title: Advanced glycation end products in idiopathic frozen shoulders.
abstract: BACKGROUND
  The pathophysiologic mechanisms behind proliferation of fibroblasts and deposition of dense collagen matrix in idiopathic frozen shoulder remain unclear. Accumulation of advanced glycation end products (AGEs) with cross-linking and stabilization of collagen has been hypothesized to contribute to this pathophysiologic process. This study investigated whether the immunoreactivity of AGEs is higher in patients with idiopathic frozen shoulder than in the control groups.
  
  
  METHODS
  Shoulder capsule samples were collected from 8 patients with idiopathic frozen shoulder, 6 with unstable shoulders (control 1), and 8 with rotator cuff tears (control 2). The samples were hematoxylin and eosin stained and analyzed by immunohistochemistry using antibodies against AGEs. Immunoreactivities were rated in a blinded fashion from none (0) to strong (3). Immunohistochemical distribution within the capsule was noted.
  
  
  RESULTS
  Frozen shoulder patients had greater frequency and severity of self-reported pain (P = .02) than rotator cuff tear patients and more restricted range of motion in all planes (P < .05) than patients of the instability and rotator cuff tear groups. Hematoxylin and eosin-stained capsular tissue from frozen shoulder showed fibroblastic proliferation, increased numbers of adipocytes, and increased subsynovial vascularity. Immunoreactivity of AGEs was stronger in frozen shoulder capsules (2.8) than in instability (0.3; P = .0001) and rotator cuff tear (1.1; P = .016) capsules.
  
  
  CONCLUSIONS
  This study highlights a potential role for AGEs in the pathogenesis of frozen shoulder. The overexpression of AGEs may explain the fibroblastic proliferation and deposition of collagen matrix in idiopathic frozen shoulder.
  
  
  METHODS
  Basic Science Study; Histology.
authors.affiliation: Orthopaedic Research Institute, St. George Hospital Campus, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Kyu Rim
authors.initials: KR
authors.lastname: Hwang
authors.affiliation: Orthopaedic Research Institute, St. George Hospital Campus, University of New South Wales, Sydney, NSW, Australia. Electronic address: murrell.g@ori.org.au.
authors.forename: George A C
authors.initials: GA
authors.lastname: Murrell
authors.affiliation: Institute of Infection, Immunity and Inflammation, College of Medicine, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Neal L
authors.initials: NL
authors.lastname: Millar
authors.affiliation: Douglass Hanly Moir Pathology, Sydney, NSW, Australia.
authors.forename: Fiona
authors.initials: F
authors.lastname: Bonar
authors.affiliation: Orthopaedic Research Institute, St. George Hospital Campus, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Patrick
authors.initials: P
authors.lastname: Lam
authors.affiliation: Orthopaedic Research Institute, St. George Hospital Campus, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Judie R
authors.initials: JR
authors.lastname: Walton
mesh_terms: D017667:Adipocytes; D000293:Adolescent; D000328:Adult; D000368:Aged; D002062:Bursitis / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D016022:Case-Control Studies; D002452:Cell Count; D049109:Cell Proliferation; D005260:Female; D005347:Fibroblasts / Q000502:physiology; D017127:Glycation End Products, Advanced / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007593:Joint Instability / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016059:Range of Motion, Articular; D000070636:Rotator Cuff Injuries / Q000378:metabolism* / Q000503:physiopathology; D012785:Shoulder Joint / Q000378:metabolism* / Q000503:physiopathology; D020069:Shoulder Pain / Q000209:etiology; D055815:Young Adult
chemical_list: D017127:Glycation End Products, Advanced
keywords: Frozen shoulder; adhesive capsulitis; advanced glycation end products; fibroblastic proliferation; immunoreactivity; stiff shoulder