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      Paraspinal muscle morphology and composition in adolescent idiopathic scoliosis: A histological analysis

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          Abstract

          Background

          Adolescent idiopathic scoliosis (AIS) is a condition resulting in spinal deformity and tissue adaptation of the paraspinal muscles. Although prior studies have demonstrated asymmetries in fiber type and other energetic features of muscle on the concave side of the curve, muscle morphology, architecture, and composition have not been evaluated. Therefore, the purpose of this study was to compare differences in paraspinal muscle microarchitecture and composition between concave and convex sides of a scoliotic curve in individuals with AIS.

          Methods

          Paraspinal muscle biopsies were obtained at the apex of the scoliotic curve in 29 individuals with AIS undergoing surgical deformity correction. Histological assays were performed to quantify fiber size, evidence of muscle degeneration and regeneration, and tissue composition (proportion of muscle, collagen, and fat). Differences between contralateral muscle samples were compared using two‐tailed paired Student's t tests, and relationships between clinical characteristics (age and curve severity) and muscle characteristics were investigated using Pearson correlations.

          Results

          Muscle fibers were significantly larger on the convex side of the curve apex ( P = .001), but were lower than literature‐based norms for healthy paraspinal muscle. There were no differences in amount of degeneration/regeneration ( P = .490) or the proportion of muscle and collagen ( P > .350) between the concave and convex sides, but high levels of collagen were observed. There was a trend toward higher fat content on the concave side ( P = .074). Larger fiber size asymmetries were associated with greater age ( r = .43, P = .046), and trended toward an association with greater curve severity ( r = .40, P = .069).

          Conclusions

          This study demonstrates that although muscle fibers are larger on the convex side of the scoliotic curve in AIS, muscles on both sides are atrophic compared to non‐scoliotic individuals, and demonstrate levels of collagen similar to severe degenerative spinal pathologies. These findings provide insight into biological maladaptations occurring in paraspinal muscle in the presence of AIS.

          Abstract

          Muscle adaptations in adolescent idiopathic scoliosis are not well described. Using intraoperative muscle biopsies from both the concave and convex side of the deformity, we found evidence of bilateral atrophy and degeneration as well as side‐specific size and compositional changes.

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          Most cited references31

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          Cellular and molecular mechanisms of muscle atrophy

          Skeletal muscle is a plastic organ that is maintained by multiple pathways regulating cell and protein turnover. During muscle atrophy, proteolytic systems are activated, and contractile proteins and organelles are removed, resulting in the shrinkage of muscle fibers. Excessive loss of muscle mass is associated with poor prognosis in several diseases, including myopathies and muscular dystrophies, as well as in systemic disorders such as cancer, diabetes, sepsis and heart failure. Muscle loss also occurs during aging. In this paper, we review the key mechanisms that regulate the turnover of contractile proteins and organelles in muscle tissue, and discuss how impairments in these mechanisms can contribute to muscle atrophy. We also discuss how protein synthesis and degradation are coordinately regulated by signaling pathways that are influenced by mechanical stress, physical activity, and the availability of nutrients and growth factors. Understanding how these pathways regulate muscle mass will provide new therapeutic targets for the prevention and treatment of muscle atrophy in metabolic and neuromuscular diseases.
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            Adolescent idiopathic scoliosis.

            Adolescent idiopathic scoliosis (AIS) is the most common form of structural spinal deformities that have a radiological lateral Cobb angle - a measure of spinal curvature - of ≥10(°). AIS affects between 1% and 4% of adolescents in the early stages of puberty and is more common in young women than in young men. The condition occurs in otherwise healthy individuals and currently has no recognizable cause. In the past few decades, considerable progress has been made towards understanding the clinical patterns and the three-dimensional pathoanatomy of AIS. Advances in biomechanics and technology and their clinical application, supported by limited evidence-based research, have led to improvements in the safety and outcomes of surgical and non-surgical treatments. However, the definite aetiology and aetiopathogenetic mechanisms that underlie AIS are still unclear. Thus, at present, both the prevention of AIS and the treatment of its direct underlying cause are not possible.
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              Histological parameters for the quantitative assessment of muscular dystrophy in the mdx-mouse.

              Duchenne muscular dystrophy is a severe X-linked hereditary disease caused by the absence of functional dystrophin. The dystrophin-deficient mdx-mouse strain is a widely used animal model for dystrophin-deficiency. Several therapeutic approaches for muscular dystrophy have been proposed by different laboratories. In order to compare the efficacy of these therapies in the mdx-mouse, it is essential to implement standardized protocols for the assessment of functional and histological parameters in this mouse model. Here, we determine that the minimal 'Feret's diameter' is a geometrical parameter that allows for reliable measure of muscle fiber cross-sectional size. Using this geometrical parameter we calculate variance coefficients of the muscle fiber size and provide reference values for the quantitative assessment of dystrophic symptoms in frequently investigated muscles of wild-type and mdx-mouse. In addition, we compare the variance coefficients of the muscle fiber size with the percentage of muscle fibers with centralized nuclei; another histological hallmark of muscular dystrophy.
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                Author and article information

                Contributors
                srward@ucsd.edu
                Journal
                JOR Spine
                JOR Spine
                10.1002/(ISSN)2572-1143
                JSP2
                JOR Spine
                John Wiley & Sons, Inc. (Hoboken, USA )
                2572-1143
                16 September 2021
                September 2021
                : 4
                : 3 ( doiID: 10.1002/jsp2.v4.3 )
                : e1169
                Affiliations
                [ 1 ] Department of Orthopaedic Surgery University of California San Diego La Jolla California USA
                [ 2 ] Rady Children's Hospital San Diego California USA
                Author notes
                [*] [* ] Correspondence

                Samuel R. Ward, Department of Orthopaedic Surgery, University of California San Diego, ACTRI Lower Level 2, 9452 Medical Center Drive, La Jolla, CA 92037, USA.

                Email: srward@ 123456ucsd.edu

                Author information
                https://orcid.org/0000-0002-7532-6940
                https://orcid.org/0000-0001-7615-3749
                Article
                JSP21169
                10.1002/jsp2.1169
                8479518
                34611591
                60cfa82f-9ad5-41d6-8249-0d5598ff20cf
                © 2021 The Authors. JOR Spine published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 02 August 2021
                : 25 May 2021
                : 21 August 2021
                Page count
                Figures: 5, Tables: 1, Pages: 7, Words: 4738
                Categories
                Research Article
                Research Articles
                Custom metadata
                2.0
                September 2021
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.0.8 mode:remove_FC converted:29.09.2021

                adolescent idiopathic scoliosis,deformity,muscle,spine
                adolescent idiopathic scoliosis, deformity, muscle, spine

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