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

Department of Orthopaedic Surgery, University of Michigan Medical School, Ann Arbor, Michigan.
The American Journal of Sports Medicine (Impact Factor: 4.36). 06/2013; 41(8). 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.

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    • "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. "
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    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.
    European Journal of Sport Science 07/2014; 15(1):1-10. DOI:10.1080/17461391.2014.936326 · 1.55 Impact Factor
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    ABSTRACT: Methods: All patients (n=86) who underwent knee joint ACI-P (from 1997 through 2001) with a postoperative follow-up of at least 10 years were invited for clinical and MR evaluation. Clinical outcomes analysis included pre-and postoperative Lysholm and numeric analog scale (NAS) for pain (10=worst, 0=best). Radiographic analysis included postoperative T2-weighted mapping of the RT, RT-associated regions, and healthy control cartilage; MOCART (magnetic resonance observation of cartilage repair tissue) score; a modified Knee Osteoarthritis Scoring System (mKOSS; 0=best, 15=worst) score; as well as numeric grading for subjective RT and whole knee joint evaluation (1=best, 6=worst).
    The American Journal of Sports Medicine 06/2014; 42(8). DOI:10.1177/0363546514536682 · 4.36 Impact Factor
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    ABSTRACT: Objective: There is an increased risk of developing knee osteoarthritis (OA) following anterior cruciate ligament (ACL) injury. Biomarkers may provide diagnostic, prognostic, or burden of disease indicators of OA before radiographic changes become apparent. Unfortunately, there has been no systematic review to clarify which biomarkers may be most informative following injury. Therefore, this review critically investigated existing studies of OA-related biomarkers in ACL-deficient (ACL-D) and reconstructed (ACL-R) patients to summarize the current evidence and identify knowledge gaps. Design: A systematic review of the literature in Web of Science and PubMed databases (1960-June 2014) was performed. All English-language case-control and longitudinal studies assessing OA-related biomarkers in ACL-D and ACL-R patients were considered. Data regarding biomarker changes over time within ACL-D and ACL-R patients as well as differences in ACL-D/ACL-R patients compared with a control group were extracted from pertinent studies. Results: A descriptive summary of 20 included studies was produced. In ACL-D patients compared with controls, synovial fluid biomarkers indicated elevated collagen turnover, while the inflammatory cytokine response was inconclusive. In ACL-R patients, serum concentrations indicated decreased collagen breakdown, but urine concentrations were indicative of greater collagen breakdown when compared to controls. Compared to preoperative values, the overall inflammatory cytokine response measured with synovial fluid biomarkers increased while plasma biomarkers did not change following reconstruction. Conclusion: Patients with ACL-D or ACL-R have altered biomarkers indicative of OA. More research with standardized reporting is needed to effectively determine which biomarkers are the most indicative for OA development and progression following ACL injury.
    Osteoarthritis and Cartilage 09/2014; 23(1). DOI:10.1016/j.joca.2014.09.004 · 4.17 Impact Factor
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