Mechanical loading rescues mechanoresponsiveness in a human osteoarthritis explant model despite Wnt activation.

OBJECTIVES: Optimizing rehabilitation strategies for osteoarthritis necessitates a comprehensive understanding of chondrocytes' mechanoresponse in both health and disease, especially in the context of the interplay between loading and key pathways involved in osteoarthritis (OA) development, like canonical Wnt signaling. This study aims to elucidate the role of Wnt signaling in the mechanoresponsiveness of healthy and osteoarthritic human cartilage. METHODS: We used an ex-vivo model involving short-term physiological mechanical loading of human cartilage explants. First, the loading protocol for subsequent experiments was determined. Next, loading was applied to non-OA-explants with or without Wnt activation with CHIR99021. Molecular read-outs of anabolic, pericellular matrix and matrix remodeling markers were used to assess the effect of Wnt on cartilage mechanoresponse. Finally, the same set-up was used to study the effect of loading in cartilage from patients with established OA. RESULTS: Our results confirm that physiological loading maintains expression of anabolic genes in non-OA cartilage, and indicate a deleterious effect of Wnt activation in the chondrocyte mechanoresponsiveness. This suggests that loading-induced regulation of chondrocyte markers occurs downstream of canonical Wnt signaling. Interestingly, our study highlighted contrasting mechanoresponsiveness in the model of Wnt activation and the established OA samples, with established OA cartilage maintaining its mechanoresponsiveness, and mechanical loading rescuing the chondrogenic phenotype. CONCLUSION: This study provides insights into the mechanoresponsiveness of human cartilage in both non-OA and OA conditions. These findings hold the potential to contribute to the development of strategies that optimize the effect of dynamic compression by correcting OA pathological cell signaling.

Contribution of collagen degradation and proteoglycan depletion to cartilage degeneration in primary and secondary osteoarthritis: an in silico study.

OBJECTIVES: Current experimental approaches cannot elucidate the effect of maladaptive changes on the main cartilage constituents during the degeneration process in osteoarthritis (OA). In silico approaches, however, allow creating 'virtual knock-out' cases to elucidate these effects in a constituent-specific manner. We used such an approach to study the main mechanisms of cartilage degeneration in different mechanical loadings associated with the following OA etiologies: (1) physiological loading of degenerated cartilage, (2) injurious loading of healthy intact cartilage and (3) physiological loading of cartilage with a focal defect. METHODS: We used the recently developed Cartilage Adaptive REorientation Degeneration (CARED) framework to simulate cartilage degeneration associated with primary and secondary OA (OA cases (1)-(3)). CARED incorporates numerical description of tissue-level cartilage degeneration mechanisms in OA, namely, collagen degradation, collagen reorientation, fixed charged density loss and tissue hydration increase following mechanical loading. We created 'virtual knock-out' scenarios by deactivating these degenerative processes one at a time in each of the three OA cases. RESULTS: In the injurious loading of intact and physiological loading of degenerated cartilage, collagen degradation drives degenerative changes through fixed charge density loss and tissue hydration rise. In contrast, the two later mechanisms were more prominent in the focal defect cartilage model. CONCLUSION: The virtual knock-out models reveal that injurious loading to intact cartilage and physiological loading to degenerated cartilage induce initial degenerative changes in the collagen network, whereas, in the presence of a focal cartilage defect, mechanical loading initially causes proteoglycans (PG) depletion, before changes in the collagen fibril network occur.

Optimizing the use of patients' individual outcome information - Development and usability tests of a Chronic Kidney Disease dashboard.

BACKGROUND: Reporting individual clinical and patient-reported outcomes to patients during consultations may add to patients' disease knowledge and activation and stimulate Shared Decision Making (SDM). These outcomes can be presented over time in a clear way by the means of dashboarding. We aimed to systematically develop a Chronic Kidney Disease (CKD) dashboard designed to support consultations, test its usability and explore conditions for optimal use in practice. METHODS: For development a participatory approach with patients and healthcare professionals (HCPs) from three hospitals was used. Working groups and patient focus groups were conducted to identify needs and inform the dashboard's design. Usability was tested in patient interviews. A focus group with HCPs was held to identify conditions for optimal use of the dashboard in daily practice. RESULTS: A dashboard was developed for CKD patients stage 3b-4 visualizing both clinical and patient-reported outcomes over time for use during consultations and accessible for patients at home. Both HCPs and patients indicated that the dashboard can: motivate patients in their treatment by providing feedback on outcomes over time; improve consultation conversations by enhanced preparation of both HCPs and patients; better inform patients, thereby facilitating shared decision making. HCPs and patients both stated that setting a topic agenda for the consultation together is important in effectively discussing the dashboard during consultations. Moreover, the dashboard should not dominate the conversation. Lastly, findings of the usability tests provided design requirements for optimal user-friendliness and clarity. CONCLUSIONS: Dashboarding can be a valuable way of reporting individual outcome information to patients and their clinicians as findings suggest it may stimulate patient activation and facilitate decision making. Co-creation with patients and HCPs was essential for successful development of the dashboard. Gained knowledge from the co-creation process can inform others wishing to develop similar digital tools for use in clinical practice.

12 Degrees of Freedom Muscle Force Driven Fibril-Reinforced Poroviscoelastic Finite Element Model of the Knee Joint.

Accurate knowledge of the joint kinematics, kinetics, and soft tissue mechanical responses is essential in the evaluation of musculoskeletal (MS) disorders. Since in vivo measurement of these quantities requires invasive methods, musculoskeletal finite element (MSFE) models are widely used for simulations. There are, however, limitations in the current approaches. Sequentially linked MSFE models benefit from complex MS and FE models; however, MS model's outputs are independent of the FE model calculations. On the other hand, due to the computational burden, embedded (concurrent) MSFE models are limited to simple material models and cannot estimate detailed responses of the soft tissue. Thus, first we developed a MSFE model of the knee with a subject-specific MS model utilizing an embedded 12 degrees of freedom (DoFs) knee joint with elastic cartilages in which included both secondary kinematic and soft tissue deformations in the muscle force estimation (inverse dynamics). Then, a muscle-force-driven FE model with fibril-reinforced poroviscoelastic cartilages and fibril-reinforced poroelastic menisci was used in series to calculate detailed tissue mechanical responses (forward dynamics). Second, to demonstrate that our workflow improves the simulation results, outputs were compared to results from the same FE models which were driven by conventional MS models with a 1 DoF knee, with and without electromyography (EMG) assistance. The FE model driven by both the embedded and the EMG-assisted MS models estimated similar results and consistent with experiments from literature, compared to the results estimated by the FE model driven by the MS model with 1 DoF knee without EMG assistance.

Botulinum toxin injections minimally affect modelled muscle forces during gait in children with cerebral palsy.

BACKGROUND: Children with cerebral palsy (CP) present altered gait patterns and electromyography (EMG) activity compared to typically developing children. To temporarily reduce muscular activity and to correct the abnormal muscle force balance, Botulinum Toxin type A (BTX-A) injections are used. RESEARCH QUESTION: What is the effect of BTX-A injections on dynamic muscle forces during gait, when calculated using an EMG-constrained approach?. METHODS: Retrospective data of ten typically developing (TD) and fourteen children with spastic diplegic CP were used for musculoskeletal modeling and dynamic simulations of gait, before and after BTX-A treatment. Individual muscle forces were calculated using an EMG-constrained optimization, in which EMG of eight muscles was used as muscle excitation signal to constrain the muscle activation patterns. Paired t-tests were used to compare average modelled muscle forces in different phases of the gait cycle pre- and post-BTX-A, summarized in the muscle profile score. Two-sample t-tests were used to determine significant differences between TD and pre- and post-BTX-A modelled muscle forces. RESULTS: For most muscles, the force was decreased in CP compared to TD children in all phases of the gait cycle, both before and after BTX-A treatment. Differences in muscle forces before and after BTX-A treatment were limited, with only few significant differences between pre- and post-BTX-A. Compared to a standard static optimization approach, imposing the EMG activity increased modelled muscle forces for most muscles. SIGNIFICANCE: Our findings indicate that BTX-A treatment has a limited effect on the muscle balance in CP children. Besides that, the use of EMG-constrained optimization is recommended when studying muscle balance in children with CP.

Discriminant validity of 3D joint kinematics and centre of mass displacement measured by inertial sensor technology during the unipodal stance task.

BACKGROUND: The unipodal stance task is a clinical task that quantifies postural stability and alignment of the lower limb joints, while weight bearing on one leg. As persons with knee osteoarthritis (KOA) have poor postural and knee joint stability, objective assessment of this task might be useful. OBJECTIVE: To investigate the discriminant validity of three-dimensional joint kinematics and centre of mass displacement (COM) between healthy controls and persons with knee KOA, during unipodal stance using inertial sensors. Additionally, the reliability, agreement and construct validity are assessed to determine the reproducibility and accuracy of the discriminating parameters. METHODS: Twenty healthy controls and 19 persons with unilateral severe KOA were included. Five repetitions of the unipodal stance task were simultaneously recorded by an inertial sensor system and a camera-based system (gold standard). Statistical significant differences in kinematic waveforms between healthy controls and persons with severe knee KOA were determined using one-dimensional statistical parametric mapping (SPM1D). RESULTS: Persons with severe knee KOA had more lateral trunk lean towards the contralateral leg, more hip flexion throughout the performance of the unipodal stance task, more pelvic obliquity and COM displacement towards the contralateral side. However, for the latter two parameters the minimum detectable change was greater than the difference between healthy controls and persons with severe knee KOA. The construct validity was good (coefficient of multiple correlation 0.75, 0.83 respectively) and the root mean squared error (RMSE) was low (RMSE <1.5°) for the discriminant parameters. CONCLUSION: Inertial sensor based movement analysis can discriminate between healthy controls and persons with severe knee KOA for lateral trunk lean and hip flexion, but unfortunately not for the knee angles. Further research is required to improve the reproducibility and accuracy of the inertial sensor measurements before they can be used to assess differences in tasks with a small range of motion.

Single-event multilevel surgery, but not botulinum toxin injections normalize joint loading in cerebral palsy patients.

BACKGROUND: Many patients with cerebral palsy present a pathologic gait pattern, which presumably induces aberrant musculoskeletal loading that interferes with natural bone growth, causing bone deformations on the long term. Botulinum toxin interventions and single-event multilevel surgeries are used to restore the gait pattern, assuming that a normal gait pattern restores musculoskeletal loading and thus prevents further bone deformation. However, it is unknown if these interventions are able to restore musculoskeletal loading. Hence, we investigated the impact of botulinum toxin injections and single-event multilevel surgery on musculoskeletal loading. METHODS: Gait data collected in 93 children with bilateral cerebral palsy, which included pre- and post multi-level botulinum toxin (49 children) and single-event multilevel surgery (44 children) assessments, and 15 typically developing children were retrospectively processed using a musculoskeletal modelling workflow to calculate joint angles, moments, muscle and joint contact force magnitudes and orientations. Differences from the typically developing waveform were expressed by a root-mean square difference were compared using paired t-tests for each intervention separately (alpha <0.05). FINDINGS: Botulinum toxin induced significant changes in the joint angles, but did not improve the muscle and joint contact forces. Single-event multilevel surgery induced significant kinematic and kinetic changes, which were associated with improved muscle and joint contact forces. INTERPRETATION: The present results indicate that botulinum toxin injections were not able to restore normal gait kinematics nor musculoskeletal loading, whereas single-event multilevel surgery did successfully restore both. Therefore, single-event multilevel surgery might be protective against the re-occurrence of bone deformation on the longer term.

A practical view of fine-mapping and gene prioritization in the post-genome-wide association era.

Over the past 15 years, genome-wide association studies (GWASs) have enabled the systematic identification of genetic loci associated with traits and diseases. However, due to resolution issues and methodological limitations, the true causal variants and genes associated with traits remain difficult to identify. In this post-GWAS era, many biological and computational fine-mapping approaches now aim to solve these issues. Here, we review fine-mapping and gene prioritization approaches that, when combined, will improve the understanding of the underlying mechanisms of complex traits and diseases. Fine-mapping of genetic variants has become increasingly sophisticated: initially, variants were simply overlapped with functional elements, but now the impact of variants on regulatory activity and direct variant-gene 3D interactions can be identified. Moreover, gene manipulation by CRISPR/Cas9, the identification of expression quantitative trait loci and the use of co-expression networks have all increased our understanding of the genes and pathways affected by GWAS loci. However, despite this progress, limitations including the lack of cell-type- and disease-specific data and the ever-increasing complexity of polygenic models of traits pose serious challenges. Indeed, the combination of fine-mapping and gene prioritization by statistical, functional and population-based strategies will be necessary to truly understand how GWAS loci contribute to complex traits and diseases.

Variation of the clavicle's muscle insertion footprints - a cadaveric study.

The muscle footprint anatomy of the clavicle is described in various anatomical textbooks but research on the footprint variation is rare. Our goal was to assess the variation and to create a probabilistic atlas of the muscle footprint anatomy. 14 right and left clavicles of anatomical specimens were dissected until only muscle fibers remained. 3D models with muscle footprints were made through CT scanning, laser scanning and photogrammetry. Then, for each side, the mean clavicle was calculated and non-rigidly registered to all other cadaveric bones. Muscle footprints were indicated on the mean left and right clavicle through the 1-to-1 mesh correspondence which is achieved by non-rigid registration. Lastly, 2 probabilistic atlases from the clavicle muscle footprints were generated. There was no statistical significant difference between the surface area (absolute and relative), of the originally dissected muscle footprints, of male and female, and left and right anatomical specimens. Visualization of all muscle footprints on the mean clavicle resulted in 72% (right) and 82% (left) coverage of the surface. The Muscle Insertion Footprint of each specimen covered on average 36.9% of the average right and 37.0% of the average left clavicle. The difference between surface coverage by all MIF and the mean surface coverage, shows that the MIF location varies strongly. From the probabilistic atlas we can conclude that no universal clavicle exists. Therefore, patient-specific clavicle fracture fixation plates should be considered to minimally interfere with the MIF. Therefore, patient-specific clavicle fracture fixation plates which minimally interfere with the footprints should be considered.

Variation of actin filament length in dogs.

As the smallest functional unit of force production, the sarcomeres are important in determining muscle function. Actin filament lengths, which are important in determining optimal sarcomere length for a species, have not yet been reported in dogs. This study aims to provide a species-specific value for actin filament length in dogs, while examining intraspecies, intermuscular and intramuscular variations. Muscle samples were taken from the tibialis anterior muscle, the lateral gastrocnemius muscle head and the medial gastrocnemius muscle head in 10 dogs including a Labrador, a Belgian Malinois, a Caucasian Shepherd, German Shepherds and some mixed-breed dogs. Actin filament lengths were determined through transmission electron microscopy. Mean actin filament length across all muscle samples was 0.90 ± 0.01 µm. The low intraspecies variation, combined with a lack of important inter- and intramuscular variation found in this study, affirms the use of a species-specific optimal sarcomere length of 1.89 µm for canine muscles.

Functional assessment of strains around a full-thickness and critical sized articular cartilage defect under compressive loading using MRI.

OBJECTIVE: The objective of this study was to evaluate the effect of full-thickness chondral defects on intratissue deformation patterns and matrix constituents in an experimental model mimicking in vivo cartilage-on-cartilage contact conditions. DESIGN: Pairs of bovine osteochondral explants, in a unique cartilage-on-cartilage model system, were compressed uniaxially by 350 N during 2 s loading and 1.4 s unloading cycles (≈1700 repetitions). Tissue deformations under quasi-steady state load deformation response were measured with displacement encoded imaging with stimulated echoes (DENSE) in a 9.4 T magnetic resonance imaging (MRI) scanner. Pre- and post-loading, T1, T2 and T1ρ relaxation time maps were measured. We analyzed differences in strain patterns and relaxation times between intact cartilage (n = 8) and cartilage in which a full-thickness and critical sized defect was created (n = 8). RESULTS: Under compressive loading, strain magnitudes were elevated at the defect rim, with elevated tensile and compressive principal strains (Δϵmax = 4.2%, P = 0.02; Δϵmin = -4.3%, P = 0.02) and maximum shear strain at the defect rim (Δγmax = 4.4%, P = 0.007). The opposing cartilage showed minimal increase in strain patterns at contact with the defect rim but decreased strains opposing the defect. After defect creation, T1, T2 and T1ρ relaxation times were elevated at the defect rim only. Following loading, the overall relaxations times of the defect tissue and especially at the rim, increased compared to intact cartilage. CONCLUSIONS: This study demonstrates that the local biomechanical changes occurring after defect creation may induce tissue damage by increasing shear strains and depletion of cartilage constituents at the defect rim under compressive loading.

A musculoskeletal model of the hand and wrist: model definition and evaluation.

To improve our understanding on the neuromechanics of finger movements, a comprehensive musculoskeletal model is needed. The aim of this study was to build a musculoskeletal model of the hand and wrist, based on one consistent data set of the relevant anatomical parameters. We built and tested a model including the hand and wrist segments, as well as the muscles of the forearm and hand in OpenSim. In total, the model comprises 19 segments (with the carpal bones modeled as one segment) with 23 degrees of freedom and 43 muscles. All required anatomical input data, including bone masses and inertias, joint axis positions and orientations as well as muscle morphological parameters (i.e. PCSA, mass, optimal fiber length and tendon length) were obtained from one cadaver of which the data set was recently published. Model validity was investigated by first comparing computed muscle moment arms at the index finger metacarpophalangeal (MCP) joint and wrist joint to published reference values. Secondly, the muscle forces during pinching were computed using static optimization and compared to previously measured intraoperative reference values. Computed and measured moment arms of muscles at both index MCP and wrist showed high correlation coefficients (r = 0.88 averaged across all muscles) and modest root mean square deviation (RMSD = 23% averaged across all muscles). Computed extrinsic flexor forces of the index finger during index pinch task were within one standard deviation of previously measured in-vivo tendon forces. These results provide an indication of model validity for use in estimating muscle forces during static tasks.

Cartilage-on-cartilage contact: effect of compressive loading on tissue deformations and structural integrity of bovine articular cartilage.

OBJECTIVE: This study aims to characterize the deformations in articular cartilage under compressive loading and link these to changes in the extracellular matrix constituents described by magnetic resonance imaging (MRI) relaxation times in an experimental model mimicking in vivo cartilage-on-cartilage contact. DESIGN: Quantitative MRI images, T1, T2 and T1ρ relaxation times, were acquired at 9.4T from bovine femoral osteochondral explants before and immediately after loading. Two-dimensional intra-tissue displacement and strain fields under cyclic compressive loading (350N) were measured using the displacement encoding with stimulated echoes (DENSE) method. Changes in relaxation times in response to loading were evaluated against the deformation fields. RESULTS: Deformation fields showed consistent patterns among all specimens, with maximal strains at the articular surface that decrease with tissue depth. Axial and transverse strains were maximal around the center of the contact region, whereas shear strains were minimal around the contact center but increased towards contact edges. A decrease in T2 and T1ρ was observed immediately after loading whereas the opposite was observed for T1. No correlations between cartilage deformation patterns and changes in relaxation times were observed. CONCLUSIONS: Displacement encoding combined with relaxometry by MRI can noninvasively monitor the cartilage biomechanical and biochemical properties associated with loading. The deformation fields reveal complex patterns reflecting the depth-dependent mechanical properties, but intra-tissue deformation under compressive loading does not correlate with structural and compositional changes. The compacting effect of cyclic compression on the cartilage tissue was revealed by the change in relaxation time immediately after loading.

Musculotendon excursion potential, tendon slack and muscle fibre length: the interaction of the canine gastrocnemius muscle and tendon.

Although the form-function relation of muscles and tendons has been studied extensively, little in vivo data exist on the musculotendon properties of the gastrocnemius complex in dogs. Using a combination of ultrasound and 3D motion tracking, musculotendon parameters were obtained in vivo from the lateral gastrocnemius muscle and the gastrocnemius tendon in nine healthy Labrador Retrievers. These parameters include musculotendon length and excursion potential, tendon slack length, muscle belly length, muscle fibre length, pennation angle and architectural index. This study also examined the variation of muscle and tendon length contributions to musculotendon length, as well as the relation between musculotendon excursion potential and muscle fibre length or tendon length. To facilitate comparison between dog breeds, the femur length as a potential scaling parameter was examined. In the Labrador gastrocnemius musculotendon complex, the tendon contributes 41% (± 9%) of musculotendon length. In longer musculotendon complexes, the contribution of the muscle belly increases while the tendon contribution decreases. Longer muscle belly and musculotendon complexes were, however, associated with shorter muscle fibres. No significant relations were found between musculotendon excursion potential and muscle fibre length or tendon slack length, and femur length did not prove to be a reliable scale factor for the length-related musculotendon parameters examined in this study. Longer musculotendon complexes exhibit relatively longer muscle bellies, which are in turn associated with shorter muscle fibre lengths. This trade-off between gastrocnemius muscle belly length and muscle fibre length might have the advantage that muscle volume stays constant regardless of the length of the limbs.

Mobile assessment of the lower limb kinematics in healthy persons and in persons with degenerative knee disorders: A systematic review.

Inertial sensor systems are increasingly used in the assessment of persons with knee osteoarthritis (KOA) and total knee replacement (TKR). This systematic review aims to (1) investigate the application of inertial sensor systems and kinematics derived from these systems, and (2) assess if current assessment protocols consist of tasks which are, according to the International Classification of Functioning, Disability and Health (ICF) for KOA, relevant for persons with KOA and TKR. A search was conducted in six electronic databases (ACM, CINAHL, EMBASE, IEEE, PubMed, Web of Science) to include papers assessing the knee and one or more adjacent joints by means of inertial sensors in healthy persons or persons with KOA or TKR. Two reviewers checked the methodological quality. Twenty-three papers were included: 18 in healthy persons and five in persons with KOA or TKR. In healthy persons, 11 tasks were related to metrics of the ICF-function and ICF-activity level. In persons with KOA, only walking was assessed. Apart from walking, four additional tasks were related to the ICF-function and ICF-activity level in persons with TKR. In healthy persons, joints located proximally and distally to the knee were assessed, while in persons with KOA and TKR, only the knee and ankle were assessed. This is a shortcoming since hip and trunk motion potentially contain clinically relevant information, in terms of identifying (mal)adaptive compensatory movement strategies. Additionally, physically more demanding tasks should be evaluated as these might be superior in detecting compensatory movement strategies. Former considerations warrant attention in future research.

Validation of plantar pressure simulations using finite and discrete element modelling in healthy and diabetic subjects.

Plantar pressure simulation driven by integrated 3D motion capture data, using both a finite element and a discrete element model, is compared for ten healthy and ten diabetic neuropathic subjects. The simulated peak pressure deviated on average between 16.7 and 34.2% from the measured peak pressure. The error in the position of the peak pressure was on average smaller than 4.2 cm. No method was more accurate than the other although statistical differences were found between them. Both techniques are thus complementary and useful tools to better understand the alteration of diabetic foot biomechanics during gait.

A prospective follow up of age related changes in the subchondral bone density of the talus of healthy Labrador Retrievers.

BACKGROUND: During growth, the skeletal structures adapt to the increased loading conditions and mature to a fully-grown skeleton. Subchondral bone density reflects the effect of long-term joint loading and it is expected to change over time. The aim of this study was to describe the long-term changes in the density distribution of the subchondral bone of the talus of healthy Labrador Retrievers in a prospective study. RESULTS: The subchondral bone density distribution was evaluated using computed tomographic osteoabsorptiometry (CTOAM). Visually, all joints showed very similar density distribution patterns. No significant differences in the topography of the density maxima were found between t1 and t2. The mean density, maximum density, and maximum area ratio (MAR) were significantly increased with increasing age. CONCLUSIONS: The subchondral bone density of the talus of healthy Labrador Retrievers increases with increasing age. It is likely an adaptive response of the subchondral bone due to increased joint loading during growth.

Differences in knee adduction moment between healthy subjects and patients with osteoarthritis depend on the knee axis definition.

OBJECTIVE: This study, firstly, investigates the effect of using an anatomical versus a functional axis of rotation (FAR) on knee adduction moment (KAM) in healthy subjects and patients with knee osteoarthritis (KOA). Secondly, this study reports KAM for models with FAR calculated using weight-bearing and non-weight-bearing motion. DESIGN: Three musculoskeletal models were created using OpenSim with different knee axis of rotation (AR): transepicondylar axis (TEA); FAR calculated based on SARA algorithm using a weight-bearing motion (wFAR) and a non-weight-bearing motion (nwFAR). KAM were calculated during gait in fifty-nine subjects (n=20 healthy, n=16 early OA, n=23 established OA) for all models and groups. RESULTS: Significant differences between the three groups in the first peak KAM were found when TEA was used (p=0.038). However, these differences were no longer present when using FAR. In subjects with established OA, KAMs were significantly reduced when using nwFAR compared to TEA models but also compared to wFAR models. CONCLUSION: The presence of excessive KAM in subjects with established KOA showed to be dependent on the definition of the AR: anatomical versus functional. Therefore, caution should be accounted when comparing KAM in different studies on KOA patients. In patients with end-stage knee OA where increased passive knee laxity is likely to exist, the use of weight-bearing motions should be considered to avoid increased variability in the location and orientation of a FAR obtained from activities with only limited joint loading.

Quantifying thumb opposition kinematics using dynamic computed tomography.

Current motion capture techniques all have shortcomings when applied to the 3D quantitative evaluation of thumb base motion. Dynamic CT might overcome these shortcomings but, so far, robustness of this technique in more than one specimen has not yet been demonstrated. The aim of the current study is to further evaluate the use of dynamic CT for quantification of thumb motion in a larger cadaveric study using a protocol which is feasible in a clinical context. A dynamic CT scan was acquired from six cadaveric human forearms, while a motion simulator imposed thumb opposition. After image acquisition and segmentation, carpal bone motion was quantified using helical axes. To enable comparisons between specimens, intersection points of the instantaneous helical axis with an anatomically defined plane were determined. Precision of the dynamic CT method, measured as variation in distances between silicon nitride beads between frames of a dynamic scan, was 0.43mm (+/-0.09mm) when fixed to the skin and 0.13mm (+/-0.04mm) when embedded into the bone. Absolute deviation between known and measured distances were not larger than 0.34mm. We could demonstrate and quantify that thumb opposition is associated with motion at the trapeziometacarpal and scaphotrapezotrapezoidal joints. High consistency in motion patterns between specimen were found, while the radiation dose was limited. We conclude that dynamic CT can be used to visualize and quantify 3D thumb kinematics, making it a promising method to explore kinematics in vivo.