Appendicular lean mass index and motor function in ambulatory patients with Duchenne muscular dystrophy.

INTRODUCTION/AIMS: Appendicular lean mass index (ALMI) has been linked to motor function in patients with Duchenne muscular dystrophy (DMD). However, quantification of the relationship between ALMI and disease-specific clinical outcome assessment trajectories is needed. The purpose of this study was to determine associations between dual-energy x-ray absorptiometry (DXA) derived estimates of ALMI and motor function in ambulatory patients with DMD. METHODS: A retrospective analysis of longitudinal clinical visit data from 137 glucocorticoid-treated patients with DMD collected via structured motor assessment protocol evaluated associations between ALMI and motor function indexed by the North Star Ambulatory Assessment (NSAA) and 10 Meter Walk/run Test (10MWT). Body composition was assessed using DXA. ALMI was calculated by dividing arm and leg lean mass by height in m2; fat mass index (FMI) was calculated by dividing whole body fat mass by height in m2. Linear mixed-effects models were used to estimate associations between ALMI and motor function, controlling for age and FMI. RESULTS: The full prediction model (age, age,2 ALMI, and FMI) explained 57% of the variance in NSAA scores and 63% of the variance in 10MWT speed. A 1 kg/m2 higher ALMI value predicted a 5.4-point higher NSAA score (p < .001) and 0.45 m/s faster 10MWT speed (p < .001). A 1 kg/m2 higher FMI value predicted a 1.5-point lower NSAA score (p < .001) and 0.14 meters/second slower 10MWT speed (p < .001). DISCUSSION: DXA-derived estimates of ALMI and FMI are associated with motor function in DMD and may explain variation in DMD disease progression.

Low lean mass with obesity in older adults with hypertension: prevalence and association with mortality rate.

BACKGROUND: The influence of sarcopenic obesity (SO) on overall survival in older adults with hypertension has not been addressed. The aim of this study was to investigate the prevalence and mortality predictive value of various body composition phenotypes, focusing mainly on SO, in older adults with hypertension. METHODS: We included 1105 hypertensive patients aged ≥ 60 years from the National Health and Nutrition Examination Survey 1999-2004. Sarcopenia was broadly defined based on low lean mass (LLM; as measured by dual-energy X-ray absorptiometry), and was defined using appendicular lean mass (ALM) divided by height squared (ALM/height2), weight (ALM/weight), and body mass index (BMI; ALM/BMI), respectively. Obesity was defined as BMI ≥ 30 kg/m2, body fat percentage ≥ 30/42%, or waist circumference ≥ 102/88 cm. The prevalence of LLM with obesity was estimated according to each ALM index (ALMI). Multivariable Cox regression analysis and sensitivity analysis were used to examine the association between various body composition phenotypes and all-cause mortality. RESULTS: In older adults with hypertension, the prevalence of LLM with obesity by the ALM/height2 index (9.8%) was lower relative to the ALM/weight (11.7%) and ALM/BMI indexes (19.6%). After a median follow-up of 15.4 years, 642 deaths occurred. In the fully adjusted models, LLM with obesity was significantly associated with a higher risk of all-cause mortality (hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.14-2.49, P = 0.008; HR 1.48, 95% CI 1.04-2.10, P = 0.028; HR 1.30, 95% CI 1.02-1.66, P = 0.037; respectively) compared with the normal body phenotype, with no statistical differences found in individuals with LLM or obesity alone. Sensitivity analysis confirmed the robustness of the results. CONCLUSIONS: The prevalence of LLM with obesity markedly differed in older adults with hypertension according to the 3 different ALMIs, varying from 9.8%, 11.7%, to 19.6%. Patients with both LLM and obesity had a higher risk of all-cause mortality. Further large, prospective, cohort studies are warranted to validate these findings and uncover underlying mechanisms.

[Evaluation of the relationship between the parameters of peripheral skeletal and respiratory muscles in patients with chronic obstructive pulmonary disease].

Chronic obstructive pulmonary disease (COPD) is a group of diseases with high levels of comorbidity. Pathological changes of peripheral skeletal and respiratory muscles in COPD patients, which are often underestimated, occupy a special place. AIM: To study the relationship between functional and quantitative parameters of the peripheral (limb muscle) and respiratory muscles in COPD patients. MATERIALS AND METHODS: 127 patients (98 men/29 women, mean age 67.68.2 years) were under observation without acute COPD. All COPD patients were classified according to GOLD (2019) into groups A, B, C, D. The algorithm of the European Working Group on Sarcopenia in Older People (EWGSOP2) was used to diagnose sarcopenia. The muscle mass was measured using dual energy X-ray absorptiometry (DXA) and the appendicular lean mass index (ASM) was estimated. Maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) were measured by body plethysmograph MasterScreen Body. Quantitative assessment of thoracic muscle cross-sectional areas were performed using the CT scan using Vidar Dicom Viewer software. RESULTS: Sarcopenia was diagnosed in 43.3% of COPD patients. Respiratory muscle dysfunction was determined in 66.1% of patients with COPD, its probability increased in groups C and D in comparison with groups A and B [chance ratio 6.6 (95% confidence interval 2.915.0); p0.0001]. Correlations between the functional parameters of sarcopenia and respiratory muscle strength as well as between the mass of peripheral skeletal muscles and respiratory muscle area have been established according to the data of computerized tomography (р0.01). Sarcopenia as well as respiratory muscle dysfunction was observed more frequently in persons with severe and extremely severe airway obstruction and in patients with predominantly emphysematic COPD phenotype (p0.01). CONCLUSION: Sarcopenia is a frequent comorbidity in COPD and its development is connected with the severity of the course of the main disease. Correlation between parameters of peripheral (limb muscle) and respiratory muscles in patients with COPD has been determined.

The Appendicular Lean Mass Index Is a Suitable Surrogate for Muscle Mass in Children with Cerebral Palsy.

BACKGROUND: Densitometrically measured lean body mass (LBM) is often used to quantify skeletal muscle mass in children with cerebral palsy (CP). Since LBM depends on the individual's height, the evaluation of $\frac{{{\rm{LBM}}}}{{heigh{t^2}}}\ $ (lean BMI) is often recommended. However, LBM includes not only skeletal muscle mass but also the mass of skin, internal organs, tendons, and other components. This limitation applies to a far lesser extent to the appendicular lean mass index (LMIapp). OBJECTIVES: The aim of the study was to evaluate skeletal muscle mass in children with CP using total lean BMI (LMItot) and LMIapp. METHODS: The present study was a monocentric retrospective analysis of prospectively collected data among children and adolescents with CP participating in a rehabilitation program. In total, 329 children with CP [148 females; Gross Motor Function Classification Scale (GMFCS) I, 32 children; GMFCS II, 73 children; GMFCS III, 133 children; GMFCS IV, 78 children; and GMFCS V, 13 children] were eligible for analysis. The mean age was 12.3 ± 2.75 y. Pediatric reference centiles for age-adjusted LMIapp were generated using data from NHANES 1999-2004. Low skeletal muscle mass was defined as a z score for DXA determined LMItot and LMIapp less than or equal to -2.0. RESULTS: The z scores for LMIapp were significantly lower than LMItot in children with CP, GMFCS levels II-V (P < 0.001), with the exception of GMFCS level I (P = 0.121), where no significant difference was found. The prevalence of low LMItot (16.1%; 95% CI: 16.1, 20.1%) was significantly lower (P < 0.001) than the prevalence of LMIapp (42.2%; 95% CI: 36.9, 47.9%) in the study population. CONCLUSIONS: The prevalence of low skeletal muscle mass in children with CP might be underestimated by LMItot. LMIapp is more suitable for the evaluation of skeletal muscle mass in children with CP.

Handgrip Strength and Muscle Quality: Results from the National Health and Nutrition Examination Survey Database.

BACKGROUND: Handgrip strength (HGS) and the appendicular lean mass index (ALMI) are important determinants of sarcopenia. Muscle quality (MQ) is a measure of muscle strength relative to muscle mass. We examined trends in handgrip strength, the appendicular lean mass index, and analyzed their relationship with age, anthropometry, and body composition in a sample of participants in the United States (US). METHODS: This cross-sectional study analyzed data from 14,741 US males (49.7%) and females (50.3%) 6-80 years old who responded to the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2014. Dual X-ray absorptiometry was used to measure appendicular skeletal muscle mass. HGS was evaluated using the Takei Digital Grip Strength Dynamometer. Smoothed normative curves for HGS and the ALMI were constructed using a generalized additive model. Multiple regression analyses were used to examine associations of HGS and the ALMI with age, nutrition-related factors, physical activity, and body composition. RESULTS: Mean HGS and the ALMI declined with advancing age. While mean HGS increased with the ALMI, it decreased with the fat mass index. HGS increased in males with an increase in body mass index, energy intake, the ALMI, and vitamins; however, HGS in females increased with albumin, but it had a negative association with the fat mass index and age, but not with increasing adiposity. CONCLUSIONS: HGS and the ALMI change with age: HGS increases with age, then stabilizes and declines; the ALMI increases with age, then stabilizes. In addition, we provide evidence for the effect of anthropometry, nutrition, physical activity, and body composition on HGS and the ALMI in US population.

Appendicular lean mass index changes in patients with Duchenne muscular dystrophy and Becker muscular dystrophy.

INTRODUCTION: Mutations in the 79 exons of the dystrophin gene result in muscle wasting and weakness of varying clinical severity, ranging from severe/typical Duchenne muscular dystrophy (DMD) to intermediate DMD and mild Becker muscular dystrophy (BMD), depending on the frameshift of the mutation. We previously reported that males with DMD have progressively declining appendicular lean mass (ALM) and ALM index (ALMI) with age and worsening functional motor ability compared with healthy controls. These indices have not been studied in patients with intermediate DMD and BMD phenotypes and across DMD genotypes. In this study, we compared age-related trajectories of ALM and ALMI of patients who had (1) BMD without functional mobility deficits with patients who had DMD at different stages of disease and healthy controls; (2) a DMD intermediate phenotype with patients who had a typical DMD phenotype; and (3) DMD categorized by genotype. METHODS: We conducted a retrospective review of ALM and ALMI data from 499 patients (ages 5-23 years) with DMD (466 typical and 33 intermediate) and 46 patients (ages 5-21 years) with BMD (without functional mobility deficits and functional mobility score of 1). Patients were grouped according to age reflecting disease stage (ages 5 to <7, 7 to <10, 10 to <14, and 14 to <20 years) and genotype (mutations in exons 1-30, 31-44, 45-62, and 63-79). RESULTS: ALM and ALMI trajectories of patients with BMD paralleled those of healthy controls until adolescence, in contrast to patients with DMD. ALMI Z-scores of patients with BMD remained within ±2 SD without decline while those of patients with DMD fell below -2 SD around age 12 years. Patients with BMD had increasing ALM and ALMI with age, with peak accrual between ages 10 to <14 years. ALMI declined after age 14 years for those with intermediate DMD compared with 10 years for patients with typical DMD. Patients with mutations in exons 63-79 had a greater decline in ALMI as compared with those with other genotypes after age 10 years. CONCLUSIONS: Age-related changes in ALMI in patients with BMD and intermediate DMD differ from those with typical DMD, reflecting their clinical phenotypes. ALM and ALMI should be further studied in patients with BMD and DMD subtypes for their potential value as surrogate markers to characterize the severity of BMD and DMD and inform clinical care decisions and clinical trial designs.

The Significance of Dual-Energy X-ray Absorptiometry (DXA) Examination in Cushing's Syndrome-A Systematic Review.

In recent years, the usefulness of dual-energy X-ray absorptiometry (DXA) as a valuable complementary method of assessing the content and distribution of adipose and lean tissue as well as bone mineral density and estimating the risk of fractures has been increasingly confirmed. The diagnosis and treatment of Cushing's syndrome remain challenging, and monitoring the effects of treatment is often necessary. DXA tests offer a potential solution to many problems related to the availability of a quick, detailed, and reliable analysis of changes in the content and distribution of individual body composition components. The article discusses total body DXA scans (FMI, VAT, ALMI), lumbar spine scans (VFA, TBS), and osteoporosis scans (BMD, T-score, Z-score)-all are of potential interest in Cushing's syndrome. The article discusses the use of the most important indicators obtained from a DXA test (FMI, VAT, ALMI, BMD, T-score, Z-score, VFA, TBS) and their clinical significance in Cushing's syndrome was verified. The literature from the last decade was used for the study, available in MEDLINE, Web of Science, and ScienceDirect.

Corrigendum: Sarcopenic Obesity in Facioscapulohumeral Muscular Dystrophy.

[This corrects the article DOI: 10.3389/fphys.2020.01008.].

The Relationship between Body Composition, Dietary Intake, Physical Activity, and Pulmonary Status in Adolescents and Adults with Cystic Fibrosis.

Measures of body fat and lean mass may better predict important clinical outcomes in patients with cystic fibrosis (CF) than body mass index (BMI). Little is known about how diet quality and exercise may impact body composition in these patients. Dual X-ray absorptiometry (DXA) body composition, 24-h dietary recall, and physical activity were assessed in a cross-sectional analysis of 38 adolescents and adults with CF and 19 age-, race-, and gender-matched healthy volunteers. Compared with the healthy volunteers, participants with CF had a lower appendicular lean mass index (ALMI), despite no observed difference in BMI, and their diets consisted of higher glycemic index foods with a greater proportion of calories from fat and a lower proportion of calories from protein. In participants with CF, pulmonary function positively correlated with measures of lean mass, particularly ALMI, and negatively correlated with multiple measures of body fat after controlling for age, gender, and BMI. Higher physical activity levels were associated with greater ALMI and lower body fat. In conclusion, body composition measures, particularly ALMI, may better predict key clinical outcomes in individuals with CF than BMI. Future longitudinal studies analyzing the effect of dietary intake and exercise on body composition and CF-specific clinical outcomes are needed.

Sarcopenia: prevalence, associated factors, and the risk of mortality and disability in Japanese older adults.

BACKGROUND: There is limited evidence on sarcopenia in Asian populations. This study aimed to clarify the prevalence, associated factors, and the magnitude of association with mortality and incident disability for sarcopenia and combinations of its components among Japanese community-dwelling older adults. METHODS: We conducted a 5.8 year prospective study of 1851 Japanese residents aged 65 years or older (50.5% women; mean age 72.0 ± 5.9) who participated in health check-ups. Sarcopenia was defined according to the Asian Working Group for Sarcopenia 2019 algorithm. Appendicular lean mass index (ALMI) was measured using direct segmental multi-frequency bioelectrical impedance analysis. A Cox proportional hazards regression model was used to identify associations of sarcopenia and the combinations of its components with all-cause mortality and incident disability. RESULTS: The prevalence of sarcopenia was 11.5% (105/917) in men and 16.7% (156/934) in women. Significant sarcopenia-related factors other than ageing were hypoalbuminaemia, cognitive impairment, low activity, and recent hospitalization (all P-values <0.05) among men and cognitive impairment (P = 0.004) and depressed mood (P < 0.001) among women. Individuals with sarcopenia had higher risks of mortality [hazard ratios (95% confidence interval): 2.0 (1.2-3.5) in men and 2.3 (1.1-4.9) in women] and incident disability [1.6 (1.0-2.7) in men and 1.7 (1.1-2.7) in women]. Compared with the individuals without any sarcopenia components, those having low grip strength and/or slow gait speed without low ALMI tended to have an increased risk of disability [1.4 (1.0-2.0), P = 0.087], but not mortality [1.3 (0.8-2.2)]. We did not find increased risks of these outcomes in participants having low ALMI in the absence of low grip strength and slow gait speed [1.2 (0.8-1.9) for mortality and 0.9 (0.6-1.3) for incident disability]. CONCLUSIONS: Japanese older men and women meeting Asian criteria of sarcopenia had increased risks of all-cause mortality and disability. There were no significant increased risks of death or incident disability for both participants with muscle weakness and/or low performance without low muscle mass and those with low muscle mass with neither muscle weakness nor low performance. Further studies are needed to examine the interaction between muscle loss, muscle weakness, and low performance for adverse health-related outcomes.

Sarcopenic Obesity in Facioscapulohumeral Muscular Dystrophy.

BACKGROUND: Sarcopenic obesity has been observed in people with neuromuscular impairment, and is linked to adverse health outcomes. It is unclear, however, if sarcopenic obesity develops in adults with facioscapulohumeral muscular dystrophy (FSHD). METHODS: The purpose of this study was to determine if adults with FSHD meet criteria for sarcopenic obesity (appendicular lean mass index (ALMI) scores of < 7.26 or 5.45 kg/m2; % fat mass (FM) ≥ 28 or 40% in men/women). Ten people with FSHD (50 ± 11 years, 2 females) and ten age/sex-matched controls (47 ± 13 years, 2 females) completed one visit, which included a full-body dual-energy x-ray absorptiometry (DXA) scan. Regional and whole body total mass, fat mass (FM), and lean mass (LM) were collected and body mass index (BMI) and sarcopenia measures were computed. RESULTS: People with FSHD and controls had a similar whole body total mass (84.5 ± 12.9 vs. 81.8 ± 13.5 kg, respectively, p = 0.65). Though BMI was 2% lower in the FSHD group (p = 0.77), the % FM was 46% higher in FSHD, compared with controls (p < 0.01). In addition, ALM volume was 23% lower (p = 0.02) and ALMI was 27% lower in FSHD compared with controls (p < 0.01). Whole body LM trended to be lower in FSHD vs. controls (p = 0.05), and arm and leg LM were both lower in FSHD compared with controls (p < 0.05). Furthermore, the % LM was 18% lower in FSHD vs. controls (p < 0.01). FSHD participants exhibited greater total body FM (p < 0.01) and total leg FM (p < 0.01), but were similar in volume of total arm FM compared with controls (p = 0.09). CONCLUSION: Findings from this study suggest that people with FSHD, although similar in BMI and total body mass compared with controls, commonly meet the definition of sarcopenic obesity. Adults with co-existing FSHD and sarcopenic obesity may be at risk for significant impairments in quality of life, and encounter additional challenges in the management of FSHD manifestations.

Sex differences in frailty and its association with low bone mineral density in rheumatoid arthritis.

OBJECTIVES: Frailty in the general population is associated with poor health outcomes including low bone mass and osteoporotic fracture. The relationship between frailty and low bone mineral density (BMD) in rheumatoid arthritis (RA) is unknown. This study examined associations between frailty and BMD in RA, controlling for established osteoporosis risk factors. METHODS: We performed a cross-sectional analysis of a longitudinal RA cohort (n = 138; 117 female, 21 male). Participants fulfilled ACR RA classification criteria. Frailty was evaluated using the Fried Index, categorizing each participant as robust, pre-frail or frail. To identify independent predictors of BMD, we performed a multivariable linear regression analysis. Because risk factors for low BMD differ between sexes, we performed additional sex-stratified multivariable analyses. RESULTS: Mean age and disease duration were 58.0 ± 10.8 and 19 ± 10.9 years, respectively. The majority of participants were categorized as pre-frail (70%) or frail (10%). Females had higher rates of frailty than males. In the whole cohort, both pre-frail and frail had independent negative associations with BMD (ß = -0.074 and -0.092 respectively, p < 0.05). In sex-stratified analyses, frailty did not have a significant association with BMD in females, but had a strong independent negative association in males (ß = -0.247, p = 0.001). CONCLUSION: Frailty was associated with BMD in patients with RA. Females had higher rates of frailty than males, yet frailty was independently associated with BMD in males but not in females. Frailty appears to be an important factor associated with low BMD; sex may influence this relationship in RA.

Sex differences in body composition and bone mineral density in phenylketonuria: A cross-sectional study.

BACKGROUND: Low bone mineral density (BMD) and subsequent skeletal fragility have emerged as a long-term complication of phenylketonuria (PKU). OBJECTIVE: To determine if there are differences in BMD and body composition between male and female participants with PKU. METHODS: From our randomized, crossover trial [1] of participants with early-treated PKU who consumed a low-phenylalanine (Phe) diet combined with amino acid medical foods (AA-MF) or glycomacropeptide medical foods (GMP-MF), a subset of 15 participants (6 males, 9 females, aged 15-50 y, 8 classical and 7 variant PKU) completed one dual energy X-ray absorptiometry (DXA) scan and 3-day food records after each dietary treatment. Participants reported lifelong compliance with AA-MF. In a crossover design, 8 participants (4 males, 4 females, aged 16-35 y) provided a 24-h urine collection after consuming AA-MF or GMP-MF for 1-3 weeks each. RESULTS: Male participants had significantly lower mean total body BMD Z-scores (means ± SE, males = - 0.9 ± 0.4; females, 0.2 ± 0.3; p = 0.01) and tended to have lower mean L1-4 spine and total femur BMD Z-scores compared to female participants. Only 50% percent of male participants had total body BMD Z-scores above - 1.0 compared to 100% of females (p = 0.06). Total femur Z-scores were negatively correlated with intake of AA-MF (r = - 0.58; p = 0.048). Males tended to consume more grams of protein equivalents per day from AA-MF (means ± SE, males: 67 ± 6 g, females: 52 ± 4 g; p = 0.057). Males and females demonstrated similar urinary excretion of renal net acid, magnesium and sulfate; males showed a trend for higher urinary calcium excretion compared to females (means ± SE, males: 339 ± 75 mg/d, females: 228 ± 69 mg/d; p = 0.13). Females had a greater percentage of total fat mass compared to males (means ± SE, males: 24.5 ± 4.8%, females: 36.5 ± 2.5%; p = 0.047). Mean appendicular lean mass index was similar between males and females. Male participants had low-normal lean mass based on the appendicular lean mass index. CONCLUSIONS: Males with PKU have lower BMD compared with females with PKU that may be related to higher intake of AA-MF and greater calcium excretion. The trial was registered at www.clinicaltrials.gov as NCT01428258.