Knee varus malalignment increases medial knee compartment loading and is associated with knee osteoarthritis (OA) progression and severity1. Altered biomechanical loading and dysregulation of joint tissue biology drive OA progression, but mechanistic links between these factors are lacking. Subchondral bone structural changes are biomechanically driven, involve bone resorption, immune cell influx, angiogenesis, and sensory nerve invasion, and contribute to joint destruction and pain2. We have investigated mechanisms underlying this involving RANKL and alkaline phosphatase (ALP), which reflect bone resorption and mineralisation respectively3 and the axonal guidance factor Sema3A. Sema3A is osteotropic, expressed by mechanically sensitive osteocytes, and an inhibitor of sensory nerve, blood vessel and immune cell invasion4. Sema3A is also differentially expressed in human OA bone5.HYPOTHESIS: Medial knee compartment overloading in varus knee malalignment patients causes dysregulation of bone derived Sema3A signalling directly linking joint biomechanics to pathology and pain. Synovial fluid obtained from 30 subjects with medial knee OA (KL grade II-IV) undergoing high tibial osteotomy surgery (HTO) was analysed by mesoscale discovery and ELISA analysis for inflammatory, neural and bone turnover markers. 11 of these patients had been previously analysed in a published patient-specific musculoskeletal model6 of gait estimating joint contact location, pressure, forces, and medial-lateral condyle load distribution in a published data set included in analyses. Data analysis was performed using Pearson's correlation matrices and principal component analyses. Principal Components (PCs) with eigenvalues greater than 1 were analysed.Abstract
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Principal Component Analysis (PCA) is a useful method for analysing human motion data. The objective of this study was to use PCA to quantify the biggest variance in knee kinematics waveforms between a Non-Pathological (NP) group and individuals awaiting High Tibial Osteotomy (HTO) surgery. Thirty knees (29 participants) who were scheduled for HTO surgery were included in this study. Twenty-eight NP volunteers were recruited into the study. Human motion analysis was performed during level gait using a modified Cleveland marker set. Subjects walked at their self-selected speed for a minimum of 6 successful trials. Knee kinematics were calculated within Visual3D (C-Motion). The first three Principal Components (PCs) of each input variable were selected. Single-component reconstruction was performed alongside representative extremes of each PC to aid interpretation of the biomechanical feature reconstructed by each component.Abstract
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Valgus high tibial osteotomy (HTO) represents an effective treatment for patients with medial compartment osteoarthritis (OA) in a varus knee. However, the mechanisms which cause this clinical improvement are unclear. Previous studies suggest a wider stance gait can reduce medial compartment loading via reduction in the external knee adduction moment (KAM); a measure implicated in progression of medial compartment OA. This study aimed to measure whether valgus HTO is associated with a postoperative increase in static stance width. 32 patients, recruited in the Biomechanics and Bioengineering Centre Versus Arthritis HTO study, underwent valgus (medial opening wedge) HTO. Weightbearing pre- and post- operative radiographs were taken showing both lower limbs. The horizontal distance, measured from a fixed point on the right talus to the corresponding point on the left, was divided by the talus width to give a standardised “stance width” for each radiograph. The difference between pre- and post- operative stance width was compared for each patient using a paired sample t-test.Abstract
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Explore whether high tibial osteotomy (HTO) changes knee contact forces and to explore the relationship between the external knee adduction moment (EKAM) pre and 12 months post HTO. Three-dimensional gait analysis was performed on 17 patients pre and 12-months post HTO using a modified Cleveland marker-set. Tibiofemoral contact forces were calculated in SIMM. The scaled musculoskeletal model integrated an extended knee model allowing for 6 degrees of freedom in the tibiofemoral and patellofemoral joint. Joint angles were calculated using inverse kinematics then muscle and contact forces and secondary knee kinematics were estimated using the COMAC algorithm. Paired samples t-test were performed using SPSS version 25 (SPSS Inc., USA). Testing for normality was undertaken with Shapiro-Wilk. Pearson correlations established the relationships between EKAM1 to medial KCF1, and EKAM2 to medial KCF2, pre and post HTO.Abstract
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