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Summary Objective To test if sagittal plane gait mechanics parameters and serum inflammation levels differ between healthy asymptomatic subjects and asymptomatic subjects with magnetic resonance imaging (MRI) evidence of cartilage loss. Design Gait mechanics and resting serum tumor necrosis factor-α (TNFα) concentrations were measured for two groups of asymptomatic subjects recruited for a previous study: Pre-Osteoarthritis (OA) subjects had MRI evidence of partial- or full-thickness knee cartilage loss in at least one compartment ( n = 52 (30 female), 1.7 ± 0.1 m, 85.3 ± 18.9 kg, 44 ± 11 years); Control subjects had no MRI features of cartilage loss, osteophytes, bone marrow lesions, nor meniscal pathology in either knee ( n = 26 (13 female), 1.7 ± 0.1 m, 74.6 ± 14.9 kg, 34 ± 10 years). Discrete measures of sagittal plane gait kinematics and kinetics were compared between subject groups and adjusted for age and body mass index (BMI) using analysis of covariance (ANCOVA). Serum TNFα concentrations were compared between groups using bootstrap t -test. Results The Pre-OA group had less extended knees ( P = 0.021) and decreased maximum external knee extension moment ( P = 0.0062) in terminal stance during gait, as well as increased resting serum TNFα concentration ( P = 0.040) as compared to Control subjects. There were no group differences in heel strike flexion angle ( P = 0.14), in maximum knee flexion moment ( P = 0.91), nor in first peak knee adduction moment (KAM) (post-hoc analysis, P = 0.39). Conclusions The finding that asymptomatic subjects with cartilage loss had gait and inflammatory characteristics similar to those previously reported in symptomatic OA patients supports the idea that there are specific mechanical and biological factors that precede the onset of knee pain in the pathogenesis of OA.

s / Osteoarthritis and Cartilage 22 (2014) S57–S489 S97 Results: Table 1 presents the correlation coefficients between the radiographic grading sub scores and kinematic parameters. Correlations with the frontal plane kinematics showed to be the strongest, with R values going from 0.641 to 0.724. Furthermore, joint space demonstrated to be strongly correlated with frontal plane kinematics based on the high weight of this x-ray sub-score in the MLR. Results in the transverse and sagittal planes showed negative correlations ranging from -0.440 to -0.497. Results show that FO is the sub-score that is the most strongly correlated (in this case negative correlation) with kinematic parameters in the transverse plane. A residues analysis was also conducted to confirm a random distribution of the residues around zero (figure 1). The absence of error patterns means that the choice of a linear regression fits well the relationship between the kinematic parameters and radiographic sub scores. Conclusions: The frontal plane presented the strongest correlation between the x-ray grading scale and the knee kinematic parameters. This analysis showed that the higher the x-ray sub scores are, meaning a more advanced state of the disease, the higher the varus angle parameters during gait are. This strengthens the link between a dynamic varus alignment and medial TF compartment OA progression. Interestingly, joint space showed a strong influence on the correlations with kinematic parameters in frontal plane. The transverse and sagittal plane both showed a negative correlation, meaning that the higher the x-ray sub scores are, the lower the kinematic parameters will be. In the sagittal plane this translate to a more fixed flexion adaptation strategy to protect the knee and in the transverse plan to a more internally rotated tibia. An offset towards internal rotation was previously linked to faster progression of OA which could also support the link with higher FO score. Further investigations, with a larger and more homogeneous sample group should lead to stronger correlations and should better define the relationships between the knee 3D kinematic parameters and radiographic grading system. This study supports the involvement of dynamic biomechanical factors in the progression of the disease. Results give new insights to develop personalized treatment plan based on kinematic parameters and x-ray OA grading scales to potentially limit the progression of the disease. Plane Kinematic Parameter Radiographic Scorn (Estimate Coefficient) R^2 R p-value Abduction Adduction (frontal) Mean 0-10% of GC FA_TA (-0.212) JS (1.608) FO (0.971) TE (2.139) 0.383 0.619 0.005 Mean 1030% of GC FA_TA (-0.357) JS (1.663) FO (0.808) TE (1.406) 0.412 0.641 0.002 Mean 3050% of GC FA_TA (-0.268) JS (1.808) FO (1.051) TE (0.865) 0.524 0.724