Changes in Circulating Biomarkers of Muscle Atrophy, Inflammation, and Cartilage Turnover in Patients Undergoing Anterior Cruciate Ligament Reconstruction and Rehabilitation

ArticleinThe American Journal of Sports Medicine 41(8) · June 2013with11 Reads
DOI: 10.1177/0363546513490651 · Source: PubMed
BACKGROUND:After anterior cruciate ligament (ACL) reconstruction, there is significant atrophy of the quadriceps muscles that can limit full recovery and place athletes at risk for recurrent injuries with return to play. The cause of this muscle atrophy is not fully understood. HYPOTHESIS:Circulating levels of proatrophy, proinflammatory, and cartilage turnover cytokines and biomarkers would increase after ACL reconstruction. STUDY DESIGN:Descriptive laboratory study. METHODS:Patients (N = 18; mean age, 28 ± 2.4 years) underwent surgical reconstruction of the ACL after a noncontact athletic injury. Circulating levels of biomarkers were measured along with Short Form-12, International Knee Documentation Committee, and objective knee strength measures preoperatively and at 6 postoperative visits. Differences were tested using repeated-measures 1-way analysis of variance. RESULTS:Myostatin, TGF-β, and C-reactive protein levels were significantly increased in the early postoperative period and returned to baseline. Cartilage oligomeric matrix protein levels decreased immediately after surgery and then returned to baseline. CCL2, CCL3, CCL4, CCL5, EGF, FGF-2, IGF-1, IL-10, IL-1α, IL-1β, IL-1ra, IL-6, myoglobin, and TNF-α were not different over the course of the study. CONCLUSION:An increase in potent atrophy-inducing cytokines and corresponding changes in knee strength and functional scores were observed after ACL reconstruction. CLINICAL RELEVANCE:Although further studies are necessary, the therapeutic inhibition of myostatin may help prevent the muscle atrophy that occurs after ACL reconstruction and provide an accelerated return of patients to sport.
    • "The inhibition of myostatin has also been suggested as a treatment strategy to promote wound healing in orthopaedic surgery patients [20]. Our myostatin findings differs from the anterior cruciate ligament (ACL) study by Mendias et al., that observed higher myostatin levels three days after surgery in comparison with baseline values, and then the values declined 4 weeks after surgery similar to our findings [21]. The different findings are most likely due to differences in patient selection. "
    [Show abstract] [Hide abstract] ABSTRACT: Muscle strength is of importance for postsurgical rehabilitation. Myostatin is a growth factor that regulates the size of muscles and could thus influence muscle mass and function in the postsurgical period. The aim of the present study was to study the changes in myostatin levels during the postsurgical inflammatory period. Myostatin was analysed in serum samples from two elective surgery groups, orthopaedic surgery (n = 24) and coronary bypass patients (n = 21). The samples were collected prior to surgery and 4 and 30 days after surgery. In the orthopaedic group, the median myostatin levels decreased from 3582 ng/L prior to surgery to 774 ng/L at day 4 (p < 0.001) and to 2016 ng/L at day 30 (p < 0.001). Median CRP increased from 2.35 mg/L preoperatively to 117 mg/L at day 4 and decreased to 5.5 mg/L at day 30 in the same group. The coronary bypass group showed a similar pattern with a decrease in myostatin from 4212 ng/L to 2574 ng/L at day 4 (p < 0.001) and to 2808 ng/L at day 30 (p = 0.002). Median CRP increased from 1.80 mg/L preoperatively to 136 mg/L at day 4 and returned to 6.12 mg/L at day 30 in the coronary bypass group. There was a significant decrease in myostatin concentrations both in the early and late postsurgical period. The lowest myostatin concentration time point coincided with the highest CRP concentration time point.
    Full-text · Article · Mar 2015
    • "Following ACL transection, CRP levels peaked at 3 days following injury, exhibiting a strong correlation to human patients undergoing ACL reconstruction, where mean CRP levels increased significantly the first postoperative day, peaked on day 3, and returned to baseline levels by day 15 [37]. Similar results were also observed in the plasma of human patients undergoing ACL reconstruction , with significantly increased plasma CRP levels noted 3 days after the operation, which returned to preoperative levels by 2 weeks post-surgery [38]. In addition, these data suggest the porcine model has a similar CRP response to the human knee, and therefore may be a reasonable surrogate for studying human joint injury. "
    [Show abstract] [Hide abstract] ABSTRACT: Background The response of the joint to anterior cruciate ligament (ACL) injury has not been fully characterized. In particular, the characterization of both catabolic factors, including interleukin-6 (IL-6), interleukin-8 (IL-8), and markers of ongoing tissue damage (CRP), and anabolic factors, including vascular endothelial growth factor (VEGF), transforming growth factor β-induced (TGFβI), and the presence of CD163+ macrophages, have not been well defined. In this study, we hypothesized ACL injury would catalyze both catabolic and anabolic processes and that these would have different temporal profiles of expression. Methods Adolescent Yucatan minipigs were subjected to ACL transection. Within the joint, gene expression levels of IL-6, IL-8, VEGF, and TGFβI were quantified in the synovium, ligament, and provisional scaffold located between the torn ligament ends at days 1, 5, 9, and 14 post-injury. Macrophage infiltration was also assessed in the joint tissues over the two week period. Serum C-reactive protein (CRP) levels were measured at multiple time points between 1 hour to 14 days after injury. Results Increases in IL-6 and IL-8 gene expression peaked at day 1 after injury in the synovium and ligament. CRP levels were significantly increased at day 3 before returning to pre-injury levels. VEGF and TGFβI gene expression did not significantly increase until day 9 in the synovium and were unchanged in the other tissues. CD163+ macrophages increased in the ligament and synovium until day 9. Conclusion Taken together, these results suggest that the response within the joint is primarily catabolic in the first three days after injury, switching to a more anabolic phase by nine days after injury. The effect of medications which alter these processes may thus depend on the timing of administration after injury.
    Full-text · Article · Dec 2014
    • "Injuries, and consequent surgery, are associated with an acute hormonal and inflammatory stress response (Mendias et al., 2013), which likely contributes to the muscle atrophy process (Bonaldo & Sandri, 2013). However, by far the greatest challenge for preserving muscle mass during recovery from injury is the severe decline in the level of muscle contraction and weight bearing activity due to the limb becoming immobilised. "
    [Show abstract] [Hide abstract] ABSTRACT: Abstract The recovery from many injuries sustained in athletic training or competition often requires an extensive period of limb immobilisation (muscle disuse). Such periods induce skeletal muscle loss and consequent declines in metabolic health and functional capacity, particularly during the early stages (1-2 weeks) of muscle disuse. The extent of muscle loss during injury strongly influences the level and duration of rehabilitation required. Currently, however, efforts to intervene and attenuate muscle loss during the initial two weeks of injury are minimal. Mechanistically, muscle disuse atrophy is primarily attributed to a decline in basal muscle protein synthesis rate and the development of anabolic resistance to food intake. Dietary protein consumption is of critical importance for stimulating muscle protein synthesis rates throughout the day. Given that the injured athlete greatly reduces physical activity levels, maintaining muscle mass whilst simultaneously avoiding gains in fat mass can become challenging. Nevertheless, evidence suggests that maintaining or increasing daily protein intake by focusing upon the amount, type and timing of dietary protein ingestion throughout the day can restrict the loss of muscle mass and strength during recovery from injury. Moreover, neuromuscular electrical stimulation may be applied to evoke involuntary muscle contractions and support muscle mass maintenance in the injured athlete. Although more applied work is required to translate laboratory findings directly to the injured athlete, current recommendations for practitioners aiming to limit the loss of muscle mass and/or strength following injury in their athletes are outlined herein.
    Full-text · Article · Jul 2014
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