The purpose of this study was to investigate the underlying cellular basis of muscle atrophy (Placebo) and atrophy reduction (essential amino acid supplementation, EAAs) in total knee arthroplasty (TKA) patients by examining satellite cells and other key histological markers of inflammation, recovery, and fibrosis. Forty-one subjects (53–76 yr) scheduled for TKA were randomized into two groups, ingesting 20 g of EAAs or placebo, twice-daily, for 7 days before TKA and for 6 wk after surgery. A first set of muscle biopsies was obtained from both legs before surgery in the operating room, and patients were randomly assigned and equally allocated to have two additional biopsies at either 1 or 2 wk after surgery. Biopsies were processed for gene expression and immunohistochemistry. Satellite cells were significantly higher in patients ingesting 20 g of essential amino acids twice daily for the 7 days leading up to surgery compared with Placebo (operative leg P = 0.03 for satellite cells/fiber and P = 0.05 for satellite cell proportions for Type I-associated cells and P = 0.05 for satellite cells/fiber for Type II-associated cells.) Myogenic regulatory factor gene expression was different between groups, with the Placebo Group having elevated MyoD expression at 1 wk and EAAs having elevated myogenin expression at 1 wk. M1 macrophages were more prevalent in Placebo than the EAAs Group. IL-6 and TNF-α transcripts were elevated postsurgery in both groups; however, TNF-α declined by 2 wk in the EAAs Group. EAAs starting 7 days before surgery increased satellite cells on the day of surgery and promoted a more favorable inflammatory environment postsurgery. NEW & NOTEWORTHY Clinical studies by our group indicate that the majority of muscle atrophy after total knee arthroplasty (TKA) in older adults occurs rapidly, within the first 2 wks. We have also shown that essential amino acid supplementation (EAAs) before and after TKA mitigates muscle atrophy; however, the mechanisms are unknown. These results suggest that satellite cell numbers are elevated with EAA ingestion before surgery, and after surgery, EAA ingestion positively influences markers of inflammation. Combined, these data may help inform further studies designed to address the accelerated sarcopenia that occurs in older adults after major surgery.

Reducing muscle atrophy following orthopedic surgery is critical during the post-operative period. Our previous work in total knee arthroplasty (TKA) patients showed that the vast majority of atrophy occurs within two weeks following surgery and that essential amino acid supplementation (EAAs) attenuates this atrophy. We used RNA-sequencing (RNA-seq) to identify genes associated with atrophy after TKA with and without EAAs. Analysis of over-represented gene-ontology (GO) terms revealed that p53 signaling and the Cytokine-Cytokine Receptor pathways were highly upregulated after TKA. Relative to Placebo, the EAAs group had altered expression of p53 regulators such as MDM2. This altered expression may account for differences between groups in timing of upregulation of some p53 targets such as apoptosis genes, and may account for the reduction in muscle loss in subjects receiving EAAs. Furthermore, we observed altered expression of a large number of cytokine signaling genes including TNFRSF12A, which plays a critical role in muscle atrophy, myogenesis, fibrosis and the non-canonical NF-kB pathway.

Context: Accurate methods for predicting percent body fat in female athletes are needed for those who lose weight for competition. Methods mandated by sports-governing bodies for minimal weight determination in such athletes lack validation. Objective: To determine whether combining anthropometry (skinfolds, SF) and bioelectrical impedance analysis (BIA) in a 3 component model (3C) would improve the prediction of percentage body fat (%Fat) in female athletes. Secondarily, the Slaughter skinfold equation was evaluated. We hypothesized that compared to outcomes for SF or BIA alone, 3C-determined %Fat would not differ from our criterion method (accuracy) and would be a stronger predictor (higher r2) of the criterion. Design: Cross sectional. Setting: Laboratory-based study during the pre-season for collegiate sport. Participants: Female athletes (n=18 D1 NCAA) recruited from swim and gymnastic teams. Main Outcome Variables: %Fat based on a four-compartment (4C) criterion incorporating body density (air displacement plethysmography), total body water (D2O dilution), and bone mineral mass (DEXA) compared to predicted %Fat using SF alone (Slaughter equation), bioelectrical impedance analysis (single frequency for TBW estimate) and combined skinfolds and BIA (3C). Results: Regression revealed that for %Fat using the criterion 4C, the highest adjusted coefficient of determination and lowest prediction error (r2 ±standard error of estimate) was 3C (r2=0.87 ±2.8%) followed by BIA (r2=0.80 ±3.5%) and SF (r2=0.76 ± 3.8%) (for all, p<0.05). Means differed for %Fat determined using BIA (26.6 ±7.5) and 3C (25.5 ±7.2) vs. the 4C (23.5 ±7.4) (ANOVA and post hoc p<0.05). The SF estimate (24.0 +7.8) did not differ from the 4C value. Conclusions: Combining SF and BIA might improve the prediction and lower the prediction error for determining %Fat in female athletes compared to SF or BIA separately. Regardless, the Slaughter skinfold equation appeared accurate for determining the mean %Fat in these female athletes.