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Abstract: Accurate measurement of underlying bone positions is important for the understanding of normal movement and function, as well as for addressing clinical musculoskeletal or post-injury problems. Non-invasive measurement techniques are limited by the analysis technique and movement of peripheral soft tissues that can introduce significant measurement errors in reproducing the kinematics of the underlying bones when using external skin markers. Reflective markers, skeletally mounted to the right hind limb of three Merino-mix sheep were measured simultaneously with markers attached to the skin of each segment, during repetitions of gait trials. The movement of the skin markers relative to the underlying bone positions was then assessed using the Point Cluster Technique (PCT), raw averaging and the Optimal Common Shape Technique (OCST), a new approach presented in this manuscript. Errors in the position of the proximal joint centre, predicted from the corresponding skin markers, were shown to be phasic and strongly associated with the amount soft tissue coverage, averaging 8.5mm for the femur, 2.8 for the tibia and 2.0 for the metatarsus. Although the results show a better prediction of bone kinematics associated with the Optimal Common Shape Technique, these errors were large for all three assessment techniques and much greater than the differences between the various techniques. Whilst individual markers moved up to 4mm from the optimal marker set configuration, average peak errors of up to 16, 5 and 3mm (hip, knee and tibio-metatarsal joints respectively) were observed, suggesting that a large amount of kinematic noise is produced from the synchronous shifting of marker sets, potentially as a result of underlying muscle firing and the inertial effects of heel impact. Current techniques are therefore limited in their ability to determine the kinematics of underlying bones based on skin markers, particularly in segments with more pronounced soft tissue coverage. [Copyright &y& Elsevier]

Despite the introduction of new surgical techniques, the treatment of cartilage defects remains challenging. Delay or complete failure of cartilage healing is associated with problems in biological regeneration. The influence of mechanical conditions on this process, however, remains unevaluated.Osteochondral defects were generated on the left femoral condyle in 18 Yucatan minipigs. After 4, 6 and 12 weeks the defect filling, trabecular orientation and bone density were compared to the intact contralateral side. The mechanical straining during this period was then analyzed using an adaptive finite element technique.Histologically, the osteochondral defects showed bone resorption at the base and bone formation from the circumference. At 12 weeks, the macroscopically healed specimens showed fibrous cartilage formation, a minimally organized trabecular structure and increased trabecular volume fraction compared to the controls (p<0.002). The amount of cancellous, cartilagineous, and fibrous tissue and the defect size as measured in histomorphometric analysis for the three time points (4, 6 and 12 weeks) was comparable in magnitude to that predicted by finite element analysis. The simulated osteochondral healing process was not fully capable of re-establishing a hyaline-like cartilage layer. The correlation between simulation and histology allows identification of mechanical factors that appear to have a larger impact on the healing of osteochondral defects than previously considered. [Copyright &y& Elsevier]

Background: The onset and progression of osteoarthritis, but also the wear and loosening of the components of an artificial joint, are commonly associated with mechanical overloading of the structures. Knowledge of the mechanical forces acting at the joints, together with an understanding of the key factors that can alter them, are critical to develop effective treatments for restoring joint function. While static anatomy is usually the clinical focus, less is known about the impact of dynamic factors, such as individual muscle recruitment, on joint contact forces.Methods: In this study, instrumented knee implants provided accurate in vivo tibio-femoral contact forces in a unique cohort of 9 patients, which were used as input for subject specific musculoskeletal models, to quantify the individual muscle forces during walking and stair negotiation.Results: Even between patients with a very similar self-selected gait speed, the total tibio-femoral peak forces varied 1.7-fold, but had only weak correlation with static alignment (varus/valgus). In some patients, muscle co-contraction of quadriceps and gastrocnemii during walking added up to 1 bodyweight (~ 50%) to the peak tibio-femoral contact force during late stance. The greatest impact of co-contraction was observed in the late stance phase of stair ascent, with an increase of the peak tibio-femoral contact force by up to 1.7 bodyweight (66%).Conclusions: Treatment of diseased and failed joints should therefore not only be restricted to anatomical reconstruction of static limb axes alignment. The dynamic activation of muscles, as a key modifier of lower limb biomechanics, should also be taken into account and thus also represents a promising target for restoring function, patient mobility, and preventing future joint failure.Trial Registration: German Clinical Trials Register: ID: DRKS00000606 , date: 05.11.2010. [ABSTRACT FROM AUTHOR]

Objective: To determine whether there are common biomechanical parameters when analysing the single leg squat movement to compare pathological and non-pathological groups and whether these parameters are able to effectively distinguish between groups., Methods: Five electronic databases were searched using MESH terms, keywords and phrases across four constructs: squat, biomechanical measures, region of interest, study design. Studies were selected based on inclusion of a quantitative biomechanical measure, compared between a pathological and a non-pathological group, and participants performed a single leg squat movement., Results: Fifteen studies were included and reviewed, where the majority of studies investigated patellofemoral pain. There was considerable variation in the biomechanical outcome measure used to compare between groups. The frontal plane projection angle was the most commonly reported measure. There was considerable variation in the manner in which the single leg squat was performed., Conclusion: Due to variation in how the single leg squat was performed, it was not possible to determine specific biomechanical parameters that distinguish between pathological and non-pathological groups. Frontal plane projection angle appeared to be a parameter that could be effectively utilised. Standardisation of the single leg squat movement is needed to allow comparison between studies of pathological and non-pathological groups., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

This paper is concerned with the primary stability of the Furlong Evolution(®) cementless short stem across a spectrum of patient morphology. A computational tool is developed that automatically selects and positions the most suitable stem from an implant system made of a total of 48 collarless stems to best match a 3D model based on a library of CT femur scans (75 males and 34 females). Finite Element contact models of reconstructed hips, subjected to physiologically-based boundary constraints and peak loads of walking mode, were simulated using a coefficient of friction of 0.4 and an interference-fit of 50 μm. Maximum and average implant micromotions across the subpopulation were predicted to be 100±7 μm and 7±5 μm with ranges [15 μm, 350 μm] and [1 μm, 25 μm], respectively. The computed percentage of implant area with micromotions greater than reported critical values of 50 μm, 100 μm and 150 μm never exceeded 14%, 8% and 7%, respectively. To explore the possible correlations between anatomy and implant performance, response surface models for micromotion metrics were constructed. Detailed morphological analyses were conducted and a clear nonlinear decreasing trend was observed between implant average micromotion and both the metaphyseal canal flare indices and average densities in Gruen zones. The present study demonstrates that the primary stability and tolerance of the short stem to variability in patient anatomy were high, reducing the need for patient stratification. In addition, the developed tool could be utilised to support implant design and planning of femoral reconstructive surgery., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Although instability of the knee joint is known to modify gait patterns, the amount that patients compensate for joint laxity during active movements remains unknown., Purpose: By developing a novel technique to allow the assessment of tibiofemoral kinematics, this study aimed to elucidate the role of passive joint laxity on active tibiofemoral kinematics during walking., Study Design: Controlled laboratory study., Methods: Using motion capture, together with combinations of advanced techniques for assessing skeletal kinematics (including the symmetrical axis of rotation approach [SARA], symmetrical center of rotation estimation [SCoRE], and optimal common shape technique [OCST]), a novel noninvasive approach to evaluate dynamic tibiofemoral motion was demonstrated as both reproducible and repeatable. Passive and active anterior-posterior translations of the tibiofemoral joint were then examined in 13 patients with anterior cruciate ligament (ACL) ruptures that were confirmed by magnetic resonance imaging and compared with those in their healthy contralateral limbs., Results: Passive tibial anterior translation was significantly greater in the ACL-ruptured knees than in the contralateral healthy controls. However, the femora of the ACL-ruptured knees generally remained more posterior (~3 mm) relative to the tibia within a gait cycle of walking compared with the healthy limbs. Surprisingly, the mean range of tibiofemoral anterior-posterior translation over an entire gait cycle was significantly lower in ACL-ruptured knees than in the healthy joints (P = .026). A positive correlation was detected between passive laxity and active joint mobility, but with a consistent reduction in the range of tibiofemoral anterior-posterior translation of approximately 3 mm in the ACL-deficient knees., Conclusion: It seems that either active stabilization of tibiofemoral kinematics or anterior subluxation of the tibia reduces joint translation in lax knees. This implies that either a muscular overcompensation mechanism or a physical limitation due to secondary passive stabilizers occurs within the joint and thus produces a situation that has a reduced range of active motion compared with knees with physiological stability., Clinical Relevance: The reduced range of active tibiofemoral translation suggests overloading of the passive structures in passively lax knees, either through excessive muscular action or joint subluxation, and could provide a plausible mechanism for explaining posttraumatic degeneration of cartilage in the joint.

Deformable surface models are often represented as triangular meshes in image segmentation applications. For a fast and easily regularized deformation onto the target object boundary, the vertices of the mesh are commonly moved along line segments (typically surface normals). However, in case of high mesh curvature, these lines may not intersect with the target boundary at all. Consequently, certain deformations cannot be achieved. We propose omnidirectional displacements for deformable surfaces (ODDS) to overcome this limitation. ODDS allow each vertex to move not only along a line segment but within the volumetric inside of a surrounding sphere, and achieve globally optimal deformations subject to local regularization constraints. However, allowing a ball-shaped instead of a linear range of motion per vertex significantly increases runtime and memory. To alleviate this drawback, we propose a hybrid approach, fastODDS, with improved runtime and reduced memory requirements. Furthermore, fastODDS can also cope with simultaneous segmentation of multiple objects. We show the theoretical benefits of ODDS with experiments on synthetic data, and evaluate ODDS and fastODDS quantitatively on clinical image data of the mandible and the hip bones. There, we assess both the global segmentation accuracy as well as local accuracy in high curvature regions, such as the tip-shaped mandibular coronoid processes and the ridge-shaped acetabular rims of the hip bones., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Diagnosis of acetabular retroversion is essential in femoroacetabular impingement (FAI), but its assessment from radiographs is complicated by pelvic tilt and the two-dimensional nature of plain films. We performed a study to validate the diagnostic accuracy of the cross-over sign (COS) and the posterior wall sign (PWS) in identifying acetabular retroversion. COS and PWS were evaluated from radiographs and computed tomography (CT) scans as the standard of reference in 50 hips of subjects with symptoms of FAI. A CT-based method using three-dimensional (3D) models was developed to measure the COS, PWS, true acetabular version, and pelvic tilt relative to the anterior pelvic plane. The new CT-based method aimed to eliminate errors resulting from variations in the position and orientation of the pelvis during imaging. A low level of agreement for COS and PWS was found between radiographs and CT scans. A positive COS strongly correlated with pelvic tilt. These results suggest that COS and PWS determined from anteroposterior radiographs are considerably limited by pelvic tilt and inherent limitations of radiographs. Their use as the sole basis for deciding whether or not surgical intervention is indicated seems questionable., (Copyright © 2012 Orthopaedic Research Society.)

Introduction: This feasibility study investigated the accuracy of anterior pelvic reference plane (APP) registration and acetabular cup orientation in two cadavers with different BMIs., Method: Five observers each registered the APP five times in the 2 cadavers (BMIs: 32 kg/m(2) and 25 kg/m(2)) using an ultrasound-based navigation system. By comparison against the CT-derived reference landmarks, the errors in determining the individual landmarks defining the APP, as well as the resulting errors in the orientation of the APP and the acetabular cup orientation were determined., Results: Across all measurements obtained with the ultrasound navigation system, the errors in rotation and version in determining the APP were 0.5° ± 1.0° and -0.4° ± 2.0°, respectively. The cup abduction and anteversion errors determined from all measurements of the five investigators for both cadavers together were -0.1° ± 1.0° and -0.4° ± 2.7°, respectively. The data further demonstrated a high reproducibility of the measurements for the resulting cup adduction and anteversion angle., Conclusion: Our preliminary results confirm that ultrasound navigation is a highly accurate tool that allows a reproducible registration of the APP and thereby enables accurate and precise intraoperative determination of the acetabular cup orientation also in patients with increased BMI.

Functional methods present a promising approach for the identification of skeletal kinematics, but their accuracy is limited by soft tissue artifacts (STAs). We hypothesized that consideration of the nonuniform distribution of STAs across the segment can lead to a significant improvement in the determination of the center of rotation at the hip. Twenty-four total hip arthroplasty (THA) patients performed repetitions of a star-arc movement. The location of the hip centers of rotation (CoRs) were estimated from the motion data using the Symmetrical Center of Rotation Estimation (SCoRE), both with and without procedures to minimize the effect of STAs. The precision of the CoR estimations was evaluated using the SCoRE residual, a measure of joint precision. Application of the newly developed weighted Optimal Common Shape Technique (wOCST) achieved the best CoR estimations with a precision of better than 3 mm, while the precision using raw data alone was up to seven times worse. Furthermore, consideration of the nonuniform distribution of STA across the surface of the skin using the wOCST produced an improvement of ∼24% over kinematics data processed using the standard OCST. Functional determination of the CoR at the hip using the newly developed wOCST can now identify the joint CoR with a precision of millimeters. Such approaches therefore offer improved precision in the assessment of skeletal kinematics and may aid in evaluating clinical treatment success and differentiating between therapy outcomes., (Copyright © 2011 Orthopaedic Research Society.)

The determination of an accurate centre of rotation (CoR) from skin markers is essential for the assessment of abnormal gait patterns in clinical gait analysis. Despite the many functional approaches to estimate CoRs, no non-invasive analytical determination of the error in the reconstructed joint location is currently available. The purpose of this study was therefore to verify the residual of the symmetrical centre of rotation estimation (SCoRE) as a reliable indirect measure of the error of the computed joint centre. To evaluate the SCoRE residual, numerical simulations were performed to evaluate CoR estimations at different ranges of joint motion. A statistical model was developed and used to determine the theoretical relationships among the SCoRE residual, the magnitude of the skin marker artefact, the corrections to the marker positions, and the error of the CoR estimations to the known centre of rotation. We found that the equation err=0.5r(s) provides a reliable relationship among the CoR error, err, and the scaled SCoRE residual, r(s), providing that any skin marker artefact is first minimised using the optimal common shape technique (OCST). Measurements on six healthy volunteers showed a reduction of SCoRE residual from 11 to below 6mm and therefore demonstrated consistency of the theoretical considerations and numerical simulations with the in vivo data. This study also demonstrates the significant benefit of the OCST for reducing skin marker artefact and thus for predicting the accuracy of determining joint centre positions in functional gait analysis. For the first time, this understanding of the SCoRE residual allows a measure of error in the non-invasive assessment of joint centres. This measure now enables a rapid assessment of the accuracy of the CoR as well as an estimation of the reproducibility and repeatability of skeletal motion patterns., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Hyperbranched polyglycerols (HPGs) with hydrophobic cores and derivatized with methoxy poly(ethylene glycol) were synthesized and further functionalized with carboxylate groups to bind and deliver cisplatin. Low and high levels of carboxylate were conjugated to HPGs (HPG-C(8/10)-MePEG(6.5)-COOH(113) and HPG-C(8/10)-MePEG(6.5)-COOH(348)) and their structures were confirmed through NMR and FTIR spectroscopy and potentiometric titration. The hydrodynamic diameter of the HPGs ranged from 5-10 nm and the addition of COOH groups decreased the zeta potential of the polymers. HPG-C(8/10)-MePEG(6.5)-COOH(113) bound up to 10% w/w cisplatin, whereas HPG-C(8/10)-MePEG(6.5)-COOH(348) bound up to 20% w/w drug with 100% efficiency. Drug was released from HPG-C(8/10)-MePEG(6.5)-COOH(113) over 7 days at the same rate, regardless of the pH. Cisplatin release from HPG-C(8/10)-MePEG(6.5)-COOH(348) was significantly slower than HPG-C(8/10)-MePEG(6.5)-COOH(113) at pH 6 and 7.4, but similar at pH 4.5. Release of cisplatin into artificial urine was considerably faster than into buffer. Carboxylated HPGs demonstrated good biocompatibility, and drug-loaded HPGs effectively inhibited proliferation of KU-7-luc bladder cancer cells.

This study investigated the hypothesis that fatiguing exercises led to increased force fluctuations during submaximal isometric knee extensions and to decreased accuracy and steadiness in the time and frequency domains. Sixteen young adults (eight males, eight females) were tested, in a seated posture with 90 degrees knee flexion, to assess their ability to reproduce target extensor torques set at 15 per cent and 20 per cent of their maximum voluntary isometric contraction, both before and after fatiguing exercises. Normalized mean (NMAE) and peak (NPAE) of the absolute error were both used to quantify accuracy, whereas normalized standard deviation of the absolute error (NSAE) was used to quantify steadiness of the torque trials in the time domain. Mean and median power frequencies (MnPF, MdPF) and normalized peak power (NPkP) were used to assess the spectral structure of the torque signals. NMAE, NSAE and NPAE all showed excellent intra- as well as intersession reliabilities (intraclass correlation values greater than 0.75 and low standard error of measurement values), demonstrating repeatability of the test set-up. NMAE, NSAE and NPAE increased significantly post-fatigue (greater than 42%), together with a shift towards higher frequency (MnPF and MdPF) components, indicating that the set-up was sensitive enough to detect the decreased force accuracy and steadiness of the musculature after fatigue. Increased force variability in both the time and frequency domains could therefore explain decreased steadiness after fatigue.

A trend in total hip arthroplasty surgery has been to design more bone-preserving procedures, especially for younger patients. This study investigated the final implant positioning of a short metaphyseal femoral neck type of implant to determine whether leg length, caput collum diaphysis (CCD) angle, and offset could be re-created with different levels of femoral neck resection. Ten cadaveric hips in 6 whole-body specimens were used, with 3 fiducial markers to allow registration of computer navigation points to computed tomography scan data. Three femoral neck resection levels were investigated: 0 mm, +5 mm (the recommended level of resection), and +10 mm from the base of the femoral neck. Results showed that the CCD angle was significantly higher with 0-mm neck cut and the offset was lower, whereas the highest neck cut had longer leg-length results. Surgeons who use a short metaphyseal stem need to realize the importance of a proper femoral neck cut to restore anatomic parameters as well as the possible benefit of computer-assisted surgery to restore these anatomic parameters during surgery., (Copyright 2009, SLACK Incorporated.)

The intrinsic antimicrobial resistance of the opportunistic human pathogen Pseudomonas aeruginosa is compounded in mutant strains that overexpress multidrug efflux pumps such as the prominent drug-proton antiporter, MexAB-OprM. The primary regulator of the mexAB-oprM operon is the MarR family repressor, MexR. An additional repressor, NalC, also regulates mexAB-oprM by controlling expression of ArmR, an antirepressor peptide that is hypothesized to prevent the binding of MexR to its cognate DNA operator via an allosteric protein-peptide interaction. To better understand how ArmR modulates MexR, we determined the MexR-binding region of ArmR as its C-terminal 25 residues and solved the crystal structure of MexR in a 2:1 complex with this ArmR fragment at 1.8 A resolution. This structure reveals that the C-terminal residues of ArmR form a kinked alpha-helix, which occupies a pseudosymmetrical and largely hydrophobic binding cavity located at the centre of the MexR dimer. Although the ArmR-binding cavity partially overlaps with the small molecule effector-binding sites of other MarR family members, it possesses a larger and more complex binding surface to accommodate the greater size and specific physicochemical properties of a peptide effector. Comparison with the structure of apo-MexR reveals that ArmR stabilizes a dramatic conformational change that is incompatible with DNA-binding. Thus, this work defines the structural mechanism by which ArmR allosterically derepresses MexR-controlled gene expression in P. aeruginosa and reveals important insights into the regulation of multidrug resistance.

Background: Short-stemmed hip implants were introduced to conserve proximal bone mass and may facilitate the use of minimally invasive surgery, in which smaller incisions limit access to the joint. This limited access may increase the risk of surgical mal-positioning of the implant, however the sensitivity of femoral loading to such mal-positioning of a short-stemmed implant has not been studied., Methods: Finite element models were developed of a femur and a short-stemmed implant positioned to reproduce the intact hip centre, as well as with the implant placed in increased anteversion or offset. The effect of these surgical variables on femoral loading was examined for walking and stair climbing using loads from a validated musculoskeletal model. Results of the implanted models were compared with an intact model to evaluate stress shielding., Findings: Implant position had little influence on cortical strains along the length of the diaphysis, although strains decreased by up to 95% at the neck resection level compared to the intact femur. In the proximal Gruen zones I and VII strain energy density among the implanted models varied by up to 0.4 kJ/m(3) (28%) and 0.6 kJ/m(3) (24%) under walking and stair climbing, respectively. All implanted models showed characteristic proximal stress shielding, indicated by a decrease in strain energy density of up to 5.4 kJ/m(3) (69%) compared to the intact femur., Interpretation: Small changes in stem placement would likely have little influence on the internal loading of the femur after bone ingrowth has been achieved, however a reduction in strain energy density and therefore stress shielding was seen even for a short-stemmed implant, which may have consequences for longer-term bone remodelling.

Pre-clinical testing of hip endoprostheses is a mandatory requirement before clinical release. Inadequate loading conditions may lead to lower elastic and plastic interface movements than those occurring post-operatively in vivo. This study investigated the influence of patient activity on the primary stability of cementless prostheses with a special emphasis on active simulation of muscle forces. A loading setup, based on validated musculo-skeletal analyses, was used to generate the hip contact force during walking and stair climbing by transmitting muscle forces through the femur. In addition, a loading configuration which only generated the hip contact force occurring during stair climbing at the prosthesis head was simulated. CLS prostheses were implanted in 18 composite femora and subjected to cyclical loading. The relative micro-movements at the bone-prosthesis interface were determined and appeared to be extremely sensitive to the specific patient activity. Compared to walking, stair climbing generated higher micro-movements, with pronounced axial and rotational components. Stair climbing with the femur loaded by the resultant hip contact force only exhibited a characteristic valgus tilt of the stem with significantly lower interface micro-movements than under active simulation of muscle forces. The analyses suggest that stair climbing induced the highest mechanical instability at the bone-prosthesis interface, a level which may compromise the necessary osseointegration process. Active simulation of muscle forces considerably affects the primary stability of cementless hip endoprostheses. Pre-clinical in vitro tests should therefore simulate stair climbing and include muscle activity in the assessment of initial implant stability, otherwise micro-movements may be underestimated and the primary stability overestimated.

The cyclic somatostatin analogue cyclo[Pro(1)-Phe(2)-D-Trp(3)-Lys(4)-Thr(5)-Phe(6)] (L-363,301) displays high biological activity in inhibiting the release of growth hormone, insulin, and glucagon. According to the sequence of L-363,301, we synthesized a number of cyclic hexa- and pentapeptides containing nonnatural alpha- and beta-amino acids. The N- fluorenylmethoxycarbonyl protected cyclic beta-amino acid [1S, 2S, 5R]-2-amino-3,5-dimethyl-2-cyclohex-3-enecarboxylic acid (cbetaAA), for the replacement of the Phe(6)-Pro(1) moiety of L-363,301, was synthesized in two steps by an enantioselective multicomponent reaction using (-)-8-phenylmenthol as a chiral auxiliary. The resulting peptide cyclo[cbetaAA(1)-Tyr(2)-D-Trp(3)-Nle(4)-Thr(Trt)(5)] (Trt = triphenylmethyl) shows high antiproliferative effects in an in vitro assay with A431 cancer cells. The same peptide without the Trt group does not reveal any biological activity, whereas L-363,301 and closely related hexapeptides show only minor activity. By comparison of the solution structure of cyclo[cbetaAA(1)-Tyr(2)-D-Trp(3)-Nle(4)-Thr(Trt)(5)] with the structure of l-363,301, a nearly perfect match of the betaII'-turn region with d-Trp in the i + 1 position was observed. The cyclic beta-amino acid cbetaAA is likely needed for the bioactive conformation of the peptide.

Background and Aim: High tibial osteotomies attempt to recreate physiologically normal joint loading. Previous studies have discussed the influence of mal-alignment on the distribution of static loads to the medial and lateral compartments of the knee. The aim of this study was to determine the influence of mal-alignment on the tibio-femoral loading conditions during dynamic activities., Material and Methods: Using a musculo-skeletal model of the lower limb, which had been previously validated with in vivo data, in this study we modified the alignment of the knee in four patients, from a normal position to the extremes of 8 degrees valgus and 10 degrees varus mal-alignment. The resulting tibio-femoral joint contact forces were examined while patients were walking and stair climbing., Results: Varying the mal-alignment resulted in a highly individual response in joint loads. Deviations from the normal alignment produced an increase in loading, with valgus generating a more rapid increase in loading than a varus deformity of the same amount. Varus deformities of 10 degrees resulted in increases in peak contact force from an average of 3.3-times bodyweight (BW) up to a peak of 7.4 BW (+45% to +114%) while patients were walking, whilst increases of 15% up to 35% were determined for stair climbing. Increases of up to 140% were calculated at 8 degrees valgus during walking and up to 53% for stair climbing., Conclusion: This study demonstrated a clear dependence of the individual joint loads on axial knee alignment. Based on the sensitivity of joint loading to valgus mal-alignment, more than 3 degrees of over-correction of a varus deformity to valgus should be carefully reconsidered.