Advanced glycation end products in idiopathic frozen shoulders

Kyu Rim Hwang, George A.C. Murrell*, Neal L. Millar, Fiona Bonar, Patrick Lam, Judie R. Walton

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

32 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)981-988
Number of pages8
JournalJournal of Shoulder and Elbow Surgery
Issue number6
Publication statusPublished - 1 Jun 2016
Externally publishedYes


  • Adhesive capsulitis
  • Advanced glycation end products
  • Fibroblastic proliferation
  • Frozen shoulder
  • Immunoreactivity
  • Stiff shoulder


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