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Osteoarthritis year in review 2021: mechanics

  • J. Harlaar
    Correspondence
    Address correspondence and reprint requests to: J. Harlaar, Dept. Biomechanical Engineering, Delft University of Technology, Delft, the Netherlands.
    Affiliations
    Dept. Biomechanical Engineering, Delft University of Technology, Delft, the Netherlands

    Dept. Orthopedics & Sports Medicine, Erasmus MC University Medical Center, Rotterdam, the Netherlands
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  • E.M. Macri
    Affiliations
    Dept. Orthopedics & Sports Medicine, Erasmus MC University Medical Center, Rotterdam, the Netherlands

    Dept. General Practice, Erasmus MC University Medical Center, Rotterdam, the Netherlands
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  • M. Wesseling
    Affiliations
    Dept. Biomechanical Engineering, Delft University of Technology, Delft, the Netherlands
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Open AccessPublished:January 23, 2022DOI:https://doi.org/10.1016/j.joca.2021.12.012

      Summary

      Osteoarthritis (OA) has a complex, heterogeneous and only partly understood etiology. There is a definite role of joint cartilage pathomechanics in originating and progressing of the disease. Although it is still not identified precisely enough to design or select targeted treatments, the progress of this year's research demonstrates that this goal became much closer. On multiple scales - tissue, joint and whole body - an increasing number of studies were done, with impressive results. (1) Technology based instrument innovations, especially when combined with machine learning models, have broadened the applicability of biomechanics. (2) Combinations with imaging make biomechanics much more precise & personalized. (3) The combination of Musculoskeletal & Finite Element Models yield valid personalized cartilage loads. (4) Mechanical outcomes are becoming increasingly meaningful to inform and evaluate treatments, including predictive power from biomechanical models. Since most recent advancements in the field of biomechanics in OA are at the level of a proof op principle, future research should not only continue on this successful path of innovation, but also aim to develop clinical workflows that would facilitate including precision biomechanics in large scale studies. Eventually this will yield clinical tools for decision making and a rationale for new therapies in OA.

      Keywords

      Introduction

      Osteoarthritis (OA) is a serious and complex condition that has long been recognized as a whole organ disease, or collection of diseases
      • Loeser R.F.
      • Goldring S.R.
      • Scanzello C.R.
      • Goldring M.B.
      Osteoarthritis: a disease of the joint as an organ.
      ,
      • Deveza L.A.
      • Loeser R.F.
      Is osteoarthritis one disease or a collection of many?.
      . Despite many potential OA phenotypes
      • Deveza L.A.
      • Loeser R.F.
      Is osteoarthritis one disease or a collection of many?.
      ,
      • Hunter D.J.
      • Bierma-Zeinstra S.
      Osteoarthritis.
      , a key overarching etiological factor in OA-related structural damage and symptoms relates to mechanics
      • Hunter D.J.
      • Bierma-Zeinstra S.
      Osteoarthritis.
      ,
      • Felson D.T.
      Osteoarthritis as a disease of mechanics.
      . Not surprisingly, the concept of mechanics is often operationalized – and thus investigated and understood – differently among various fields of research
      • Andriacchi T.P.
      • Griffin T.M.
      • Loeser R.F.
      • Chu C.R.
      • Roos E.M.
      • Hawker G.A.
      • et al.
      Bridging disciplines as a pathway to finding new solutions for osteoarthritis a collaborative program presented at the 2019 orthopaedic research society and the osteoarthritis research society international.
      . On account of work done in this field to date, this annual presentation often focuses on joint-level, primarily knee, biomechanics. However, through growing interdisciplinary collaborations and novel research methods, new evidence regarding mechanical characteristics in OA reflects a bridging across multiple perspectives, and an expansion towards linking multiple biological scales, from the molecular level through to the level of the ‘whole person’
      • Andriacchi T.P.
      • Griffin T.M.
      • Loeser R.F.
      • Chu C.R.
      • Roos E.M.
      • Hawker G.A.
      • et al.
      Bridging disciplines as a pathway to finding new solutions for osteoarthritis a collaborative program presented at the 2019 orthopaedic research society and the osteoarthritis research society international.
      .
      For this Year in Review, we conducted a narrative review of evidence published in the past year to highlight key new findings relating to mechanics and OA.

      Methods

      We performed a literature search using Pubmed. We searched for peer-reviewed publications published between April 1, 2020 and April 1, 2021. Our search terms were based on key words (“osteoarthritis”) AND (“biomechanics” OR “mechanics” OR “gait”), including related keywords and MeSH terms (Box 1). Our initial search yielded 958 titles, from which we selected 398 publications of interest. Several themes emerged, and from those we narrowed our focus to emerging evidence within four key topics: (i) joint-level biomechanics; (ii) computational modeling and methodology; (iii) wearable technology; and (iv) use of mechanics as outcomes in clinical research. Fig. 1 presents a graphical summary of data acquisition methods and modeling modalities that have been highlighted in this review.
      ((“biomechanical phenomena”[MeSH Terms] OR (“biomechanical”[tiab] AND “phenomena”[tiab]) OR “biomechanical phenomena”[tiab] OR “biomechanic”[tiab] OR “biomechanics”[tiab] OR “biomechanical”[tiab] OR “biomechanically”[tiab]) OR (“mechanical”[tiab] OR “mechanically”[tiab] OR “mechanicals”[tiab] OR “mechanics”[MeSH Terms] OR “mechanics“[tiab] OR “mechanic”[tiab]) OR (“gait”[MeSH Terms] OR “gait”[tiab])) AND (“osteoarthritis”[MeSH Terms] OR “osteoarthritis”[tiab] OR “osteoarthritides”[tiab]) AND (2020/04/01:2021/04/01[Date - Publication])
      Fig. 1
      Fig. 1Graphical summary of the OA Year in Review, Mechanics: Aim is to quantify or understand cartilage load (in the middle) in the context of OA as a target, recognizing different levels of precision. Data acquisition methods (blue outlines): (A) wearables, (B) motion capture, and (C) imaging; Modeling modalities (green outlines): (D) deep learning networks, (E) musculoskeletal models, and (F) finite element models.

      Results

      Joint-level biomechanics, knee OA

      As in previous years, the knee was the most studied joint, and different data acquisition methods and modelling modalities were used (Fig. 1). In this section we highlight insights gained primarily from joint-level biomechanical studies using motion capture and imaging, which were most prominent this year. Knee OA studies using other methodologies are highlighted in other sections.
      This year, several studies focussed on differentiating biomechanics in different stages of knee OA. For example, using fluoroscopy, more severe knee OA (n = 39) was associated with increased tibial external rotation and posterior translation during squatting
      • Ikuta F.
      • Yoneta K.
      • Miyaji T.
      • Kidera K.
      • Yonekura A.
      • Osaki M.
      • et al.
      Knee kinematics of severe medial knee osteoarthritis showed tibial posterior translation and external rotation: a cross-sectional study.
      , During gait initiation, individuals with moderate and severe knee OA (n = 48) demonstrated reduced centre of pressure displacements and slower, longer lasting anticipatory postural adjustments
      • da Silva Soares F.
      • Moreira V.
      • Alves L.V.
      • Dionisio V.C.
      What is the influence of severity levels of knee osteoarthritis on gait initiation?.
      . Individuals with knee OA and joint instability (n = 20) responded to gait perturbations with higher knee flexion angles and greater muscle co-contractions compared to stable OA knees and controls
      • Schrijvers J.C.
      • van den Noort J.C.
      • van der Esch M.
      • Harlaar J.
      Neuromechanical assessment of knee joint instability during perturbed gait in patients with knee osteoarthritis.
      . These studies suggest that biomechanics may differ across stages of OA.
      New evidence, including relatively large observational studies, demonstrated the clinical importance of kinetic changes in knee OA. A study of muscle activation patterns in individuals with knee OA (n = 54) demonstrated that higher hamstrings activation, greater lateral co-contraction, and prolonged quadriceps and hamstrings stance activation was associated with undergoing total knee arthroplasty 5–8 years later, suggesting higher and more sustained knee loading in these individuals
      • Hatfield G.L.
      • Costello K.E.
      • Astephen Wilson J.L.
      • Stanish W.D.
      • Hubley-Kozey C.L.
      Baseline gait muscle activation patterns differ for osteoarthritis patients who undergo total knee arthroplasty five to eight years later from those who do not.
      . Sustained knee loading was also suggested by the Multicenter Osteoarthritis Study (MOST) (n = 1576), showing less dynamic and more sustained vertical ground reaction force (vGRF) patterns in individuals with knee OA compared to controls, adjusting for gait speed
      • Costello K.E.
      • Felson D.T.
      • Neogi T.
      • Segal N.A.
      • Lewis C.E.
      • Gross K.D.
      • et al.
      Ground reaction force patterns in knees with and without radiographic osteoarthritis and pain: descriptive analyses of a large cohort (the Multicenter Osteoarthritis Study).
      . Another large observational study of individuals with medial knee OA (n = 691) showed a lower cadence was associated with higher knee loading per step, controlling for gait speed
      • Hart H.F.
      • Birmingham T.B.
      • Primeau C.A.
      • Pinto R.
      • Leitch K.
      • Giffin J.R.
      Associations between cadence and knee loading in patients with knee osteoarthritis.
      . The results suggest that increasing cadence from 100 to 120 steps/min could lead to a 25% decrease in knee adduction moment (KAM) angular impulse. Gait retraining focused on cadence may thus represent a novel intervention to improve mechanical loading in knee OA, which might mitigate symptoms or slow disease progression.
      Aiming at the prediction of more detailed biomechanical measures, novel methodologies were presented. To easily estimate knee contact forces, one study acquired in vivo force measures in instrumented knee implants, then used machine learning to predict medial tibiofemoral peak contact forces from gait speed, peak KAM and peak vertical knee reaction force
      • Brisson N.M.
      • Gatti A.A.
      • Damm P.
      • Duda G.N.
      • Maly M.R.
      Association of machine learning based predictions of medial knee contact force with cartilage loss over 2.5 years in knee osteoarthritis.
      . When predicting peak medial contact force in knee OA participants, this model explained 35% of the variance in reduced medial tibial cartilage volume over 2.5 years
      • Brisson N.M.
      • Gatti A.A.
      • Damm P.
      • Duda G.N.
      • Maly M.R.
      Association of machine learning based predictions of medial knee contact force with cartilage loss over 2.5 years in knee osteoarthritis.
      . This study demonstrates that higher loads predict future cartilage damage, but also that machine learning may facilitate less invasive and more accurate methods for acquiring biomechanical measures that relate to cartilage degeneration.
      Caution is indicated when interpreting biomechanical measures. Ismailidis et al.
      • Ismailidis P.
      • Egloff C.
      • Hegglin L.
      • Pagenstert G.
      • Kernen R.
      • Eckardt A.
      • et al.
      Kinematic changes in patients with severe knee osteoarthritis are a result of reduced walking speed rather than disease severity.
      report differences in sagittal plane kinematics mainly resulted from reduced walking speed in knee OA, indicating this should be controlled for. However, despite correcting for gait speed, differences in kinematics and kinetics often persist in individuals with OA
      • Costello K.E.
      • Felson D.T.
      • Neogi T.
      • Segal N.A.
      • Lewis C.E.
      • Gross K.D.
      • et al.
      Ground reaction force patterns in knees with and without radiographic osteoarthritis and pain: descriptive analyses of a large cohort (the Multicenter Osteoarthritis Study).
      ,
      • Hart H.F.
      • Birmingham T.B.
      • Primeau C.A.
      • Pinto R.
      • Leitch K.
      • Giffin J.R.
      Associations between cadence and knee loading in patients with knee osteoarthritis.
      . External factors should also be considered, as inter-laboratory results differ in kinematics, kinetics and muscle activity patterns in individuals with knee OA, potentially limiting generalizability among studies
      • Schrijvers J.C.
      • Rutherford D.
      • Richards R.
      • van den Noort J.C.
      • van der Esch M.
      • Harlaar J.
      Inter-laboratory comparison of knee biomechanics and muscle activation patterns during gait in patients with knee osteoarthritis.
      .

      Joint-level biomechanics, anterior cruciate ligament (ACL) studies

      Given the elevated risk for developing OA following traumatic knee injury, anterior cruciate ligament (ACL) studies continue to serve a prominent role in knee OA research. Below we highlight several studies linking altered biomechanics with both structural and symptomatic findings, which may explain the elevated risk for developing post-traumatic knee OA.
      In individuals with ACL-deficient knees up to 1 year post-injury, magnetic resonance imaging (MRI) was acquired before and after 20 min of walking (double echo steady state) to measure changes in load-related compressive strain
      • Crook B.S.
      • Collins A.T.
      • Lad N.K.
      • Spritzer C.E.
      • Wittstein J.R.
      • DeFrate L.E.
      Effect of walking on in vivo tibiofemoral cartilage strain in ACL-deficient versus intact knees.
      . Cartilage strain was higher in the medial intercondylar notch and tibial plateau regions in the ACL-deficient compared to the contralateral knee (6 vs 2 %). This suggests that ACL injury may result in either a change in mechanical loading pattern or an increased susceptibility to cartilage loading. Evidence for the former was found in a study of individuals up to 2 years following ACL reconstruction
      • Li A.K.
      • Ochoa J.K.
      • Pedoia V.
      • Amano K.
      • Souza R.B.
      • Li X.
      • et al.
      Altered tibiofemoral position following ACL reconstruction is associated with cartilage matrix changes: a voxel-based relaxometry analysis.
      . Compared to contralateral knees, reconstructed knees demonstrated 1–2 mm greater anterior tibial translation; further, increased translation was associated with longer T1ρ and T2 relaxation times
      • Li A.K.
      • Ochoa J.K.
      • Pedoia V.
      • Amano K.
      • Souza R.B.
      • Li X.
      • et al.
      Altered tibiofemoral position following ACL reconstruction is associated with cartilage matrix changes: a voxel-based relaxometry analysis.
      . In another study in ACL-deficient knees, lower KAM angular impulse was related to longer T2 relaxation times in the medial tibiofemoral compartment and shorter times in the lateral compartment
      • Wellsandt E.
      • Kallman T.
      • Golightly Y.
      • Podsiadlo D.
      • Dudley A.
      • Vas S.
      • et al.
      Knee joint unloading and daily physical activity associate with cartilage T2 relaxation times 1 month after ACL injury.
      . Three months after ACL reconstruction, inter-limb differences in peak KAM and peak knee flexion moments were related to deep layer tibiofemoral joint T2 relaxation times
      • Williams J.R.
      • Neal K.
      • Alfayyadh A.
      • Lennon K.
      • Capin J.J.
      • Khandha A.
      • et al.
      Knee cartilage T(2) relaxation times 3 Months after ACL reconstruction are associated with knee gait variables linked to knee osteoarthritis.
      . Two years after reconstruction, increased knee flexion and external rotation angles at heel strike were related to patellofemoral deep cartilage matrix disruption, as assessed by ultra short echo time T2∗ MRI
      • Williams A.A.
      • Erhart-Hledik J.C.
      • Asay J.L.
      • Mahtani G.B.
      • Titchenal M.R.
      • Lutz A.M.
      • et al.
      Patient-reported outcomes and knee mechanics correlate with patellofemoral deep cartilage UTE-T2∗ 2 Years after anterior cruciate ligament reconstruction.
      . Collectively, these studies suggest altered loading is associated with early cartilage changes following ACL injury.
      In addition to the association between altered biomechanics and early structural changes, researchers also found a prospective link between biomechanics and symptoms
      • Erhart-Hledik J.C.
      • Chu C.R.
      • Asay J.L.
      • B. Mahtani G.
      • Andriacchi T.P.
      Vertical ground reaction force 2 years after anterior cruciate ligament reconstruction predicts 10-year patient-reported outcomes.
      . Two years after ACL reconstruction, two distinct patterns of gait were seen: approximately half of the sample (n = 13) showed reduced early stance peak vGRF during gait compared to the contralateral side, and the other half (n = 15) showed increased peak vGRF. Despite no mean differences in vGRF compared to the contralateral side, higher vGRF at 2 years was associated with worse patient-reported outcome scores 10 years after reconstruction. This study suggests that following ACL injuries, as in individuals with knee OA, simple biomechanical measures may predict long-term outcomes.

      Joint-level biomechanics, other joints

      Despite the usual focus on knee OA research as in previous years, we acknowledge the work done this year to elucidate the role of biomechanics in other joints affected by OA. For example, 42 individuals with hip OA demonstrated altered kinematics during stair climbing compared to 30 controls
      • Popovic T.
      • Samaan M.A.
      • Link T.M.
      • Majumdar S.
      • Souza R.B.
      Patients with symptomatic hip osteoarthritis have altered kinematics during stair ambulation.
      . However, another study showed that among 55 individuals with hip OA, variability in hip joint kinematics during gait was not explained by pain severity or radiographic OA severity
      • Hall M.
      • Fox A.
      • Bonacci J.
      • Metcalf B.R.
      • Pua Y.H.
      • Diamond L.E.
      • et al.
      Hip joint kinematics and segment coordination variability according to pain and structural disease severity in hip osteoarthritis.
      , calling into question what factors might be driving hip OA–related changes in kinematics.
      More distally, 52 individuals with isolated ankle OA showed altered ankle kinematics and kinetics during walking compared to 25 controls, however there were no changes in distal foot biomechanics, suggesting there was no distal compensation for mechanical ankle dysfunction
      • Eerdekens M.
      • Deschamps K.
      • Wuite S.
      • Matricali G.A.
      Loss of mechanical ankle function is not compensated by the distal foot joints in patients with ankle osteoarthritis.
      . A systematic review of midfoot OA revealed that, compared to controls, individuals had more foot protonation, more first ray mobility, less subtalar and first metatarsophalangeal joint range of motion, longer central metatarsals, and during gait they had increased peak plantar pressures, pressure time integrals and contact times in the heel and midfoot
      • Lithgow M.J.
      • Munteanu S.E.
      • Buldt A.K.
      • Arnold J.B.
      • Kelly L.A.
      • Menz H.B.
      Foot structure and lower limb function in individuals with midfoot osteoarthritis: a systematic review.
      . .
      Biomechanics may also play a role in OA of non-weightbearing joints. In glenohumeral OA, resting scapula position did not differ from controls, however during shoulder flexion with internal rotation, scapula anterior tilt was greater, possibly as an adaptation to limited glenohumeral motion
      • Lädermann A.
      • Athwal G.S.
      • Bothorel H.
      • Collin P.
      • Mazzolari A.
      • Raiss P.
      • et al.
      Scapulothoracic alignment alterations in patients with walch type B osteoarthritis: an in vivo dynamic analysis and prospective comparative study.
      . To more accurately measure finger, hand and wrist forces, wearable sensors
      • Riddle M.
      • MacDermid J.
      • Robinson S.
      • Szekeres M.
      • Ferreira L.
      • Lalone E.
      Evaluation of individual finger forces during activities of daily living in healthy individuals and those with hand arthritis.
      and multi-scale computational models
      • Faudot B.
      • Milan J.L.
      • Goislard de Monsabert B.
      • Le Corroller T.
      • Vigouroux L.
      Estimation of joint contact pressure in the index finger using a hybrid finite element musculoskeletal approach.
      were developed this year, enabling future studies to understand the role of mechanics in hand OA and the effects of joint protection strategies.

      Computational modelling

      For several years, in silico modelling has been employed to study biomechanics with the potential to inform clinical decision making
      • Andriacchi T.P.
      • Mundermann A.
      • Smith R.L.
      • Alexander E.J.
      • Dyrby C.O.
      • Koo S.
      A framework for the in vivo pathomechanics of osteoarthritis at the knee.
      . Models at different scales have been developed, from whole body to joint, tissue and cell levels. Based on input from acquired data, mostly motion capture and imaging, modelling can provide tissue scale biomechanical measures to quantify cartilage load (Fig. 1). Types of models include musculoskeletal, discrete element and finite element models.
      Musculoskeletal models enable researchers to determine joint contact forces. Within the past year, several papers employed musculoskeletal models to answer clinical questions
      • Wellsandt E.
      • Khandha A.
      • Capin J.
      • Buchanan T.S.
      • Snyder-Mackler L.
      Operative and nonoperative management of anterior cruciate ligament injury: differences in gait biomechanics at 5 years.
      • Ding Z.
      • Jarvis H.L.
      • Bennett A.N.
      • Baker R.
      • Bull A.M.J.
      Higher knee contact forces might underlie increased osteoarthritis rates in high functioning amputees: a pilot study.
      • Gaffney B.M.M.
      • Harris-Hayes M.
      • Clohisy J.C.
      • Harris M.D.
      Effect of simulated rehabilitation on hip joint loading during single limb squat in patients with hip dysplasia.
      • Kawada M.
      • Takeshita Y.
      • Miyazaki T.
      • Nakai Y.
      • Hata K.
      • Nakatsuji S.
      • et al.
      Contribution of hip and knee muscles to lateral knee stability during gait.
      • Sepp L.
      • Baum B.S.
      • Nelson-Wong E.
      • Silverman A.
      Hip joint contact forces during running with a transtibial amputation.
      • Song K.
      • Gaffney B.M.M.
      • Shelburne K.B.
      • Pascual-Garrido C.
      • Clohisy J.C.
      • Harris M.D.
      Dysplastic hip anatomy alters muscle moment arm lengths, lines of action, and contributions to joint reaction forces during gait.
      • Starkey S.C.
      • Lenton G.K.
      • Saxby D.J.
      • Hinman R.S.
      • Bennell K.L.
      • Wrigley T.
      • et al.
      Effect of exercise on knee joint contact forces in people following medial partial meniscectomy: a secondary analysis of a randomised controlled trial.
      • van Drongelen S.
      • Wesseling M.
      • Holder J.
      • Meurer A.
      • Stief F.
      Knee load distribution in hip osteoarthritis patients after total hip replacement.
      • Vignos M.F.
      • Smith C.R.
      • Roth J.D.
      • Kaiser J.M.
      • Baer G.S.
      • Kijowski R.
      • et al.
      Anterior cruciate ligament graft tunnel placement and graft angle Are primary determinants of internal knee mechanics after reconstructive surgery.
      • Sritharan P.
      • Schache A.G.
      • Culvenor A.G.
      • Perraton L.G.
      • Bryant A.L.
      • Crossley K.M.
      Between-limb differences in patellofemoral joint forces during running at 12 to 24 Months after unilateral anterior cruciate ligament reconstruction.
      , with a focus on joint contact forces in individuals at risk for OA. In individuals with transtibial amputations, increased contact forces at the hip
      • Sepp L.
      • Baum B.S.
      • Nelson-Wong E.
      • Silverman A.
      Hip joint contact forces during running with a transtibial amputation.
      and knee
      • Ding Z.
      • Jarvis H.L.
      • Bennett A.N.
      • Baker R.
      • Bull A.M.J.
      Higher knee contact forces might underlie increased osteoarthritis rates in high functioning amputees: a pilot study.
      joints were reported. In individuals with developmental dysplasia of the hip, an altered contribution of muscles to hip contact forces was reported
      • Song K.
      • Gaffney B.M.M.
      • Shelburne K.B.
      • Pascual-Garrido C.
      • Clohisy J.C.
      • Harris M.D.
      Dysplastic hip anatomy alters muscle moment arm lengths, lines of action, and contributions to joint reaction forces during gait.
      as well as changes in hip contact forces resulting from rehabilitation exercises
      • Gaffney B.M.M.
      • Harris-Hayes M.
      • Clohisy J.C.
      • Harris M.D.
      Effect of simulated rehabilitation on hip joint loading during single limb squat in patients with hip dysplasia.
      . After total hip arthroplasty, small but significantly increased lateral knee loading in the contralateral leg was reported
      • van Drongelen S.
      • Wesseling M.
      • Holder J.
      • Meurer A.
      • Stief F.
      Knee load distribution in hip osteoarthritis patients after total hip replacement.
      .
      A major limitation of computational modelling studies is small sample sizes. Only three modelling studies in this review included more than 20 participants
      • Wellsandt E.
      • Khandha A.
      • Capin J.
      • Buchanan T.S.
      • Snyder-Mackler L.
      Operative and nonoperative management of anterior cruciate ligament injury: differences in gait biomechanics at 5 years.
      ,
      • Starkey S.C.
      • Lenton G.K.
      • Saxby D.J.
      • Hinman R.S.
      • Bennell K.L.
      • Wrigley T.
      • et al.
      Effect of exercise on knee joint contact forces in people following medial partial meniscectomy: a secondary analysis of a randomised controlled trial.
      ,
      • Sritharan P.
      • Schache A.G.
      • Culvenor A.G.
      • Perraton L.G.
      • Bryant A.L.
      • Crossley K.M.
      Between-limb differences in patellofemoral joint forces during running at 12 to 24 Months after unilateral anterior cruciate ligament reconstruction.
      . Starkey et al.
      • Starkey S.C.
      • Lenton G.K.
      • Saxby D.J.
      • Hinman R.S.
      • Bennell K.L.
      • Wrigley T.
      • et al.
      Effect of exercise on knee joint contact forces in people following medial partial meniscectomy: a secondary analysis of a randomised controlled trial.
      used data from a randomized clinical trial (RCT) to determine the effect of physical exercise on knee contact forces. They included 41 patients following partial medial meniscectomy, and included participant-specific information using electromyography (EMG). Although exercise did not affect knee contact forces, the large within-patient variability suggested that individual changes are important to consider. Wellsandt et al.
      • Wellsandt E.
      • Khandha A.
      • Capin J.
      • Buchanan T.S.
      • Snyder-Mackler L.
      Operative and nonoperative management of anterior cruciate ligament injury: differences in gait biomechanics at 5 years.
      also estimated knee contact forces using an EMG-driven workflow in individuals 5 years after ACL injury treated either surgically (n = 40) or non-surgically (n = 17). Individuals treated non-surgically had increased medial compartment contact forces compared to the surgical group, despite no differences in radiographic tibiofemoral OA prevalence. Sritharan et al.
      • Sritharan P.
      • Schache A.G.
      • Culvenor A.G.
      • Perraton L.G.
      • Bryant A.L.
      • Crossley K.M.
      Between-limb differences in patellofemoral joint forces during running at 12 to 24 Months after unilateral anterior cruciate ligament reconstruction.
      compared patellofemoral joint contact forces between injured and non-injured limbs in 55 participants following ACL reconstruction. Despite no difference in lower limb kinematics, patellofemoral joint contact forces were lower in ACL-reconstructed limbs.
      The use of finite element models in OA research was less common than musculoskeletal models this past year
      • Kitamura K.
      • Fujii M.
      • Ikemura S.
      • Hamai S.
      • Motomura G.
      • Nakashima Y.
      Does patient-specific functional pelvic tilt affect joint contact pressure in hip dysplasia? A finite-element analysis study.
      • Koh Y.G.
      • Lee J.A.
      • Kim P.S.
      • Kim H.J.
      • Kang K.
      • Kang K.T.
      Effects of the material properties of a focal knee articular prosthetic on the human knee joint using computational simulation.
      • Pan D.
      • TianYe L.
      • Peng Y.
      • JingLi X.
      • HongZhu L.
      • HeRan Z.
      • et al.
      Effects of proximal fibular osteotomy on stress changes in mild knee osteoarthritis with varus deformity: a finite element analysis.
      • Sano H.
      • Komatsuda T.
      • Abe H.
      • Ozawa H.
      • Kumagai J.
      • Yokobori Jr., T.A.
      Intraarticular biomechanical environment following modified bristow and latarjet procedures in shoulders with large glenoid defects: relationship with postoperative complications.
      . Virtual surgeries were used to simulate post-surgical outcomes in two studies
      • Koh Y.G.
      • Lee J.A.
      • Kim P.S.
      • Kim H.J.
      • Kang K.
      • Kang K.T.
      Effects of the material properties of a focal knee articular prosthetic on the human knee joint using computational simulation.
      • Pan D.
      • TianYe L.
      • Peng Y.
      • JingLi X.
      • HongZhu L.
      • HeRan Z.
      • et al.
      Effects of proximal fibular osteotomy on stress changes in mild knee osteoarthritis with varus deformity: a finite element analysis.
      • Sano H.
      • Komatsuda T.
      • Abe H.
      • Ozawa H.
      • Kumagai J.
      • Yokobori Jr., T.A.
      Intraarticular biomechanical environment following modified bristow and latarjet procedures in shoulders with large glenoid defects: relationship with postoperative complications.
      . Sano et al.
      • Sano H.
      • Komatsuda T.
      • Abe H.
      • Ozawa H.
      • Kumagai J.
      • Yokobori Jr., T.A.
      Intraarticular biomechanical environment following modified bristow and latarjet procedures in shoulders with large glenoid defects: relationship with postoperative complications.
      studied cartilage stress distribution following virtual surgery for anterior shoulder instability. A concentration of stress was found in the humeral head cartilage, which authors speculated could lead to glenohumeral OA. Pan et al.
      • Pan D.
      • TianYe L.
      • Peng Y.
      • JingLi X.
      • HongZhu L.
      • HeRan Z.
      • et al.
      Effects of proximal fibular osteotomy on stress changes in mild knee osteoarthritis with varus deformity: a finite element analysis.
      studied the effect of proximal fibular osteotomies in individuals with mild knee OA and varus deformity. Under the assumptions of an equal vertical load pre- and post-surgery, these osteotomies shifted stress concentration in the knee towards the lateral compartment, thereby reducing medial compartment stress, suggesting that proximal fibular osteotomy may alter knee load distributions.
      Besides publications that apply in silico models for clinically relevant questions, there is ongoing development and validation of these computational models at different scales, i.e., musculoskeletal
      • Dumas R.
      • Moissenet F.
      Accuracy of the tibiofemoral contact forces estimated by a subject-specific musculoskeletal model with fluoroscopy-based contact point trajectories.
      ,
      • van Veen B.C.
      • Mazza C.
      • Viceconti M.
      The uncontrolled manifold theory could explain part of the inter-trial variability of knee contact force during level walking.
      , discrete element
      • Benemerito I.
      • Modenese L.
      • Montefiori E.
      • Mazzà C.
      • Viceconti M.
      • Lacroix D.
      • et al.
      An extended discrete element method for the estimation of contact pressure at the ankle joint during stance phase.
      , and finite element
      • Khajehsaeid H.
      • Abdollahpour Z.
      Progressive deformation-induced degradation of knee articular cartilage and osteoarthritis.
      • Kusins J.
      • Knowles N.
      • Columbus M.
      • Oliviero S.
      • Dall'Ara E.
      • Athwal G.S.
      • et al.
      The application of digital volume correlation (DVC) to evaluate strain predictions generated by finite element models of the osteoarthritic humeral head.
      • Liu D.
      • Ma S.
      • Stoffel M.
      • Markert B.
      A biphasic visco-hyperelastic damage model for articular cartilage: application to micromechanical modelling of the osteoarthritis-induced degradation behaviour.
      • Mohammadi A.
      • Myller K.A.H.
      • Tanska P.
      • Hirvasniemi J.
      • Saarakkala S.
      • Töyräs J.
      • et al.
      Rapid CT-based estimation of articular cartilage biomechanics in the knee joint without cartilage segmentation.
      • Moo E.K.
      • Tanska P.
      • Federico S.
      • Al-Saffar Y.
      • Herzog W.
      • Korhonen R.K.
      Collagen fibres determine the crack morphology in articular cartilage.
      • Naghibi H.
      • Janssen D.
      • van den Boogaard T.
      • van Tienen T.
      • Verdonschot N.
      The implications of non-anatomical positioning of a meniscus prosthesis on predicted human knee joint biomechanics.
      • Schwer J.
      • Rahman M.M.
      • Stumpf K.
      • Rasche V.
      • Ignatius A.
      • Dürselen L.
      • et al.
      Degeneration affects three-dimensional strains in human menisci: in situ MRI acquisition combined with image registration.
      • Zanjani-Pour S.
      • Giorgi M.
      • Dall'Ara E.
      Development of subject specific finite element models of the mouse knee joint for preclinical applications.
      models. Naghibi et al.
      • Naghibi H.
      • Janssen D.
      • van den Boogaard T.
      • van Tienen T.
      • Verdonschot N.
      The implications of non-anatomical positioning of a meniscus prosthesis on predicted human knee joint biomechanics.
      validated models in a clinical study investigating the effect of positional changes of a medial meniscus prosthesis. They validated calculated contact pressures from finite element models by comparing to cadaveric experiments under axial loading. Using the validated model, during gait an anatomically positioned meniscal prosthesis could improve pressure distribution in the knee joint, but it did not fully restore the distribution seen in intact knee joints.
      While these models involve a single scale, multi-scale in silico modelling couples multiple biological scales. Multi-scale modelling is a promising tool for better understanding OA
      • Andriacchi T.P.
      • Mundermann A.
      • Smith R.L.
      • Alexander E.J.
      • Dyrby C.O.
      • Koo S.
      A framework for the in vivo pathomechanics of osteoarthritis at the knee.
      ,
      • Wang X.
      • Neu C.P.
      • Pierce D.M.
      Advances toward multiscale computational models of cartilage mechanics and mechanobiology.
      • Erdemir A.
      • Bennetts C.
      • Davis S.
      • Reddy A.
      • Sibole S.
      Multiscale cartilage biomechanics: technical challenges in realizing a high-throughput modelling and simulation workflow.
      • Halloran J.P.
      • Sibole S.
      • van Donkelaar C.C.
      • van Turnhout M.C.
      • Oomens C.W.
      • Weiss J.A.
      • et al.
      Multiscale mechanics of articular cartilage: potentials and challenges of coupling musculoskeletal, joint, and microscale computational models.
      . In the past year, few studies were published that link joint and tissue scales in relation to the OA development
      • Faudot B.
      • Milan J.L.
      • Goislard de Monsabert B.
      • Le Corroller T.
      • Vigouroux L.
      Estimation of joint contact pressure in the index finger using a hybrid finite element musculoskeletal approach.
      ,
      • Bolcos P.O.
      • Mononen M.E.
      • Tanaka M.S.
      • Yang M.
      • Suomalainen J.S.
      • Nissi M.J.
      • et al.
      Identification of locations susceptible to osteoarthritis in patients with anterior cruciate ligament reconstruction: combining knee joint computational modelling with follow-up T(1ρ) and T(2) imaging.
      • Gustafson J.A.
      • Elias J.J.
      • Fitzgerald G.K.
      • Tashman S.
      • Debski R.E.
      • Farrokhi S.
      Combining advanced computational and imaging techniques as a quantitative tool to estimate patellofemoral joint stress during downhill gait: a feasibility study.
      • Orozco G.A.
      • Bolcos P.
      • Mohammadi A.
      • Tanaka M.S.
      • Yang M.
      • Link T.M.
      • et al.
      Prediction of local fixed charge density loss in cartilage following ACL injury and reconstruction: a computational proof-of-concept study with MRI follow-up.
      • Shriram D.
      • Yamako G.
      • Kumar G.P.
      • Chosa E.
      • Cui F.
      • Subburaj K.
      Non-anatomical placement adversely affects the functional performance of the meniscal implant: a finite element study.
      . Two studies aimed to validate a multi-scale workflow by comparing predicted changes in loss of proteoglycan fixed charged density
      • Orozco G.A.
      • Bolcos P.
      • Mohammadi A.
      • Tanaka M.S.
      • Yang M.
      • Link T.M.
      • et al.
      Prediction of local fixed charge density loss in cartilage following ACL injury and reconstruction: a computational proof-of-concept study with MRI follow-up.
      or collagen degeneration and proteoglycan depletion
      • Bolcos P.O.
      • Mononen M.E.
      • Tanaka M.S.
      • Yang M.
      • Suomalainen J.S.
      • Nissi M.J.
      • et al.
      Identification of locations susceptible to osteoarthritis in patients with anterior cruciate ligament reconstruction: combining knee joint computational modelling with follow-up T(1ρ) and T(2) imaging.
      to follow-up MRI T1ρ and T2 relaxation times. Gustafson et al.
      • Gustafson J.A.
      • Elias J.J.
      • Fitzgerald G.K.
      • Tashman S.
      • Debski R.E.
      • Farrokhi S.
      Combining advanced computational and imaging techniques as a quantitative tool to estimate patellofemoral joint stress during downhill gait: a feasibility study.
      combined biplane fluoroscopy with discrete element models to estimate changes in patellofemoral joint stress. Eskelinen et al.
      • Eskelinen A.S.A.
      • Tanska P.
      • Florea C.
      • Orozco G.A.
      • Julkunen P.
      • Grodzinsky A.J.
      • et al.
      Mechanobiological model for simulation of injured cartilage degradation via pro-inflammatory cytokines and mechanical stimulus.
      presented a novel mechanobiological framework using biochemically and biomechanically-driven mechanisms to predict cartilage degradation
      • Eskelinen A.S.A.
      • Tanska P.
      • Florea C.
      • Orozco G.A.
      • Julkunen P.
      • Grodzinsky A.J.
      • et al.
      Mechanobiological model for simulation of injured cartilage degradation via pro-inflammatory cytokines and mechanical stimulus.
      . The model was able to predict matrix losses occurring near the free surfaces especially near the lesion, while no losses were predicted away from the lesion, and results were validated by experimental data. Multi-scale modelling is also relevant in non-weight bearing joints. Changes in finger muscle co-contraction ratios altered contact pressure distributions among finger joints, which could promote OA development
      • Faudot B.
      • Milan J.L.
      • Goislard de Monsabert B.
      • Le Corroller T.
      • Vigouroux L.
      Estimation of joint contact pressure in the index finger using a hybrid finite element musculoskeletal approach.
      .
      The importance of considering multiple scales is also highlighted by Putignano et al.
      • Putignano C.
      • Burris D.
      • Moore A.
      • Dini D.
      Cartilage rehydration: the sliding-induced hydrodynamic triggering mechanism.
      . They present a novel numerical multi-scale lubrication theory to explain a motion-induced cartilage rehydration mechanism and showed the sliding-induced fluid recovery, also within the loaded contact area. They concluded that this rehydration is activated by hydrodynamic pressure originating from sliding.
      Multi-scale in silico models are a very promising tool for assessing cartilage structure and function, as the models appear to yield valid estimates of cartilage loads. However, in order to introduce in silico models as a clinical tool, they should be personalized for each patient (e.g., based on imaging), as similarly stated for musculoskeletal models
      • Smith S.H.L.
      • Coppack R.J.
      • van den Bogert A.J.
      • Bennett A.N.
      • Bull A.M.J.
      Review of musculoskeletal modelling in a clinical setting: current use in rehabilitation design, surgical decision making and healthcare interventions.
      . Moreover, combining this with wearables or deep learning networks will enable the efficient handling of larger sample sizes ((Fig. 1).

      Wearables

      The use of wearable sensors, such as inertial measurement units (IMU) and accelerometers, is becoming increasingly popular in OA research. A scoping review found an exceptional increase over the last 5 years
      • Kobsar D.
      • Masood Z.
      • Khan H.
      • Khalil N.
      • Kiwan M.Y.
      • Ridd S.
      • et al.
      Wearable inertial sensors for gait analysis in adults with osteoarthritis-A scoping review.
      . Wearables, when properly processed and calibrated, provide the possibility to more easily measure biomechanics in clinical practice or OA self-management, and the ability to acquire biomechanics data in many participants in a time efficient manner.
      For data acquisition over a long duration, an activity monitor, usually a single sensor, is secured at a convenient location. Lisee et al.
      • Lisee C.M.
      • Montoye A.H.K.
      • Lewallen N.F.
      • Hernandez M.
      • Bell D.R.
      • Kuenze C.M.
      Assessment of free-living cadence using ActiGraph accelerometers between individuals with and without anterior cruciate ligament reconstruction.
      used a hip-worn accelerometer that classified each 60-s epoch for its type of activity and measured the cadence when walking. After ACL reconstruction, participants spent 17% less time walking, especially at a moderate-to vigorous-intensity. Using a thigh-worn accelerometer, activities of women with knee OA did not differ from their non-OA peers
      • Vangeneugden J.
      • Verlaan L.
      • Oomen P.
      • Liu W.Y.
      • Peters M.
      • Natour N.
      • et al.
      Signatures of knee osteoarthritis in women in the temporal and fractal dynamics of human gait.
      . To feedback cumulative joint load based on activity classification, a smartphone app was co-created with OA patients and healthcare providers
      • Emmerzaal J.
      • De Brabandere A.
      • Vanrompay Y.
      • Vranken J.
      • Storms V.
      • De Baets L.
      • et al.
      Towards the monitoring of functional status in a free-living environment for people with hip or knee osteoarthritis: design and evaluation of the JOLO blended care app.
      . The app uses the built-in smartphone accelerometer, with joint load estimations for each activity derived from previous studies. Though preliminary, we consider this a very promising tool to support OA self-management.
      IMUs can be used to measure joint kinematics during gait. Validation for a full IMU setup (i.e., an IMU for each body segment, up to 15 in total
      • van der Straaten R.
      • Wesseling M.
      • Jonkers I.
      • Vanwanseele B.
      • Bruijnes A.
      • Malcorps J.
      • et al.
      Discriminant validity of 3D joint kinematics and centre of mass displacement measured by inertial sensor technology during the unipodal stance task.
      ) has been further established this year
      • van der Straaten R.
      • Wesseling M.
      • Jonkers I.
      • Vanwanseele B.
      • Bruijnes A.
      • Malcorps J.
      • et al.
      Discriminant validity of 3D joint kinematics and centre of mass displacement measured by inertial sensor technology during the unipodal stance task.
      ,
      • Robert-Lachaine X.
      • Mecheri H.
      • Muller A.
      • Larue C.
      • Plamondon A.
      Validation of a low-cost inertial motion capture system for whole-body motion analysis.
      , enabling a more accessible way of performing biomechanical evaluations. Several studies used different subsets of a full IMU sensor setup to demonstrate the presence of joint kinematic differences in knee OA and hip OA
      • Boekesteijn R.J.
      • Smolders J.M.H.
      • Busch V.
      • Geurts A.C.H.
      • Smulders K.
      Independent and sensitive gait parameters for objective evaluation in knee and hip osteoarthritis using wearable sensors.
      • Ibara T.
      • Anan M.
      • Karashima R.
      • Hada K.
      • Shinkoda K.
      • Kawashima M.
      • et al.
      Coordination pattern of the thigh, pelvic, and lumbar movements during the gait of patients with hip osteoarthritis.
      • Ismailidis P.
      • Hegglin L.
      • Egloff C.
      • Pagenstert G.
      • Kernen R.
      • Eckardt A.
      • et al.
      Side to side kinematic gait differences within patients and spatiotemporal and kinematic gait differences between patients with severe knee osteoarthritis and controls measured with inertial sensors.
      • Lebleu J.
      • Fonkoue L.
      • Bandolo E.
      • Fossoh H.
      • Mahaudens P.
      • Cornu O.
      • et al.
      Lower limb kinematics improvement after genicular nerve blockade in patients with knee osteoarthritis: a milestone study using inertial sensors.
      • van der Straaten R.
      • Wesseling M.
      • Jonkers I.
      • Vanwanseele B.
      • Bruijnes A.
      • Malcorps J.
      • et al.
      Functional movement assessment by means of inertial sensor technology to discriminate between movement behaviour of healthy controls and persons with knee osteoarthritis.
      . Besides overall joint kinematics, specific kinematic targets like trunk lean/center of mass position
      • van der Straaten R.
      • Wesseling M.
      • Jonkers I.
      • Vanwanseele B.
      • Bruijnes A.
      • Malcorps J.
      • et al.
      Discriminant validity of 3D joint kinematics and centre of mass displacement measured by inertial sensor technology during the unipodal stance task.
      or knee varus thrust
      • Costello K.E.
      • Eigenbrot S.
      • Geronimo A.
      • Guermazi A.
      • Felson D.T.
      • Richards J.
      • et al.
      Quantifying varus thrust in knee osteoarthritis using wearable inertial sensors: a proof of concept.
      can be feasibly tracked with IMUs, making IMUs useful for targeted biomechanics studies in OA.
      Therapeutic reduction of joint load might be achieved by adapting a movement pattern that avoids high impact or prolonged loading. Gait retraining to achieve this has been successful
      • Cheung R.T.H.
      • Ho K.K.W.
      • Au I.P.H.
      • An W.W.
      • Zhang J.H.W.
      • Chan Z.Y.S.
      • et al.
      Immediate and short-term effects of gait retraining on the knee joint moments and symptoms in patients with early tibiofemoral joint osteoarthritis: a randomized controlled trial.
      , but feedback is required for an individual to sustain new walking styles. Wouda et al.
      • Wouda F.J.
      • Jaspar S.
      • Harlaar J.
      • van Beijnum B.F.
      • Veltink P.H.
      Foot progression angle estimation using a single foot-worn inertial sensor.
      used a single foot-worn IMU and a dedicated algorithm to calculate walking direction and real-time Foot Progression Angle (FPA). In a study by Xia et al.
      • Xia H.
      • Charlton J.M.
      • Shull P.B.
      • Hunt M.A.
      Portable, automated foot progression angle gait modification via a proof-of-concept haptic feedback-sensorized shoe.
      , the FPA sensor was built into the sole of the shoe, and together with a haptic device (vibrator), they showed that participants could control FPA very precisely (within 3°) on a treadmill.
      Although manipulating FPA does affect the KAM and therefore the joint load, it remains an indirect measure and might not hold for every person with knee OA. Unfortunately, a direct estimation of the KAM seems not possible using wearables alone. Machine Learning might be able to bypass the need for force plates and biomechanical models. Wang and colleagues delivered an impressive study that demonstrated the real-time estimation from just two ankle-worn IMUs. An Artificial Neural Network was trained with 78 persons with knee OA and 12 asymptomatic persons
      • Wang C.
      • Chan P.P.K.
      • Lam B.M.F.
      • Wang S.
      • Zhang J.H.
      • Chan Z.Y.S.
      • et al.
      Real-time estimation of knee adduction moment for gait retraining in patients with knee osteoarthritis.
      . The IMUs were linked to a smartphone, and the artificial neural network was run in the cloud. Excellent correlation (r2 > 0.94) between the estimated KAM and the lab-derived KAM was achieved, including validation with toeing-in and toeing-out. After independent replication, this approach could become an important tool in gait retraining. Boswell et al.
      • Boswell M.A.
      • Uhlrich S.D.
      • Thomas K.
      • Kolesar J.A.
      • Gold G.E.
      • Beaupre G.S.
      • et al.
      A neural network to predict the knee adduction moment in patients with osteoarthritis using anatomical landmarks obtainable from 2D video analysis.
      applied machine learning to estimate KAM. Using frontal kinematics of gait as input, the artificial neural network predicted peak KAM (r2 = 0.85). This approach could be applied to estimate KAM from frontal plane video recordings, enabling point-of-care mechanical diagnostics in knee OA. This again highlights that machine learning in combination with wearables (Fig. 1) are promising tools for more easily obtaining meaningful biomechanical measures.

      Biomechanics in OA treatment

      Given the important role of biomechanics in OA onset and progression, biomechanics interventions continued to be investigated this year - see OARSI Year in Review Rehab for more detail. In addition, where clinical trials often focus on pain and function as a study outcome, a growing number of studies are incorporating biomechanical outcomes into their study design. Various data acquisition methods and modelling modalities are used, although the use of wearables and machine learning is still limited (Fig. 1). Below we outline several key papers in which biomechanical outcomes have been included in intervention studies.
      A systematic review found that in healthy individuals, both toe-in and toe-out gait reduced KAM and KAM angular impulse compared to natural gait, while in individuals with knee OA, only toe-out gait appeared to reduce these gait parameters
      • Wang S.
      • Mo S.
      • Chung R.C.K.
      • Shull P.B.
      • Ribeiro D.C.
      • Cheung R.T.H.
      How foot progression angle affects knee adduction moment and angular impulse in people with and without medial knee osteoarthritis: a meta-analysis.
      . Using standing MRI, a small amount of lateralization of contact for both toe-out and toe-in postures in individuals with mild knee OA was found
      • Hunt M.A.
      • Cochrane C.K.
      • Schmidt A.M.
      • Zhang H.
      • Stockton D.J.
      • Black A.H.
      • et al.
      Tibiofemoral contact measures during standing in toe-in and toe-out postures.
      , indicating accurate analyses of joint kinematics during gait may be needed to reveal more subtle changes. Another study considered other gait modifications such as trunk lean and medial knee thrust and concluded that addressing multiple gait modifications in future study designs might demonstrate a more optimal reduction in KAM
      • Lindsey B.
      • Bruce S.
      • Eddo O.
      • Caswell S.
      • Cortes N.
      Relationship between kinematic gait parameters during three gait modifications designed to reduce peak knee abduction moment.
      .
      One way to conduct preliminary explorations of different or novel types of interventions without the undue burden of conducting clinical trials is through the use of musculoskeletal modelling simulations. Biomechanics data from eight healthy participants was used to simulate the effect of three different designs of a tricompartmental unloader brace
      • McGibbon C.A.
      • Brandon S.
      • Bishop E.L.
      • Cowper-Smith C.
      • Biden E.N.
      Biomechanical study of a tricompartmental unloader brace for patellofemoral or multicompartment knee osteoarthritis.
      . All three brace simulations showed reduced knee joint loads of 30–50% at knee flexion angles of more than 30 °, providing proof-of-concept and informing the design of these novel braces.
      The effects of an existing medial offloader brace was evaluated in vivo with fluoroscopy while individuals with knee OA performed their usual gait both with and without the brace on
      • Dessinger G.M.
      • LaCour M.T.
      • Dennis D.A.
      • Kleeman-Forsthuber L.T.
      • Komistek R.D.
      Can an OA knee brace effectively offload the medial condyle? An in vivo fluoroscopic study.
      . With the brace on, mean joint space width increased 1.6 (±0.8) mm at both heel strike and contralateral toe off. Use of fluoroscopy in a gait laboratory represents recent advances in technology that make it possible to measure the effects of biomechanical interventions such as braces, where previously instruments were not precise enough to detect such changes.
      Several RCTs were published this year that evaluated the efficacy of various biomechanical interventions in knee OA. One crossover RCT (n = 24) of three types of knee braces worn for 3 months each found an unloader brace with both valgus and external rotation functions to be more comfortable and to decrease KAM both at baseline and after treatment (with brace donned), however interpretation of the results are limited by a carryover effect
      • Robert-Lachaine X.
      • Dessery Y.
      • Belzile É L.
      • Turmel S.
      • Corbeil P.
      Three-month efficacy of three knee braces in the treatment of medial knee osteoarthritis in a randomized crossover trial.
      . An RCT investigating footwear with individually adjustable external convex pods attached to the outsole (compared to control shoes) showed reduced pain in the treatment group of limited clinical relevance and mildly increased velocity and step length compared to controls
      • Reichenbach S.
      • Felson D.T.
      • Hincapié C.A.
      • Heldner S.
      • Bütikofer L.
      • Lenz A.
      • et al.
      Effect of biomechanical footwear on knee pain in people with knee osteoarthritis: the BIOTOK randomized clinical trial.
      . An RCT of minimalist footwear in women with knee OA that had previously shown reduced KAM and KAM impulse after 6 months
      • Trombini-Souza F.
      • Matias A.B.
      • Yokota M.
      • Butugan M.K.
      • Goldenstein-Schainberg C.
      • Fuller R.
      • et al.
      Long-term use of minimal footwear on pain, self-reported function, analgesic intake, and joint loading in elderly women with knee osteoarthritis: a randomized controlled trial.
      conducted secondary analyses to explain the mechanism of reduction of KAM
      • Trombini-Souza F.
      • Fuller R.
      • Goldenstein-Schainberg C.
      • Sacco I.C.N.
      Long-term use of minimal footwear in older adult women with knee osteoarthritis: mechanisms of action in the knee adduction moment.
      . They found no association with other lower limb joint kinematics and frontal moments, center of pressure displacement, or FPA, concluding specifically that changes in KAM were not related to increased hip moments or ankle inversion angles. RCTs of lateral wedge insoles were also published this year. One study compared 12 weeks of lateral wedge insole wear to neutral insoles and found lateral wedge insoles were no more effective than neutral insoles at reducing KAM and KAM impulse
      • Ferreira V.
      • Machado L.
      • Vilaça A.
      • Xará-Leite F.
      • Roriz P.
      Effects of tailored lateral wedge insoles on medial knee osteoarthritis based on biomechanical analysis: 12-week randomized controlled trial.
      . A second RCT compared 6 weeks of insole wear to an ankle foot orthosis, and found lateral wedge insoles to be less effective than the ankle foot orthosis at reducing KAM and KAM impulse, though the between-group differences were of doubtful clinical relevance
      • Schwarze M.
      • Bartsch L.P.
      • Block J.
      • Alimusaj M.
      • Jaber A.
      • Schiltenwolf M.
      • et al.
      A comparison between laterally wedged insoles and ankle-foot orthoses for the treatment of medial osteoarthritis of the knee: a randomized cross-over trial.
      .
      High tibial osteotomy is a common surgical approach to correct severely abnormal biomechanics in individuals with or at risk for knee OA. This year, a study of 50 individuals who underwent a biplanar open wedge technique with rigid plate fixation demonstrated a mean correction in frontal plane alignment of approximately 14°
      • Kumagai K.
      • Fujimaki H.
      • Yamada S.
      • Nejima S.
      • Matsubara J.
      • Inaba Y.
      Changes of Synovial Fluid Biomarker Levels after Opening Wedge High Tibial Osteotomy in Patients with Knee Osteoarthritis.
      . Moreover, improved cartilage scores were noted in 38% of participants, and various synovial markers of inflammation were reduced by 14–49%. Another study investigating unilateral medial open wedge high tibial osteotomy with internal fixation in 36 participants showed a frontal plane correction of approximately 7 °, but also reduced effusion-synovitis volume, KAM and KAM impulse, and shorter T2 relaxation times in the medial tibiofemoral joint
      • Atkinson H.F.
      • Birmingham T.B.
      • Primeau C.A.
      • Schulz J.M.
      • Appleton C.T.
      • Pritchett S.L.
      • et al.
      Association between changes in knee load and effusion-synovitis: evidence of mechano-inflammation in knee osteoarthritis using high tibial osteotomy as a model.
      ,
      • Atkinson H.F.
      • Birmingham T.B.
      • Schulz J.M.
      • Primeau C.A.
      • Leitch K.M.
      • Pritchett S.L.
      • et al.
      High tibial osteotomy to neutral alignment improves medial knee articular cartilage composition.
      . Together, these studies suggest that the surgical correction of severe varus alignment may result not only in biomechanical improvements but also in improvements in inflammation and cartilage health. Taken together, these studies demonstrate the potential of incorporating pre-post biomechanical outcomes into OA clinical trials to better understand the mechanisms underpinning effects (or lack thereof) for various interventions.

      Conclusion

      In this narrative review we reported on emerging evidence in four key topics: (i) joint-level biomechanics; (ii) computational modeling; (iii) wearable technology; and (iv) mechanics as outcomes in clinical research. Computational and experimental innovations have enabled more detailed analyses of cartilage load. There was a main focus on knee OA, including a prominent role of ACL research. Although generally with small sample sizes, in silico single scale models were used to evaluate clinically relevant questions. Multi-scale in silico models yield valid estimates of cartilage loads and are a promising tool for further assessing cartilage structure and function. The use of wearable sensors is becoming increasingly popular in OA research, enabling low cost measurements in the free-living environment and providing feedback for gait retraining. Machine learning is used to extract higher fidelity estimates of cartilage load from lower fidelity information. Clinical trials increasingly incorporate biomechanical outcomes into their study design. These results further elucidate the role that mechanics plays in OA onset and progression, and to harness its potential as an effective treatment target. Since most recent advancements in the field of biomechanics in OA are at the level of proof-of-principle, future research should continue on this path of innovation, but also aim to develop clinical workflows that would allow inclusion of precision biomechanics into large scale studies.

      Author contributions

      All authors performed the literature search and review, selected the articles, identified themes, summarized results and wrote the manuscript.

      Conflict of interest

      The authors have no conflict of interest.

      Acknowledgements

      The authors wish to acknowledge the Osteoarthritis Research Society International (OARSI) for the invitation to present this review at the 2021 annual meeting. This study was funded by ZonMw (grant# 09120011910052); Medical Delta (grant# IMT-P91480); Delft University of Technology and Erasmus Medical Center Rotterdam.

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