Associations Between Surgically-Induced Changes in Knee Loading and Biochemical Markers of Knee Inflammation

Purpose: Mechanically-induced inflammation is thought to contribute to osteoarthritis (OA) and may be a target for treatment. Substantial changes in knee load produced by high tibial osteotomy (HTO) provide a model to explore the relationship between changes in knee inflammation and load. Therefore, the objectives of this study were to 1) investigate changes in synovial fluid cytokines, chemokines, growth factors and matrix metalloproteases (MMPs), 1 year after HTO and 2) explore the associations of changes in these markers with changes in MRI measures of knee effusion-synovitis and surrogate measures of knee load during walking. Methods: Twenty-six patients (21 males, age; 54 ± 5 years, BMI; 30.2 ± 4.2 kg/m2, K/L grades: 1=3, 2=7, 3=16) with varus alignment and OA primarily affecting the medial compartment of the tibiofemoral joint underwent synovial fluid sample collection, 3-Tesla MRI and 3D gait analysis within 6 weeks prior to and 1 year after unilateral medial opening wedge HTO. Commercial Luminex Multiplex Assays were used to measure biomarker concentrations. Effusion-synovitis volume was manually segmented from MRIs, approximately 6 weeks after hardware removal, by a single reader blinded to timepoint. The external knee moments in the frontal and sagittal planes during walking were calculated using inverse dynamics and summarized as the peak adduction moment (PKAM), adduction moment impulse (KAMI) and peak flexion moment (PKFM). Postoperative measures were compared to preoperative measures by calculating mean changes with 95% confidence intervals (CI) and standardized response means (SRM). The associations between change in biomarker concentration and change in effusion-synovitis and knee moments during walking were analysed using Pearson’s correlation coefficients (r). Results: : From baseline to 1 year after HTO, there were small-to-moderate decreases (SRM 0.4-0.6) in concentrations of most MMPs, TIMP-1 and some pro-inflammatory cytokines, and small increases in growth factors (SRM < 0.2, Table 1). Effusion-synovitis, PKAM and KAMI were also reduced substantially (SRM > 1.2, Table 1). The decrease in effusion-synovitis was moderately associated (r, 95% CI) with the decreases in MMP-1 (0.44, 0.05-0.71), and IL-7 (0.41, 0.001-0.69) and increase in MIP-1β (0.47, 0.10-0.73). The decrease in PKAM was moderately associated with a decrease in MMP-1 (0.41, 0.03-0.69), IL-4 (0.42, 0.06-0.69) and IL-7 (0.59, 0.002-0.79). The decrease in KAMI was moderately associated with the decrease in MMP-1 (0.43, 0.05-0.70), IL-4 (0.39, 0.003-0.68) and IL-7 (0.53, 0.17-0.76) The decrease in KFM was moderately associated with a decrease in Flt-3L (0.42, 0.03-0.70) (Fig. 1). Conclusions: In patients with varus alignment and knee OA undergoing HTO, a decrease in knee medial compartment load is associated with a decrease in knee inflammation, with greater load reduction related to greater changes in knee effusion-synovitis, cytokines and proteases.View Large Image Figure ViewerDownload Hi-res image Download (PPT)