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      Validation of a Low-Cost Portable Device for Inducing Noninvasive Anterior Cruciate Ligament Injury in Mice

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          Abstract

          Noninvasive compression-induced anterior cruciate ligament rupture (ACL-R) is an easy and reproducible model for studying post-traumatic osteoarthritis (PTOA) in mice. However, equipment typically used for ACL-R is expensive, immobile, and not available to all researchers. In this study, we compared PTOA progression in mice injured with a low-cost custom ACL-rupture device (CARD) to mice injured with a standard system (ElectroForce 3200). We quantified anterior–posterior (AP) joint laxity immediately following injury, epiphyseal trabecular bone microstructure, and osteophyte volume at 2 and 6 weeks post injury using micro-computed tomography, and osteoarthritis progression and synovitis at 2 and 6 weeks post injury using whole-joint histology. We observed no significant differences in outcomes in mice injured with the CARD system compared to mice injured with the Electroforce (ELF) system. However, AP joint laxity data and week 2 micro-CT and histology outcomes suggested that injuries may have been slightly more severe and PTOA progressed slightly faster in mice injured with the CARD system compared to the ELF system. Altogether, these data confirm that ACL-R can be successfully and reproducibly performed with the CARD system and that osteoarthritis (OA) progression is mostly comparable to that of mice injured with the ELF system, though potentially slightly faster. The CARD system is low cost and portable, and we are making the plans and instructions freely available to all interested investigators in the hopes that they will find this system useful for their studies of OA in mice.

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          Most cited references20

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          Guidelines for assessment of bone microstructure in rodents using micro-computed tomography.

          Use of high-resolution micro-computed tomography (microCT) imaging to assess trabecular and cortical bone morphology has grown immensely. There are several commercially available microCT systems, each with different approaches to image acquisition, evaluation, and reporting of outcomes. This lack of consistency makes it difficult to interpret reported results and to compare findings across different studies. This article addresses this critical need for standardized terminology and consistent reporting of parameters related to image acquisition and analysis, and key outcome assessments, particularly with respect to ex vivo analysis of rodent specimens. Thus the guidelines herein provide recommendations regarding (1) standardized terminology and units, (2) information to be included in describing the methods for a given experiment, and (3) a minimal set of outcome variables that should be reported. Whereas the specific research objective will determine the experimental design, these guidelines are intended to ensure accurate and consistent reporting of microCT-derived bone morphometry and density measurements. In particular, the methods section for papers that present microCT-based outcomes must include details of the following scan aspects: (1) image acquisition, including the scanning medium, X-ray tube potential, and voxel size, as well as clear descriptions of the size and location of the volume of interest and the method used to delineate trabecular and cortical bone regions, and (2) image processing, including the algorithms used for image filtration and the approach used for image segmentation. Morphometric analyses should be based on 3D algorithms that do not rely on assumptions about the underlying structure whenever possible. When reporting microCT results, the minimal set of variables that should be used to describe trabecular bone morphometry includes bone volume fraction and trabecular number, thickness, and separation. The minimal set of variables that should be used to describe cortical bone morphometry includes total cross-sectional area, cortical bone area, cortical bone area fraction, and cortical thickness. Other variables also may be appropriate depending on the research question and technical quality of the scan. Standard nomenclature, outlined in this article, should be followed for reporting of results. 2010 American Society for Bone and Mineral Research.
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            The long-term consequence of anterior cruciate ligament and meniscus injuries: osteoarthritis.

            The objectives of this study are to review the long-term consequences of injuries to the anterior cruciate ligament and menisci, the pathogenic mechanisms, and the causes of the considerable variability in outcome. Injuries of the anterior cruciate ligament and menisci are common in both athletes and the general population. At 10 to 20 years after the diagnosis, on average, 50% of those with a diagnosed anterior cruciate ligament or meniscus tear have osteoarthritis with associated pain and functional impairment: the young patient with an old knee. These individuals make up a substantial proportion of the overall osteoarthritis population. There is a lack of evidence to support a protective role of repair or reconstructive surgery of the anterior cruciate ligament or meniscus against osteoarthritis development. A consistent finding in a review of the literature is the often poor reporting of critical study variables, precluding data pooling or a meta-analysis. Osteoarthritis development in the injured joints is caused by intra-articular pathogenic processes initiated at the time of injury, combined with long-term changes in dynamic joint loading. Variation in outcome is reinforced by additional variables associated with the individual such as age, sex, genetics, obesity, muscle strength, activity, and reinjury. A better understanding of these variables may improve future prevention and treatment strategies. In evaluating medical treatment, we now expect large randomized clinical trials complemented by postmarketing monitoring. We should strive toward a comparable level of quality of evidence in surgical treatment of knee injuries. In instances in which a randomized clinical trial is not feasible, natural history and other observational cohort studies need to be as carefully designed and reported as the classic randomized clinical trial, to yield useful information.
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              Number of Persons With Symptomatic Knee Osteoarthritis in the US: Impact of Race and Ethnicity, Age, Sex, and Obesity.

              The prevalence of symptomatic knee osteoarthritis (OA) has been increasing over the past several decades in the US, concurrent with an aging population and the growing obesity epidemic. We quantify the impact of these factors on the number of persons with symptomatic knee OA in the early decades of the 21st century.
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                Author and article information

                Journal
                J Biomech Eng
                J Biomech Eng
                BIO
                Journal of Biomechanical Engineering
                American Society of Mechanical Engineers
                0148-0731
                1528-8951
                01 November 2023
                08 August 2023
                : 145
                : 11
                : 114501
                Affiliations
                [1]Lawrence J. Ellison Musculoskeletal Research Center, Department of Orthopaedic Surgery, University of California Davis Health, 2700 Stockton Blvd, Suite 2301, Sacramento, CA 95817
                [2]Department of Mechanical and Industrial Engineering, Montana State University , P.O. Box 173820, Bozeman, MT 59717
                Author notes
                Article
                BIO-22-1241
                10.1115/1.4062904
                10777735
                37417814
                30763c9c-309a-42f1-a057-8bd5cb920aa0
                Copyright © 2023 by ASME

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 30 August 2022
                : 27 June 2023
                Page count
                Pages: 7
                Funding
                Funded by: National Institute of Arthritis and Musculoskeletal and Skin Diseases, doi 10.13039/100000069;
                Award ID: AR075013
                Categories
                Technical Briefs

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