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Purpose: To evaluate in vivo T 2 mapping as quantitative, imaging-based biomarker for meniscal degeneration in humans, by studying the correlation between T 2 relaxation time and degree of histological degeneration as reference standard., Methods: In this prospective validation study, 13 menisci from seven patients with radiographic knee osteoarthritis (median age 67 years, three males) were included. Menisci were obtained during total knee replacement surgery. All patients underwent pre-operative magnetic resonance imaging using a 3-T MR scanner which included a T 2 mapping pulse sequence with multiple echoes. Histological analysis of the collected menisci was performed using the Pauli score, involving surface integrity, cellularity, matrix organization, and staining intensity. Mean T 2 relaxation times were calculated in meniscal regions of interest corresponding with the areas scored histologically, using a multi-slice multi-echo postprocessing algorithm. Correlation between T 2 mapping and histology was assessed using a generalized least squares model fit by maximum likelihood., Results: The mean T 2 relaxation time was 22.4 ± 2.7 ms (range 18.5-27). The median histological score was 10, IQR 7-11 (range 4-13). A strong correlation between T 2 relaxation time and histological score was found (r s  = 0.84, CI 95% 0.64-0.93)., Conclusion: In vivo T 2 mapping of the human meniscus correlates strongly with histological degeneration, suggesting that T 2 mapping enables the detection and quantification of early compositional changes of the meniscus in knee OA., Key Points: • Prospective histology-based study showed that in vivo T 2 mapping of the human meniscus correlates strongly with histological degeneration. • Meniscal T 2 mapping allows detection and quantifying of compositional changes, without need for contrast or special MRI hardware. • Meniscal T 2 mapping provides a biomarker for early OA, potentially allowing early treatment strategies and prevention of OA progression.

Purpose: The Osteoarthritis Research Society International has identified a core set of performance-based tests of physical function for use in people with knee osteoarthritis (OA). The core set consists of the 30-second chair stand test (30-s CST), 4 × 10 m fast-paced walk test (40 m FPWT) and a stair climb test. The aim of this study was to evaluate the reliability, validity and responsiveness of these performance-based measures to assess the ability to measure physical function in knee OA patients., Methods: A prospective cohort study of 85 knee OA patients indicated for total knee arthroplasty (TKA) was performed. Construct validity and responsiveness were assessed by testing of predefined hypotheses. A subgroup (n = 30) underwent test-retest measurements for reliability analysis. The Oxford Knee Score, Knee injury and Osteoarthritis Outcome Score-Physical Function Short Form, pain during activity score and knee extensor strength were used as comparator instruments. Measurements were obtained at baseline and 12 months after TKA., Results: Appropriate test-retest reliability was found for all three tests. Intraclass correlation coefficient (ICC) for the 30-s CST was 0.90 (95% CI 0.68; 0.96), 40 m FPWT 0.93 (0.85; 0.96) and for the 10-step stair climb test (10-step SCT) 0.94 (0.89; 0.97). Adequate construct validity could not be confirmed for the three tests. For the 30-s CST, 42% of the predefined hypotheses were confirmed; for the 40 m FPWT, 27% and for the 10-step SCT 36% were confirmed. The 40 m FPWT was found to be responsive with 75% of predefined hypothesis confirmed, whereas the responsiveness for the other tests could not be confirmed. For the 30 s CST and 10-step SCT, only 50% of hypotheses were confirmed., Conclusions: The three performance-based tests had good reliability, but poor construct validity and responsiveness in the assessment of function for the domains sit-to-stand movement, walking short distances and stair negotiation. The findings of the present study do not justify their use for clinical practice., Level of Evidence: Level 1. Diagnostic study.

Aims: Little is known about the risk factors that predispose to a rupture of the posterior cruciate ligament (PCL). Identifying risk factors is the first step in trying to prevent a rupture of the PCL from occurring. The morphology of the knee in patients who rupture their PCL may differ from that of control patients. The purpose of this study was to identify any variations in bone morphology that are related to a PCL., Patients and Methods: We compared the anteroposterior (AP), lateral, and Rosenberg view radiographs of 94 patients with a ruptured PCL to a control group of 168 patients matched by age, sex, and body mass index (BMI), but with an intact PCL after a knee injury. Statistical shape modelling software was used to assess the shape of the knee and determine any difference in anatomical landmarks., Results: We found shape variants on the AP and Rosenberg view radiographs to be significantly different between patients who tore their PCL and those with an intact PCL after a knee injury. Overall, patients who ruptured their PCL have smaller intercondylar notches and smaller tibial eminences than control patients., Conclusion: This study shows that differences in the shape of the knee are associated with the presence of a PCL rupture after injury. A smaller and more sharply angled intercondylar notch and a more flattened tibial eminence are related to PCL rupture. This suggests that the morphology of the knee is a risk factor for sustaining a PCL rupture. Cite this article: Bone Joint J 2019;101-B:1058-1062.

Purpose: To determine the face and construct validity as well as educational value and user-friendliness of the Simendo knee arthroscopy virtual reality simulator., Methods: Sixty participants were recruited and equally divided into novices (0 arthroscopic procedures), intermediates (1-59 arthroscopic procedures), and experts (60 or more arthroscopic procedures). Participants were excluded if they had previously trained with the studied simulator. Construct validity, that is, the ability to discriminate between different levels of expertise, was examined by a navigation task. All participants were asked to perform 5 navigation trials within 10 minutes. Face validity, educational value, and user-friendliness were examined by questionnaires before and after the navigation trials. Face validity is the subjective impression of how closely the simulation replicates the real environment., Results: The novices were significantly slower than the intermediates in the first (P < .001) and the third (P = .031) trial. The novices were significantly slower than the experts in all trials (P = .016), except for the fifth (P = .054). The experts were significantly faster than the intermediates in every trial except for the fourth (P = .069). Median task time for the fifth trial was 63 seconds (44-80 seconds) for novices, 58 seconds (46-80 seconds) for intermediates, and 41 seconds (33-55 seconds) for experts. Ninety-two percent of all participants agreed that the simulator can be used to train for surgical inspection, and 95% indicated sufficient user-friendliness., Conclusions: Based on the results, this knee simulator can be applied to train the basic arthroscopic hand-eye coordination skills at the start of resident education programs. Further testing is necessary to determine whether the skills are retained., Clinical Relevance: The simulator is partly validated, which contributes to training of basic arthroscopic skills without compromising patient safety., (Copyright © 2019 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Objective: To assess whether targeted neuromuscular exercises can decrease knee loading of adolescent pre-professional footballers with high knee loading as identified with the field-based Drop Vertical Jump Test (DVJT)., Design: Prospective controlled trial, conducted between August and November 2016 at Erasmus Medical Centre, The Netherlands., Methods: Pre-professional football players (aged 14-21years) were evaluated at baseline and after 12weeks follow-up with the field-based DVJT. The field-based DVJT is a standardised test in which a player drops from a box and jumps up immediately after landing; knee load is calculated based on five parameters. Players with high knee load (probability≥0.75) from one club performed regular training(control group), and players with high knee load from another other club performed targeted neuromuscular exercises for 12weeks (intervention group). The difference of change in knee load between both groups after 12weeks was the primary outcome measure., Results: Of 107 eligible players, 75 had a high knee loading. Knee loading decreased in both groups after 12weeks of training, but change in probability of high knee load was not significantly different between both groups (95% Confidence Interval [-0.012-0.082], p=0.139)., Conclusion: Targeted neuromuscular exercises had no additional effect in decreasing knee loading of adolescent male pre-professional football players compared to regular training., Trial Registration Number: The Netherlands Trial Register (ID number: 6044)., (Copyright © 2018 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.)

Background: One out of five patients is unsatisfied to some extent after total knee arthroplasty (TKA). Unmet expectations are the main driver of post-operative dissatisfaction. Improved pre-operative education on realistic expectations for long-term outcome after TKA potentially leads to higher post-operative satisfaction. The effect of expectation modification on post-operative satisfaction in TKA patients has not yet been studied. The primary objective of the presented study is to examine whether an educational module on long-term recovery after TKA will improve patient satisfaction compared to usual pre-operative education., Methods: The EKSPECT study is a randomized controlled trial. Patients with symptomatic and radiographic knee osteoarthritis who are indicated for a primary TKA will be randomized to the usual pre-operative education (control group) or usual education plus an additional module on realistic expectations for long-term recovery (intervention group). Patients will be naïve to study objective and difference between study groups. Outcome expectations will be measured blinded for group allocation using the HSS Knee Replacement Expectations Survey at baseline (before the intervention), pre-operatively (after the intervention) and fulfillment of expectations at 12-month follow-up. Baseline physical function, quality of life and psychological factors are measured using self-reported questionnaires. The primary outcome measure is satisfaction with treatment result at the 12-month follow-up., Discussion: The EKSPECT study should provide evidence on the effectiveness of an education module on long-term recovery after TKA to improve treatment satisfaction. If beneficial, the education module is a simple intervention with a low burden for patients, which can easily be implemented in clinical practice., Trial Registration: Dutch Trial Registry registration number: NTR5779 . Registered on 17 March 2016.

T2-mapping is a widely used quantitative MRI technique in osteoarthritis research. An important challenge for its application in the context of high tibial osteotomy (HTO) is the presence of metallic fixation devices. In this study, we evaluated the possibility of performing T2-mapping after a HTO, by assessing the extent of magnetic susceptibility artifacts and the influence on T2 relaxation times caused by two commonly used fixation devices. T2-mapping with a 3D fast spin-echo sequence at three Tesla was performed on 11 human cadaveric knee joints before and after implantation of a titanium plate and screws (n = 5) or cobalt chrome staples (n = 6). Mean T2 relaxation times were calculated in six cartilage regions, located in the distal and posterior cartilage of femoral condyles and the cartilage of tibial plateaus, both medially and laterally. T2 relaxation times before and after the implantation were compared with paired t-tests and Wilcoxon rank tests. Due to the extent of the magnetic susceptibility artifact, it was not possible to segment the knee cartilage and thus calculate T2 relaxation times in the lateral weight-bearing femoral and tibial cartilage regions only in the cobalt chrome group. In all cartilage regions of the titanium implanted knees and those unaffected by artifacts due to cobalt chrome implants, T2 relaxation times did not significantly differ between the two scans. Our results suggest that accurate T2-mapping after a HTO procedure is possible in all areas after implantation of a titanium fixation device and in most areas after implantation of a cobalt chrome fixation device. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1206-1212, 2018., (© 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Objective: To evaluate the possibility of assessing knee cartilage with T2-mapping and delayed gadolinium enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) in one post-contrast MR examination at 3 Tesla (T)., Design: T2 mapping was performed in 10 healthy volunteers at baseline; directly after baseline; after 10 min of cycling; and after 90 min delay, and in 16 osteoarthritis patients before and after intravenous administration of a double dose gadolinium dimeglumine contrast agent, reflecting key dGEMRIC protocol elements. Differences in T2 relaxation times between each timepoint and baseline were calculated for 6 cartilage regions using paired t tests or Wilcoxon signed-rank tests and the smallest detectable change (SDC)., Results: After cycling, a significant change in T2 relaxation times was found in the lateral weight-bearing tibial plateau (+1.0 ms, P = 0.04). After 90 min delay, significant changes were found in the lateral weight-bearing femoral condyle (+1.2 ms, P = 0.03) and the lateral weight-bearing tibial plateau (+1.3 ms, P = 0.01). In these regions of interests (ROIs), absolute differences were small and lower than the corresponding SDCs. T2-mapping after contrast administration only showed statistically significantly lower T2 relaxation times in the medial posterior femoral condyle (-2.4 ms, P < 0.001) with a change exceeding the SDC., Conclusion: Because dGEMRIC protocol elements resulted in only small differences in T2 relaxation times that were not consistent and lower than the SDC in the majority of regions, our results suggest that T2-mapping and dGEMRIC can be performed reliably in a single imaging session to assess cartilage biochemical composition in knee osteoarthritis (OA) at 3 T., (Copyright © 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Background: The results of conservative treatment of knee osteoarthritis (OA) are generally evaluated in epidemiological studies with clinical outcome measures as primary outcomes. Biomechanical evaluation of orthoses shows that there are potentially beneficial biomechanical changes to joint loading; however, evaluation in relation to clinical outcome measures in longitudinal studies is needed., Questions/purposes: We asked (1) is there an immediate effect on gait in patients using a laterally wedged insole or valgus knee brace; (2) is there a late (6 weeks) effect; and (3) is there a difference between subgroups within each group with respect to patient compliance, body mass index, and OA status?, Methods: This was a secondary analysis of data from a previous randomized controlled trial of patients with early medial knee OA. A total of 91 patients were enrolled in that trial, and 73 (80%) completed it after 6 months. Of the enrolled patients, 80 (88%) met prespecified inclusion criteria for analysis in the present study. The patients were randomized to an insole or brace. Gait was analyzed with and without wearing the orthosis (insole or brace) at baseline and after 6 weeks. Measurements were taken of the knee adduction moment, ground reaction force, moment arm, walking speed, and toe-out angle. Data were analyzed with regression analyses based on an intention-to-treat principle., Results: A mean reduction of 4% (±10) (95% confidence interval [CI], -0.147 to -0.03, p=0.003) of the peak knee adduction moment and 4% (±13) (95% CI, -0.009 to -0.001, p=0.01) of the moment arm at baseline was observed in the insole group when walking with an insole was compared with walking without an insole. A mean reduction of 1% (±10) (95% CI, -0.002 to -0.001, p=0.001) of the peak knee adduction moment and no reduction of the moment arm were measured after 6 weeks. No reduction of knee adduction moment, moment arm, or ground reaction force was seen in the brace group at baseline and after 6 weeks. Subgroup analysis showed no differences in biomechanical effect for obesity, stage of OA, and whether patients showed a clinical response to the treatment., Conclusions: Laterally wedged insoles unload the medial compartment only at baseline in patients with varus alignment and by an amount that might not be clinically important. No biomechanical alteration was seen after 6 weeks of wearing the insole. Valgus brace therapy did not result in any biomechanical alteration. Taken together, this study does not show a clinically relevant biomechanical effect of insole and brace therapy in patients with varus medial knee OA., Level of Evidence: Level I, therapeutic study. See Instructions for Authors for a complete description of levels of evidence.

Study Design: Systematic literature review., Objectives: To summarize and evaluate research on factors predictive of progression to surgery after nonoperative treatment for an anterior cruciate ligament (ACL) rupture., Background: Anterior cruciate ligament rupture is a common injury among young, active individuals. Surgical reconstruction is often required for patients who do not regain satisfactory knee function following nonsurgical rehabilitation. Knowledge of factors that predict the need for surgical reconstruction of the ACL would be helpful to guide the decision-making process in this population., Methods: A search was performed for studies predicting the need for surgery after nonoperative treatment for ACL rupture in the Embase, MEDLINE (OvidSP), Web of Science, CINAHL, Cochrane Central Register of Controlled Trials, PubMed, and Google Scholar digital databases from inception to October 2013. Two reviewers independently selected the studies and performed a quality assessment. Best-evidence synthesis was used to summarize the evidence of factors predicting the need for surgical reconstruction after nonoperative treatment for an ACL rupture., Results: Seven studies were included, 3 of which were of high quality. Based on these studies, neither sex (strong evidence) nor the severity of knee joint laxity (moderate evidence) can predict whether, soon after ACL injury, a patient will need ACL reconstruction following nonoperative treatment. All other factors identified in this review either had conflicting or only minimal evidence as to their level of association with the need for surgical reconstruction. Noteworthy is that 1 high-quality study reported that the spherical shape of the femoral condyle was predictive of the need for ACL reconstruction., Conclusion: Sex and knee joint laxity tests do not predict the need for ACL reconstruction soon after an ACL rupture. Independent validation in future research will be necessary to establish whether knee shape is a predictive factor., Level of Evidence: Prognosis, level 1a-.

We have investigated whether shape of the knee can predict the clinical outcome of patients after an anterior cruciate ligament rupture. We used statistical shape modelling to measure the shape of the knee joint of 182 prospectively followed patients on lateral and Rosenberg view radiographs of the knee after a rupture of the anterior cruciate ligament. Subsequently, we associated knee shape with the International Knee Documentation Committee subjective score at two years follow-up. The mean age of patients was 31 years (21 to 51), the majority were male (n = 121) and treated operatively (n = 135). We found two modes (shape variations) that were significantly associated with the subjective score at two years: one for the operatively treated group (p = 0.002) and one for the non-operatively treated group (p = 0.003). Operatively treated patients who had higher subjective scores had a smaller intercondylar notch and a smaller width of the intercondylar eminence. Non-operatively treated patients who scored higher on the subjective score had a more pyramidal intercondylar notch as opposed to one that was more dome-shaped. We conclude that the shape of the femoral notch and the intercondylar eminence is predictive of clinical outcome two years after a rupture of the anterior cruciate ligament., (©2014 The British Editorial Society of Bone & Joint Surgery.)

Objective: The pathophysiology of anterior cruciate ligament (ACL) rupture leading to knee osteoarthritis (OA) remains largely unknown. It seems that bone loss occurs after ACL rupture. The purpose of our study was to determine bone mineral density (BMD) changes in the knee after ACL rupture during 2-year follow-up period and to compare BMD changes between the injured and healthy contralateral knee., Design: Patients were included in an observational prospective follow-up study within 6 months after ACL trauma and evaluated for 2 years. Patients were treated operatively or non-operatively. At baseline and at the one- and 2-year follow-ups, BMD was measured in six regions of the tibia and femur for both knees (medial, central, lateral) using a Dual-energy X-ray Absorptiometry (DXA) scanner., Results: One hundred forty-one patients were included, with the following characteristics: 66% were male, median age at baseline was 25.3 (inter-quartile range 11.3) years, and 63% were treated operatively. After 1 year, BMD was significantly lower in all regions of the injured knee of the operatively treated patients compared to baseline. After 2 years, BMD was significantly increased, but remained lower than the baseline levels. In all regions for all measurements, the mean BMD was significantly lower in the injured knee than in the healthy contralateral knee., Conclusions: During a 2-year follow-up period after ACL rupture, the BMD level in the injured knee was found to be lower than in the healthy contralateral knee. In operatively treated patients, the BMD decreased in the first year and increased in the second follow-up year., (Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Introduction: Intra-articular needle placement in the knee joint, such as injection or aspirations, are commonly used for therapeutic, diagnostic, and research purposes. Although several approaches can be used to establish an intra-articular injection or aspiration of the knee joint, the accuracy differs per approach., Objective: To summarize the evidence concerning the accuracy of different approaches for intra-articular needle placements in the knee. Additionally, to assess whether the accuracy of different approaches is related to factors such as underlying disease, severity of underlying disease, approach-related factors, and/or the rate of local reactions., Methods: The literature was systemically reviewed until July 2010. Risk of bias of the included studies was assessed by the QUADAS tool. Study characteristics were extracted; accuracy results were pooled per approach., Results: Nine studies were included. The superolateral approach with the leg in extension was studied most (230 injections) and resulted in the highest pooled accuracy of 91% (95% CI 84-99%). The lateral midpatellar approach, the anterolateral approach, and the anteromedial approach resulted in the lowest pooled accuracy rates, 85% (95% CI 68-100%), 67% (95% CI 43-91%) and 72% (95% CI 65-78%), respectively., Conclusions: The superolateral approach was investigated most and resulted in the highest pooled accuracy rate of 91% (95% CI 84-99%). Nevertheless, this approach still results in a substantial amount of extra-articular needle placements. Guidance of intra-articular needle placements by imaging techniques may enhance the accuracy. The costs and extra time associated with these techniques should be taken into consideration., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: After total knee arthroplasty (TKA) only 75-89% of patients are satisfied. Because patient satisfaction is a prime goal of all orthopaedic procedures, optimization of patient satisfaction is of major importance. Factors related to patient satisfaction after TKA have been explored, but no studies have included two potentially relevant factors, i.e. the functional capacity of daily activities and actual daily activity. This present prospective study examines whether functional capacity and actual daily activity (in addition to an extensive set of potential factors) contribute to patient satisfaction six months after TKA., Methods: A total of 44 patients were extensively examined preoperatively and six months post surgery. Functional capacity was measured with three capacity tests, focusing on walking, stair climbing, and chair rising. Actual daily activity was measured in the patient's home situation by means of a 48-hour measurement with an Activity Monitor. To establish which factors were related to patient satisfaction six months post surgery, logistic regression analyses were used to calculate odds ratios., Results: Preoperative and postoperative functional capacity and actual daily activity had no relation with patient satisfaction. Preoperatively, only self-reported mental functioning was positively related to patient satisfaction. Postoperatively, based on multivariate analysis, only fulfilled expectations regarding pain and experienced pain six months post surgery were related to patient satisfaction., Conclusions: Functional capacity and actual daily activity do not contribute to patient satisfaction after TKA. Patients with a better preoperative self-reported mental functioning, and patients who experienced less pain and had fulfilled expectations regarding pain postoperatively, were more often satisfied.

Background: Previous osteotomy may compromise subsequent knee replacement, but no guidelines considering knee arthroplasty after prior osteotomy have been developed. We describe a systematic review of non-randomized studies to analyze the effect of high tibial osteotomy on total knee arthroplasty., Methods: A computerized search for relevant studies published up to September 2007 was performed in Medline and Embase using a search strategy that is highly sensitive to find nonrandomized studies. Included were observational studies in which patients had total knee arthroplasty performed after prior high tibial osteotomy. Studies that fulfilled these criteria, were assessed for methodologic quality by two independent reviewers using the critical appraisal of observational studies developed by Deeks and the MINORS instrument. The study characteristics and data on the intervention, follow-up, and outcome measures, were extracted using a pre-tested standardized form. Primary outcomes were: knee range of motion, knee clinical score, and revision surgery. The grade of evidence was determined using the guidelines of the GRADE working group., Results: Of the 458 articles identified using our search strategy, 17 met the inclusion criteria. Fifteen studies were cohort study with a concurrent control group, one was a historical cohort study and one a case-control study. Nine studies scored 50% or more on both methodological quality assessments. Pooling of the results was not possible due to the heterogeneity of the studies, and our analysis could not raise the overall low quality of evidence. No significant differences between primary total knee arthroplasty and total knee arthroplasty after osteotomy were found for knee range of motion in four out of six studies, knee clinical scores in eight out of nine studies, and revision surgery in eight out of eight studies after a median follow-up of 5 years., Conclusion: Our analysis suggests that osteotomy does not compromise subsequent knee replacement. However, the low quality of evidence precludes solid clinical conclusions.

We have analysed retrospectively the influence of different sources of knee deformity on failure of closing wedge high tibial valgus osteotomy (HTO). Preoperative frontal plane varus deformities of the lower extremity, distal femur and proximal tibia, and medial convergence of the knee joint line were assessed on a standard whole leg radiograph in 76 patients. Using the logistic regression model, the probability of survival for HTO was 77% (SD 4%) at 10-years follow-up. Varus deformity of the lower extremity (< 175 degrees ), and medial convergence of the knee joint line (> 3 degrees ) were identified as preoperative risk factors for conversion to arthroplasty (P = 0.03 and P = 0.006). We found no evidence that varus inclination of the proximal tibia or distal femur influences long-term survival of HTO.

Surgical therapeutic procedures such as knee osteotomy and knee replacement depend on proper knee alignment assessment. The aim of this study was to evaluate if femorotibial (FT) measurement on short knee films may be used in clinical settings. The study population comprised 68 patients with symptomatic medial compartmental knee osteoarthritis. We measured the FT angle with the use of mid-diaphyseal lines (FTa), and the knee joint centre (FTb) to determine anatomical knee alignment on a short knee image. Then, the accuracy of alignment was compared to the gold standard Hip-Knee-Ankle (HKA) angle on a full-limb view. FTa angle assessment correlated well (r=0.65) with the HKA angle. However, this method showed poor inter-observer agreement (ICC=0.37). 3% of patients were incorrectly classified as having valgus alignment. Good intra- and inter-observer agreements were observed for FTb angle measurement (ICC=0.89 and 0.79; respectively). But correlation between HKA and FTb angles was low (r=0.34). 15% of patients were incorrectly classified as having valgus alignment. Short knee images cannot substitute whole leg views when accurate assessment of knee alignment is essential.

Objective: Although knee malalignment is assumed to correlate with knee osteoarthritis (OA), it is still unknown whether malalignment precedes the development of OA or whether it is a result of OA. The aim of this study was to assess the relationship between malalignment and the development of knee OA as well as progression of knee OA., Methods: A total of 1,501 participants in the Rotterdam study were randomly selected. Knee OA at baseline and at followup (mean followup 6.6 years) was scored according to the Kellgren/Lawrence (K/L) grading system. Alignment was measured by the femorotibial angle on radiographs at baseline. Multivariable logistic regression for repeated measurements was used to analyze the association of malalignment with the development and progression of OA., Results: Of 2,664 knees, 1,012 (38%) were considered to have normal alignment, 693 (26%) had varus alignment, and 959 (36%) had valgus alignment. A comparison of valgus alignment and normal alignment showed that valgus alignment was associated with a borderline significant increase in development of knee OA (odds ratio [OR] 1.54, 95% confidence interval [95% CI] 0.97-2.44), and varus alignment was associated with a 2-fold increased risk (OR 2.06, 95% CI 1.28-3.32). Stratification for body mass index showed that this increased risk was especially seen in overweight and obese individuals but not in non-overweight persons. The risk of OA progression was also significantly increased in the group with varus alignment compared with the group with normal alignment (OR 2.90, 95% CI 1.07-7.88)., Conclusion: An increasing degree of varus alignment is associated not only with progression of knee OA but also with development of knee OA. However, this association seems particularly applicable to overweight and obese persons.