A focused review of myokines as a potential contributor to muscle hypertrophy from resistance-based exercise.

PURPOSE: Resistance exercise induces muscle growth and is an important treatment for age-related losses in muscle mass and strength. Myokines are hypothesized as a signal conveying physiological information to skeletal muscle, possibly to "fine-tune" other regulatory pathways. While myokines are released from skeletal muscle following contraction, their role in increasing muscle mass and strength in response to resistance exercise or training is not established. Recent research identified both local and systemic release of myokines after an acute bout of resistance exercise. However, it is not known whether myokines with putative anabolic function are mechanistically involved in producing muscle hypertrophy after resistance exercise. Further, nitric oxide (NO), an important mediator of muscle stem cell activation, upregulates the expression of certain myokine genes in skeletal muscle. METHOD: In the systemic context of complex hypertrophic signaling, this review: (1) summarizes literature on several well-recognized, representative myokines with anabolic potential; (2) explores the potential mechanistic role of myokines in skeletal muscle hypertrophy; and (3) identifies future research required to advance our understanding of myokine anabolism specifically in skeletal muscle. RESULT: This review establishes a link between myokines and NO production, and emphasizes the importance of considering systemic release of potential anabolic myokines during resistance exercise as complementary to other signals that promote hypertrophy. CONCLUSION: Investigating adaptations to resistance exercise in aging opens a novel avenue of interdisciplinary research into myokines and NO metabolites during resistance exercise, with the longer-term goal to improve muscle health in daily living, aging, and rehabilitation.

The systemic myokine response of decorin, interleukin-6 (IL-6) and interleukin-15 (IL-15) to an acute bout of blood flow restricted exercise.

PURPOSE: Blood flow restricted resistance exercise (BFR-RE) is an emerging hypertrophy training modality. A complete profile of its mechanisms of action has yet to be elucidated. Cytokines are universal intercellular messengers. Recent research has implicated certain cytokines (termed "myokines") in skeletal muscle hypertrophy pathways; however, little research has been conducted on the systemic myokine response to BFR-RE as potential hypertrophic biomarkers. Therefore, this project was conducted to determine any differences in the systemic myokine response between BFR-RE and control conditions. METHODS: The appearance of systemic myokines interleukin-6 (IL-6), interleukin-15 (IL-15), and decorin were measured following acute bouts of low-load resistance exercise, BFR-RE, and high-load resistance exercise in physically active young males to determine if BFR-RE modifies the exercise-induced systemic myokine response. RESULTS: No measurable levels of IL-6 were observed during the project. No significant effects were observed for IL-15. A significant time (11.91% increase pre to post exercise; p < 0.05) but no condition or condition by time effect was observed for decorin. CONCLUSION: These findings suggest that BFR-RE does not modify the systemic myokine appearance of IL-6, IL-15, or decorin when compared to control conditions.

A preliminary study on the effect of loaded and unloaded exercise on N-propeptide of type II collagen and serum cartilage oligomeric matrix protein activity of articular cartilage in healthy young adults.

The serum concentration of cartilage oligomeric matrix protein (sCOMP) is considered a mechanosensitive biomarker of articular cartilage turnover, and N-propeptide of type II collagen (PIIANP), a proposed biomarker of type II collagen synthesis. Few studies have investigated the anabolic and turnover response of articular cartilage in response to acute changes in body mass during exercise. Using a repeated measure cross-over design, 15 healthy adults (age 18-30 years) performed three 30 min bouts of treadmill walking exercise under three loading conditions: (1) control (no alteration to body mass); (2) loaded (12% increase in body mass using a weighted vest); and (3) unloaded (12% decrease in body mass using lower body positive pressure). Venous blood was collected before, immediately after, and 15 and 30 min after exercise to investigate cartilage turnover (sCOMP) and anabolism (PIIANP). A main time effect (p ≤ 0.05) revealed that sCOMP levels were significantly greater post-exercise (for all three body loading conditions) as compared to before exercise, 15 and 30 min post-exercise. There was a significant condition × time interaction (p ≤ 0.05) for PIIANP, indicating that in the loaded condition, PIIANP concentrations at 15 min post-exercise were 13.8% greater than immediately following exercise, and 12.9% greater than before exercise. In summary, sCOMP concentration was acutely increased with all three loading conditions. However, PIIANP increased only after exercise in the loaded condition, suggesting an acute anabolic effect on articular cartilage. NCT05925244.

Safety and Effectiveness of a Perturbation-based Neuromuscular Training Program on Dynamic Balance in Adolescent Females: A Randomized Controlled Trial.

BACKGROUND: Adolescent females are at much greater risk for ACL injury than their male counterparts when participating in the same sports. Preventative and pre-operative rehabilitation neuromuscular (NM) exercise programs are often recommended to improve knee function and reduce injury rates. The effectiveness of perturbation-based NM training program has been established in an adult population but has yet to be investigated in the at-risk adolescent female population. PURPOSE: To determine the effectiveness of a perturbation-based NM exercise program in a group of physically active adolescent females. STUDY DESIGN: Prospective randomized trial. METHODS: Twenty-four healthy and an exploratory group of 10 ACL-injured females (ages 12-18) were equally randomized into a perturbation-based NM training or control group and evaluated before and after a five-week intervention period. The primary outcome of dynamic balance was measured using the Y-Balance test (YBT); secondary outcome measures included lower limb strength, proprioception, and flexibility. RESULTS: The perturbation-based NM training intervention was safely completed by all participants but had no significant effect on YBT scoring, lower limb strength, proprioception or flexibility in either the healthy or ACL-injured groups. CONCLUSIONS: Perturbation-based NM training is safe, but may offer little preventative benefit for healthy or pre-operative rehabilitation benefit for ACL-injured adolescent females. Future research should examine whether the effectiveness of perturbation-based NM training is influenced by the length of the training intervention, training intensity, or when it is combined with other forms of prophylactic or pre-surgical rehabilitation frequently used with at-risk adolescent females who regularly participate in sport. LEVEL OF EVIDENCE: Level 3.

Lower Extremity Kinematics of the Y-Balance Test in Healthy and ACL Injured Adolescent Females.

BACKGROUND: Adolescent females are at significant risk for sustaining an ACL injury. The Y-Balance Test (YBT) is frequently used to evaluate neuromuscular control and lower extremity function. However, few studies have quantified 2D lower extremity kinematics during performance of the YBT, and there is an absence of kinematic data specific to at-risk adolescent females. PURPOSE: To examine lower extremity joint kinematics during execution of the YBT by healthy and ACL-injured adolescent females. STUDY DESIGN: Prospective cohort. METHODS: Twenty-five healthy and ten ACL-injured (mean time from injury 143 days) adolescent females were assessed using the YBT. Sagittal and frontal plane knee and ankle motion was video recorded during execution of the YBT anterior reach movement. Ankle dorsi-flexion, knee flexion, and knee valgus angles were quantified via kinematic analysis. ANOVAs with a post hoc Bonferroni correction were used to compare YBT scoring (%LL) and kinematic data between groups. Pearson product-moment correlations determined the relationship between kinematic data and YBT scoring. RESULTS: Healthy and ACL-injured subjects demonstrated similar YBT scores and lower extremity kinematic data. Healthy subjects demonstrated a weak positive correlation between ankle dorsiflexion and YBT scoring, and a weak negative correlation between knee valgus and YBT scoring. These relationships did not exist for ACL-injured subjects. Kinematic data for both groups also demonstrated a large degree of variability, regardless of YBT score. CONCLUSIONS: Adolescent females frequently utilize a variety of lower extremity movement strategies when performing a functional movement task, and scoring on the YBT offers limited insight regarding lower extremity joint kinematics and ACL-injury risk in a physically active adolescent female population. LEVEL OF EVIDENCE: Level 3.

No effect of creatine monohydrate supplementation on inflammatory and cartilage degradation biomarkers in individuals with knee osteoarthritis.

The study purpose was to evaluate the effectiveness of creatine monohydrate supplementation (20 grams/day for 1 week and then 5 grams/day for 11 weeks) on inflammation (C-reactive protein, interleukin-1ß, interleukin-6, s100 A8/A9, and tumor necrosis factor-α) and cartilage degradation (serum cartilage oligomeric matrix protein) in patients with knee osteoarthritis. We hypothesized that supplementing with creatine monohydrate for 12 weeks would lower biomarkers of inflammation and cartilage degradation in patients with knee osteoarthritis when compared to placebo. A total of 18 patients with mild to moderate knee osteoarthritis were recruited and randomized in a double blind fashion to either a creatine supplementation group (N = 9) or a placebo (N = 9). At baseline and after 12 weeks of supplementation patients had inflammatory and cartilage degradation biomarkers measured in the systemic blood. Further, patients completed the Knee injury and Osteoarthritis Outcome (KOOS) questionnaire as well as had their isometric thigh strength evaluated using an isokinetic dynamometer at both time points. Results indicated that there was no difference between the creatine and placebo groups at 12 week follow up in the inflammatory biomarkers measured nor was there any difference between the groups for cartilage degradation (all P>.05). No statistical differences were noted for the KOOS questionnaire subscales or total score (all P>.05). Muscle strength testing indicated a main effect of time for both groups where isometric thigh strength at 0° of knee flexion was lowered significantly (P=.047). No other significant differences were found in the strength data. We conclude that 12 weeks of supplementation with creatine monohydrate does not affect inflammatory biomarkers, cartilage degradation, KOOS scores, or muscle strength in patients with mild to moderate knee osteoarthritis.

Lower body positive pressure: an emerging technology in the battle against knee osteoarthritis?

BACKGROUND: Knee osteoarthritis (OA) is the most prevalent medical condition in individuals over the age of 65 years, and is a progressive joint degenerative condition with no known cure. Research suggests that there is a strong relationship between knee pain and loss of physical function. The resulting lifestyle modifications negatively impact not only disease onset and progression but also overall health, work productivity, and quality of life of the affected individual. PURPOSE: The goal of this investigation was to examine the feasibility of using an emerging technology called lower body positive pressure (LBPP) to simulate weight loss and reduce acute knee pain during treadmill walking exercise in overweight individuals with radiographically confirmed symptomatic knee OA. DESIGN: Prospective case series. METHODS: Twenty-two overweight individuals with knee OA completed two 20-minute treadmill walking sessions (one full weight bearing and one LBPP supported) at a speed of 3.1 mph, 0% incline. Acute knee pain was assessed using a visual analog scale, and the percentage of LBPP support required to minimize knee pain was evaluated every 5 minutes. Knee Osteoarthritis Outcome Scores were used to quantify knee pain and functional status between walking sessions. The order of testing was randomized, with sessions occurring a minimum of 1 week apart. RESULTS: A mean LBPP of 12.4% of body weight provided participants with significant pain relief during walking, and prevented exacerbation of acute knee pain over the duration of the 20-minute exercise session. Patients felt safe and confident walking with LBPP support on the treadmill, and demonstrated no change in Knee Osteoarthritis Outcome Scores over the duration of the investigation. CONCLUSION: Results suggest that LBPP technology can be used safely and effectively to simulate weight loss and reduce acute knee pain during weight-bearing exercise in an overweight knee OA patient population. These results could have important implications for the development of future treatment strategies used in the management of at-risk patients with progressive knee OA.

Novel application of lower body positive-pressure in the rehabilitation of an individual with multiple lower extremity fractures.

OBJECTIVE: Lower extremity fractures, if not treated appropriately, can increase the risk of morbidity. Partial weight-bearing after surgical repair is recommended; however, current methods of partial weight-bearing may cause excessive loads through the lower extremity. A new rehabilitation tool that uses lower body positive-pressure is described, that may allow partial weight-bearing while preventing excessive loads, thereby improving functional outcomes. METHODS: A patient with multiple lower extremity fractures underwent a 6-month rehabilitation programme using bodyweight support technology 3 times per week, post-surgery. RESULTS: The patient experienced a reduction in pain and an improvement in ankle range of motion (p=0.002), walking speed (p>0.05) and physical function (p=0.004), as assessed by the Foot and Ankle Module of the American Academy of Orthopaedic Surgeons Lower Limb Outcomes Assessment Instrument. Training did not appear to affect fracture healing, as was evident on radiograph. The effect of lower body positive-pressure on effusion, which has not previously been reported in the literature, was also investigated. No significant difference in effusion of the foot and ankle when using lower body positive-pressure was found. CONCLUSION: Initial results suggest that this new technology may be a useful rehabilitation tool that allows partial weight-bearing during the treatment of lower extremity injuries.

Reliability limits of the modified Thomas test for assessing rectus femoris muscle flexibility about the knee joint.

CONTEXT: The modified Thomas test is commonly used in the clinical setting to assess flexibility about the thigh region. OBJECTIVE: To evaluate the clinical reliability of the modified Thomas test for evaluating the flexibility of the rectus femoris muscle about the knee joint. DESIGN: Descriptive laboratory study using a test-retest design. SETTING: Institution-based clinical orthopaedic setting. PATIENTS OR OTHER PARTICIPANTS: Fifty-seven individuals between the ages of 18 and 45 years with no history of trauma participated. Of those, 54 completed the study. INTERVENTION(S): Three Board-certified athletic therapists with an average of 12.67 years of sport medicine expertise assessed rectus femoris flexibility using pass/fail and goniometer scoring systems. A retest session was completed 7 to 10 days later. MAIN OUTCOME MEASURE(S): Parametric and nonparametric tests were used to compare participants' test-retest results. RESULTS: Chance-corrected kappa values (intrarater x = 0.40, 95% confidence interval [CI] = 0.30, 0.54; interrater x = 0.33, 95% CI = 0.23, 0.41) indicated generally poor levels of reliability for pass/fail scoring. Intraclass correlation coefficient (ICC) values (intrarater x = 0.67, 95% CI = 0.55, 0.76; interrater x = 0.50, 95% CI = 0.40, 0.60) indicated fair to moderate levels of reliability for goniometer data. Measurement error values (standard error of measurement = 7 degrees , method error = 6 degrees , and coefficient of variation = 13%) and Bland-Altman plots (with 95% limits of agreement) further demonstrated the degree of intrarater variance for each examiner when conducting the test. CONCLUSIONS: These results call into question the statistical reliability of the modified Thomas test and provide clinicians with important information regarding its reliability limits when used to clinically assess flexibility of the rectus femoris muscle about the knee joint in a physically active population. More research is needed to ascertain the variables that may confound the statistical reliability of this orthopaedic technique.