Inflammation and post-operative recovery in patients undergoing total knee arthroplasty-secondary analysis of a randomized controlled trial.
Reduced function persists for many patients after total knee arthroplasty (TKA). Inflammation is part of osteoarthritis' pathophysiology, and surgery induces a marked inflammatory response. We therefore wanted to explore the role of inflammation in long-term recovery after TKA, and thus conducted this secondary analysis of our randomized controlled trial (RCT) of physical rehabilitation ± progressive strength training (PST). We aimed to investigate whether (1) inflammation is associated with functional performance, knee-extension strength, and knee pain before TKA; (2) PST affects inflammation, and the inflammatory state over time; (3) baseline or surgery-induced inflammation modifies the effect of rehabilitation ± PST on change in 6-min walk test (Δ6MWT); and (4) baseline or surgery-induced inflammation is associated with Δ6MWT following TKA.



In the primary trial report's per-protocol analysis, 72/82 patients were included. Sixty had ≥1 blood sample before and after TKA, and were included in this secondary analysis. Inflammation was measured by interferon γ-inducible protein (IP)-10, soluble urokinase plasminogen activator receptor (suPAR), interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-α at baseline; day 1, week 4, 8, and 26 after TKA.



At baseline, suPAR (P = 006) was negatively associated with 6MWT. Neither baseline nor surgery-induced inflammation modified the response to rehabilitation ± PST. Only surgery-induced IL-10 was associated with Δ6MWT26 weeks-baseline(P = 0.001), also adjusted for 6MWTbaseline, age, sex and body mass index (BMI).



In this secondary analysis, only increased surgery-induced IL-10 response was associated with decreased long-term functional performance after TKA. The importance of controlling the surgery-induced immune response remains to be investigated further.



NCT01351831.
Optimed, Clinical Research Centre, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark. Electronic address: anne.langkilde@regionh.dk.
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Langkilde
Optimed, Clinical Research Centre, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark; Section for Orthopaedic and Sports Rehabilitation (SOS-R), Health Centre, Nørrebro, City of Copenhagen, Denmark; Lundbeck Foundation Centre for Fast-Track Hip and Knee Arthroplasty, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark. Electronic address: tlj26@hotmail.com.
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Jakobsen
Optimed, Clinical Research Centre, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark; Physical Medicine & Rehabilitation Research - Copenhagen (PMR-C), Clinical Research Centre, Department of Physical- and Occupational Therapy, Department of Orthopedic Surgery, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark. Electronic address: thomas.quaade.bandholm@regionh.dk.
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Bandholm
Clinical Research Centre, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark. Electronic address: Jespereugenolsen@gmail.com.
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Eugen-Olsen
Department of Infectious Disease Immunology, Statens Serum Institut, Denmark. Electronic address: THBL@ssi.dk.
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Blauenfeldt
Optimed, Clinical Research Centre, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark; Department of Biostatistics, University of Copenhagen, Denmark. Electronic address: janne.petersen.01@regionh.dk.
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Petersen
Optimed, Clinical Research Centre, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark. Electronic address: ove.andersen@regionh.dk.
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Andersen
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018771:Arthralgia / Q000209:etiology / Q000503:physiopathology / Q000532:radiotherapy; D019645:Arthroplasty, Replacement, Knee / Q000534:rehabilitation*; D015415:Biomarkers / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D008875:Middle Aged; D053580:Muscle Strength / Q000502:physiology; D020370:Osteoarthritis, Knee / Q000503:physiopathology / Q000534:rehabilitation / Q000601:surgery*; D010149:Postoperative Pain / Q000209:etiology / Q000503:physiopathology; D016059:Range of Motion, Articular / Q000502:physiology; D020127:Recovery of Function / Q000502:physiology; D055815:Young Adult
D015415:Biomarkers; D016207:Cytokines
Inflammation; Randomized controlled trial; Recovery of function; Strength training; Surgery; Total knee arthroplasty