title: Muscle inflammation susceptibility: a prognostic index of recovery potential after hip arthroplasty?
abstract: While elective total hip arthroplasty (THA) for end-stage osteoarthritis (OA) improves pain, mobility function, and quality of life in most cases, a large proportion of patients suffer persistent muscle atrophy, pain, and mobility impairment. Extensive skeletal muscle damage is unavoidable in these surgical procedures, and it stands to reason that poor recovery and long-term mobility impairment among some individuals after THA is linked to failed muscle regeneration and regrowth following surgery and that local muscle inflammation susceptibility (MuIS) is a major contributing factor. Here we present results of two integrated studies. In study 1, we compared muscle inflammation and protein metabolism signaling in elective THA (n=15) vs. hip fracture/trauma (HFX; n=11) vs. nonsurgical controls (CON; n=19). In study 2, we compared two subgroups of THA patients dichotomized into MuIS⁺ (n=7) or MuIS⁻ (n=7) based on muscle expression of TNF-like weak inducer of apoptosis (TWEAK) receptor (Fn14). As expected, HFX demonstrated overt systemic and local muscle inflammation and hypermetabolism. By contrast, no systemic inflammation was detected in elective THA patients; however, local muscle inflammation in the perioperative limb was profound in MuIS⁺ and was accompanied by suppressed muscle protein synthesis compared with MuIS⁻. Muscle from the contralateral limb of MuIS⁺ was unaffected, providing evidence of a true inflammation susceptibility localized to the muscle surrounding the hip with end-stage OA. We suggest MuIS status assessed at the time of surgery may be a useful prognostic index for muscle recovery potential and could therefore provide the basis for a personalized approach to postsurgery rehabilitation.
authors: Department of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama; Univeristy of Alabama at Birmingham Center for Exercise Medicine, University of Alabama at Birmingham, Birmingham, Alabama; Comprehensive Arthritis, Musculoskeletal, and Autoimmunity Center, University of Alabama at Birmingham, Birmingham, Alabama; Geriatric Research, Education, and Clinical Center, Birmingham Veterans Affairs Medical Center, Birmingham, Alabama; mbamman@uab.edu.
authors: Marcas M
authors: MM
authors: Bamman
authors: Department of Geriatrics and Center for Translational Research in Aging and Longevity, University of Arkansas for Medical Sciences, Little Rock, Arkansas;
authors: Arny A
authors: AA
authors: Ferrando
authors: Department of Orthopedic Surgery, University of Arkansas for Medical Sciences, Little Rock, Arkansas;
authors: Richard P
authors: RP
authors: Evans
authors: Department of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama; Univeristy of Alabama at Birmingham Center for Exercise Medicine, University of Alabama at Birmingham, Birmingham, Alabama;
authors: Michael J
authors: MJ
authors: Stec
authors: Department of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama; Univeristy of Alabama at Birmingham Center for Exercise Medicine, University of Alabama at Birmingham, Birmingham, Alabama;
authors: Neil A
authors: NA
authors: Kelly
authors: Department of Trauma Surgery, University of Arkansas for Medical Sciences, Little Rock, Arkansas;
authors: Johannes M
authors: JM
authors: Gruenwald
authors: Department of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama;
authors: Katie L
authors: KL
authors: Corrick
authors: Department of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama;
authors: Jesse R
authors: JR
authors: Trump
authors: Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama; Univeristy of Alabama at Birmingham Center for Exercise Medicine, University of Alabama at Birmingham, Birmingham, Alabama; Comprehensive Arthritis, Musculoskeletal, and Autoimmunity Center, University of Alabama at Birmingham, Birmingham, Alabama; Medicine Service, Birmingham Veterans Affairs Medical Center, Birmingham, Alabama; and Research Collaborator, Mayo Clinic College of Medicine, Rochester, Minnesota.
authors: Jasvinder A
authors: JA
authors: Singh
mesh_terms: D001131:Arkansas; D019644:Arthroplasty, Replacement, Hip / Q000009:adverse effects* / Q000534:rehabilitation; D015415:Biomarkers / Q000378:metabolism; D001707:Biopsy, Needle; D016207:Cytokines / Q000097:blood; D004198:Disease Susceptibility; D042241:Early Diagnosis; D005260:Female; D006785:Hospitals, University; D006801:Humans; D008297:Male; D008875:Middle Aged; D009220:Myositis / Q000175:diagnosis* / Q000209:etiology / Q000276:immunology / Q000378:metabolism; D015207:Osteoarthritis, Hip / Q000503:physiopathology / Q000534:rehabilitation / Q000601:surgery*; D010044:Outpatient Clinics, Hospital; D011183:Postoperative Complications / Q000175:diagnosis* / Q000209:etiology / Q000276:immunology / Q000378:metabolism; D057285:Precision Medicine; D011237:Predictive Value of Tests; D011379:Prognosis; D052097:Quadriceps Muscle / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism*; D012086:Reoperation / Q000009:adverse effects / Q000534:rehabilitation; D000074050:TWEAK Receptor
chemical_list: D015415:Biomarkers; D016207:Cytokines; D018124:Receptors, Tumor Necrosis Factor; C000613297:TNFRSF12A protein, human; D000074050:TWEAK Receptor
keywords: inflammation; muscle atrophy; muscle protein metabolism; muscle regeneration; total hip arthroplasty