Bone Fracture Acute Phase Response--A Unifying Theory of Fracture Repair: Clinical and Scientific Implications

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Publisher: Springer
Document Type: Report
Length: 684 words

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Byline: Courtney E. Baker (1), Stephanie N. Moore-Lotridge (2,3), Alexander A. Hysong (4), Samuel L. Posey (4), J. Patton Robinette (4), Deke M. Blum (4), Michael A. Benvenuti (2), Heather A. Cole (2), Satoru Egawa (2,5), Atsushi Okawa (5), Masanori Saito (2,5), Jason R. McCarthy (6), Jeffry S. Nyman (2,7,8), Masato Yuasa (2,5), Jonathan G. Schoenecker (2,3,9,10) Keywords: Fracture repair; Fracture vascularity; Strain; Acute phase response; Endochondral ossification; Non-union Abstract: Bone fractures create five problems that must be resolved: bleeding, risk of infection, hypoxia, disproportionate strain, and inability to bear weight. There have been enormous advancements in our understanding of the molecular mechanisms that resolve these problems after fractures, and in best clinical practices of repairing fractures. We put forth a modern, comprehensive model of fracture repair that synthesizes the literature on the biology and biomechanics of fracture repair to address the primary problems of fractures. This updated model is a framework for both fracture management and future studies aimed at understanding and treating this complex process. This model is based upon the fracture acute phase response (APR), which encompasses the molecular mechanisms that respond to injury. The APR is divided into sequential stages of "survival" and "repair." Early in convalescence, during "survival," bleeding and infection are resolved by collaborative efforts of the hemostatic and inflammatory pathways. Later, in "repair," avascular and biomechanically insufficient bone is replaced by a variable combination of intramembranous and endochondral ossification. Progression to repair cannot occur until survival has been ensured. A disproportionate APR--either insufficient or exuberant--leads to complications of survival (hemorrhage, thrombosis, systemic inflammatory response syndrome, infection, death) and/or repair (delayed- or non-union). The type of ossification utilized for fracture repair is dependent on the relative amounts of strain and vascularity in the fracture microenvironment, but any failure along this process can disrupt or delay fracture healing and result in a similar non-union. Therefore, incomplete understanding of the principles herein can result in mismanagement of fracture care or application of hardware that interferes with fracture repair. This unifying model of fracture repair not only informs clinicians how their interventions fit within the framework of normal biological healing but also instructs investigators about the critical variables and outputs to assess during a study of fracture repair. Author Affiliation: (1) 0000 0004 0459 167X, grid.66875.3a, Department of Orthopaedics, Mayo Clinic, 200 1st Ave SW, Rochester, MN, 55903, USA (2) 0000 0004 1936 9916, grid.412807.8, Department of Orthopaedics and Rehabilitation, Vanderbilt University Medical Center, 1215 21st Ave. South, Suite 4200 MCE, South Tower, Nashville, TN, 37232, USA (3) 0000 0004 1936 9916, grid.412807.8, Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, 1161 21st Ave. South, Nashville, TN, 37232, USA (4) 0000 0001 2264 7217, grid.152326.1, Vanderbilt University School of Medicine, 1161 21st Ave S, D3300, Nashville, TN, 37232, USA (5) 0000 0001 1014 9130, grid.265073.5, Department of Orthopaedic Surgery, Tokyo Medical and Dental University, Yushima Bunkyo Ward, Tokyo, 113-8519, Japan (6) Masonic Research Institute, 2150 Bleecker St, Utica, NY, 13501, USA (7) 0000 0001 2264 7217, grid.152326.1, Department of Biomedical Engineering, Vanderbilt University, PMB 351631, 2301 Vanderbilt Place, Nashville, TN, 37235, USA (8) Department of Veterans Affairs, Tennessee Valley Health Care System, F-519 VA Acre Building, 1210 24th Ave. South, Nashville, TN, 37232, USA (9) 0000 0001 2264 7217, grid.152326.1, Department of Pharmacology, Vanderbilt University, 2200 Pierce Ave, Robinson Research Building, Nashville, TN, 37232, USA (10) 0000 0004 1936 9916, grid.412807.8, Department of Pediatrics, Vanderbilt University Medical Center, 4202 Doctor's Office Tower, 2200 Children's Way, Nashville, TN, 37232, USA Article History: Registration Date: 12/12/2018 Online Date: 29/12/2018 Article note: UNIFYING RULES OF FRACTURE REPAIR acents Fractures create five principal problems: bleeding, susceptibility to infection, excessive strain, hypoxia, and inability to bear weight. acents The acute phase response is divided into two distinct phases--"survival" and "repair"--and sequentially resolves the principal problems of fractures. acents The "survival" and "repair" stages of fracture healing occur in series, not in parallel. acents A disproportionate acute phase response--either insufficient or exuberant--leads to complications. acents Strain and vascularity are essential factors for fracture repair and dictate the type of ossification that occurs--either intramembranous or endochondral.

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Gale Document Number: GALE|A570329648