Kyu Rim Hwang1, George A C Murrell2, Neal L Millar3, Fiona Bonar4, Patrick Lam1, Judie R Walton1. 1. Orthopaedic Research Institute, St. George Hospital Campus, University of New South Wales, Sydney, NSW, Australia. 2. Orthopaedic Research Institute, St. George Hospital Campus, University of New South Wales, Sydney, NSW, Australia. Electronic address: murrell.g@ori.org.au. 3. Institute of Infection, Immunity and Inflammation, College of Medicine, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK. 4. Douglass Hanly Moir Pathology, Sydney, NSW, Australia.
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. CONCLUSION: 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. LEVEL OF EVIDENCE: Basic Science Study; Histology.
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. CONCLUSION: 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. LEVEL OF EVIDENCE: Basic Science Study; Histology.
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