Quadriceps Cross-sectional Area Research Articles

Evaluation of quadriceps muscle cross-sectional area using an ultrasonic diagnostic equipment with a wide field of view.

Skeletal muscle index measurement via dual-energy X-ray absorptiometry or bioelectrical impedance analysis is used to evaluate muscle mass when diagnosing sarcopenia. However, inherent challenges exist with these methods. We previously focused on muscle mass evaluation in the quadriceps femoris by using computed tomography (CT). In this observational study, we utilized a new ultrasound device with a wide field of view that can obtain CT-like images and investigated its usefulness. Reproducibility was investigated by calculating the intra- and inter-examiner intraclass correlation coefficient (ICC) by using three examiners and performing five measurements in 12 participants. In 123 participants (48 men, 75 women, mean age 78.2 ± 8.1 years), we investigated the correlation between the quadriceps cross-sectional area measured with supine ultrasound and CT images as well as between supine and sitting ultrasound images. Unadjusted, age-adjusted, and age-sex-adjusted correlations were calculated. Reproducibility was excellent (intra-examiner ICC[1,1]: 0.978, 0.987, and 0.994; inter-examiner ICC[2,1]: 0.993). The unadjusted, age-adjusted, and age-sex-adjusted correlations between the quadriceps cross-sectional area measured using supine ultrasound and CT were 0.949, 0.940, and 0.894, respectively. For sitting ultrasound, the corresponding values were 0.958, 0.953, and 0.912, respectively. Correlations between the supine and sitting ultrasound measurements were also good, with corresponding values of 0.952, 0.945, and 0.904, respectively. The tested ultrasound device showed excellent measurement reproducibility and had good correlations with CT images. Further studies with an increased numbers of clinical cases and additional evaluations should allow the device to become a screening tool for diagnosing sarcopenia.

Effect of Different Reduced Training Frequencies after 12 Weeks of Concurrent Resistance and Aerobic Training on Muscle Strength and Morphology.

The aim of the study was to investigate the effect of two long-term reduced concurrent training modalities, in which participants performed one training session every either 7 or 14 days, after 12 weeks of systematic concurrent resistance and aerobic training, on lower extremities' muscle strength, power, and morphology in young females. After the 12-week training period, participants were assigned into three groups and performed either one training session every 7 days (G7) or once every 14 days (G14), or detraining (GD), for 12 weeks, followed by 12 additional weeks of detraining. The following were measured before, after the systematic training period, after the end of the reduced training frequency period, and after the end of complete detraining: body composition, leg press 1-RM, countermovement jump, quadriceps cross-sectional area (CSA), vastus lateralis muscle architecture, and maximum aerobic power. Performance and muscle mass increased after the initial 12-week training period. Thereafter, leg press 1-RM, quadriceps CSA, and aerobic power remained unchanged in the G7 group, but decreased in G14 (-4.4 ± 3.5%; -5.9 ± 1.8%; -9.0 ± 7.8%, respectively, p < 0.05), maintaining 95.6 ± 3.5%, 94.1 ± 1.8%, and 91.0 ± 7.8% of the initial training adaptations, respectively. In conclusion, performing one training session every 2 weeks for 3 months may preserve 90 to 95% of the muscle mass/strength and aerobic power adaptations achieved with systematic concurrent training.

Becoming a World Champion Powerlifter at 71Years of Age: It Is Never Too Late to Start Exercising.

This case study assessed body composition, muscle strength, cardiorespiratory fitness, and metabolic health of the present female world champion powerlifter in the 70+ age category who started resistance exercise training at 63years of age with no prior experience with structured exercise training. Measures of body composition (magnetic resonance imaging, computed tomography, and dual-energy X-ray absorptiometry scanning, leg volume); strength (one-repetition maximum leg press and extension, maximum voluntary contraction, and handgrip strength); physical function (short physical performance battery); cardiorespiratory fitness (peak oxygen consumption); and metabolic health (oral glucose tolerance test) were assessed. In addition, a muscle biopsy was collected to assess muscle fiber type distribution and cross-sectional area (CSA). Where possible, data were compared with previously (un)published sex- and age-matched data using z scores. Skeletal muscle mass index was calculated by dividing limb muscle mass by height squared. Data from the control groups are expressed as mean ± 95% confidence interval. Our participant (age: 71years; body mass: 64.5kg; body mass index: 27.6kg/m2) reported a good bone mineral density of 1.09g/cm2 (T score between -1 and +1) and very low values of abdominal and organ body fat (i.e.,between 20% and 70% lower compared with a reference group of postmenopausal women). In addition, she showed a 33% greater skeletal muscle mass index when compared with healthy, older female control subjects (7.9 vs. 5.9 [5.7-6.2] kg/m2; n = 61) as well as 37% greater muscle quadriceps CSA (63.8 vs. 46.6 [44.5-48.7] cm2; n = 48) and 46% greater Type II muscle fiber CSA (4,536 vs. 3,097 [2,707-3,488] μm2; n = 19). Absolute leg press muscle strength was 36% greater (190 vs. 140 [132-147] kg; n = 30) and handgrip strength was 33% greater (33 vs. 25 [23-26] kg; n = 48) when compared with healthy, age-matched controls. In conclusion, even for resistance exercise naïve individuals, starting exercise at an advanced age can lead to improvements in body composition and muscle strength allowing older adults to reduce the risk for developing metabolic syndrome, live independently, and even compete at a world class level.

Effects of Blood Flow Restriction Training in Patients before and after Anterior Cruciate Ligament Reconstruction: A Systematic Review and Meta-Analysis.

(1) Objective: To examine the effects of blood flow restriction (BFR) training on muscle strength, cross-sectional area and knee-related function in patients selected for anterior cruciate ligament reconstruction (ACLR). (2) Methods: A literature search was conducted in PubMed, PEDro, Cochrane Library, Web of Science, SCOPUS, and ProQuest databases until 20 May 2024. Controlled clinical trials comparing the effects of BFR training with unrestricted training in patients before or after ACLR were selected. The GRADE approach was used to assess the degree of certainty for each meta-analysis. (3) Results: Ten studies were included (n = 287 participants). Standardized mean differences in favor of BFR training applied postoperatively were observed in knee extensor (SMD = 0.79; 95% CI = 0.06 to 1.52; I2: 68%) and flexor isokinetic strength (SMD = 0.53; 95% CI = 0.04 to 1.01; I2: 0%), and quadriceps cross-sectional area (SMD = 0.76; 95% CI = 0.27 to 1.26; I2: 0%). No changes were found in knee extensor isometric strength and knee-related function. The degree of certainty according to the GRADE was very low. (4) Conclusions: Very low degree of certainty suggests that BFR training provides additional benefits to unrestricted training on isokinetic strength and quadriceps cross-sectional area in patients undergoing ACLR.

Association of mid-thigh quadriceps muscle quality with postoperative outcomes in patients with hip osteoarthritis undergoing total hip arthroplasty: a retrospective cohort study.

Muscle quality is more important than muscle mass for assessing physical function. Computed tomography (CT) is used to evaluate intramuscular fatty infiltration. The mid-thigh quadriceps CT attenuation values (CTV) expressed in Hounsfield units (HU) negatively correlate with physical function. Patients with hip osteoarthritis (HOA) have lower extremity muscle atrophy, including decreased cross-sectional area (CSA), CTV, and muscle strength. Using preoperative CT images, we investigated the association between mid-thigh quadriceps CSA, CTV, and postoperative outcomes in patients with HOA. This study included 62 patients who had unilateral HOA (62 hips) and underwent total hip arthroplasty (THA). We investigated the association between preoperative and postoperative Japanese Orthopaedic Association (JOA) hip scores, 12-item Short Form survey (SF-12), mid-thigh quadriceps CSA, and CTV. The mean age was 64.7 ± 10.1years, with 15 men (24.2%), and the mean body mass index was 24.3 ± 4.3kg/m2. Secondary HOA was present in 79.0% of patients. The mean CSA and CTV of the mid-thigh quadriceps on the operative side were 38.8 ± 9.8 cm2 and 40.3 ± 7.8 HU, respectively. Multiple regression analyses adjusted for age and sex showed that preoperative mid-thigh quadriceps CSA was not associated with preoperative and postoperative JOA hip scores or SF-12. The preoperative mid-thigh quadriceps CTV was associated with the postoperative JOA hip score in the gait ability domain and SF-12 in the physical component summary domain. Preoperative muscle quality is associated with postoperative outcomes in patients who have HOA regardless of age and sex.

Changes in muscle quality and biomarkers of neuromuscular junctions and muscle protein turnover following 12 weeks of resistance training in older men.

The present study aimed to investigate the effects of 12 weeks of resistance training (RT) on body composition [fat mass (FM), lean body mass (LBM)], muscle quality upper and lower (MQU, MQL), muscle size [cross sectional area (CSA), quadriceps cross-sectional area (QCSA)], biomarkers of neuromuscular junctions [C-terminal agrin fragment (CAF)], and muscle protein turnover [N-terminal peptide (P3NP), 3-methylhistidine (3MH), skeletal muscle-specific isoform of troponin T (sTnT)] in older men. Thirty elderly men (age 66.23 ± 0.57 years) were randomly divided into two groups: resistance training group (RT, n=15) and control group (CON, n=15). Participants in RT performed resistance training protocols with the intensity of 60% one-repetition maximum (3 × /week, 4 sets of the six exercise circuits). Blood samples were assessed before (pre-test) and after (post-test) a 12-week intervention. The ANCOVA (2 × 2; group × time; with the baseline variable as the covariate) revealed significant interaction effects; the greater increases for LBM (P < 0.001), CSA (P < 0.001), QCSA (P < 0.001), MQU (P < 0.05), MQL (P < 0.01), 3MH (P < 0.05) were noted in RT than CON, and greater decreases for FM (P < 0.001) and CAF (P < 0.001) in RT than CON. No interaction effect was found for P3NP and sTnT. The time effect was found for all variables besides P3NP in RT, but no time effect was revealed in CON. The 12-week RT was an effective strategy for improving the concentrations of neuromuscular junction biomarkers such as 3-MH and CAF in older adults, and may lead to favourable changes in body composition, muscle quality, and muscle size.

Muscle Mass and Strength Gains Following Resistance Exercise Training in Older Adults 65-75Years and Older Adults Above 85Years.

Resistance exercise training (RET) can be applied effectively to increase muscle mass and function in older adults (65-75years). However, it has been speculated that older adults above 85years are less responsive to the benefits of RET. This study compares the impact of RET on muscle mass and function in healthy older adults 65-75years versus older adults above 85years. We subjected 17 healthy older adults 65-75years (OLDER 65-75, n = 13/4 [female/male]; 68 ± 2years; 26.9 ± 2.3kg/m2) and 12 healthy older adults above 85years (OLDER 85+, n = 7/5 [female/male]; 87 ± 3years; 26.0 ± 3.6kg/m2) to 12weeks of whole-body RET (three times per week). Prior to, and after 6 and 12weeks of training, quadriceps and lumbar spine vertebra 3 muscle cross-sectional area (computed tomography scan), whole-body lean mass (dual-energy X-ray absorptiometry scan), strength (one-repetition maximum test), and physical performance (timed up and go and short physical performance battery) were assessed. Twelve weeks of RET resulted in a 10% ± 4% and 11% ± 5% increase in quadriceps cross-sectional area (from 46.5 ± 10.7 to 51.1 ± 12.1cm2, and from 38.9 ± 6.1 to 43.1 ± 8.0cm2, respectively; p < .001; η2 = .67); a 2% ± 3% and 2% ± 3% increase in whole-body lean mass (p = .001; η2 = .22); and a 38% ± 20% and 46% ± 14% increase in one-repetition maximum leg extension strength (p < .001; η2 = .77) in the OLDER 65-75 and OLDER 85+ groups, respectively. No differences in the responses to RET were observed between groups (Time × Group, all p > .60; all η2 ≤ .012). Physical performance on the short physical performance battery and timed up and go improved (both p < .01; η2 ≥ .22), with no differences between groups (Time × Group, p > .015; η2 ≤ .07). Prolonged RET increases muscle mass, strength, and physical performance in the aging population, with no differences between 65-75years and 85+years older adults.

Effects of blood-flow restricted exercise versus conventional resistance training in musculoskeletal disorders—a systematic review and meta-analysis

ObjectiveTo compare the effect of low-load blood flow restricted resistance training (BFR-RT) versus high-load resistance training (HL-RT) on muscle strength, muscle mass, physical function, patient-reported outcomes, and adherence to training in clinical musculoskeletal populations.Data sourcesWeb of Science, Cochrane Central, Medline, Embase, SportDiscus was searched on the 30th May 2022.Review methodsThis study was conducted as a systematic review and meta-analysis. Randomized Controlled Trials (RCTs) were included if they (i) included patients, (ii) comprised of a BFR-RT intervention protocol and a group who performed HL-RT (≥ 70%1RM) for at least eight exercise sessions, and (iii) involved at least 1 exercise that targeted the lower limbs. The Cochrane Risk of Bias tool was used to evaluate the risk of bias. The meta-analyses were performed using a random effects model with an adjustment to the confidence interval.ResultsSeven RCTs comprising 303 participants (BFR-RT: n = 151; HL-RT: n = 152) were identified. HL-RT and BFR-RT showed similar gains in dynamic (1-10RM) knee extensor strength and leg press strength, quadriceps cross sectional area, sit-to-stand performance, and patient reported pain and function. There was a moderate effect favoring BFR-RT for increasing maximal isometric knee extensor strength. The grading of certainty in evidence was low-to-very low for all outcome variables.ConclusionThis systematic review and meta-analysis extends our current knowledge about BFR-RT and HL-RT as equally effective exercise methods for inducing gains in maximal muscle strength in healthy populations, by now also comprising patients suffering from various clinical musculoskeletal conditions. The certainty in the estimates was low-to-very low, prompting the inclusion of future higher-quality trials.Trial registrationPROSPERO ID (CRD42022337173). Registered June 18th 2022.

A single bout of prior resistance exercise attenuates muscle atrophy and declines in myofibrillar protein synthesis during bed-rest in older men.

Impairments in myofibrillar protein synthesis (MyoPS) during bed rest accelerate skeletal muscle loss in older adults, increasing the risk of adverse secondary health outcomes. We investigated the effect of prior resistance exercise (RE) on MyoPS and muscle morphology during a disuse event in 10 healthy older men (65-80years). Participants completed a single bout of unilateral leg RE the evening prior to 5days of in-patient bed-rest. Quadriceps cross-sectional area (CSA) was determined prior to and following bed-rest. Serial muscle biopsies and dual stable isotope tracers were used to determine rates of integrated MyoPS (iMyoPS) over a 7day habitual 'free-living' phase and the bed-rest phase, and rates of acute postabsorptive and postprandial MyoPS (aMyoPS) at the end of bed rest. Quadriceps CSA at 40%, 60% and 80% of muscle length significantly decreased in exercised (EX) and non-exercised control (CTL) legs with bed-rest. The decline in quadriceps CSA at 40% and 60% of muscle length was attenuated in EX compared with CTL. During bed-rest, iMyoPS rates decreased from habitual values in CTL, but not EX, and were significantly different between legs. Postprandial aMyoPS rates increased above postabsorptive values in EX only. The change in iMyoPS over bed-rest correlated with the change in quadriceps CSA in CTL, but not EX. A single bout of RE attenuated the decline in iMyoPS rates and quadriceps atrophy with 5days of bed-rest in older men. Further work is required to understand the functional and clinical implications of prior RE in older patient populations. KEY POINTS: Age-related skeletal muscle deterioration, linked to numerous adverse health outcomes, is driven by impairments in muscle protein synthesis that are accelerated during periods of disuse. Resistance exercise can stimulate muscle protein synthesis over several days of recovery and therefore could counteract impairments in this process that occur in the early phase of disuse. In the present study, we demonstrate that the decline in myofibrillar protein synthesis and muscle atrophy over 5days of bed-rest in older men was attenuated by a single bout of unilateral resistance exercise performed the evening prior to bed-rest. These findings suggest that concise resistance exercise intervention holds the potential to support muscle mass retention in older individuals during short-term disuse, with implications for delaying sarcopenia progression in ageing populations.

Changes in Muscle Mass and Strength During Follow-Up After One-Year Resistance Training Interventions in Older Adults.

Mertz, KH, Reitelseder, S, Rasmussen, MA, Bülow, J, Højfeldt, G, Jensen, M, Hjulmand, M, Lindberg, J, Kramer, MU, Bechshøft, R, and Holm, L. Changes in muscle mass and strength during follow-up after one-year resistance training interventions in older adults. J Strength Cond Res 37(10): 2064-2070, 2023-The aim of this study was to investigate if home-based resistance training compared with center-based resistance training was associated with better preservation of muscle mass and strength in older individuals, 6 months after the interventions ended. One hundred four healthy older individuals (>65 years) who had completed 1 year of either home-based light-intensity training with daily whey protein supplementation (LITW), center-based heavy resistance training with whey protein supplementation (HRTW), or daily whey protein supplementation alone (WHEY) returned for follow-up measurement 6 months after the interventions. Measures of muscle mass, strength, and power were assessed at the end of intervention as well as at follow-up. Furthermore, we compared changes in these parameters between subjects who continued resistance training (≥1 weekly training session) during follow-up (CONT) with those who stopped (STOP). Resistance training continuation during follow-up did not differ between HRTW and LITW (41 vs. 41%, P = 1.0) but was higher for both groups compared with WHEY (18%, P = 0.04-0.05). However, no between-group differences were observed between LITW/HRTW/WHEY in changes in muscle mass, strength, or power during follow-up. STOP was associated with a poorer preservation of quadriceps cross-sectional area compared with CONT (-1.7 cm 2 [-0.4 to -3.0], P = 0.01, effect size: 0.79). No effect of training continuation was observed on changes in muscle strength and power. In conclusion, maintenance of muscle mass and strength is not superior after home-based resistance training compared with center-based training. However, training continuation seems crucial for the maintenance of muscle mass, irrespective of the training intervention.

Poster 328: Pre-Operative Low-Intensity Blood Flow Restriction Training Does Not Improve Quadriceps Strength or Hypertrophy After Anterior Cruciate Ligament Reconstruction

Objectives: The purpose of this study is to evaluate the effect of low-intensity blood flow restriction (LI- BFR) training utilized in a pre-rehabilitative setting for patients undergoing anterior cruciate ligament reconstruction (ACLR) on postoperative outcomes by minimizing postoperative atrophy and impairment of the quadriceps. We hypothesize that postoperative strength and hypertrophy of the quadriceps will be greater in a population that undergoes preoperative LI-BFR training than that of a population that undergoes low-intensity sham control (LI-SHAM) training. Methods: Twenty-eight subjects undergoing primary ACLR underwent 2 weeks of either a BFR intervention or a SHAM intervention at a rate of 2 sessions per week before surgery. Quadriceps strength and cross-sectional area were measured as well as other exploratory outcomes were measured before and after the intervention before surgery and at 5 different time points after surgery, through 6 months postoperative. Quadriceps strength was assessed through handheld dynamometry and a leg press test and quadriceps cross-sectional area was assessed using musculoskeletal ultrasound imaging. Results: Adjusting for sex, time, and strength/hypertrophy at baseline, there were no significant differences found between treatment groups for the primary endpoints. Compared to 24-48 hours pre- op, this suggests that the post-op average hypertrophy remains significantly lower through 24 weeks post-op, while leg strength is similar at 24 weeks post-op as measured by handheld dynamometer and even significantly larger at 24 weeks as measured by the leg press test. Conclusions: A 2-week preoperative program of LI-BFR training may not be effective to improve postoperative quadriceps strength and hypertrophy after ACLR.

Greater myofibrillar protein synthesis following weight-bearing activity in obese old compared with non-obese old and young individuals

The mechanisms through which obesity impacts age-related muscle mass regulation are unclear. In the present study, rates of integrated myofibrillar protein synthesis (iMyoPS) were measured over 48-h prior-to and following a 45-min treadmill walk in 10 older-obese (O-OB, body fat[%]: 33 ± 3%), 10 older-non-obese (O-NO, 20 ± 3%), and 15 younger-non-obese (Y-NO, 13 ± 5%) individuals. Surface electromyography was used to determine thigh muscle “activation”. Quadriceps cross-sectional area (CSA), volume, and intramuscular thigh fat fraction (ITFF) were measured by magnetic resonance imaging. Quadriceps maximal voluntary contraction (MVC) was measured by dynamometry. Quadriceps CSA and volume were greater (muscle volume, Y-NO: 1182 ± 232 cm3; O-NO: 869 ± 155 cm3; O-OB: 881 ± 212 cm3, P < 0.01) and ITFF significantly lower (m. vastus lateralis, Y-NO: 3.0 ± 1.0%; O-NO: 4.0 ± 0.9%; O-OB: 9.1 ± 2.6%, P ≤ 0.03) in Y-NO compared with O-NO and O-OB, with no difference between O-NO and O-OB in quadriceps CSA and volume. ITFF was significantly higher in O-OB compared with O-NO. Relative MVC was lower in O-OB compared with Y-NO and O-NO (Y-NO: 5.5 ± 1.6 n·m/kg−1; O-NO: 3.9 ± 1.0 n·m/kg−1; O-OB: 2.9 ± 1.1 n·m/kg−1, P < 0.0001). Thigh muscle “activation” during the treadmill walk was greater in O-OB compared with Y-NO and O-NO (Y-NO: 30.5 ± 13.5%; O-NO: 35.8 ± 19.7%; O-OB: 68.3 ± 32.3%, P < 0.01). Habitual iMyoPS did not differ between groups, whereas iMyoPS was significantly elevated over 48-h post-walk in O-OB (+ 38.6 ± 1.2%·day−1, P < 0.01) but not Y-NO or O-NO (+ 11.4 ± 1.1%·day−1 and + 17.1 ± 1.1%·day−1, respectively, both P > 0.271). Equivalent muscle mass in O-OB may be explained by the muscle anabolic response to weight-bearing activity, whereas the age-related decline in indices of muscle quality appears to be exacerbated in O-OB and warrants further exploration.

Age-related alterations in human motor units properties and in muscle innervation profile

Introduction: Mounting evidence suggests that motoneuron and neuromuscular junction (NMJ) degeneration, muscle fiber denervation and loss of motor units contribute to muscle wasting and weakness in old age. However, these aspects are still poorly investigated in humans. This study aimed at comparing the neuromuscular system integrity and function of young and older adults, with particular focus on NMJ and motor unit potential (MUP) characteristics. We hypothesized that older individuals would present altered electrophysiological properties and innervation profile. Methods: We recruited 55 healthy young individuals (YI) (aged 26.1±4.5 yr; 50% females) and 88 older individuals (OI) (aged 75.9±4.7 yr; 55% females). Muscle force was evaluated by isometric dynamometry, muscle morphology by ultrasound and neuromuscular excitability by compound motor unit action potential (CMAP). MUP properties and motor unit number estimate (iMUNE) were obtained by intramuscular electromyography (iEMG). In a sub-cohort of individuals (n=16 YI and n=34 OI), vastus lateralis (VL) muscle biopsies were obtained. We assessed denervation status by scoring neural cell adhesion molecule (NCAM) positive fibers. Generalized linear mixed models were carried out for iEMG data, while unpaired t-tests were carried out for all the other parameters. Results: OI showed alterations in muscle morphology when compared to YI, evident as smaller whole quadriceps cross-sectional area (p&lt;0.001) and VL fiber diameter (p&lt;0.01), together with smaller VL pennation angles (p&lt;0.001) and fascicle lengths (p&lt;0.05), resulting in an increased ultrasound sarcopenia index (p=0.001). Muscle force (p&lt;0.001) and CMAP (p&lt;0.001) were also largely impaired in OI, suggesting that muscle function and neuromuscular excitability are considerably affected by aging. iEMG analysis revealed changes in MUP turns (p&lt;0.001), near fiber (NF) MUP duration (p&lt;0.001) and NF count (p&lt;0.001) in OI, pointing towards an increased MUP complexity, in absence of sex differences. The iMUNE was reduced (p&lt;0.001) and the NMJ transmission stability was significantly altered in OI, as suggested by elevated NF jiggle (p&lt;0.001) and segmented jitter (p&lt;0.05). These electrophysiological alterations seem likely due to altered muscle innervation profile, as highlighted by an increased percentage of NCAM-positive fiber (p&lt;0.001). Conclusions: This study showed that changes in muscle morphology and function, MUP properties, motor units loss and denervation status occur in older humans; these may be serve as useful markers of human neuromuscular aging. The present work was funded by PRIN project NeuAge (2017CBF8NJ_001) to MVN and the Milky Way Foundation, the Baxter Foundation, and the Li Ka Shing Foundation to HMB. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Levothyroxine use and longitudinal changes in thigh muscles in at-risk participants for knee osteoarthritis: preliminary analysis from Osteoarthritis Initiative cohort

BackgroundWe examined the association between levothyroxine use and longitudinal MRI biomarkers for thigh muscle mass and composition in at-risk participants for knee osteoarthritis (KOA) and their mediatory role in subsequent KOA incidence.MethodsUsing the Osteoarthritis Initiative (OAI) data, we included the thighs and corresponding knees of participants at risk but without established radiographic KOA (baseline Kellgren-Lawrence grade (KL) < 2). Levothyroxine users were defined as self-reported use at all annual follow-up visits until the 4th year and were matched with levothyroxine non-users for potential confounders (KOA risk factors, comorbidities, and relevant medications covariates) using 1:2/3 propensity score (PS) matching. Using a previously developed and validated deep learning method for thigh segmentation, we assessed the association between levothyroxine use and 4-year longitudinal changes in muscle mass, including cross-sectional area (CSA) and muscle composition biomarkers including intra-MAT (within-muscle fat), contractile percentage (non-fat muscle CSA/total muscle CSA), and specific force (force per CSA). We further assessed whether levothyroxine use is associated with an 8-year risk of standard KOA radiographic (KL ≥ 2) and symptomatic incidence (incidence of radiographic KOA and pain on most of the days in the past 12 months). Finally, using a mediation analysis, we assessed whether the association between levothyroxine use and KOA incidence is mediated via muscle changes.ResultsWe included 1043 matched thighs/knees (266:777 levothyroxine users:non-users; average ± SD age: 61 ± 9 years, female/male: 4). Levothyroxine use was associated with decreased quadriceps CSAs (mean difference, 95%CI: − 16.06 mm2/year, − 26.70 to − 5.41) but not thigh muscles’ composition (e.g., intra-MAT). Levothyroxine use was also associated with an increased 8-year risk of radiographic (hazard ratio (HR), 95%CI: 1.78, 1.15–2.75) and symptomatic KOA incidence (HR, 95%CI: 1.93, 1.19–3.13). Mediation analysis showed that a decrease in quadriceps mass (i.e., CSA) partially mediated the increased risk of KOA incidence associated with levothyroxine use.ConclusionsOur exploratory analyses suggest that levothyroxine use may be associated with loss of quadriceps muscle mass, which may also partially mediate the increased risk of subsequent KOA incidence. Study interpretation should consider underlying thyroid function as a potential confounder or effect modifier. Therefore, future studies are warranted to investigate the underlying thyroid function biomarkers for longitudinal changes in the thigh muscles.

Does initial skeletal muscle size or sex affect the magnitude of muscle loss in response to 14 days immobilization?

We aimed to determine if there was a relationship between pre-immobilization skeletal muscle size and the magnitude of muscle atrophy following 14 d of unilateral lower limb immobilization. Our findings (n=30) show that pre-immobilization leg fat-free mass and quadriceps cross-sectional area (CSA) were unrelated to the magnitude of muscle atrophy. However, sex-based differences may be present, but confirmatory work is required. In women, pre-immobilization leg fat-free mass and CSA were associated with changes in quadriceps CSA after immobilization (n=9, r2=0.54-0.68; P<0.05). The extent of muscle atrophy is not affected by initial muscle mass, but there is potential for sex-based differences.

Onset of androgen deprivation therapy leads to rapid deterioration of body composition, physical performance, cardiometabolic health and quality-of-life in prostate cancer patients

Objectives To assess the adverse impact of the first 5 months of androgen deprivation therapy on body composition, physical performance, cardiometabolic health and health-related quality-of-life in prostate cancer patients. Materials and Methods Thirty-four prostate cancer patients (70 ± 7 years) were assessed shortly after initiation of androgen deprivation therapy and again 5 months thereafter. Measurements consisted of whole-body dual-energy x-ray absorptiometry (body composition), computed tomography scanning of the upper leg (muscle mass), one-repetition maximum leg press (muscle strength), cardiopulmonary exercise testing (aerobic capacity), blood draws (metabolic parameters), accelerometry (habitual physical activity) and questionnaires (health-related quality-of-life). Data were analyzed with Student’s paired t-tests. Results Over time, whole-body fat mass (from 26.2 ± 7.7 to 28.4 ± 8.3 kg, p < 0.001) and fasting insulin (from 9.5 ± 5.8 to 11.3 ± 6.9 mU/L, p < 0.001) increased. Declines were observed for quadriceps cross-sectional area (from 66.3 ± 9.1 to 65.0 ± 8.5 cm2, p < 0.01), one-repetition maximum leg press (from 107 ± 27 to 100 ± 27 kg, p < 0.01), peak oxygen uptake (from 23.2 ± 3.7 to 20.3 ± 3.4 mL/min/kg body weight, p < 0.001), step count (from 7,048 ± 2,277 to 5,842 ± 1,749 steps/day, p < 0.01) and health-related quality-of-life (from 84.6 ± 13.5 to 77.0 ± 14.6, p < 0.001). Conclusions Androgen deprivation therapy induces adverse changes in body composition, muscle strength, cardiometabolic health and health-related quality-of-life already within 5 months after the start of treatment, possibly largely contributed by diminished habitual physical activity. Prostate cancer patients should, therefore, be stimulated to increase their habitual physical activity immediately after initiation of androgen deprivation therapy, to limit adverse side-effects and to improve health-related quality-of-life.

Vicia faba Peptide Network Supplementation Does Not Differ From Milk Protein in Modulating Changes in Muscle Size During Short-Term Immobilization and Subsequent Remobilization, but Increases Muscle Protein Synthesis Rates During Remobilization in Healthy Young Men

BackgroundMuscle mass and strength decrease during short periods of immobilization and slowly recover during remobilization. Recent artificial intelligence applications have identified peptides that appear to possess anabolic properties in in vitro assays and murine models. ObjectivesThis study aimed to compare the impact of Vicia faba peptide network compared with milk protein supplementation on muscle mass and strength loss during limb immobilization and regain during remobilization. MethodsThirty young (24 ± 5 y) men were subjected to 7 d of one-legged knee immobilization followed by 14 d of ambulant recovery. Participants were randomly allocated to ingest either 10 g of the Vicia faba peptide network (NPN_1; n = 15) or an isonitrogenous control (milk protein concentrate; MPC; n = 15) twice daily throughout the study. Single-slice computed tomography scans were performed to assess quadriceps cross-sectional area (CSA). Deuterium oxide ingestion and muscle biopsy sampling were applied to measure myofibrillar protein synthesis rates. ResultsLeg immobilization decreased quadriceps CSA (primary outcome) from 81.9 ± 10.6 to 76.5 ± 9.2 cm2 and from 74.8 ± 10.6 to 71.5 ± 9.8 cm2 in the NPN_1 and MPC groups, respectively (P < 0.001). Remobilization partially recovered quadriceps CSA (77.3 ± 9.3 and 72.6 ± 10.0 cm2, respectively; P = 0.009), with no differences between the groups (P > 0.05). During immobilization, myofibrillar protein synthesis rates (secondary outcome) were lower in the immobilized leg (1.07% ± 0.24% and 1.10% ± 0.24%/d, respectively) than in the non-immobilized leg (1.55% ± 0.27% and 1.52% ± 0.20%/d, respectively; P < 0.001), with no differences between the groups (P > 0.05). During remobilization, myofibrillar protein synthesis rates in the immobilized leg were greater with NPN_1 than those with MPC (1.53% ± 0.38% vs. 1.23% ± 0.36%/d, respectively; P = 0.027). ConclusionNPN_1 supplementation does not differ from milk protein in modulating the loss of muscle size during short-term immobilization and the regain during remobilization in young men. NPN_1 supplementation does not differ from milk protein supplementation in modulating the myofibrillar protein synthesis rates during immobilization but further increases myofibrillar protein synthesis rates during remobilization.

Muscle fiber type grouping does not change in response to prolonged resistance exercise training in healthy older men

BackgroundAgeing of skeletal muscle is characterized in some by muscle fiber type grouping due to denervation-reinnervation cycles, but the severity of fiber type grouping varies widely across individuals of the same chronological age. It remains unknown whether fiber type grouping is associated with lower muscle mass and/or reduced physical function in elderly. Therefore, we assessed the relationship between fiber type grouping and indices of muscle mass and physical function in older adults. In addition, we assessed whether fiber type grouping is affected by prolonged resistance training in older adults. MethodsTwenty young (21 ± 2 y) and twenty older (70 ± 4 y) healthy men participated in the present study. Body composition (DXA-scan), quadriceps cross-sectional area (CT-scan) and muscle strength (1RM) were assessed at baseline (young and old) and following 12 weeks of resistance training (old only). Percutaneous skeletal muscle biopsies from the vastus lateralis were collected at baseline (young and old) and following exercise training (old only). Immunohistochemical analyses were performed to evaluate type I and type II muscle fiber distribution, size, myonuclear content and grouping. ResultsAt baseline, type II fibers were significantly (P < 0.05) smaller in older compared with young adults (5366 ± 1288 vs 6705 ± 1168 μm2). Whereas no differences were observed in type I, type II fiber grouping was significantly (P < 0.05) lower in older (18 ± 18 %) compared with young (32 ± 25 %) men. No significant correlations were observed between fiber type grouping and muscle mass or physical function. Prolonged resistance training in old men resulted in a significant increase (P < 0.05) in type II fiber size (from 5366 ± 1288 to 6165 ± 1484 μm2) with no significant changes in the proportion of type I muscle fibers found grouped. ConclusionMuscle fiber type grouping is not associated with lower body strength or muscle mass in healthy, older men. In addition, twelve weeks of resistance exercise training results in type II muscle fiber specific hypertrophy but does not affect fiber type grouping.

Plasma proteome profiling of healthy subjects undergoing bed rest reveals unloading-dependent changes linked to muscle atrophy.

Inactivity and unloading induce skeletal muscle atrophy, loss of strength and detrimental metabolic effects. Bed rest is a model to study the impact of inactivity on the musculoskeletal system. It not only provides information for bed-ridden patients care, but it is also a ground-based spaceflight analogue used to mimic the challenges of long space missions for the human body. In both cases, it would be desirable to develop a panel of biomarkers to monitor muscle atrophy in a minimally invasive way at point of care to limit the onset of muscle loss in a personalized fashion. We applied mass spectrometry-based proteomics to measure plasma protein abundance changes in response to 10days of bed rest in 10 young males. To validate the correlation between muscle atrophy and the significant hits emerging from our study, we analysed in parallel, with the same pipeline, a cohort of cancer patients with or without cachexia and age-matched controls. Our analysis resulted in the quantification of over 500 proteins. Unloading affected plasma concentration of proteins of the complement cascade, lipid carriers and proteins derived from tissue leakage. Among the latter, teneurin-4 increased 1.6-fold in plasma at bed rest day 10 (BR10) compared with BR0 (6.E9 vs. 4.3E9, P=0.02) and decreased to 0.6-fold the initial abundance after 2days of recovery at normal daily activity (R+2, 2.7E9, P=3.3E-4); the extracellular matrix protein lumican was decreased to 0.7-fold (1.2E9 vs. 8.5E8, P=1.5E-4) at BR10 and remained as low at R+2. We identified six proteins distinguishing subjects developing unloading-mediated muscle atrophy (decrease of >4% of quadriceps cross-sectional area) from those largely maintaining their initial muscle mass. Among them, transthyretin, a thyroid hormone-binding protein, was significantly less abundant at BR10 in the plasma of subjects with muscle atrophy compared with those with no atrophy (1.6E10 vs. 2.6E10, P=0.001). Haptoglobin-related protein was also significantly reduced in the serum of cancer patients with cachexia compared with that of controls. Our findings highlight a combination or proteomic changes that can be explored as potential biomarkers of muscle atrophy occurring under different conditions. The panel of significant proteomic differences distinguishing atrophy-prone and atrophy-resistant subjects after 10days of bed rest need to be tested in a larger cohort to validate their potential to predict inactivity-triggered muscle loss in humans.

Association of vastus lateralis diffusion properties with in vivo quadriceps contractile function in premenopausal women.

Diffusion tensor imaging (DTI) parameters correlate with muscle fiber composition, but it is unclear how these relate to in vivo contractile function. To determine the relationship between DTI parameters of the vastus lateralis (VL) and in vivo knee extensor contractile. Thirteen healthy, premenopausal women underwent magnetic resonance imaging of the mid-thigh to determine patellar tendon moment arm length and quadriceps cross-sectional area. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) of the VL were determined using diffusion tensor imaging (DTI). Participants underwent an interpolated twitch (ITT) experiment before and after a fatiguing concentric-eccentric isokinetic knee extension (60°·s-1 ). During the ITT, supramaximal electrical stimuli were delivered to elicit twitch responses from the knee extensors before, during, and after a maximal voluntary isometric contraction (MVIC). Knee extensor-specific tension during twitch and MVIC were calculated from isometric torque data. Pearson's correlations were used to determine the relationship between muscle contractile properties and DTI parameters. MD and RD were moderately correlated with peak twitch force and rate of force development. FA and AD were moderately inversely related to percent change in MVIC following exercise. MD and RD are associated with in vivo quadriceps twitch properties but not voluntary strength, which may reflect the mechanical properties of constituent fiber types. FA and AD appear to relate to MVIC strength following fatiguing exercise.