appendicular lean body mass [(ALM) divided by height squared (ALM/h2)], muscle strength (handgrip/sit to stand), and physical performance [gait speed, timed up and go (TUG) and SPPB] were assessed using validated procedures, while participants were diagnosed with sarcopenia following the EWGSOP1 and EWGSOP2 criteria. Diagnostic ability of the SPPB independently and combined with ALM/h2 for sarcopenia was determined using area under the curve (AUC). Potential cut-points were identified, and sensitivity and specificity calculated.ResultsPrevalence of sarcopenia ranged from 4 to 16% depending on the definition. The SPPB demonstrated moderate (AUC = 0.644–0.770) value in diagnosing sarcopenia, and a cut-point of ≤8points in SPPB performance resulted in high sensitivity (82–100%) but low specificity (36–41%) for diagnosing those with severe sarcopenia.ConclusionsThe SPPB displayed acceptable value in diagnosing older adults with severe sarcopenia. Moreover, the high sensitivity of the SPPB when using the cut-point of ≤8 suggests it may be a favorable screening tool for sarcopenia in clinical settings where ALM measurements are not available.

Leucine-Enriched Protein Supplementation Increases Lean Body Mass in Healthy Korean Adults Aged 50 Years and Older: A Randomized, Double-Blind, Placebo-Controlled Trial.

Early prevention of sarcopenia could be an important strategy for muscle retention, but most studies have focused on subjects aged 65 or older. Therefore, in this study we investigated the effects of leucine-enriched protein supplementation on muscle condition in a sample including late middle-aged adults. A 12-week intervention was performed for 120 healthy community-dwelling adults by providing either leucine-enriched protein supplement [protein 20g(casein 50%+ whey 40%+ soy 10%, total leucine 3000 mg), vitamin D 800IU(20 ug), calcium 300 mg, fat 1.1 g, carbohydrate 2.5 g] or isocaloric carbohydrate supplement twice per day. Appendicular skeletal muscle mass (ASM) and lean body mass (LBM) were measured by dual-energy X-ray absorptiometry. A total of 111 participants completed the study, with a dropout rate of 9.2%. LBM normalized by body weight (LBM/Wt) was significantly increased (p < 0.001) in the intervention group (0 wk: 63.38 ± 0.85 vs. 12 wk 63.68 ± 0.83 in the intervention group; 0 wk: 63.85 ± 0.82 vs. 12 wk: 63.29 ± 0.81 in the control group). In subgroup analyses, significant differences remained only in subjects between 50 and 64 years of age. We concluded that leucine-enriched protein supplementation can have beneficial effects by preventing muscle loss, mainly for late middle-aged adults.

Longitudinal Comparison of Lean Body Mass by Dual Energy X-Ray Absorptiometry and Muscle Mass by Creatine (methyl-d3) Dilution in Response to a 28-d Severe Energy Deficit

Abstract Objectives We reported that healthy males supplemented with testosterone gained lean body mass (LBM) during 28-d of energy deficit and 14 d of ad libitium feeding when measured by dual energy x-ray absorptiometry (DXA), but with no increase in muscle strength. We were unable to determine whether LBM gains were due to muscle mass accrual since DXA does not deliniate muscle from visceral organs and body water. Objectives: To assess the effects of testosterone supplementation on muscle mass as measured by creatine (methyl-d3) dilution, and determine the relationship between muscle mass and DXA-measured LBM in response to short-term energy deficit. Methods Secondary analysis of a 3-phase, randomised, double-blind, placebocontrolled trial in healthy males: 14-d free-living, eucaloric phase (P1); 28-d live-in, 55% energy deficit phase with (200 mg testosterone enanthate/wk, TEST, n = 24) or without (PLA, n = 26) testosterone (P2); and 14-d free-living, ad libitum feeding phase (P3). Muscle mass was measured by creatine dilution and LBM by DXA at the end of each phase. Results We previously reported increased LBM in TEST (mean change from P1 ± SEM; 2.5 ± 0.4, P &amp;lt; 0.01), but not PLA (−0.3 ± 0.3 kg, P &amp;gt; 0.05), following P2. Both TEST (5.2 ± 0.4 kg) and PLA (2.2 ± 0.4 kg) gained LBM in P3 (P &amp;lt; 0.01). There was a treatment-by-phase trend for change in muscle mass (P-interaction = 0.054), but muscle mass data were highly variable and no post-hoc comparisons met statistical significance (PLA, P2: −0.3 ± 1.6; TEST, P2: −0.7 ± 1.7; PLA, P3: −0.3 ± 1.6; TEST, P3: 3.8 ± 1.7 kg; P &amp;gt; 0.05). Cross-sectional measures of muscle mass were correlated (P &amp;lt; 0.001) with total and appendicular LBM at P1 (r = 0.63 and 0.67), P2 (r = 0.71 and 0.72), and P3 (r = 0.55 and 0.48), respectively. However, changes in muscle mass were not associated with changes in total or appendicular LBM at P2 or P3 (P &amp;gt; 0.05). Conclusions Testosterone supplementation increased LBM in response to short-term energy deficit and recovery feeding, but had no significant effect on muscle mass or muscle function. The discordance between changes in LBM and muscle mass underscore the inherent limitations of LBM as a surrogate measure for skeletal muscle mass, particularly in response to short-term intervention studies. Funding Sources DHP JPC-5/MOMRP; authors’ views not official U.S. Army or DoD policy.

Interaction of body fat percentage and height with appendicular functional muscle-bone unit.

For the clinical evaluation of the functional muscle-bone unit, it was proposed to evaluate the adaptation of the bone to the acting forces. A frequently used parameter for this is the total body less head bone mineral content (TBLH-BMC) determined by dual-energy X-ray absorptiometry (DXA) in relation to the total body lean body mass (LBM). Body fat percentage seemed to correlate negatively and height positively with TBLH-BMC for LBM. It was supposed that appendicular BMC for LBM is a more accurate surrogate for the functional muscle-bone unit since appendicular LBM does not incorporate the mass of internal organs. The aim of this study was to analyze the interaction of body fat percentage and height with appendicular BMC for LBM. As part of the National Health and Nutrition Examination Survey (NHANES) study, between the years 1999 and 2004, whole-body DXA scans on randomly selected Americans from 8years of age were carried out. From all eligible DXA scans, three major US ethnic groups were evaluated (non-Hispanic Whites, non-Hispanic Blacks, and Mexican Americans) for further statistical analysis. For the statistical analysis, the DXA scans of 8190 non-Hispanic White children and adults (3903 female), of 4931 non-Hispanic Black children and adults (2250 female), and 5421 of Mexican American children and adults (2424 female) were eligible. Only body fat had a significant negative correlation with the appendicular BMC for LBM. Only body fat had significant negative correlation with appendicular BMC for LBM, and thus, should be addressed when evaluating functional muscle-bone unit.

Physical performance measures in screening for reduced lean body mass in adult females with obesity

Background & aimsLittle is known about the reduction of lean body mass (LBM) in obesity, or how to identify it in standard clinical settings. We therefore aimed to assess the prevalence of low LBM in adult females with obesity, and to identify the reliability of simple tools for its screening in this population. Methods and ResultsDual-energy X-ray absorptiometry (DXA) body composition assessment was used to categorise 147 female participants with obesity as with or without low LBM, according to the new definition that takes into account both appendicular lean mass (ALM) and body mass index (BMI)—ALM/BMI <0.512. Participants were also administered the six-minute walking test, handgrip-strength test and 4-metre gait-speed test.Of the sample of 147 participants, 93 (63.3%) met the criteria for reduced LBM. Stepwise multivariate logistic regression analysis showed that the six-minute walking test was the only independent test associated with low LBM (OR = 0.992, 95%CI 0.987–0.998). Receiver operating characteristic (ROC) curve analysis found that the discriminating cut-off points of the tests considered were 470 m, 3.30 s (gait speed = 1.2 m/sec) and 23.5 kg respectively; the 4-metre gait-speed test seems to provide the best balance of sensitivity and specificity, and the greatest discriminatory power at 90% sensitivity. ConclusionsTreatment-seeking adult females with obesity display a great prevalence of reduced LBM. The six-minute walking test was the only independent test associated with low LBM, but the 4-metre gait-speed test seems to be the most accurate functional test for screening for this condition in that population.

Healthy community-living older men differ from women in associations between myostatin levels and skeletal muscle mass.

BackgroundMyostatin is a negative regulator of muscle growth but the relationship between serum myostatin levels and muscle mass is unclear. This study investigated the association between serum myostatin levels and skeletal muscle mass among healthy older community residents in Taiwan, to evaluate the potential of serum myostatin as a biomarker for diagnosing sarcopenia and/or evaluating the effect of its treatment.MethodsStudy data were excerpted from a random subsample of the I‐Lan Longitudinal Aging Study population. Serum myostatin levels were determined and categorized into tertiles (low, medium, high). Relative appendicular skeletal muscle mass (RASM) was calculated as appendicular lean body mass by dual‐energy X‐ray absorptiometry divided by height squared (kg/m2). Low muscle mass was defined as recommended by the Asian Working Group for Sarcopenia.ResultsThe analytic study sample comprised 463 adults (mean age: 69.1 years; 49.5% men). Compared with subjects with normal RASM, those with lower RASM were older and frailer, with significantly higher prevalence of malnutrition, lower serum dehydroepiandrosterone (DHEA) levels, and were more likely to have low serum myostatin status. Multivariable logistic regression analysis showed that male sex (OR 3.60, 95% CI 1.30–9.92), malnutrition (OR 4.39, 95% CI 1.56–12.36), DHEA (OR 0.99, 95% CI 0.99–1.00), and low myostatin (OR 3.23, 95% CI 1.49–7.01) were all independent risk factors for low RASM (all P < 0.05). In men, DHEA (OR 0.99, 95% CI 0.98–1.00) and low myostatin (OR 4.89, 95% CI 1.79–13.37) were significantly associated with low RASM (both P < 0.05); however, only malnutrition was associated with low RASM in women (OR 13.59, 95% CI 2.22–83.25, P < 0.05).ConclusionsAmong healthy community‐living older adults, low serum myostatin levels were associated with low skeletal muscle mass in men, but not in women. Our results do not support using serum myostatin levels to diagnose sarcopenia, or to monitor how it responds to treatments. Further research is needed to understand why men apparently differ from women in the interrelationship between their myostatin levels and muscle mass.

Muscle Mass, Muscle Morphology and Bone Health Among Community-Dwelling Older Men: Findings from the Hertfordshire Sarcopenia Study (HSS)

Sarcopenia and osteoporosis are associated with poor health outcomes in older people. Relationships between muscle and bone have typically been reported at a functional or macroscopic level. The aims of this study were to describe the relationships between muscle morphology and bone health among participants of the Hertfordshire Sarcopenia Study (HSS). 105 older men, mean age 72.5 (SD 2.5) years, were recruited into the HSS. Whole body lean mass as well as appendicular lean mass, lumbar spine and femoral neck bone mineral content (BMC) and bone mineral density (BMD) were obtained through dual-energy X-ray absorptiometry scanning. Percutaneous biopsy of the vastus lateralis was performed successfully in 99 participants. Image analysis was used to determine the muscle morphology variables of slow-twitch (type I) and fast-twitch (type II) myofibre area, myofibre density, capillary and satellite cell (SC) density. There were strong relationships between whole and appendicular lean body mass in relation to femoral neck BMC and BMD (r ≥ 0.43, p < 0.001). Type II fibre area was associated with both femoral neck BMC (r = 0.27, p = 0.01) and BMD (r = 0.26, p = 0.01) with relationships robust to adjustment for age and height. In unadjusted analysis, SC density was associated with whole body area (r = 0.30, p = 0.011) and both BMC (r = 0.26, p = 0.031) and area (r = 0.29, p = 0.017) of the femoral neck. We have demonstrated associations between BMC and changes in muscle at a cellular level predominantly involving type II myofibres. Interventions targeted at improving muscle mass, function and quality may improve overall musculoskeletal health. Larger studies that include women are needed to explore these relationships further.

Large meta-analysis of genome-wide association studies identifies five loci for lean body mass

Lean body mass, consisting mostly of skeletal muscle, is important for healthy aging. We performed a genome-wide association study for whole body (20 cohorts of European ancestry with n = 38,292) and appendicular (arms and legs) lean body mass (n = 28,330) measured using dual energy X-ray absorptiometry or bioelectrical impedance analysis, adjusted for sex, age, height, and fat mass. Twenty-one single-nucleotide polymorphisms were significantly associated with lean body mass either genome wide (p < 5 × 10−8) or suggestively genome wide (p < 2.3 × 10−6). Replication in 63,475 (47,227 of European ancestry) individuals from 33 cohorts for whole body lean body mass and in 45,090 (42,360 of European ancestry) subjects from 25 cohorts for appendicular lean body mass was successful for five single-nucleotide polymorphisms in/near HSD17B11, VCAN, ADAMTSL3, IRS1, and FTO for total lean body mass and for three single-nucleotide polymorphisms in/near VCAN, ADAMTSL3, and IRS1 for appendicular lean body mass. Our findings provide new insight into the genetics of lean body mass.

Treatment of Sarcopenia with Bimagrumab: Results from a Phase II, Randomized, Controlled, Proof‐of‐Concept Study

To assess the effects of bimagrumab on skeletal muscle mass and function in older adults with sarcopenia and mobility limitations. A 24-week, randomized, double-blind, placebo-controlled, parallel-arm, proof-of-concept study. Five centers in the United States. Community-dwelling adults (N=40) aged 65 and older with gait speed between 0.4 and 1.0m/s over 4m and an appendicular skeletal muscle index of 7.25kg/m2 or less for men and 5.67kg/m2 or less for women. Intravenous bimagrumab 30mg/kg (n=19) or placebo (n=21). Change from baseline in thigh muscle volume (TMV), subcutaneous and intermuscular fat, appendicular and total lean body mass, grip strength, gait speed, and 6-minute walk distance (6MWD). Thirty-two (80%) participants completed the study. TMV increased by Week 2, was sustained throughout the treatment period, and remained above baseline at the end of study in bimagrumab-treated participants, whereas there was no change with placebo treatment (Week 2: 5.15±2.19% vs -0.34±2.59%, P<.001; Week 4: 6.12±2.56% vs 0.16±3.42%, P<.001; Week 8: 8.01±3.70% vs 0.35±3.32%, P<.001; Week 16: 7.72±5.31% vs 0.42±5.14%, P<.001; Week 24: 4.80±5.81% vs -1.01±4.43%, P=.002). Participants with slower walking speed at baseline receiving bimagrumab had clinically meaningful and statistically significantly greater improvements in gait speed (mean 0.15m/s, P=.009) and 6MWD (mean 82m, P=.022) than those receiving placebo at Week 16. Adverse events in the bimagrumab group included muscle-related symptoms, acne, and diarrhea, most of which were mild in severity and resolved by the end of study. Treatment with bimagrumab over 16weeks increased muscle mass and strength in older adults with sarcopenia and improved mobility in those with slow walking speed.

Effect on body composition and bone mineral density of walking with a robotic exoskeleton in adults with chronic spinal cord injury.

To examine the effect on body composition and bone mineral density of locomotor training using a robotic exoskeleton in individuals with spinal cord injury. Interventional study. Five adults with a non-progressive traumatic complete sensorimotor spinal cord injury who were using a wheelchair as a primary mode of mobility. Participants performed a personalized 6-week progressive locomotor training programme using a robotic exoskeleton 3 times/week for up to 60 min. Body composition measures were determined using dual energy X-ray absorptiometry and peripheral quantitative computed tomography. A significant increase in leg and appendicular lean body mass and a decrease in total, leg and appendicular fat mass was observed after the intervention. Furthermore, the calf muscle cross-sectional area increased significantly after the intervention. Finally, although not statistically significant, there was an increase of 14.5% in bone mineral density of the tibia, which may be clinically significant. A decrease of > 5 % was also noted for subcutaneous adipose tissue and intramuscular adipose tissue. Locomotor training using a robotic exoskeleton appears to be associated with improvements in body composition and, potentially, bone health.

Comparison of Bone Mineral Density and Appendicular Lean Body Mass between Osteoporotic Distal Radius Fracture and Degenerative Rotator Cuff Tear in Women Patients.

BackgroundAuthors assessed lean body mass (fat free tissue), upper and lower, and bone mineral density (BMD) in patients of osteoporotic bone distal radius fracture (DRF) and degenerative rotator cuff tear (RCT) patients of shoulder. We predict inferior muscle mass and osteoporosis are more frequent in DRF group than RCT group.MethodsBetween January 2016 and June 2017, overall 38 of DRF and 30 of RCT were eligible for this retrospective comparison study after excluding of patients with compounding factors. BMD and other body composition, fat and lean body mass, were assessed with a single dual energy X-ray absorptiometry in one hospital.ResultsT-score of spine were −2.2 and −1.6 in DRF and RCT patients with significant difference (P=0.040). Final BMD score, lower score of patient between spine and femoral score, of both group also presented difference with significance, −2.4 of DRF and −1.9 of RCT patients (P=0.047). Diagnosis of osteoporosis was confirmed in 19 patients (50%) from DRF compared with 9 patients (30%) from RCT. The mean lean soft tissue mass of the arm was 3.7 kg and 3.8 kg in the DRF and RCT, respectively, without significant difference (P=0.882). The mean lean body mass of the leg was 11.0 kg and 10.5 kg in the DRF and RCT, respectively, without significant difference (P=0.189). The relative overall appendicular lean mass was not significantly different between groups.ConclusionsEven though BMD difference, we did not find muscle mass difference between DRF and RCT patients.

P1.06-003 Anamorelin in Cachectic Patients with Advanced NSCLC, a Post-Hoc Pooled Efficacy Data Analysis of Two Phase 3 Trials

Anorexia-cachexia is a multifactorial syndrome frequently experienced by patients with non-small cell lung cancer (NSCLC). It is characterized by decreased body weight (mainly due to muscle loss) and is associated with worsen morbidity, poor tolerance of chemotherapy and reduced survival. The randomized, double-blind ROMANA 1 and ROMANA 2 phase 3 trials in cachectic NSCLC patients, demonstrated that the ghrelin receptor agonist anamorelin was well tolerated, improved body weight, lean body mass (LBM), fat mass (FM) and anorexia/cachexia symptoms and concerns, with no difference in handgrip strength compared to placebo. Here we assessed pooled efficacy and numbers needed to treat (NNT) from ROMANA 1 and ROMANA 2 studies. Stage III/IV NSCLC patients with cachexia (≥5% weight loss during prior 6 months or BMI<20 kg/m2) were randomized (2:1) to daily oral 100 mg anamorelin or placebo for 12 weeks. Endpoints included changes in LBM, FM, total body mass (TBM) and in self-reported anorexia/cachexia symptoms and concerns. We present the pooled efficacy data from a post-hoc analysis from both trials (anamorelin, N=552; placebo, N=277); treatment differences, 95% CI, NNT and nominal p values from baseline to end of study. At the end of study, compared with placebo, anamorelin-treated patients significantly increased body composition parameters (LBM, appendicular LBM, FM and TBM), and a greater proportion of patients showed improvements in these parameters (Table). The anamorelin group also significantly improved anorexia/cachexia symptoms and concerns, and compared to placebo, more patients in the anamorelin arm achieved the minimally important difference of 4 points. Anamorelin has anabolic activity while improving symptom burden in cachectic patients with NSCLC. A significantly greater proportion of patients increased lean mass, fat mass and improved anorexia/cachexia symptoms and concern score in the anamorelin arm versus the placebo arm, with favorable NNT.