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Objective: To introduce an integrated joint system (IJS) model of joint health and osteoarthritis (OA) pathophysiology through a systematic review of the cross-sectional relationships among three knee properties (cartilage thickness, gait mechanics, and subchondral bone mineral density)., Methods: Searches using keywords associated with the three knee properties of interest were performed in PubMed, Scopus, and Ovid databases. English-language articles reporting cross-sectional correlations between at least two knee properties in healthy or tibiofemoral OA human knees were included. A narrative synthesis of the data was conducted., Results: Of the 5600 retrieved articles, 13 were included, eight of which reported relationships between cartilage thickness and gait mechanics. The 744 tested knees were separated into three categories based on knee health: 199 healthy, 340 at-risk/early OA, and 205 late OA knees. Correlations between knee adduction moment and medial-to-lateral cartilage thickness ratios were generally positive in healthy, inconclusive in at-risk/early OA, and negative in late OA knees. Knee adduction moment was positively correlated with medial-to-lateral tibial subchondral bone mineral density ratios in knees of all health categories. One study reported a positive correlation between lateral tibial subchondral bone mineral density and femoral cartilage thickness in at-risk/early OA knees., Conclusions: The correlations identified between knee properties in this review agreed with the proposed relationship-based IJS model of OA pathophysiology. Accordingly, the IJS model could provide insights into overcoming current barriers to developing disease-modifying treatments by considering multiple aspects of OA disease, aspects that could be assessed simultaneously at an in vivo system level., (Copyright © 2018 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

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., (Copyright © 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)