title: Effects of enobosarm on muscle wasting and physical function in patients with cancer: a double-blind, randomised controlled phase 2 trial. Effects of a vitamin D and leucine-enriched whey protein nutritional supplement on measures of sarcopenia in older adults, the PROVIDE study: a randomized, double-blind, placebo-controlled trial. Exercise and Nutritional Supplementation on Community-Dwelling Elderly Japanese Women With Sarcopenic Obesity: A Randomized Controlled Trial. Treatment of sporadic inclusion body myositis with bimagrumab Collagen peptide supplementation in combination with resistance training improves body composition and increases muscle strength in elderly sarcopenic men: a randomised controlled trial Anamorelin for patients with cancer cachexia: an integrated analysis of two phase 2, randomised, placebo-controlled, double-blind trials. Impacts of High-Protein Oral Nutritional Supplements Among Malnourished Men and Women with Sarcopenia: A Multicenter, Randomized, Double-Blinded, Controlled Trial. A phase I/IItrial of MYO‐029 in adult subjects with muscular dystrophy Effects of progressive resistance training on body composition in frail older adults: results of a randomized, controlled trial. A single ascending-dose study of muscle regulator ACE-031 in healthy volunteers. Vitamin D serum levels are associated with handgrip strength but not with muscle mass or length of hospital stay after hip fracture. Sarcopenia and mortality risk in frail older persons aged 80 years and older: results from ilSIRENTE study. Accuracy of segmental multi-frequency bioelectrical impedance analysis for assessing whole-body and appendicular fat mass and lean soft tissue mass in frail women aged 75 years and older Pharmacological inhibition of myostatin and changes in lean body mass and lower extremity muscle size in patients receiving androgen deprivation therapy for prostate cancer. Effects of exercise and amino acid supplementation on body composition and physical function in community-dwelling elderly Japanese sarcopenic women: a randomized controlled trial. Validating the SARC-F: a suitable community screening tool for sarcopenia? Growth hormone and sex steroid administration in healthy aged women and men: a randomized controlled trial. Effects of exercise and tea catechins on muscle mass, strength and walking ability in community-dwelling elderly Japanese sarcopenic women: a randomized controlled trial. A phase IIA randomized, placebo-controlled clinical trial to study the efficacy and safety of the selective androgen receptor modulator (SARM), MK-0773 in female participants with sarcopenia High-speed resistance training in elderly women: Effects of cluster training sets on functional performance and quality of life Effect of structured physical activity on prevention of major mobility disability in older adults: the LIFE study randomized clinical trial. Cross-Cultural Adaptation and Validation of the Spanish-Language Version of the SARC-F to Assess Sarcopenia in Mexican Community-Dwelling Older Adults.
abstract: BACKGROUND Cancer-induced muscle wasting begins early in the course of a patient 's malignant disease , result ing in declining physical function and other detrimental clinical consequences . This r and omised , double-blind , placebo-controlled phase 2 trial assessed the efficacy and safety of enobosarm , a selective and rogen receptor modulator , in patients with cancer . METHODS We enrolled male ( > 45 years ) and female ( postmenopausal ) patients with cancer who were not obese and who had at least 2 % weight loss in the previous 6 months . Participants were r and omly assigned ( 1:1:1 ratio , by computer generated list , block size three , stratified by cancer type ) to receive once-daily oral enobosarm 1 mg , 3 mg , or placebo for up to 113 days at US and Argentinian oncology clinics . The sponsor , study personnel , and participants were masked to assignment . The primary endpoint was change in total lean body mass from baseline , assessed by dual-energy x-ray absorptiometry . Efficacy analyses were done only in patients who had a baseline and an on-treatment assessment in the protocol -specified window of within 10 days before baseline or first study drug , and within 10 days of day 113 or end of study ( evaluable efficacy population ) . Adverse events and other safety measurements were assessed in the intention-to-treat ( safety ) population . This trial is registered with Clinical Trials.gov , number NCT00467844 . FINDINGS Enrolment started on July 3 , 2007 , and the last patient completed the trial on Aug 1 , 2008 . 159 patients were analysed for safety ( placebo , n=52 ; enobosarm 1 mg , n=53 ; enobosarm 3 mg , n=54 ) . The evaluable efficacy population included 100 participants ( placebo , n=34 ; enobosarm 1 mg , n=32 ; enobosarm 3 mg , n=34 ) . Compared with baseline , significant increases in total lean body mass by day 113 or end of study were noted in both enobosarm groups ( enobosarm 1 mg median 1·5 kg , range -2·1 to 12·6 , p=0·0012 ; enodosarm 3 mg 1·0 kg , -4·8 to 11·5 , p=0·046 ) . Change in total lean body mass within the placebo group ( median 0·02 kg , range -5·8 to 6·7 ) was not significant ( p=0·88 ) . The most common serious adverse events were malignant neoplasm progression ( eight of 52 [ 15 % ] with placebo vs five of 53 [ 9 % ] with enobosarm 1 mg vs seven of 54 [ 13 % ] with enobosarm 3 mg ) , pneumonia ( two [ 4 % ] vs two [ 4 % ] vs three [ 6 % ] ) , and febrile neutropenia ( three [ 6%vs one [ 2 % ] vs none ) . None of these events were deemed related to study drug . INTERPRETATION Cancer cachexia is an unmet medical need and our data suggest that use of enobosarm might lead to improvements in lean body mass , without the toxic effects associated with and rogens and progestational agents . FUNDING GTx BACKGROUND Age-related losses of muscle mass , strength , and function ( sarcopenia ) pose significant threats to physical performance , independence , and quality of life . Nutritional supplementation could positively influence aspects of sarcopenia and thereby prevent mobility disability . OBJECTIVE To test the hypothesis that a specific oral nutritional supplement can result in improvements in measures of sarcopenia . DESIGN A multicenter , r and omized , controlled , double-blind , 2 parallel-group trial among 380 sarcopenic primarily independent-living older adults with Short Physical Performance Battery ( SPPB ; 0 - 12 ) scores between 4 and 9 , and a low skeletal muscle mass index . The active group ( n = 184 ) received a vitamin D and leucine-enriched whey protein nutritional supplement to consume twice daily for 13 weeks . The control group ( n = 196 ) received an iso-caloric control product to consume twice daily for 13 weeks . Primary outcomes of h and grip strength and SPPB score , and secondary outcomes of chair-st and test , gait speed , balance score , and appendicular muscle mass ( by DXA ) were measured at baseline , week 7 , and week 13 of the intervention . RESULTS H and grip strength and SPPB improved in both groups without significant between-group differences . The active group improved more in the chair-st and test compared with the control group , between-group effect ( 95 % confidence interval ) : -1.01 seconds ( -1.77 to -0.19 ) , P = .018 . The active group gained more appendicular muscle mass than the control group , between-group effect : 0.17 kg ( 0.004 - 0.338 ) , P = .045 . CONCLUSIONS This 13-week intervention of a vitamin D and leucine-enriched whey protein oral nutritional supplement result ed in improvements in muscle mass and lower-extremity function among sarcopenic older adults . This study shows proof-of-principle that specific nutritional supplementation alone might benefit geriatric patients , especially relevant for those who are unable to exercise . These results warrant further investigations into the role of a specific nutritional supplement as part of a multimodal approach to prevent adverse outcomes among older adults at risk for disability OBJECTIVES To investigate the effects of exercise and /or nutritional supplementation on body composition , blood components , and physical function in community-dwelling elderly Japanese women with sarcopenic obesity . DESIGN R and omized controlled trial . SETTING Urban community in Tokyo , Japan . PARTICIPANTS Among 1213 community-dwelling elderly women over 70 years of age , 307 were defined with sarcopenic obesity , and 139 women participated in the study . INTERVENTION Participants were r and omly assigned to one of four intervention groups . The exercise and nutrition ( Ex + N ) and exercise only ( Ex ) groups attended 60-minute exercise classes twice a week for 3 months . The Ex + N and nutrition only ( N ) groups were provided with essential amino acid supplementation and tea fortified with catechins to be taken daily for 3 months . Health education classes were provided to the control ( HE ) group every 2 weeks . MEASUREMENTS Bioelectric impedance analysis was used to measure body composition . Skeletal muscle mass index was calculated using measures of muscle mass and height . Physical function measures included grip strength , knee extension strength , usual walking speed , and walking parameters ( stride , step length , width , walking angles ) . Blood sample s were obtained to analyze levels of albumin , triglycerides , cholesterol , hemoglobin A1c , leptin , cystatin C , vitamin D , interleukin-6 , and high-sensitivity C-reactive protein . RESULTS Significant between-group × time interactions were observed in usual walking speed ( P = .012 ) , stride ( P = .004 ) , right step length ( P = .003 ) , average number of steps ( P = .029 ) , and vitamin D ( P < .001 ) . Compared to the HE group , the Ex + N intervention significantly decreased total body fat mass ( P = .036 ) and increased stride ( P = .038 ) and vitamin D ( P < .001 ) . Significant reductions in trunk fat were observed in the Ex group compared with HE ( P = .014 ) . The Ex + N and Ex interventions were over four times as likely ( odds ratio [ 95 % confidence interval ] ) to reduce body fat mass than the HE group ( 4.42 [ 1.21 - 16.19 ] ; 4.50 [ 1.13 - 17.9 ] , respectively ) . Significant odds ratios of the Ex + N intervention improving walking speed ( 3.05 [ 1.01 - 9.19 ] ) , vitamin D ( 14.22 [ 1.64 - 123.02 ] ) , and leptin ( 3.86 [ 1.19 - 12.47 ] ) were also observed . CONCLUSION Although exercise and nutrition have beneficial effects on individual variables of body composition , blood components , and physical function , improvements in muscle mass and variable combinations such as percent fat + skeletal muscle mass index or percent fat + physical functions were not observed in this population . Further large-scale and long-term investigation is necessary Objective : To study activin signaling and its blockade in sporadic inclusion body myositis ( sIBM ) through translational studies and a r and omized controlled trial . Methods : We measured transforming growth factor β signaling by SMAD2/3 phosphorylation in muscle biopsies of 50 patients with neuromuscular disease ( 17 with sIBM ) . We tested inhibition of activin receptors IIA and IIB ( ActRII ) in 14 patients with sIBM using one dose of bimagrumab ( n = 11 ) or placebo ( n = 3 ) . The primary outcome was the change in right thigh muscle volume by MRI at 8 weeks . Lean body mass , strength , and function were secondary outcomes . Twelve of the patients ( 10 bimagrumab , 2  placebo )  participated in a subsequent 16-week observation phase . Results : Muscle SMAD2/3 phosphorylation was higher in sIBM than in other muscle diseases studied ( p = 0.003 ) . Eight weeks after dosing , the bimagrumab-treated patients increased thigh muscle volume ( right leg + 6.5 % compared with placebo , p = 0.024 ; left leg + 7.6 % , p = 0.009 ) and lean body mass ( + 5.7 % compared with placebo , p = 0.014 ) . Subsequently , bimagrumab-treated patients had improved 6-minute walking distance , which peaked at 16 weeks ( + 14.6 % , p = 0.008 ) compared with placebo . There were no serious adverse events ; the main adverse events with bimagrumab were mild acne and transient involuntary muscle contractions . Conclusions : Transforming growth factor β superfamily signaling , at least through ActRII , is implicated in the pathophysiology of sIBM . Inhibition of ActRII increased muscle mass and function in this pilot trial , offering a potential novel treatment of sIBM . Classification of evidence : This study provides Class I evidence that for patients with inclusion body myositis  , bimagrumab increases thigh muscle volume at 8 weeks Protein supplementation in combination with resistance training may increase muscle mass and muscle strength in elderly subjects . The objective of this study was to assess the influence of post-exercise protein supplementation with collagen peptides v. placebo on muscle mass and muscle function following resistance training in elderly subjects with sarcopenia . A total of fifty-three male subjects ( 72·2 ( sd 4·68 ) years ) with sarcopenia ( class I or II ) completed this r and omised double-blind placebo-controlled study . All the participants underwent a 12-week guided resistance training programme ( three sessions per week ) and were supplemented with either collagen peptides ( treatment group ( TG ) ) ( 15 g/d ) or silica as placebo ( placebo group ( PG ) ) . Fat-free mass ( FFM ) , fat mass ( FM ) and bone mass ( BM ) were measured before and after the intervention using dual-energy X-ray absorptiometry . Isokinetic quadriceps strength ( IQS ) of the right leg was determined and sensory motor control ( SMC ) was investigated by a st and ardised one-leg stabilisation test . Following the training programme , all the subjects showed significantly higher ( P<0·01 ) levels for FFM , BM , IQS and SMC with significantly lower ( P<0·01 ) levels for FM . The effect was significantly more pronounced in subjects receiving collagen peptides : FFM ( TG + 4·2 ( sd 2·31 ) kg/PG + 2·9 ( sd 1·84 ) kg ; P<0·05 ) ; IQS ( TG + 16·5 ( sd 12·9 ) Nm/PG + 7·3 ( sd 13·2 ) Nm ; P<0·05 ) ; and FM ( TG –5·4 ( sd 3·17 ) kg/PG –3·5 ( sd 2·16 ) kg ; P<0·05 ) . Our data demonstrate that compared with placebo , collagen peptide supplementation in combination with resistance training further improved body composition by increasing FFM , muscle strength and the loss in FM BACKGROUND Cancer anorexia-cachexia syndrome is associated with increased morbidity and mortality . Anamorelin is an oral ghrelin-receptor agonist with appetite-enhancing and anabolic activity . We assessed the effects of anamorelin on body composition , strength , quality of life , biochemical markers , and safety in patients with cancer anorexia-cachexia . METHODS Data were pooled , a priori , from two completed phase 2 , multicentre , placebo-controlled , double-blind trials in patients with advanced or incurable cancer and weight loss of 5 % or more . Patients were stratified by weight loss severity ( 5 - 15 % , > 15 % ) and r and omly allocated ( 1:1 ) with a computer-generated r and omisation schedule to anamorelin hydrochloride 50 mg or placebo once-daily for 12 weeks . Primary outcome was lean body mass by dual-energy x-ray absorptiometry over the 12 week treatment period in eligible patients who had at least one dose of study drug and post-treatment efficacy assessment .  We assessed safety in all patients who received at least one dose of study drug . The trials are registered with Clinical Trials.gov , numbers NCT00219817 and NCT00267358 . FINDINGS Between June 29 , 2005 , and Oct 26 , 2006 , we enrolled 44 patients in the anamorelin group and 38 patients in the placebo group . 74 patients were eligible for the efficacy analyses . Over 12 weeks , lean body mass increased in 38 patients in the anamorelin group by a least-squares mean of 1.89 kg ( 95 % CI 0.84 to 2.95 ) compared with a decrease of a least-squares mean of -0.20 kg ( -1.23 to 0.83 ) for 36 patients in the placebo group ( difference 2.09 kg [ 0.94 - 3.25 ] ; p=0.0006 ) . 42 ( 95 % ) of 44 patients treated with anamorelin and 33 ( 87 % ) of 38 patients treated with placebo had adverse events . The most common grade 3 - 4 adverse events ( treatment-related or not ) in the anamorelin group were fatigue , asthenia , atrial fibrillation , and dyspnoea ( two [ 5 % ] each ) ; in the placebo group , such events were pneumonia ( three [ 8 % ] ) and anaemia , thrombocytopenia , abdominal pain , anxiety , and dyspnoea ( two [ 5 % ] each ) . INTERPRETATION Anamorelin treatment for 12 weeks had a favourable clinical response profile in patients with cancer anorexia-cachexia syndrome . These findings support further investigation in this setting . FUNDING Helsinn Therapeutics ( US ) , Helsinn Healthcare SA BACKGROUND Recent evidence suggests that nutritional interventions may improve muscle outcomes in malnutrition and sarcopenia . OBJECTIVES We evaluated the effects of 2 high- quality oral nutritional supplements ( ONS ) differing in amount and type of key nutrients in older adult men and women . DESIGN A multicenter , r and omized , double-blinded , controlled clinical trial . PARTICIPANTS Malnourished and sarcopenic men and women , 65 years and older ( n = 330 ) . INTERVENTION A 24-week intervention period with 2 energy-rich ( 330 kcal ) ONS treatment groups : Control ONS ( CONS , 14 g protein ; 147 IU vitamin D3 ) versus Experimental ONS ( EONS , 20 g protein ; 499 IU vitamin D3 ; 1.5 g CaHMB ) taken twice daily . Both ONS also contained other vitamins , minerals , and nutrients in varying amounts . MEASUREMENTS Isokinetic peak torque ( PT , Nm ) leg strength , grip strength ( kg ) , and gait speed ( m·s-1 ) were assessed at baseline and 12 and 24 weeks . Left and right leg muscle mass ( LMM , kg ) were assessed by dual-energy x-ray absorptiometry ( DXA ) . Muscle quality ( MQ ) was leg strength expressed relative to the tested LMM ( Nm·kg-1 ) . Subgroup analyses were performed : severe sarcopenia ( low skeletal mass index , low grip strength [ < 30 kg men ; < 20 kg women ] , low gait speed [ < 0.8 m·s-1 ] ) and mild-moderate sarcopenia ( low skeletal mass index , normal gait speed , or normal grip strength ) . RESULTS Both ONS groups ( EONS and CONS ) improved PT , MQ , grip strength , and gait speed from baseline with no treatment differences . Those with severe sarcopenia ( 44 % ) exhibited lower baseline PT and MQ , with no differences in strength improvements between treatments . However , participants with mild-moderate sarcopenia exhibited higher baseline PT and MQ , with differences in strength improvements at 12 weeks ( EONS > CONS , P = .032 ) in those with normal grip strength . There were no treatment differences based on sarcopenic severity for either grip strength or gait speed . CONCLUSION ONS improved strength outcomes in malnourished older adults with sarcopenia . In those with mild-moderate sarcopenia , but not severe sarcopenia , consumption of the EONS improved leg muscle strength and quality compared with the st and ard CONS Myostatin is an endogenous negative regulator of muscle growth and a novel target for muscle diseases . We conducted a safety trial of a neutralizing antibody to myostatin , MYO‐029 , in adult muscular dystrophies ( Becker muscular dystrophy , facioscapulohumeral dystrophy , and limb‐girdle muscular dystrophy ) BACKGROUND Progressive resistance exercise training ( PRT ) has been shown to increase muscle strength and fat-free mass ( FFM ) in elderly persons . Limited information is available regarding the effects of PRT on lean and fat mass in frail elderly persons . METHODS Ninety-one community-dwelling sedentary men and women , 78 years and older with physical frailty ( defined using st and ardized objective criteria ) were enrolled in a 9-month trial of exercise training ( ET ) . Physical frailty was defined as having 2 of the 3 following criteria : modified Physical Performance Test score between 18 and 32 , peak aerobic power between 10 and 18 ml/kg/min , or self-report of difficulty or assistance with two instrumental activities of daily living or one basic activity of daily living . Participants were r and omly assigned to either a control ( CTL ) group that performed a low intensity home exercise program or a supervised ET group that performed 3 months of low intensity exercise and 3 months of PRT . RESULTS After completion of PRT , ET participants had greater improvements than did CTL participants in maximal voluntary force production for knee extension ( mean Delta + 5.3 + /- 13 ft/lb vs + 1.1 + /- 11 ft/lb , p = .05 ) , measured using isokinetic dynamometry . Total body FFM ( measured using dual energy x-ray absorptiometry ) increased in the ET group , but not in the CTL group ( mean Delta + 0.84 + /- 1.4 kg vs + 0.01 + /- 1.5 kg , p = .005 ) . Total , trunk , intra-abdominal , and subcutaneous fat mass ( measured using dual energy x-ray absorptiometry and (1)H-magnetic resonance imaging ) did not change in response to PRT . CONCLUSIONS Three months of supervised PRT induced improvements in maximal voluntary thigh muscle strength and whole body FFM in frail , community-dwelling elderly women and men . This supervised exercise program may not be sufficient to reduce whole-body or intra-abdominal fat area in this population INTRODUCTION ACE-031 is a soluble form of activin receptor type IIB ( ActRIIB ) . ACE-031 promotes muscle growth by binding to myostatin and other negative regulators of muscle mass . METHODS This double-blind , placebo-controlled study evaluated the safety , pharmacokinetics , and pharmacodynamics of ACE-031 in 48 healthy , postmenopausal women r and omized to receive 1 dose of ACE-031 ( 0.02 - 3 mg/kg s.c . ) or placebo ( 3:1 ) . RESULTS ACE-031 was generally well-tolerated . Adverse events included injection site erythema . Mean ACE-031 AUC(0-∞ ) and C(max ) increased linearly with dose ; mean T(½ ) was 10 - 15 days . Statistically significant increases in mean total body lean mass ( 3.3 % ; P = 0.03 , by DXA ) and thigh muscle volume ( 5.1 % ; P = 0.03 , by MRI ) were observed at day 29 in the 3 mg/kg group . Statistically significant changes in serum biomarkers suggest ACE-031 also improved bone and fat metabolism . CONCLUSIONS Single-dose ACE-031 treatment was generally well-tolerated and result ed in increases in muscle mass in healthy postmenopausal women OBJECTIVES The aim of this study was to evaluate the association between serum levels of 25(OH ) vitamin D3  with midupper arm muscle circumference ( MUAMC ) , h and grip strength and length of hospital stay ( LOS ) after hip fracture . METHODS In total , 102 consecutive patients with hip fracture over the age of 65 were admitted to the orthopedic unit and prospect ively evaluated . All of the patients were treated according to specific protocol s depending on the type of fracture .  Anthropometric measurements and h and grip strength were performed , and blood sample s were taken for serum biochemistry and 25(OH ) vitamin D3 analysis within the first 72 h of admission . All of the patients were followed during their hospital stay , and the length of stay was recorded . RESULTS Of the patients , two were excluded because of pathologic fractures . In total , 100 patients with a mean age of 80 ± 7 y were included in the analysis . Among these patients , 73 % were female , and 37 % had vitamin D deficiency . The median LOS was 7 ( 5 - 11 ) d. Patients with vitamin D deficiency had lower h and grip strength in univariate analysis . In the multiple linear regression analysis with robust st and ard error , serum vitamin D levels adjusted by age and sex were associated with h and grip strength but not with MUAMC and LOS after hip fracture . CONCLUSIONS In conclusion , vitamin D serum levels were associated with h and grip strength but not with muscle mass or length of hospital stay after hip fracture BACKGROUND AND AIMS sarcopenia has been indicated as a reliable marker of frailty and poor prognosis among the oldest individuals . We evaluated the impact of sarcopenia on the risk of all-cause death in a population of frail older persons living in community . METHODS we analysed data from the Aging and Longevity Study , a prospect i ve cohort study that collected data on all subjects aged 80 years and older residing in the Sirente geographic area ( n = 364 ) . The present analysis was conducted among those subjects who were between 80 and 85 years of age at the time of the baseline assessment ( n = 197 ) . The main outcome measure was all-cause mortality over 7-year follow-up . According to the European Working Group on Sarcopenia in Older People ( EWGSOP ) criteria , the diagnosis of sarcopenia required the documentation of low muscle mass and the documentation of either low muscle strength or low physical performance . Cox proportional regression models were used to estimate crude and adjusted hazard ratios and 95 % confidence intervals of death by the presence of sarcopenia . RESULTS using the EWGSOP-suggested criteria , 43 subjects with sarcopenia ( 21.8 % ) were identified . During the 7-year follow-up , 29 ( 67.4 % ) participants died among subjects with sarcopenia compared with 63 subjects ( 41.2 % ) without sarcopenia ( P < 0.001 ) . After adjusting for potential confounders including age , gender , education , activities of daily living ( ADL ) impairment , body mass index , hypertension , congestive heart failure , chronic obstructive pulmonary disease , number of diseases , TNF-α , participants with sarcopenia had a higher risk of death for all causes compared with non-sarcopenic subjects ( HR : 2.32 , 95 % CI : 1.01 - 5.43 ) . CONCLUSIONS our results obtained from a representative sample of very old and frail subjects show that sarcopenia is associated with mortality , independently of age and other clinical and functional variables BACKGROUND / OBJECTIVE : We aim ed to examine the accuracy of segmental multi-frequency bioelectrical impedance analysis ( SMF-BIA ) for the assessment of whole-body and appendicular fat mass ( FM ) and lean soft tissue mass ( LM ) in frail older women , using dual-energy X-ray absorptiometry ( DXA ) as a reference method .SUBJECTS/ METHODS : All 129 community-dwelling Japanese frail older women with a mean age of 80.9 years ( range , 75–89 years ) from the Frailty Intervention Trial were recruited . The agreements between SMF-BIA and DXA for whole-body and appendicular body composition were assessed using simple linear regression and Bl and –Altman analysis . RESULTS : High coefficients of determination ( R2 ) for whole-body FM ( R2=0.94 , s.e . of estimate (SEE)=1.2 kg ) , whole-body LM ( R2=0.85 , SEE=1.4 kg ) , and appendicular FM ( R2=0.82 , SEE=1.1 kg ) were observed between SMF-BIA and DXA . The R2 coefficient for appendicular LM was moderate ( R2=0.76 , SEE=0.8 kg ) . Bl and –Altman plots demonstrated that there was systematic ( constant ) bias ( that is , DXA minus SMF-BIA ) with overestimation of whole-body FM ( bias=−1.2 kg , 95 % confidence interval (CI)=−1.5 to −0.1 ) and underestimation of whole-body LM ( bias=2.1 kg , 95 % CI=1.8–2.3 ) by SMF-BIA . Similar , the appendicular measurements also demonstrated systematic bias with overestimation of appendicular FM ( bias=−0.3 kg , 95 % CI=−0.5 to −0.1 ) and underestimation of whole-body LM ( bias=1.5 kg , 95 % CI=1.4–1.7 ) by SMF-BIA . In addition , the individual level accuracy demonstrated a non-proportional bias for whole-body LM ( r=0.08 , P=0.338 ) and appendicular FM ( r=0.07 , P=0.413 ) . CONCLUSIONS : SMF-BIA had acceptable accuracy for the estimation of whole-body and appendicular FM and LM in frail older women , although SMF-BIA underestimated LM and overestimated FM relative to DXA CONTEXT Myostatin is a negative regulator of muscle growth . And rogen deprivation ( ADT ) is associated with muscle loss and increased body fat , and currently available therapies have limited efficacy to treat this complication . The antimyostatin peptibody ( AMG 745/Mu-S ) markedly attenuated muscle loss and decreased fat accumulation in orchiectomized mice . OBJECTIVE The objective of the study was to evaluate the safety , pharmacokinetics , and muscle efficacy of AMG 745 in men undergoing ADT for nonmetastatic prostate cancer . METHODS This was a r and omized , blinded , placebo-controlled , multiple-dose , phase 1 study of AMG 745 given for 28 days . The end point of percentage change from baseline in lean body mass ( LBM ) as assessed by dual x-ray absorptiometry was prespecified . RESULTS Rates of adverse events  ( AMG 745 vs placebo ) were the following : diarrhea ( 13 % vs 9 % ) , fatigue ( 13 % vs 4 % ) , contusion ( 10 % vs 0 % ) , and injection site bruising ( 6 % vs 4 % ) . Exposure increased linearly from 0.3 mg/kg to 3 mg/kg . AMG 745 significantly increased LBM in the 3 mg/kg vs the placebo groups on day 29 by 2.2 % ( ±0.8 % SE , P = 0.008 ) ; in exploratory fat mass analysis , a decrease of -2.5 % ( ±1.0 % SE , P = 0.021 ) was observed . Pharmacodynamic changes in muscle and fat were maintained at follow-up , 1 month after day 29 . CONCLUSION Four weekly s.c . doses of AMG 745 were well tolerated and were associated with increased LBM and decreased fat  in the men receiving ADT for nonmetastatic prostate cancer . RESULTS support further investigation of AMG 745 in clinical setting s with muscle loss and atrophy OBJECTIVES To evaluate the effectiveness of exercise and amino acid supplementation in enhancing muscle mass and strength in community-dwelling elderly sarcopenic women . DESIGN R and omized controlled trial . SETTING Urban community in Tokyo , Japan . PARTICIPANTS One hundred fifty-five women aged 75 and older were defined as sarcopenic and r and omly assigned to one of four groups : exercise and amino acid supplementation ( exercise + AAS ; n = 38 ) , exercise ( n = 39 ) , amino acid supplementation ( AAS ; n = 39 ) , or health education ( HE ; n = 39 ) . INTERVENTION The exercise group attended a 60-minute comprehensive training program twice a week , and the AAS group ingested 3 g of a leucine-rich essential amino acid mixture twice a day for 3 months . MEASUREMENTS Body composition was determined using bioelectrical impedance analysis . Data from interviews and functional fitness parameters such as muscle strength and walking ability were collected at baseline and after the 3-month intervention . RESULTS A significant group × time interaction was seen in leg muscle mass ( P = .007 ) , usual walking speed ( P = .007 ) , and knee extension strength ( P = .017 ) . The within-group analysis showed that walking speed significantly increased in all three intervention groups , leg muscle mass in the exercise + AAS and exercise  groups , and knee extension strength only in the exercise + AAS group ( 9.3 % increase , P = .01 ) . The odds ratio for leg muscle mass and knee extension strength improvement was more than four times as great in the exercise + AAS group ( odds ratio = 4.89 , 95 % confidence interval = 1.89 - 11.27 ) as in the HE group . CONCLUSION The data suggest that exercise and AAS together may be effective in enhancing not only muscle strength , but also combined variables of muscle mass and walking speed and of muscle mass and strength in sarcopenic women OBJECTIVES Using data from the Hong Kong Mr and Ms Os study , we vali date d the SARC-F against 3 consensus definitions of sarcopenia from Europe , Asia , and an international group , and compared the ability of all 4 measures to predict 4-year physical limitation , walking speed , and repeated chair st and s. DESIGN Prospect i ve cohort study . SETTING Hong Kong community . PARTICIPANTS Four thous and men and women living in the community . MEASUREMENTS A question naire regarding ability to carry a heavy load , walking , rising from a chair , climbing stairs , and falls frequency was administered . These questions were used to calculate the SARC-F score . Measurements , including appendicular muscle mass , were taken using dual-energy X-ray , grip strength using a dynamometer , 6-m gait speed , and time taken for repeated chair st and . Classification using the SARC-F score was compared using consensus panel criteria from international , European , and Asian sarcopenia working groups . The performance of all 4 methods was compared by examining the predictive ability for 4-year outcomes using ROC curve . RESULTS The SARC-F has excellent specificity but poor sensitivity for sarcopenia classification ; however , all 4 methods have comparable but modest predictive power for 4-year physical limitation . CONCLUSION The SARC-F may be considered a suitable tool for community screening for sarcopenia CONTEXT Hormone administration to elderly individuals can increase lean body mass ( LBM ) and decrease fat , but interactive effects of growth hormone ( GH ) and sex steroids and their influence on strength and endurance are unknown . OBJECTIVE To evaluate the effects of recombinant human GH and /or sex steroids on body composition , strength , endurance , and adverse outcomes in aged persons . DESIGN , SETTING , AND PARTICIPANTS A 26-week r and omized , double-blind , placebo-controlled parallel-group trial in healthy , ambulatory , community-dwelling US women ( n = 57 ) and men ( n = 74 ) aged 65 to 88 years recruited between June 1992 and July 1998 . INTERVENTIONS Participants were r and omized to receive GH ( starting dose , 30 micro g/kg , reduced to 20 micro g/kg , subcutaneously 3 times/wk ) + sex steroids ( women : transdermal estradiol , 100 micro g/d , plus oral medroxyprogesterone acetate , 10 mg/d , during the last 10 days of each 28-day cycle [ HRT ] ; men : testosterone enanthate , biweekly intramuscular injections of 100 mg ) ( n = 35 ) ; GH + placebo sex steroid ( n = 30 ) ; sex steroid + placebo GH ( n = 35 ) ; or placebo GH + placebo sex steroid ( n = 31 ) in a 2 x 2 factorial design . MAIN OUTCOME MEASURES Lean body mass , fat mass , muscle strength , maximum oxygen uptake ( VO(2)max ) during treadmill test , and adverse effects . RESULTS In women , LBM increased by 0.4 kg with placebo , 1.2 kg with HRT ( P = .09 ) , 1.0 kg with GH ( P = .001 ) , and 2.1 kg with GH + HRT ( P<.001 ) . Fat mass decreased significantly in the GH and GH + HRT groups . In men , LBM increased by 0.1 kg with placebo , 1.4 kg with testosterone ( P = .06 ) , 3.1 kg with GH ( P<.001 ) , and 4.3 kg with GH + testosterone ( P<.001 ) . Fat mass decreased significantly with GH and GH + testosterone . Women 's strength decreased in the placebo group and increased nonsignificantly with HRT ( P = .09 ) , GH ( P = .29 ) , and GH + HRT ( P = .14 ) . Men 's strength also did not increase significantly except for a marginally significant increase of 13.5 kg with GH + testosterone ( P = .05 ) . Women 's VO(2)max declined by 0.4 mL/min/kg in the placebo and HRT groups but increased with GH ( P = .07 ) and GH + HRT ( P = .06 ) . Men 's VO(2)max declined by 1.2 mL/min/kg with placebo and by 0.4 mL/min/kg with testosterone ( P = .49 ) but increased with GH ( P = .11 ) and with GH + testosterone ( P<.001 ) . Changes in strength ( r = 0.355 ; P<.001 ) and in VO(2)max ( r = 0.320 ; P = .002 ) were directly related to changes in LBM . Edema was significantly more common in women taking GH ( 39 % vs 0 % ) and GH + HRT ( 38 % vs 0 % ) . Carpal tunnel symptoms were more common in men taking GH + testosterone ( 32 % vs 0 % ) and arthralgias were more common in men taking GH ( 41 % vs 0 % ) . Diabetes or glucose intolerance occurred in 18 GH-treated men vs 7 not receiving GH ( P = .006 ) . CONCLUSIONS In this study , GH with or without sex steroids in healthy , aged women and men increased LBM and decreased fat mass .  Sex steroid + GH increased muscle strength marginally and VO ( 2)max in men , but women had no significant change in strength or cardiovascular endurance . Because adverse effects were frequent ( importantly , diabetes and glucose intolerance ) , GH interventions in the elderly should be confined to controlled studies AIM To investigate the effects of exercise and /or tea catechin supplementation on muscle mass , strength and walking ability in elderly Japanese women with sarcopenia . METHODS A total of 128 women aged over 75 years were defined as sarcopenic and r and omly assigned into four groups : exercise and tea catechin supplementation ( n = 32 ) , exercise ( n = 32 ) , tea catechin supplementation ( n = 32 ) or health education ( n = 32 ) . The exercise group attended a 60-min comprehensive training program twice a week and the tea catechin supplementation group ingested 350 mL of a tea beverage fortified with catechin daily for 3 months . Body composition was determined by bioelectrical impedance analysis . Interview data and functional fitness measurements , such as muscle strength , balance and walking ability , were collected at baseline and after the 3-month intervention . RESULTS There were significant group × time interactions observed in timed up & go ( P < 0.001 ) , usual walking speed ( P = 0.007 ) and maximum walking speed ( P < 0.001 ) . The exercise + catechin group showed a significant effect ( odds ratio 3.61 , 95 % confidence interval 1.05 - 13.66 ) for changes in the combined variables of leg muscle mass and usual walking speed compared with the health education group . CONCLUSIONS The combination of exercise and tea catechin supplementation had a beneficial effect on physical function measured by walking ability and muscle mass Background Sarcopenia , the age-related loss of muscle mass [ defined as appendicular LBM/Height2 ( aLBM/ht2 ) below peak value by>1SD ] , strength and function , is a major contributing factor to frailty in the elderly .  MK-0773 is a selective and rogen receptor modulator design ed to improve muscle function while minimizing effects on other tissues . Objectives The primary objective of this study was to demonstrate an improvement in muscle strength and lean body mass ( LBM ) in sarcopenic frail elderly women treated with MK-0773 relative to placebo . Design This was a r and omized , double-blind , parallel-arm , placebo-controlled , multicenter , 6-month study . Participants were r and omized in a 1:1 ratio to receive either MK-0773 50 mg b.i.d . or placebo ; all participants received Vitamin D and protein supplementation . Setting General community . Participants 170 Women aged ≥65 with sarcopenia and moderate physical dysfunction . Measurements Dual energy X-ray absorptiometry , muscle strength and power , physical performance measures . Results Participants receiving MK-0773 showed a statistically significant increase in LBM from baseline at Month 6 vs. placebo ( p<0.001 ) . Participants receiving both MK-0773 and placebo showed a statistically significant increase in strength from baseline to Month 6 , but the mean difference between the two groups was not significant ( p=0.269 ) . Both groups showed significant improvement from baseline at Month 6 in physical performance measures , but there were no statistically significant differences between participants receiving MK-0773 and placebo . A greater number of participants experienced elevated transaminases in the MK-0773 group vs. placebo , which resolved after discontinuation of study therapy . MK-0773 was generally well-tolerated with no evidence of and rogenization . Conclusions The MK-0773-induced  increase in LBM did not translate to improvement in strength or function vs. placebo . The improvement of strength and physical function in the placebo group could be at least partly attributed to protein and vitamin D supplementation Objective : To compare the effects of 12 weeks of high‐speed resistance training on functional performance and quality of life  in elderly women when using either a traditional‐set ( TS ) or a cluster‐set ( CS ) configuration for inter‐set rest . Methods : Three groups of subjects were formed by block‐ design r and omization as follows : ( i ) control group ( CG , n = 17 ; age , 66.5 ± 5.4 years ) ; ( ii ) 12‐week high‐speed resistance training group under a CS configuration ( CSG , n = 15 ; age , 67.6 ± 5.4 years ) ; and ( iii ) 12‐week high‐speed resistance training group under a TS configuration ( TSG , n = 20 ; age , 68.0 ± 5.3 years ) . Training was undertaken three times per week , including high‐speed resistance training exercises . The main difference between the training groups was the recovery set structure . In the TSG , women rested for 150 s after each set of eight repetitions , whereas the CSG used an interest rest redistribution , such that after two consecutive repetitions , a 30‐s rest was allowed . Results : Group × test interactions were observed for a 10‐m walking speed test , an 8‐foot up‐ and ‐go test , a sit‐to‐st and test , and physical quality of life ( p < 0.05 ; d = 0.12–0.81 ) . The main results suggest that both training methods improve functional performance and quality of life , however , the CS configuration induced significantly greater improvements in functional performance and quality of life than the TS configuration . Conclusion : These results should be considered when design ing appropriate and better resistance training programs for older adults . HighlightsFunctional performance and quality of life may be hindered during aging . High‐speed resistance‐training may increase functional performance and quality of life . High‐speed resistance‐training may be particularly effective using a cluster training sets configuration IMPORTANCE In older adults reduced mobility is common and is an independent risk factor for morbidity , hospitalization , disability , and mortality . Limited evidence suggests that physical activity may help prevent mobility disability ; however , there are no definitive clinical trials examining whether physical activity prevents or delays mobility disability . OBJECTIVE To test the hypothesis that a long-term structured physical activity program is more effective than a health education program ( also referred to as a successful aging program ) in reducing the risk of major mobility disability . DESIGN , SETTING , AND PARTICIPANTS The Lifestyle Interventions and Independence for Elders ( LIFE ) study was a multicenter , r and omized trial that enrolled participants between February 2010 and December 2011 , who participated for an average of 2.6 years . Follow-up ended in December 2013 . Outcome assessors were blinded to the intervention assignment . Participants were recruited from urban , suburban , and rural communities at 8 centers throughout the United States . We r and omized a volunteer sample of 1635 sedentary men and women aged 70 to 89 years who had physical limitations , defined as a score on the Short Physical Performance Battery of 9 or below , but were able to walk 400 m. INTERVENTIONS Participants were r and omized to a structured , moderate-intensity physical activity program ( n = 818 ) conducted in a center ( twice/wk ) and at home ( 3 - 4 times/wk ) that included aerobic , resistance , and flexibility training activities or to a health education program ( n = 817 ) consisting of workshops on topics relevant to older adults and upper extremity stretching exercises . MAIN OUTCOMES AND MEASURES The primary outcome was major mobility disability objective ly defined by loss of ability to walk 400 m. RESULTS Incident major mobility disability occurred in 30.1 % ( 246 participants ) of the physical activity group and 35.5 % ( 290 participants ) of the health education group ( hazard ratio [ HR ] , 0.82 [ 95 % CI , 0.69 - 0.98 ] , P = .03).Persistent mobility disability was experienced by 120 participants ( 14.7 % ) in the physical activity group and 162 participants ( 19.8 % ) in the health education group ( HR , 0.72 [ 95 % CI , 0.57 - 0.91 ] ; P = .006 ) . Serious adverse events were reported by 404 participants ( 49.4 % ) in the physical activity group and 373 participants ( 45.7 % ) in the health education group ( risk ratio , 1.08 [ 95 % CI , 0.98 - 1.20 ] ) . CONCLUSIONS AND RELEVANCE A structured , moderate-intensity physical activity program compared with a health education program reduced major mobility disability over 2.6 years among older adults at risk for disability . These findings suggest mobility benefit from such a program in vulnerable older adults . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01072500 OBJECTIVES To cross-culturally adapt and vali date the Spanish- language version of the SARC-F  in Mexican community-dwelling older adults . DESIGN Cross-sectional analysis of a prospect i ve cohort . SETTING The FraDySMex study , a 2-round evaluation of community-dwelling adults from 2 municipalities in Mexico City . PARTICIPANTS Participants were 487 men and women older than 60 years , living in the design ated area in Mexico City . MEASUREMENTS Information from question naires regarding demographic characteristics , comorbidities , mental status , nutritional status , dependence in activities of daily living , frailty , and quality of life . Objective measurements of muscle mass , strength and function were as follows : skeletal muscle mass index ( SMI ) was taken using dual-energy x-ray , grip strength using a h and dynamometer , 6-meter gait speed using a GAIT Rite instrumented walkway , peak torque and power for knee extension using a isokinetic dynamometer , lower extremity functioning measured by the Short Physical Performance Battery ( SPPB ) , and balance using evaluation on a foam surface , with closed eyes , in the Modified Clinical Test of Sensory Integration . The SARC-F scale translated to Spanish and the consensus panels ' criteria from European , international , and Asian sarcopenia working groups were applied to evaluate sarcopenia . RESULTS The Spanish language version of the SARC-F scale showed reliability ( Cronbach alfa = 0.641 . All items in the scale correlated to the scale 's total score , rho = 0.43 to 0.76 ) , temporal consistency evaluated by test-retest ( CCI = 0.80 ) , criterion validity when compared to the consensus panels ' criteria ( high specificity and negative predictive values ) . The scale was also correlated to other measures related to sarcopenia ( such as age , quality of life , self-rated health status , cognition , dependence in activities of daily living , nutritional status , depression , gait speed , grip strength , peak torque and power for knee extension , SPPB , balance , SMI , and frailty ) . CONCLUSION The SARC-F scale was successfully adapted to Spanish language and vali date d in community-dwelling Mexican older adults
target: There is a lack of robust evidence to assess the strength of other treatment options
background: Objectives Sarcopenia , defined as an age-associated loss of skeletal muscle function and muscle mass , occurs in approximately 6 - 22 % of older adults .
  This paper presents evidence -based clinical practice guidelines for screening , diagnosis and management of sarcopenia from the task force of the International Conference on Sarcopenia and Frailty Research ( ICSFR ) .