Inflammation and Post-operative Recovery in Patients undergoing Total Knee Arthroplasty- Secondary Analysis of a Randomized Controlled Trial

OBJECTIVE: 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 of physical rehabilitation +/- progressive strength training (PST). We aimed to investigate whether A) inflammation is associated with functional performance, knee-extension strength, and knee pain before TKA; B) PST affects inflammation, and the inflammatory state over time; C) baseline or surgery-induced inflammation modifies the effect of rehabilitation +/- PST on change in 6-minute walk test (Δ6MWT); and D) baseline or surgery-induced inflammation is associated with Δ6MWT following TKA.

DESIGN: 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.

RESULTS: At baseline, suPAR (p=0.03) 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 BMI.

CONCLUSION: 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.

TRIAL IDENTIFICATION: NCT01351831.