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Grafts placed too anteriorly on the femur are reportedly a common cause of failure in anterior cruciate ligament reconstruction. Some studies suggest more anatomic femoral tunnel placement improves kinematics. The ability of the transtibial technique and a tibial tunnel-independent technique (placed transfemorally outside-in) to place the guide pin near the center of the femoral attachment of the anterior cruciate ligament was compared in 12 cadavers. After arthroscopic placement of the guide pins, the femur was dissected and the three-dimensional geometry of the femur, anterior cruciate ligament footprint, and positions of each guide pin were measured. The transtibial guide-pin placement was 7.9 +/- 2.2 mm from the center of the footprint (near its anterior border), whereas the independent technique positioned the guide pin 1.9 +/- 1.0 mm from the center. The center of the footprint was within 2 mm of an anteroposterior line through the most posterior border of the femoral cartilage in the notch and a proximodistal line through the proximal margin of the cartilage at the capsular reflection. More accurate placement of the femoral tunnel might reduce the incidence of graft failure and might reduce long-term degeneration observed after reconstruction although both would require clinical confirmation. [ABSTRACT FROM AUTHOR]

Background The anterior cruciate ligament (ACL) constrains the anterior translation and axial rotation of the tibia. However, the effect of ACL injury on the mediolateral translation and varus-valgus rotation of the tibia is unknown. Because of the oblique orientation of the ACL, we hypothesized that ACL deficiency alters mediolateral translation and varus-valgus rotation. Methods The kinematics of 9 cadavers from full extension to 90 degrees of flexion under various loading conditions were measured before and after ACL resection using a robotic testing system. Results ACL deficiency increased the medial translation of the tibia and valgus rotation, especially at 15 degrees and 30 degrees of flexion. For example, at 15 degrees , ACL deficiency increased the medial translation from 1.2 (SD 0.9) mm to 1.8 (SD 1.1) mm in response to a quadriceps load. The valgus rotation also increased from 0.8 degrees (SD 0.6) to 1.7 degrees (SD 0.8). Interpretation ACL deficiency altered both the mediolateral tibial translation and valgus-varus rotation under various loading conditions. The increased medial tibial translation could shift the contact in the medial compartment towards the medial tibial spine, a region where degeneration is observed in ACL-deficient patients. In addition to restoring anterior laxity, ACL reconstruction might need to restore the mediolateral translation of the tibia and varus-valgus rotation of the knee. [ABSTRACT FROM AUTHOR]

BACKGROUND: Recent follow-up studies have reported a high incidence of joint degeneration in patients with anterior cruciate ligament reconstruction. Abnormal kinematics after anterior cruciate ligament reconstruction have been thought to contribute to the degeneration. HYPOTHESIS: Anterior cruciate ligament reconstruction, which was designed to restore anterior knee laxity under anterior tibial loads, does not reproduce knee kinematics under in vivo physiological loading conditions. STUDY DESIGN: Controlled laboratory study. METHODS: Both knees of 7 patients with complete unilateral rupture of the anterior cruciate ligament were magnetic resonance imaged, and 3D models were constructed from these images. The anterior cruciate ligament of the injured knee was arthroscopically reconstructed using a bone-patellar tendon-bone autograft. Three months after surgery, the kinematics of the intact contralateral and reconstructed knees were measured using a dual-orthogonal fluoroscopic system while the subjects performed a single-legged weightbearing lunge. The anterior laxity of both knees was measured using a KT-1000 arthrometer. RESULTS: The anterior laxity of the reconstructed knee as measured with the arthrometer was similar to that of the intact contralateral knee. However, under weightbearing conditions, there was a statistically significant increase in anterior translation of the reconstructed knee compared with the intact knee at full extension (approximately 2.9 mm) and 15 degrees (approximately 2.2 mm) of flexion. In addition, there was a mean increase in external tibial rotation of the anterior cruciate ligament-reconstructed knee beyond 30 degrees of flexion (approximately 2 degrees at 30 degrees of flexion), although no statistical significance was detected. CONCLUSION: The data demonstrate that although anterior laxity was restored during KT-1000 arthrometer testing, anterior cruciate ligament reconstruction did not restore normal knee kinematics under weightbearing loading conditions. CLINICAL RELEVANCE: Future reconstruction techniques should aim to restore function of the knee under physiological loading conditions. [ABSTRACT FROM AUTHOR]

Background: Long-term follow-up studies have indi-cated that there is an increased incidence of arthrosis following anterior cruciate ligament (ACL) reconstruc-tion, suggesting that the reconstruction may not repro-duce intact ACL biomechanics. We studied not only the magnitude but also the orientation of the ACL and ACL graft forces. Methods: 10 knee specimens were tested on a robotic testing system with the ACL intact, deficient, and recon-structed (using a bone-patella tendon-bone graft). The magnitude and orientation of the ACL and ACL graft forces were determined under an anterior tibial load of 130 N at full extension, and 15, 30, 60, and 90 degrees of flexion. Orientation was described using elevation angle (the angle formed with the tibial plateau in the sagit-tal plane) and deviation angle (the angle formed with respect to the anteroposterior direction in the transverse plane). Results: ACL reconstruction restored anterior tibial translation to within 2.6 mm of that of the intact knee under the 130-N anterior load. Average internal tibial rotation was reduced after ACL reconstruction at all flexion angles. The force vector of the ACL graft was significantly different from the ACL force vector. The average values of the elevation and deviation angles of the ACL graft forces were higher than that of the intact ACL at all flexion angles. Interpretation: Contemporary single bundle ACL reconstruction restores anterior tibial translation under anterior tibial load with different forces (both magni-tude and orientation) in the graft compared to the intact ACL. Such graft function might alter knee kinematics in other degrees of freedom and could overly constrain the tibial rotation. An anatomic ACL reconstruction should reproduce the magnitude and orientation of the intact ACL force vector, so that the 6-degrees-of-freedom knee kinematics and joint reaction forces can be restored. [ABSTRACT FROM AUTHOR]

BACKGROUND: Quantifying the in vivo cartilage contact mechanics of the knee may improve our understanding of the mechanisms of joint degeneration and may therefore improve the surgical repair of the joint after injury. OBJECTIVE: To measure tibiofemoral articular cartilage contact kinematics during in vivo knee flexion. STUDY DESIGN: Descriptive laboratory study. METHODS: Orthogonal fluoroscopic images and magnetic resonance image-based computer models were used to measure the motion of the cartilage contact points during a quasi-static lunge in 5 human subjects. RESULTS: On the tibial plateau, the contact point moved in both the anteroposterior and the mediolateral directions during knee flexion. On the medial tibial plateau, flexion angle did not have a statistically significant effect on the location of the contact points. The total translation of the contact point from full extension to 90 degrees of flexion was less than 1.5 mm in the anteroposterior direction, whereas the translation in the mediolateral direction was more than 5.0 mm. In the anteroposterior direction, the contact points were centered on the medial tibial plateau. On the lateral tibial plateau, there was a statistically significant difference between the location of the contact point at full extension and the locations of the contact points at other flexion angles in the anteroposterior direction. No significant difference was detected between the location of the contact points at other flexion angles. The overall range of contact point motion was about 9.0 mm in the anteroposterior direction and about 4.0 mm in the mediolateral direction. The contact points were primarily on the inner half of the medial and lateral tibial plateaus (the half closest to the tibial spine). The contact points on both femoral condyles were also on the inner half of the condyles (near the condylar notch). CONCLUSIONS: The tibiofemoral contact points move in 3 dimensions during weightbearing knee flexion. The medial tibiofemoral contact points remained within the central portion of the tibial plateau in the anteroposterior direction. Both the medial and lateral tibiofemoral contact points were located on the inner portions of the tibial plateau and femoral condyles (close to the tibial spine), indicating that the tibial spine may play an important role in knee stability. CLINICAL RELEVANCE: The results of this study may provide important insight as to the mechanisms contributing to the development of osteoarthritis after ligament injuries. [ABSTRACT FROM AUTHOR]

BACKGROUND: Most knowledge regarding cruciate ligament function is based on in vitro experiments. PURPOSE: To investigate the in vivo elongation of the functional bundles of the anterior cruciate ligament and posterior cruciate ligament during weightbearing flexion. HYPOTHESIS: The biomechanical role of functional bundles of the anterior cruciate ligament and posterior cruciate ligament under in vivo loading is different from that measured in cadavers. STUDY DESIGN: In vivo biomechanical study. METHODS: Elongation of the anterior cruciate ligament and posterior cruciate ligament was measured during a quasi-static lunge using imaging and 3-dimensional computer-modeling techniques. RESULTS: The anterior-medial bundle of the anterior cruciate ligament had a relatively constant length from full extension to 90 degrees of flexion. The posterior-lateral bundle of the anterior cruciate ligament decreased in length with flexion. Both bundles of the posterior cruciate ligament had increased lengths with flexion. CONCLUSION: The data did not demonstrate the reciprocal function of the 2 bundles of the anterior cruciate ligament or the posterior cruciate ligament with flexion observed in previous studies. Instead, the data suggest that there is a reciprocal function between the anterior cruciate ligament and posterior cruciate ligament with flexion. The anterior cruciate ligament plays a more important role in low-flexion angles, whereas the posterior cruciate ligament plays a more important role in high flexion. CLINICAL RELEVANCE: Understanding the biomechanical role of the knee ligaments in vivo is essential to reproduce the structural behavior of the ligament after injury (especially for 2-bundle reconstructions) and thus improve surgical outcomes. [ABSTRACT FROM AUTHOR]

BACKGROUND: The effectiveness of posterior cruciate ligament reconstruction in restoring normal kinematics under physiologic loading is unknown. HYPOTHESIS: Posterior cruciate ligament reconstruction does not restore normal knee kinematics under muscle loading. STUDY DESIGN: In vitro biomechanical study. METHODS: Kinematics of knees with an intact, resected, and reconstructed posterior cruciate ligament were measured by a robotic testing system under simulated muscle loads. Anteroposterior tibial translation and internal-external tibial rotation were measured at 0 degrees, 30 degrees, 60 degrees, 90 degrees, and 120 degrees of flexion under posterior drawer loading, quadriceps muscle loading, and combined quadriceps and hamstring muscle loading. RESULTS: Reconstruction reduced the additional posterior tibial translation caused by ligament deficiency at all flexion angles tested under posterior drawer loading. Ligament deficiency increased external rotation and posterior translation at angles higher than 60 degrees of flexion when simulated muscle loading was applied. Posterior cruciate ligament reconstruction reduced the posterior translation and external rotation observed in posterior cruciate ligament-deficient knees at higher flexion angles, but differences were not significant. CONCLUSION: Under physiologic loading conditions, posterior cruciate ligament reconstruction does not restore six degree of freedom knee kinematics. Clinical Relevance: Abnormal knee kinematics may lead to development of long-term knee arthrosis. [ABSTRACT FROM AUTHOR]

As anterior cruciate ligament (ACL) injuries are highly prevalent among active individuals, it is vital to better understand the loading conditions which lead to injury. One method for doing so is through measurement of dynamic, in vivo ACL strain. To measure strain, it is necessary to normalize elongation of the ACL to a 'reference length' which corresponds to the point at which the ligament transitions from being unloaded to carrying tension. The purpose of this study was to compare the length of the ACL in three different positions to evaluate their utility for establishing a reference (or zero-strain) length of the ACL. ACL reference length was determined using three different methods for each of ten healthy participants. Using magnetic resonance and biplanar radiographic imaging techniques, we measured the length of the ACL during supine resting, quiet standing, and anterior/posterior (AP) drawer testing. During the AP drawer testing, the slack-taut transition point was defined as the inflection point of the AP translation vs ACL elongation curve. There was good consistency between the three ACL length measurements (ICC=0.80). Differences in mean ACL length between the three methods were within 1 mm. While determining the precise zero-strain length of the ACL in vivo remains a challenge, the reference positions utilized in this study produce consistent measurements of ACL length. These findings are important because reliable measurements of in vivo ACL strain have the potential to serve as indicators of propensity for injury., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Diffusion magnetic resonance imaging (MRI) allows for the quantification of water diffusion properties in soft tissues. The goal of this study was to characterize the 3D collagen fiber network in the porcine meniscus using high angular resolution diffusion imaging (HARDI) acquisition with both diffusion tensor imaging (DTI) and generalized q-sampling imaging (GQI)., Methods: Porcine menisci (n=7) were scanned ex vivo using a three-dimensional (3D) HARDI spin-echo pulse sequence with an isotropic resolution of 500 µm at 7.0 Tesla. Both DTI and GQI reconstruction techniques were used to quantify the collagen fiber alignment and visualize the complex collagen network of the meniscus. The MRI findings were validated with conventional histology., Results: DTI and GQI exhibited distinct fiber orientation maps in the meniscus using the same HARDI acquisition. We found that crossing fibers were only resolved with GQI, demonstrating the advantage of GQI over DTI to visualize the complex collagen fiber orientation in the meniscus. Furthermore, the MRI findings were consistent with conventional histology., Conclusions: HARDI acquisition with GQI reconstruction more accurately resolves the complex 3D collagen architecture of the meniscus compared to DTI reconstruction. In the future, these technologies have the potential to nondestructively assess both normal and abnormal meniscal structure., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-1355/coif). A.L.M. reports receiving NIH support through grants (Nos. AR073221, AR079184, AR078245). The other authors have no conflicts of interest to declare., (2024 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

There is limited data quantifying the influence of running on hip cartilage mechanics. The goal of this investigation was to quantify changes in hip joint bone-to-bone distance in response to a 3-mile treadmill run. We acquired magnetic resonance (MR) images of the dominant hip of eight young, asymptomatic runners (five males, three females) before and immediately after they ran 3 miles at a self-selected pace on a level treadmill. The femoral heads and acetabula were semiautomatically segmented from the pre- and post-exercise MR images to generate three-dimensional models of each participant's hip that were used to compute changes in the bone-to-bone distances incurred by the running exercise. We observed a significant 3% decrease in bone-to-bone distance from 3.47 ± 0.20 to 3.36 ± 0.22 mm between the femoral head and acetabulum after a 3-mile treadmill run (mean ± 95% confidence interval; p = 0.03). These findings provide new baseline data describing how running impacts the hip joint in young, asymptomatic runners., (© 2023 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)

Objective: The measurement of in vivo intervertebral disc (IVD) mechanics may be used to understand the etiology of IVD degeneration and low back pain (LBP). To this end, our lab has developed methods to measure IVD morphology and uniaxial compressive deformation (% change in IVD height) resulting from dynamic activity, in vivo , using magnetic resonance images (MRI). However, due to the time-intensive nature of manual image segmentation, we sought to validate an image segmentation algorithm that could accurately and reliably reproduce models of in vivo tissue mechanics., Design: Therefore, we developed and evaluated two commonly employed deep learning architectures (2D and 3D U-Net) for the segmentation of IVDs from MRI. The performance of these models was evaluated for morphological accuracy by comparing predicted IVD segmentations (Dice similarity coefficient, mDSC; average surface distance, ASD) to manual (ground truth) measures. Likewise, functional reliability and precision were assessed by evaluating the intraclass correlation coefficient (ICC) and standard error of measurement (SE m ) of predicted and manually derived deformation measures., Results: Peak model performance was obtained using the 3D U-net architecture, yielding a maximum mDSC ​= ​0.9824 and component-wise ASD x  ​= ​0.0683 ​mm; ASD y  ​= ​0.0335 ​mm; ASD z  ​= ​0.0329 ​mm. Functional model performance demonstrated excellent reliability ICC ​= ​0.926 and precision SE m  ​= ​0.42%., Conclusions: This study demonstrated that a deep learning framework can precisely and reliably automate measures of IVD function, drastically improving the throughput of these time-intensive methods., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Objective: To examine the effects of a 6-month weight loss intervention on physical function, inflammatory biomarkers, and metabolic biomarkers in both those with and without osteoarthritis (OA)., Design: 59 individuals ≥60 years old with obesity and a functional impairment were enrolled into this IRB approved clinical trial and randomized into one of two 6-month weight loss arms: a higher protein hypocaloric diet or a standard protein hypocaloric diet. All participants were prescribed individualized 500-kcal daily-deficit diets, with a goal of 10% weight loss. Additionally, participants participated in three, low-intensity, exercise sessions per week. Physical function, serum biomarkers and body composition data were assessed at the baseline and 6-month timepoints. Statistical analyses assessed the relationships between biomarkers, physical function, body composition, and OA status as a result of the intervention., Results: No group effects of dietary intervention were detected on any outcome measures (multiple p ​> ​0.05). During the 6-month trial, participants lost 6.2 ​± ​4.0% of their bodyweight (p ​< ​0.0001) and experienced improved physical function on the Short-Performance-Physical-Battery (p ​< ​0.0001), 8-foot-up-and-go (p ​< ​0.0001), and time to complete 10-chair-stands (p ​< ​0.0001). Adiponectin concentrations (p ​= ​0.0480) were elevated, and cartilage oligomeric matrix protein (COMP) concentrations (p ​< ​0.0001) were reduced; further analysis revealed that reductions in serum COMP concentrations were greater in OA-negative individuals., Conclusions: These results suggest that weight loss in older adults with and without OA may provide a protective effect to cartilage and OA. In particular, OA-negative individuals may be able to mitigate changes associated with OA through weight loss., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

The ability to efficiently and reproducibly generate subject-specific 3D models of bone and soft tissue is important to many areas of musculoskeletal research. However, methodologies requiring such models have largely been limited by lengthy manual segmentation times. Recently, machine learning, and more specifically, convolutional neural networks, have shown potential to alleviate this bottleneck in research throughput. Thus, the purpose of this work was to develop a modified version of the convolutional neural network architecture U-Net to automate segmentation of the tibia and femur from double echo steady state knee magnetic resonance (MR) images. Our model was trained on a dataset of over 4,000 MR images from 34 subjects, segmented by three experienced researchers, and reviewed by a musculoskeletal radiologist. For our validation and testing sets, we achieved dice coefficients of 0.985 and 0.984, respectively. As further testing, we applied our trained model to a prior study of tibial cartilage strain and recovery. In this analysis, across all subjects, there were no statistically significant differences in cartilage strain between the machine learning and ground truth bone models, with a mean difference of 0.2 ± 0.7 % (mean ± 95 % confidence interval). This difference is within the measurement resolution of previous cartilage strain studies from our lab using manual segmentation. In summary, we successfully trained, validated, and tested a machine learning model capable of segmenting MR images of the knee, achieving results that are comparable to trained human segmenters., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Noncontact anterior cruciate ligament (ACL) injuries typically occur during deceleration movements such as landing or cutting. However, conflicting data have left the kinematic mechanisms leading to these injuries unclear. Quantifying the influence of sagittal and coronal plane knee kinematics on in vivo ACL strain may help to elucidate noncontact ACL injury mechanisms., Purpose/hypothesis: The purpose of this study was to measure in vivo sagittal and coronal plane knee kinematics and ACL strain during a single-leg jump. We hypothesized that ACL strain would be modulated primarily by motion in the sagittal plane and that limited coronal plane motion would be measured during this activity., Study Design: Descriptive laboratory study., Methods: Seventeen healthy participants (8 male/9 female) underwent magnetic resonance imaging (MRI) followed by high-speed biplanar radiography, obtained as participants performed a single-leg jump. Three-dimensional models of the femur, tibia, and associated ACL attachment site footprints were created from the MRIs and registered to the radiographs to reproduce the position of the knee during the jump. ACL strain, knee flexion/extension angles, and varus/valgus angles were measured throughout the jump. Spearman rank correlations were used to assess relationships between mean ACL strain and kinematic variables., Results: Mean ACL strain increased with decreasing knee flexion angle (ρ = -0.3; P = .002), and local maxima in ACL strain occurred with the knee in a straight position in both the sagittal and the coronal planes. In addition, limited coronal plane motion (varus/valgus angle) was measured during this activity (mean ± SD, -0.5°± 0.3°). Furthermore, we did not detect a statistically significant relationship between ACL strain and varus/valgus angle (ρ = -0.01; P = .9)., Conclusion: ACL strain was maximized when the knee was in a straight position in both the sagittal and coronal planes. Participants remained in <1° of varus/valgus position on average throughout the jump. As a ligament under elevated strain is more vulnerable to injury, landing on a straight knee may be an important risk factor for ACL rupture., Clinical Relevance: These data may improve understanding of risk factors for noncontact ACL injury, which may be useful in designing ACL injury prevention programs.

Purpose of Review: Meniscus injury often leads to joint degeneration and post-traumatic osteoarthritis (PTOA) development. Therefore, the purpose of this review is to outline the current understanding of biomechanical and biological repercussions following meniscus injury and how these changes impact meniscus repair and PTOA development. Moreover, we identify key gaps in knowledge that must be further investigated to improve meniscus healing and prevent PTOA., Recent Findings: Following meniscus injury, both biomechanical and biological alterations frequently occur in multiple tissues in the joint. Biomechanically, meniscus tears compromise the ability of the meniscus to transfer load in the joint, making the cartilage more vulnerable to increased strain. Biologically, the post-injury environment is often characterized by an increase in pro-inflammatory cytokines, catabolic enzymes, and immune cells. These multi-faceted changes have a significant interplay and result in an environment that opposes tissue repair and contributes to PTOA development. Additionally, degenerative changes associated with OA may cause a feedback cycle, negatively impacting the healing capacity of the meniscus. Strides have been made towards understanding post-injury biological and biomechanical changes in the joint, their interplay, and how they affect healing and PTOA development. However, in order to improve clinical treatments to promote meniscus healing and prevent PTOA development, there is an urgent need to understand the physiologic changes in the joint following injury. In particular, work is needed on the in vivo characterization of the temporal biomechanical and biological changes that occur in patients following meniscus injury and how these changes contribute to PTOA development., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To assess the in vivo relationship between the mechanical response of intervertebral discs (IVDs) to dynamic activity and IVD biochemical composition assessed via T1rho relaxation imaging., Design: Eighteen asymptomatic participants with no history of low back pain (LBP), injury, or surgery underwent magnetic resonance (MR) imaging of their lumbar spine prior to and immediately following a treadmill walking "stress test." Anatomic (SPACE, FLASH) MR images were obtained pre- and post-exercise and utilized to measure IVD mechanical deformation. Quantitative (T1rho) imaging was performed pre-exercise to reflect IVD composition. Pre-exercise anatomic images were also utilized to assess IVD degenerative status based on the modified Pfirrmann scale. To quantify mechanical response, 3D surface models of the L1-L2-L5-S1 IVDs were created from manual segmentations of pre- and post-exercise anatomic images and utilized to assess changes in IVD height. IVD strain (%) was defined as change in IVD height normalized to pre-activity height. Linear mixed models were used to assess the relationships between IVD mechanical deformation (strain), composition (T1rho relaxation time), and degenerative status (Pfirrmann grade)., Results: Increased compressive IVD strain was associated with lower T1rho relaxation times in the nucleus pulposus (NP) of the disc (β T1rho =5.07,CI:[1.52,7.77],R marg 2 =0.52,p=0.005). Thus, an inverse relationship between IVD strain and NP T1rho relaxation time was observed., Conclusion: The in vivo mechanical response of the IVD to the "stress test" was sensitive to differences in NP composition. The results of this study suggest that quantification of in vivo IVD mechanical function and composition may provide insight into IVD health., Competing Interests: Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: To determine the incidence and worsening of lumbar spine structure and low back pain (LBP) and whether they are predicted by demographic characteristics or clinical characteristics or appendicular joint osteoarthritis (OA)., Methods: Paired baseline (2003-2004) and follow-up (2006-2010) lumbar spine radiographs from the Johnston County Osteoarthritis Project were graded for osteophytes (OST), disc space narrowing (DSN), spondylolisthesis, and presence of facet joint OA (FOA). Spine OA was defined as at least mild OST and mild DSN at the same level for any level of the lumbar spine. LBP, comorbidities, and back injury were self-reported. Weibull models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) of spine phenotypes accounting for potential predictors including demographic characteristics, clinical characteristics, comorbidities, obesity, and appendicular OA., Results: Obesity was a consistent and strong predictor of incidence of DSN (HR 1.80 [95% CI 1.09-2.98]), spine OA (HR 1.56 [95% CI 1.01-2.41]), FOA (HR 4.99 [95% CI 1.46-17.10]), spondylolisthesis (HR 1.87 [95% CI 1.02-3.43]), and LBP (HR 1.75 [95% CI 1.19-2.56]), and worsening of DSN (HR 1.51 [95% CI 1.09-2.09]) and LBP (HR 1.51 [95% CI 1.12-2.06]). Knee OA was a predictor of incident FOA (HR 4.18 [95% CI 1.44-12.2]). Spine OA (HR 1.80 [95% CI 1.24-2.63]) and OST (HR 1.85 [95% CI 1.02-3.36]) were predictors of incidence of LBP. Hip OA (HR 1.39 [95% CI 1.04-1.85]) and OST (HR 1.58 [95% CI 1.00-2.49]) were predictors of LBP worsening., Conclusion: Among the multiple predictors of spine phenotypes, obesity was a common predictor for both incidence and worsening of lumbar spine degeneration and LBP., (© 2021 American College of Rheumatology.)

Background: Quadriceps loading of the anterior cruciate ligament (ACL) may play a role in the noncontact mechanism of ACL injury. Musculoskeletal modeling techniques are used to estimate the intrinsic force of the quadriceps acting at the knee joint., Purpose/hypothesis: The purpose of this paper was to develop a novel musculoskeletal model of in vivo quadriceps force during dynamic activity. We used the model to estimate quadriceps force in relation to ACL strain during a single-leg jump. We hypothesized that quadriceps loading of the ACL would reach a local maximum before initial ground contact with the knee positioned in extension., Study Design: Descriptive laboratory study., Methods: Six male participants underwent magnetic resonance imaging in addition to high-speed biplanar radiography during a single-leg jump. Three-dimensional models of the knee joint, including the femur, tibia, patellofemoral cartilage surfaces, and attachment-site footprints of the patellar tendon, quadriceps tendon, and ACL, were created from the magnetic resonance imaging scans. The bone models were registered to the biplanar radiographs, thereby reproducing the positions of the knee joint at the time of radiographic imaging. The magnitude of quadriceps force was determined for each knee position based on a 3-dimensional balance of the forces and moments of the patellar tendon and the patellofemoral cartilage contact acting on the patella. Knee kinematics and ACL strain were determined for each knee position., Results: A local maximum in average quadriceps force of approximately 6500 N (8.4× body weight) occurred before initial ground contact. ACL strain increased concurrently with quadriceps force when the knee was positioned in extension., Conclusion: This novel participant-specific modeling technique provides estimates of in vivo quadriceps force during physiologic dynamic loading. A local maximum in quadriceps force before initial ground contact may tension the ACL when the knee is positioned in extension., Clinical Relevance: These data contribute to understanding noncontact ACL injury mechanisms and the potential role of quadriceps activation in these injuries.

Segmentation of medical images into different tissue types is essential for many advancements in orthopaedic research; however, manual segmentation techniques can be time- and cost-prohibitive. The purpose of this work was to develop a semi-automatic segmentation algorithm that leverages gradients in spatial intensity to isolate the patella bone from magnetic resonance (MR) images of the knee that does not require a training set. The developed algorithm was validated in a sample of four human participants (in vivo) and three porcine stifle joints (ex vivo) using both magnetic resonance imaging (MRI) and computed tomography (CT). We assessed the repeatability (expressed as mean ± standard deviation) of the semi-automatic segmentation technique on: (1) the same MRI scan twice (Dice similarity coefficient = 0.988 ± 0.002; surface distance = - 0.01 ± 0.001 mm), (2) the scan/re-scan repeatability of the segmentation technique (surface distance = - 0.02 ± 0.03 mm), (3) how the semi-automatic segmentation technique compared to manual MRI segmentation (surface distance = - 0.02 ± 0.08 mm), and (4) how the semi-automatic segmentation technique compared when applied to both MRI and CT images of the same specimens (surface distance = - 0.02 ± 0.06 mm). Mean surface distances perpendicular to the cartilage surface were computed between pairs of patellar bone models. Critically, the semi-automatic segmentation algorithm developed in this work reduced segmentation time by approximately 75%. This method is promising for improving research throughput and potentially for use in generating training data for deep learning algorithms., (© 2022. The Author(s).)

Background: The lumbar discs are large, dense tissues that are primarily avascular, and cells residing in the central region of the disc are up to 6-8 mm from the nearest blood vessel in adults. To maintain homeostasis, disc cells rely on nutrient transport between the discs and adjacent vertebrae. Thus, diminished transport has been proposed as a factor in age-related disc degeneration., Methods: In this study, we used magnetic resonance imaging (MRI) to quantify diurnal changes in T2 relaxation time, an MRI biomarker related to disc hydration, to generate 3D models of disc fluid distribution and determine how diurnal changes in fluid varied by spinal level. We recruited 10 participants (five males/five females; age: 21-30 years; BMI: 19.1-29.0 kg/m 2 ) and evaluated the T2 relaxation time of each disc at 8:00 AM and 7:00 PM, as well as degeneration grade (Pfirrmann). We also measured disc height, volume, and perimeter in a subset of individuals as a preliminary comparison of geometry and transport properties., Results: We found that the baseline (AM) T2 relaxation time and the diurnal change in T2 relaxation time were greatest in the cranial lumbar discs, decreasing along the lumbar spine from cranial to caudal. In cranial discs, T2 relaxation times decreased in each disc region (nucleus pulposus [NP], inner annulus fibrosus [IAF], and outer annulus fibrosus [OAF]), whereas in caudal discs, T2 relaxation times decreased in the NP but increased in the AF., Conclusions: Fluid transport varied by spinal level, where transport was greatest in the most cranial lumbar discs and decreased from cranial to caudal along the lumbar spine. Future work should evaluate what level-dependent factors affect transport., Competing Interests: The authors declare no conflicts of interest., (© 2022 The Authors. JOR Spine published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)

Purpose: Magnetic resonance imaging (MRI) is routinely used to evaluate spine pathology; however, standard imaging findings weakly correlate to low back pain. Abnormal disc mechanical function is implicated as a cause of back pain but is not assessed using standard clinical MRI. Our objective was to utilize our established MRI protocol for measuring disc function to quantify disc mechanical function in a healthy cohort., Methods: We recruited young, asymptomatic volunteers (6 male/6 female; age 18-30 years; BMI < 30) and used MRI to determine how diurnal deformations in disc height, volume, and perimeter were affected by spinal level, disc region, MRI biomarkers of disc health (T2, T1rho), and Pfirrmann grade., Results: Lumbar discs deformed by a mean of -6.1% (95% CI: -7.6%, -4.7%) to -8.0% (CI: -10.6%, -5.4%) in height and -5.4% (CI: -7.6%, -3.3%) to -8.5% (CI: -11.0%, -6.0%) in volume from AM to PM across spinal levels. Regional deformations were more uniform in cranial lumbar levels and concentrated posteriorly in the caudal levels, reaching a maximum of 13.1% at L5-S1 (CI:-16.1%, -10.2%). T2 and T1rho relaxation times were greatest in the nucleus and varied circumferentially within the annulus. T2 relaxation times were greatest at the most cranial spinal levels and decreased caudally. In this young healthy cohort, we identified a weak association between nucleus T2 and the diurnal change in the perimeter., Conclusions: Spinal level is a key factor in determining regional disc deformations. Interestingly, deformations were concentrated in the posterior regions of caudal discs where disc herniation is most prevalent., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Obesity is a primary risk factor for osteoarthritis. While previous work has addressed relationships between in vivo cartilage mechanics, composition, and obesity in the tibiofemoral joint, there is limited information on these relationships in the patellofemoral joint. The purpose of this study was to compare the patellofemoral cartilage mechanical response to walking in participants with normal and obese body mass indices (BMIs). Additionally, patellar cartilage T1rho relaxation times were measured before exercise to characterize the biochemical composition of the tissue. Fifteen participants (eight with normal BMI and seven with obese BMI) underwent baseline magnetic resonance imaging (MRI) of their right knee. They then walked on a treadmill for 20 min at a speed normalized to their leg length before a second MRI scan. Subsequently, three-dimensional models of the bones and articular surfaces of the patellofemoral joint were created via manual segmentation of the pre- and post-exercise MR images to compute cartilage thickness and strain. Strain was defined as the change in patellofemoral cartilage thickness normalized to the baseline thickness. Results showed that participants with an obese BMI exhibited significantly increased patellofemoral cartilage strain compared to those with a normal BMI (5.4 ± 4% vs. 1.7 ± 3%, respectively; p = 0.003). Furthermore, patellar cartilage T1rho values were significantly higher in participants with obese versus normal BMIs (95 ms vs. 83 ms, respectively; p = 0.049), indicative of decreased proteoglycan content in those with an obese BMI. In summary, the altered patellofemoral cartilage strain and composition observed in those with an obese BMI may be indicative of cartilage degeneration., (Copyright © 2022. Published by Elsevier Ltd.)

Changes in cartilage structure and composition are commonly observed during the progression of osteoarthritis (OA). Importantly, quantitative magnetic resonance imaging (MRI) methods, such as T1rho relaxation imaging, can noninvasively provide in vivo metrics that reflect changes in cartilage composition and therefore have the potential for use in early OA detection. Changes in cartilage mechanical properties are also hallmarks of OA cartilage; thus, measurement of cartilage mechanical properties may also be beneficial for earlier OA detection. However, the relative predictive ability of compositional versus mechanical properties in detecting OA has yet to be determined. Therefore, we developed logistic regression models predicting OA status in an ex vivo environment using several mechanical and compositional metrics to assess which metrics most effectively predict OA status. Specifically, in this study the compositional metric analyzed was the T1rho relaxation time, while the mechanical metrics analyzed were the stiffness and recovery (defined as a measure of how quickly cartilage returns to its original shape after loading) of the cartilage. Cartilage recovery had the best predictive ability of OA status both alone and in a multivariate model including the T1rho relaxation time. These findings highlight the potential of cartilage recovery as a non-invasive marker of in vivo cartilage health and motivate future investigation of this metric clinically., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Hip fractures are a significant burden on the aging population, often resulting in reduced mobility, loss of independence, and elevated risk of mortality. While fracture risk is generally inversely related to bone mineral density (BMD), people with diabetes suffer a higher fracture rate despite having a higher BMD. To better understand the connection between diabetes and fracture risk, we developed a method to measure the minimum moment of inertia (mMOI; a geometric factor associated with fracture risk) from clinical CT scans of the pelvis. Since hip fractures are more prevalent in women, we focused on females in this study. We hypothesized that females with diabetes would have a lower mMOI along the femoral neck than those without diabetes, indicative of a higher fracture risk. Three-dimensional models of each hip were created from clinical CT scans of 40 older women (27 with diabetes: 10 fracture/17 non-fractured; 13 without diabetes: non-fractured controls). The mMOI of each hip (n = 80) was reported as the average from three trials. People with diabetes had an 18% lower mMOI as compared to those without diabetes after adjusting for age and BMI (p = 0.02). No differences in the mMOIs between the fractured and contralateral hips in the diabetic group were observed (p = 0.78). Similarly, no differences were observed between the fractured and non-fractured hips of people with diabetes (p = 0.29) when accounting for age and BMI. This suggests structural differences in the hips of individuals with diabetes (measured by the mMOI) may be associated with their elevated fracture risk., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Anterior cruciate ligament (ACL) and meniscus tears are common knee injuries. Despite the high rate of post-traumatic osteoarthritis (PTOA) following these injuries, the contributing factors remain unclear. In this study, we characterized the immune cell profiles of normal and injured joints at the time of ACL and meniscal surgeries., Methods: Twenty-nine patients (14 meniscus-injured and 15 ACL-injured) undergoing ACL and/or meniscus surgery but with a normal contralateral knee were recruited. During surgery, synovial fluid was aspirated from both normal and injured knees. Synovial fluid cells were pelleted, washed, and stained with an antibody cocktail consisting of fluorescent antibodies for cell surface proteins. Analysis of immune cells in the synovial fluid was performed by polychromatic flow cytometry. A broad spectrum immune cell panel was used in the first 10 subjects. Based on these results, a T cell-specific panel was used in the subsequent 19 subjects., Results: Using the broad spectrum immune cell panel, we detected significantly more total viable cells and CD3 T cells in the injured compared to the paired normal knees. In addition, there were significantly more injured knees with T cells above a 500-cell threshold. Within the injured knees, CD4 and CD8 T cells were able to be differentiated into subsets. The frequency of total CD4 T cells was significantly different among injury types, but no statistical differences were detected among CD4 and CD8 T cell subsets by injury type., Conclusions: Our findings provide foundational data showing that ACL and meniscus injuries induce an immune cell-rich microenvironment that consists primarily of T cells with multiple T helper phenotypes. Future studies investigating the relationship between immune cells and joint degeneration may provide an enhanced understanding of the pathophysiology of PTOA following joint injury., (© 2021. The Author(s).)

Meniscus injuries are common and a major cause of long-term joint degeneration and disability. Current treatment options are limited, so novel regenerative therapies or tissue engineering strategies are urgently needed. The development of new therapies is hindered by a lack of knowledge regarding the cellular biology of the meniscus and a lack of well-established methods for studying meniscus cells in vitro. The goals of this study were to (1) establish baseline expression profiles and dedifferentiation patterns of inner and outer zone primary meniscus cells, and (2) evaluate the utility of poly(ethylene glycol) diacrylate (PEGDA) and gelatin methacrylate (GelMA) polymer hydrogels to reverse dedifferentiation trends for long-term meniscus cell culture. Using reverse transcription-quantitative polymerase chain reaction, we measured expression levels of putative meniscus phenotype marker genes in freshly isolated meniscus tissue, tissue explant culture, and monolayer culture of inner and outer zone meniscus cells from porcine knees to establish baseline dedifferentiation characteristics, and then compared these expression levels to PEGDA/GelMA embedded passaged meniscus cells. COL1A1 showed robust upregulation, while CHAD, CILP, and COMP showed downregulation with monolayer culture. Expression levels of COL2A1, ACAN, and SOX9 were surprisingly similar between inner and outer zone tissue and were found to be less sensitive as markers of dedifferentiation. When embedded in PEGDA/GelMA hydrogels, expression levels of meniscus cell phenotype genes were significantly modulated by varying the ratio of polymer components, allowing these materials to be tuned for phenotype restoration, meniscus cell culture, and tissue engineering applications., (© 2020 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

High body mass index (BMI) and obesity have been implicated as risk factors for lumbar degenerative disc disease and low back pain. Despite this, there is limited in vivo data to quantify how obesity influences the mechanical function of intervertebral discs (IVD) in response to activities of daily living. Recently, our lab has developed methodologies to non-invasively measure in vivo IVD deformation resulting from activities of daily living using magnetic resonance (MR) imaging and solid modeling techniques. This pilot study expands on these methodologies to assess how BMI influences IVD deformation following treadmill walking in eight asymptomatic individuals. Ordinary least squares regression analyses revealed a statistically significant relationship between BMI and compressive deformation (strain (%)) in the L5-S1 IVD (R 2  = 0.61, p < 0.05). This relationship was weaker in the L3-L4 (R 2  = 0.28, p > 0.05) and L4-L5 IVDs (R 2  = 0.28, p > 0.05). Importantly, no relationship between pre-exercise disc height and BMI was identified (p > 0.05). Therefore, the results of this study suggest that BMI may alter the mechanical response of lumbar spine IVDs, particularly at the L5-S1 level. Furthermore, the observed relationship between increased BMI and IVD compressive deformation, in the absence of a detected relationship between pre-exercise disc height and BMI, suggests that changes in IVD mechanical function may be more sensitive to alterations in disc health than static clinical imaging alone. This finding highlights the importance of quantifying disc mechanical function when examining the relationship between BMI and IVD degeneration., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: There is little in vivo data that describe the relationships between patellar tendon orientation, patellar tendon strain, and anterior cruciate ligament (ACL) strain during dynamic activities. Quantifying how the quadriceps load the ACL via the patellar tendon is important for understanding ACL injury mechanisms., Hypothesis: We hypothesized that flexion angle, patellar tendon orientation, and patellar tendon strain influence ACL strain during a single-leg jump. Specifically, we hypothesized that patellar tendon and ACL strains would increase concurrently when the knee is positioned near extension during the jump., Study Design: Descriptive laboratory study., Methods: Models of the femur, tibia, ACL, patellar tendon, and quadriceps tendon attachment sites of 8 male participants were generated from magnetic resonance imaging (MRI). High-speed biplanar radiographs during a single-leg jump were obtained. The bone models were registered to the radiographs, thereby reproducing the in vivo positions of the bones, ligament, and tendon attachment sites. Flexion angle, patellar tendon orientation, patellar tendon strain, and ACL strain were measured from the registered models. ACL and patellar tendon strains were approximated by normalizing their length at each knee position to their length at the time of MRI. Two separate bivariate linear regression models were used to assess relationships between flexion angle and patellar tendon orientation and between ACL strain and patellar tendon strain. A multivariate linear regression model was used to assess whether flexion angle and patellar tendon strain were significant predictors of ACL strain during the inflight and landing portions of the jump., Results: Both flexion angle and patellar tendon strain were significant predictors ( P < .05) of ACL strain. These results indicate that elevated ACL and patellar tendon strains were observed concurrently when the knee was positioned near extension., Conclusion: Concurrent increases in patellar tendon and ACL strains indicate that the quadriceps load the ACL via the patellar tendon when the knee is positioned near extension., Clinical Relevance: Increased ACL strain when the knee is positioned near extension before landing may be due to quadriceps contraction. Thus, landing with unanticipated timing on an extended knee may increase vulnerability to ACL injury as a taut ligament is more likely to fail., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: This work was supported by grants from the National Institutes of Health (AR065527, AR075399, and AR074800). B.C.L. has received grant support from Zimmer and DJO, education payments from Smith & Nephew, and hospitality payments from Wright Medical. J.R.W. has received nonconsulting fees from Arthrex, education payments from Prodigy Surgical Distribution, and hospitality payments from Aesculap Biologics. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2021.)

Anterior cruciate ligament (ACL) rupture alters knee kinematics and contributes to premature development of osteoarthritis. However, there is limited data regarding the in vivo biomechanical response of tibiofemoral cartilage to activities of daily living (ADLs) in ACL-deficient knees. In this study, eight otherwise healthy participants with chronic unilateral ACL deficiency completed a stress test to assess the effect of 20 min of level treadmill walking at a speed of 2.5 mph on tibiofemoral cartilage in their ACL-deficient and contralateral ACL-intact knees. Three-dimensional surface models developed from pre- and post-activity magnetic resonance (MR) images of the injured and uninjured knees were used to determine compressive strain across multiple regions of tibiofemoral cartilage (medial and lateral tibial plateaus, medial and lateral femoral condyles, medial aspect of femoral condyle adjacent to intercondylar notch of the femur). In the ACL-deficient knees, we observed significantly increased cartilage strain in the region of the medial femoral condyle adjacent to the intercondylar notch (6% in deficient vs. 2% in contralateral, p = 0.01) as well as across the medial and lateral tibial plateaus (4% vs. 3%, p = 0.01) relative to the contralateral ACL-intact knees. Increased compressive strain at the medial intercondylar notch and tibial plateau suggests alterations in mechanical loading or the response to load in these regions, presumably related to altered knee kinematics. These changes may disrupt cartilage homeostasis and contribute to subsequent development of osteoarthritis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Bone contusions are commonly observed on magnetic resonance imaging (MRI) in individuals who have sustained a noncontact anterior cruciate ligament (ACL) injury. Time from injury to image acquisition affects the ability to visualize these bone contusions, as contusions resolve with time., Purpose: To quantify the number of bone contusions and their locations (lateral tibial plateau [LTP], lateral femoral condyle [LFC], medial tibial plateau [MTP], and medial femoral condyle [MFC]) observed on MRI scans of noncontact ACL-injured knees acquired within 6 weeks of injury., Study Design: Cross-sectional study; Level of evidence, 3., Methods: We retrospectively reviewed clinic notes, operative notes, and imaging of 136 patients undergoing ACL reconstruction. The following exclusion criteria were applied: MRI scans acquired beyond 6 weeks after injury, contact ACL injury, and previous knee trauma. Fat-suppressed fast spin-echo T2-weighted MRI scans were reviewed by a blinded musculoskeletal radiologist. The number of contusions and their locations (LTP, LFC, MTP, and MFC) were recorded., Results: Contusions were observed in 135 of 136 patients. Eight patients (6%) had 1 contusion, 39 (29%) had 2, 41 (30%) had 3, and 47 (35%) had 4. The most common contusion patterns within each of these groups were 6 (75%) with LTP for 1 contusion, 29 (74%) with LTP/LFC for 2 contusions, 33 (80%) with LTP/LFC/MTP for 3 contusions, and 47 (100%) with LTP/LFC/MTP/MFC for 4 contusions. No sex differences were detected in contusion frequency in the 4 locations ( P > .05). Among the participants, 50 (37%) had medial meniscal tears and 52 (38%) had lateral meniscal tears., Conclusion: The most common contusion patterns observed were 4 locations (LTP/LFC/MTP/MFC) and 3 locations (LTP/LFC/MTP).

Osteoarthritis is a debilitating disease characterized by cartilage degradation and altered cartilage mechanical properties. Furthermore, it is well established that obesity is a primary risk factor for osteoarthritis. The purpose of this study was to investigate the influence of obesity on the mechanical properties of murine knee cartilage. Two-month old wild type mice were fed either a normal diet or a high fat diet for 16 weeks. Atomic force microscopy-based nanoindentation was used to quantify the effective indentation modulus of medial femoral condyle cartilage. Osteoarthritis progression was graded using the OARSI system. Additionally, collagen organization was evaluated with picrosirius red staining imaged using polarized light microscopy. Significant differences between diet groups were assessed using t tests with p < 0.05. Following 16 weeks of a high fat diet, no significant differences in OARSI scoring were detected. However, we detected a significant difference in the effective indentation modulus between diet groups. The reduction in cartilage stiffness is likely the result of disrupted collagen organization in the superficial zone, as indicated by altered birefringence on polarized light microscopy. Collectively, these results suggest obesity is associated with changes in knee cartilage mechanical properties, which may be an early indicator of disease progression.

One of the primary functions of bone is to support the skeleton by withstanding load. In the diseased state, bone's ability to perform this function is altered. Quantification of the features of bone that support its functional behavior, and how they may change with disease, is accomplished through mechanical testing. As such, mechanical testing is a useful tool for scientists studying orthopedic-related diseases. Furthermore, a common animal model used to investigate disease and its treatment is the mouse. Therefore, in this chapter we (1) describe central concepts of mechanical testing, (2) describe factors that influence the mechanical behavior of bone, and (3) describe the application of a widely used mechanical testing technique, four-point bending, to the mouse bone for characterization of its structural properties.

Background: Running is a common recreational activity that provides many health benefits. However, it remains unclear how patellofemoral cartilage is affected by varied running distances and how long it takes the cartilage to recover to its baseline state after exercise., Hypothesis: We hypothesized that patellofemoral cartilage thickness would decrease immediately after exercise and return to its baseline thickness by the following morning in asymptomatic male runners. We further hypothesized that we would observe a significant distance-related dose response, with larger compressive strains (defined here as the mean change in cartilage thickness measured immediately after exercise, divided by the pre-exercise cartilage thickness) observed immediately after 10-mile runs compared with 3-mile runs., Study Design: Descriptive laboratory study., Methods: Eight asymptomatic male participants underwent magnetic resonance imaging of their dominant knee before, immediately after, and 24 hours after running 3 and 10 miles at a self-selected pace (on separate visits)., Results: Mean patellar cartilage thicknesses measured before exercise and after the 24-hour recovery period were significantly greater than the thicknesses measured immediately after both the 3- and 10-mile runs ( P < .001). This relationship was not observed in trochlear cartilage. Mean patellar cartilage compressive strains were significantly greater after 10-mile runs compared with 3-mile runs (8% vs 5%; P = .01)., Conclusion: Patellar cartilage thickness decreased immediately after running and returned to its baseline thickness within 24 hours of running up to 10 miles. Furthermore, patellar cartilage compressive strains were dose-dependent immediately after exercise., Clinical Relevance: These findings provide critical baseline data for understanding patellofemoral cartilage biomechanics in asymptomatic male runners that may be used to optimize exercise protocols and investigations targeting those with running-induced patellofemoral pain., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: This study was supported by grants from the National Institutes of Health (R01 AR065527, R01 AR074800, R01 AR075399, and F32 AR066477). AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2020.)

Background: Obesity, which potentially increases loading at the knee, is a common and modifiable risk factor for the development of knee osteoarthritis. The menisci play an important role in distributing joint loads to the underlying cartilage. However, the influence of obesity on the role of the menisci in cartilage load distribution in vivo is currently unknown., Purpose: To measure tibial cartilage thickness and compressive strain in response to walking in areas covered and uncovered by the menisci in participants with normal body mass index (BMI) and participants with high BMI., Study Design: Controlled laboratory study., Methods: Magnetic resonance (MR) images of the right knees of participants with normal BMI (<25 kg/m 2 ; n = 8) and participants with high BMI (>30 kg/m 2 ; n = 7) were obtained before and after treadmill walking. The outer margins of the tibia, the medial and lateral cartilage surfaces, and the meniscal footprints were segmented on each MR image to create 3-dimensional models of the joint. Cartilage thickness was measured before and after walking in areas covered and uncovered by the menisci. Cartilage compressive strain was then determined from changes in thickness resulting from the walking task., Results: Before exercise, medial and lateral uncovered cartilage of the tibial plateau was significantly thicker than covered cartilage in both BMI groups. In the uncovered region of the lateral tibial plateau, participants with high BMI had thinner preexercise cartilage than those with a normal BMI. Cartilage compressive strain was significantly greater in medial and lateral cartilage in participants with high BMI compared with those with normal BMI in both the regions covered and those uncovered by the menisci., Conclusion: Participants with high BMI experienced greater cartilage strain in response to walking than participants with normal BMI in both covered and uncovered regions of cartilage, which may indicate that the load-distributing function of the meniscus is not sufficient to moderate the effects of obesity., Clinical Relevance: These findings demonstrate the critical effect of obesity on cartilage function and thickness in regions covered and uncovered by the menisci., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: This study was supported by the National Institutes of Health (AR066477, AR065527, and AR073221) and an Orthopaedic Research and Education Foundation grant with funding provided by the Musculoskeletal Transplant Foundation. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2020.)

Background: Some cadaveric studies have indicated that the anterior cruciate ligament (ACL) consists of anteromedial and posterolateral bundles that display reciprocal function with regard to knee flexion. However, several in vivo imaging studies have suggested that these bundles elongate in parallel with regard to flexion. Furthermore, the most appropriate description of the functional anatomy of the ACL is still debated, with the ACL being described as consisting of 2 or 3 bundles or as a continuum of fibers., Hypothesis: As long as their origination and termination locations are defined within the ACL attachment site footprints, ACL bundles elongate in parallel with knee extension during gait., Study Design: Descriptive laboratory study., Methods: High-speed biplanar radiographs of the right knee joint were obtained during gait in 6 healthy male participants (mean ± SD: body mass index, 25.5 ± 1.2 kg/m 2 ; age, 29.2 ± 3.8 years) with no history of lower extremity injury or surgery. Three-dimensional models of the right femur, tibia, and ACL attachment sites were created from magnetic resonance images. The bone models were registered to the biplanar radiographs, thereby reproducing the in vivo positions of the knee joint. For each knee position, the distances between the centroids of the ACL attachment sites were used to represent ACL length. The lengths of 1000 virtual bundles were measured for each participant by randomly sampling locations on the attachment site surfaces and measuring the distances between each pair of locations. Spearman rho rank correlations were performed between the virtual bundle lengths and ACL length., Results: The virtual bundle lengths were highly correlated with the length of the ACL, defined as the distance between the centroids of the attachment sites (rho = 0.91 ± 0.1, across participants; P < 5 × 10 -5 ). The lengths of the bundles that originated and terminated in the anterior and medial aspects of the ACL were positively correlated (rho = 0.81 ± 0.1; P < 5 × 10 -5 ) with the lengths of the bundles that originated and terminated in the posterior and lateral aspects of the ACL., Conclusion: As long as their origination and termination points are specified within the footprint of the attachment sites, ACL bundles elongate in parallel as the knee is extended., Clinical Relevance: These data elucidate ACL functional anatomy and may help guide ACL reconstruction techniques.

The purpose of this work is to determine the relationship between biomarkers of inflammation, structure, and pain with radiographic disc space narrowing (DSN) in community-based participants. A total of 74 participants (37 cases and 37 controls) enrolled in the Johnston County Osteoarthritis Project during 2006-2010 were selected. The cases had at least mild radiographic DSN and low back pain (LBP). The controls had neither radiographic evidence of DSN nor LBP. The measured analytes from human serum included N-cadherin, Keratin-19, Lumican, CXCL6, RANTES, IL-17, IL-6, BDNF, OPG, and NPY. A standard dolorimeter measured pressure-pain threshold. The coefficients of variation were used to evaluate inter- and intra-assay reliability. Participants with similar biomarker profiles were grouped together using cluster analysis. The binomial regression models were used to estimate risk ratios (RR) and 95% confidence intervals (CI) in propensity score-matched models. Significant associations were found between radiographic DSN and OPG (RR = 3.90; 95% CI: 1.83, 8.31), IL-6 (RR = 2.54; 95% CI: 1.92, 3.36), and NPY (RR = 2.06 95% CI: 1.62, 2.63). Relative to a cluster with low levels of biomarkers, a cluster representing elevated levels of OPG, RANTES, Lumican, Keratin-19, and NPY (RR = 3.04; 95% CI: 1.22, 7.54) and a cluster representing elevated levels of NPY (RR = 2.91; 95% CI: 1.15, 7.39) were significantly associated with radiographic DSN. Clinical Significance: These findings suggest that individual and combinations of biochemical biomarkers may reflect radiographic DSN. This is just one step toward understanding the relationships between biochemical biomarkers and DSN that may lead to improved intervention delivery. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:1027-1037, 2020., (© 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Roughly 20% of Americans run annually, yet how this exercise influences knee cartilage health is poorly understood. To address this question, quantitative magnetic resonance imaging (MRI) can be used to infer the biochemical state of cartilage. Specifically, T1rho relaxation times are inversely related to the proteoglycan concentration in cartilage. In this study, T1rho MRI was performed on the dominant knee of eight asymptomatic, male runners before, immediately after, and 24 hours after running 3 and 10 miles. Overall, (mean ± SEM) patellar, tibial, and femoral cartilage T1rho relaxation times significantly decreased immediately after running 3 (65 ± 3 ms to 62 ± 3 ms; p = 0.04) and 10 (69 ± 4 ms to 62 ± 3 ms; p < 0.001) miles. No significant differences between pre-exercise and recovery T1rho values were observed for either distance (3 mile: p = 0.8; 10 mile: p = 0.08). Percent decreases in T1rho relaxation times were significantly larger following 10 mile runs as compared to 3 mile runs (11 ± 1% vs. 4 ± 1%; p = 0.02). This data suggests that alterations to the relative proteoglycan concentration of knee cartilage due to water flow are mitigated within 24 hours of running up to 10 miles. This information may inform safe exercise and recovery protocols in asymptomatic male runners by characterizing running-induced changes in knee cartilage composition.

The diagnosis of osteoarthritis (OA) currently depends on the presence of pain and radiographic imaging findings, which generally do not present until later stages of the disease when the condition is difficult to treat. Therefore, earlier detection of OA pathology is needed for improved disease management. Ex vivo cartilage studies indicate that changes in the mechanical function of cartilage occur as degeneration progresses during OA. Thus, measurement of the in vivo cartilage mechanical response may serve as an earlier indicator of OA pathology. Though mechanical characterization is classically performed during loading, the unloading (recovery) response of cartilage may also enable determination of mechanical response. Therefore, the purpose of this study was to validate the use of the recovery response for mechanical characterization of cartilage in a controlled, ex vivo environment. To do so, confined compression creep and recovery tests were conducted on cartilage explants (N = 10), and the resulting mechanical properties from both the creep and recovery phases were compared. No statistically significant differences were found in the mechanical properties between the two phases, reinforcing the hypothesis that unloading (recovery) may be a good surrogate for loading.

Background: The in vivo mechanics of the anterior cruciate ligament (ACL) and its bundles during dynamic activities are not completely understood. An improved understanding of how the ACL stabilizes the knee is likely to aid in the identification and prevention of injurious maneuvers., Purpose/hypothesis: The purpose was to measure in vivo ACL strain during a single-legged jump through use of magnetic resonance imaging (MRI) and high-speed biplanar radiography. We hypothesized that ACL strain would increase with the knee near extension, and a peak in ACL strain would occur just before landing from the jump, potentially due to quadriceps contraction in anticipation of landing., Study Design: Descriptive laboratory study., Methods: Models of the femur, tibia, and ACL attachment sites of 8 male participants were generated from MRI scans through use of solid modeling. High-speed biplanar radiographs were obtained from these participants as they performed a single-legged jump. The bone models were registered to the biplanar radiographs, thereby reproducing the in vivo positions of the joint throughout the jump. ACL and bundle elongations were defined as the centroid to centroid distances between attachment sites for each knee position. ACL strain was defined as ACL length normalized to its length measured in the position of the knee at the time of MRI., Results: Peaks in ACL strain were observed before toe-off and 55 ± 35 milliseconds before initial ground contact. These peaks were associated with the knee positioned at low flexion angles. Mean ACL strain was inversely related to mean flexion angle (rho = -0.73, P < .001), such that ACL strain generally increased with knee extension throughout the jumping motion. ACL bundle lengths were significantly (rho > 0.85, P < .001) correlated with overall ACL length., Conclusion: These findings provide insight into how landing in extension can increase the risk of ACL injury. Specifically, this study shows that peak ACL strain can occur just before landing from a single-legged jump. Thus, when an individual lands on an extended knee, the ACL is relatively taut, which may make it particularly vulnerable to injury, especially in the presence of a movement perturbation or unanticipated change in landing strategy., Clinical Relevance: This study provides a novel measurement of dynamic ACL strain during an athletic maneuver and lends insight into how landing in extension can increase the likelihood of ACL failure.

Meniscal tears have a poor healing capacity, and damage to the meniscus is associated with significant pain, disability, and progressive degenerative changes in the knee joint that lead to osteoarthritis. Therefore, strategies to promote meniscus repair and improve meniscus function are needed. The objective of this study was to generate porcine meniscus-derived matrix (MDM) scaffolds and test their effectiveness in promoting meniscus repair via migration of endogenous meniscus cells from the surrounding meniscus or exogenously seeded human bone marrow-derived mesenchymal stem cells (MSCs). Both endogenous meniscal cells and MSCs infiltrated the MDM scaffolds. In the absence of exogenous cells, the 8% MDM scaffolds promoted the integrative repair of an in vitro meniscal defect. Dehydrothermal crosslinking and concentration of the MDM influenced the biochemical content and shear strength of repair, demonstrating that the MDM can be tailored to promote tissue repair. These findings indicate that native meniscus cells can enhance meniscus healing if a scaffold is provided that promotes cellular infiltration and tissue growth. The high affinity of cells for the MDM and the ability to remodel the scaffold reveals the potential of MDM to integrate with native meniscal tissue to promote long-term repair without necessarily requiring exogenous cells.

A potential cause of non-contact anterior cruciate ligament (ACL) injury is landing on an extended knee. In line with this hypothesis, studies have shown that the ACL is elongated with decreasing knee flexion angle. Furthermore, at low flexion angles the patellar tendon is oriented to increase the anterior shear component of force acting on the tibia. This indicates that knee extension represents a position in which the ACL is taut, and thus may have an increased propensity for injury, particularly in the presence of excessive force acting via the patellar tendon. However, there is very little in vivo data to describe how patellar tendon orientation and ACL elongation interact during flexion. Therefore, this study measured the patellar tendon tibial shaft angle (indicative of the relative magnitude of the shear component of force acting via the patellar tendon) and ACL length in vivo as subjects performed a quasi-static lunge at varying knee flexion angles. Spearman rho rank correlations within each individual revealed that flexion angles were inversely correlated to both ACL length (rho = -0.94 ± 0.07, mean ± standard deviation, p < 0.05) and patellar tendon tibial shaft angle (rho = -0.99 ± 0.01, p < 0.05). These findings indicate that when the knee is extended, the ACL is both elongated and the patellar tendon tibial shaft angle is increased, resulting in a relative increase in anterior shear force on the tibia acting via the patellar tendon. Therefore, these data support the hypothesis that landing with the knee in extension is a high risk scenario for ACL injury., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: To review recent biomechanics literature focused on the interactions between biomechanics and articular cartilage health, particularly focused on macro-scale and human studies., Design: A literature search was conducted in PubMed using the search terms (biomechanics AND osteoarthritis) OR (biomechanics AND cartilage) OR (mechanics AND osteoarthritis) OR (mechanics AND cartilage) for publications from April 2017 to April 2018., Results: Abstracts from the 559 articles generated from the literature search were reviewed. Due to the wide range of topics, 62 full texts with a focus on in vivo biomechanical studies were included for further discussion. Several overarching themes in the recent literature were identified and are summarized, including 1) new methods to detect early osteoarthritis (OA) development, 2) studies describing healthy and OA cartilage and biomechanics, 3) ACL injury and OA development, 4) meniscus injury and OA development, and 5) OA prevention, treatment, and management., Conclusions: Mechanical loading is a critical factor in the maintenance of joint health. Abnormal mechanical loading can lead to the onset and progression of OA. Thus, recent studies have utilized various biomechanical models to better describe the etiology of OA development and the subsequent effects of OA on the mechanics of joint tissues and whole body biomechanics., (Copyright © 2018 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Cartilage metabolism-both the synthesis and breakdown of cartilage constituents and architecture-is influenced by its mechanical loading. Therefore, physical activity is often recommended to maintain cartilage health and to treat or slow the progression of osteoarthritis, a debilitating joint disease causing cartilage degeneration. However, the appropriate exercise frequency, intensity, and duration cannot be prescribed because direct in vivo evaluation of cartilage following exercise has not yet been performed. To address this gap in knowledge, we developed a cartilage stress test to measure the in vivo strain response of healthy human subjects' tibial cartilage to walking exercise. We varied both walk duration and speed in a dose-dependent manner to quantify how these variables affect cartilage strain. We found a nonlinear relationship between walk duration and in vivo compressive strain, with compressive strain initially increasing with increasing duration, then leveling off with longer durations. This work provides innovative measurements of cartilage creep behavior (which has been well-documented in vitro but not in vivo) during walking. This study showed that compressive strain increased with increasing walking speed for the speeds tested in this study (0.9-2.0 m/s). Furthermore, our data provide novel measurements of the in vivo strain response of tibial cartilage to various doses of walking as a mechanical stimulus, with maximal strains of 5.0% observed after 60 minutes of walking. These data describe physiological benchmarks for healthy articular cartilage behavior during walking and provide a much-needed baseline for studies investigating the effect of exercise on cartilage health.

Background: Knee positions involved in noncontact anterior cruciate ligament (ACL) injury have been studied via analysis of injury videos. Positions of high ACL strain have been identified in vivo. These methods have supported different hypotheses regarding the role of knee abduction in ACL injury., Purpose/hypothesis: The purpose of this study was to compare knee abduction angles measured by 2 methods: using a 3-dimensional (3D) coordinate system based on anatomic features of the bones versus simulated 2-dimensional (2D) videographic analysis. We hypothesized that knee abduction angles measured in a 2D videographic analysis would differ from those measured from 3D bone anatomic features and that videographic knee abduction angles would depend on flexion angle and on the position of the camera relative to the patient., Study Design: Descriptive laboratory study., Methods: Models of the femur and tibia were created from magnetic resonance images of 8 healthy male participants. The models were positioned to match biplanar fluoroscopic images obtained as participants posed in lunges of varying flexion angles (FLAs). Knee abduction angle was calculated from the positioned models in 2 ways: (1) varus-valgus angle (VVA), defined as the angle between the long axis of the tibia and the femoral transepicondylar axis by use of a 3D anatomic coordinate system; and (2) coronal plane angle (CPA), defined as the angle between the long axis of the tibia and the long axis of the femur projected onto the tibial coronal plane to simulate a 2D videographic analysis. We then simulated how changing the position of the camera relative to the participant would affect knee abduction angles., Results: During flexion, when CPA was calculated from a purely anterior or posterior view of the joint-an ideal scenario for measuring knee abduction from 2D videographic analysis-CPA was significantly different from VVA ( P < .0001). CPA also varied substantially with the position of the camera relative to the participant., Conclusion: How closely CPA (derived from 2D videographic analysis) relates to VVA (derived from a 3D anatomic coordinate system) depends on FLA and camera orientation., Clinical Relevance: This study provides a novel comparison of knee abduction angles measured from 2D videographic analysis and those measured within a 3D anatomic coordinate system. Consideration of these findings is important when interpreting 2D videographic data regarding knee abduction angle in ACL injury., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: This study was supported by a grant from the NIH (RO1AR065527) to L.E.D. W.E.G. has received grants from and is a paid consultant for Arthrex. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

Quantitative T1rho magnetic resonance imaging (MRI) can potentially help identify early-stage osteoarthritis (OA) by non-invasively assessing proteoglycan concentration in articular cartilage. T1rho relaxation times are negatively correlated with proteoglycan concentration. Cartilage compresses in response to load, resulting in water exudation, a relative increase in proteoglycan concentration, and a decrease in the corresponding T1rho relaxation times. To date, there is limited information on changes in cartilage composition resulting from daily activity. Therefore, the objective of this study was to quantify changes in tibial cartilage T1rho relaxation times in healthy human subjects following activities of daily living. It was hypothesized that water exudation throughout the day would lead to decreased T1rho relaxation times. Subjects underwent MR imaging in the morning and afternoon on the same day and were free to go about their normal activities between scans. Our findings confirmed the hypothesis that tibial cartilage T1rho relaxation times significantly decreased (by 7%) over the course of the day with loading, which is indicative of a relative increase in proteoglycan concentration. Additionally, baseline T1rho values varied with position within the cartilage, supporting a need for site-specific measurements of T1rho relaxation times. Understanding how loading alters the proteoglycan concentration in healthy cartilage may hold clinical significance pertaining to cartilage homeostasis and potentially help to elucidate a mechanism for OA development. These results also indicate that future studies using T1rho relaxation times as an indicator of cartilage health should control the loading history prior to image acquisition to ensure the appropriate interpretation of the data., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Changes in knee kinematics after anterior cruciate ligament (ACL) injury may alter loading of the cartilage and thus affect its homeostasis, potentially leading to the development of posttraumatic osteoarthritis. However, there are limited in vivo data to characterize local changes in cartilage thickness and strain in response to dynamic activity among patients with ACL deficiency., Purpose/hypothesis: The purpose was to compare in vivo tibiofemoral cartilage thickness and cartilage strain resulting from dynamic activity between ACL-deficient and intact contralateral knees. It was hypothesized that ACL-deficient knees would show localized reductions in cartilage thickness and elevated cartilage strains., Study Design: Controlled laboratory study., Methods: Magnetic resonance images were obtained before and after single-legged hopping on injured and uninjured knees among 8 patients with unilateral ACL rupture. Three-dimensional models of the bones and articular surfaces were created from the pre- and postactivity scans. The pre- and postactivity models were registered to each other, and cartilage strain (defined as the normalized difference in cartilage thickness pre- and postactivity) was calculated in regions across the tibial plateau, femoral condyles, and femoral cartilage adjacent to the medial intercondylar notch. These measurements were compared between ACL-deficient and intact knees. Differences in cartilage thickness and strain between knees were tested with multiple analysis of variance models with alpha set at P < .05., Results: Compressive strain in the intercondylar notch was elevated in the ACL-deficient knee relative to the uninjured knee. Furthermore, cartilage in the intercondylar notch and adjacent medial tibia was significantly thinner before activity in the ACL-deficient knee versus the intact knee. In these 2 regions, thinning was significantly influenced by time since injury, with patients with more chronic ACL deficiency (>1 year since injury) experiencing greater thinning., Conclusion: Among patients with ACL deficiency, the medial femoral condyle adjacent to the intercondylar notch in the ACL-deficient knee exhibited elevated cartilage strain and loss of cartilage thickness, particularly with longer time from injury. It is hypothesized that these changes may be related to posttraumatic osteoarthritis development., Clinical Relevance: This study suggests that altered mechanical loading is related to localized cartilage thinning after ACL injury.

Our objective was to determine the relationship of T1rho and T2 relaxation mapping to the biochemical and biomechanical properties of articular cartilage through selective digestion of proteoglycans and collagens. Femoral condyles were harvested from porcine knee joints and treated with either chondroitinase ABC (cABC) followed by collagenase, or collagenase followed by cABC. Magnetic resonance images were acquired and cartilage explants were harvested for biochemical, biomechanical, and histological analyses before and after each digestion. Targeted enzymatic digestion of proteoglycans with cABC resulted in elevated T1rho relaxation times and decreased sulfated glycosaminoglycan content without affecting T2 relaxation times. In contrast, extractable collagen and T2 relaxation times were increased by collagenase digestion; however, neither was altered by cABC digestion. Aggregate modulus decreased with digestion of both components. Overall, we found that targeted digestion of proteoglycans and collagens had varying effects on biochemical, biomechanical, and imaging properties. T2 relaxation times were altered with changes in extractable collagen, but not changes in proteoglycan. However, T1rho relaxation times were altered with proteoglycan loss, which may also coincide with collagen disruption. Since it is unclear which matrix components are disrupted first in osteoarthritis, both markers may be important for tracking disease progression.