Advanced glycation end products in idiopathic frozen shoulders

https://doi.org/10.1016/j.jse.2015.10.015Get rights and content

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

Section snippets

Study design

A prospective case-control study was conducted at the Orthopaedics Research Institute, St. George Hospital, and the National Day Surgery, Sydney, NSW, Australia, during a 9-month period.

Inclusion and exclusion criteria

The study included patients with primary frozen shoulders who were receiving arthroscopic capsular releases. It also included patients with unstable shoulders undergoing arthroscopic stabilization and patients with rotator cuff tears undergoing rotator cuff repair as control groups. Instability and rotator cuff

Patient demographics

The study included 8 patients (6 nondiabetic and 2 diabetic patients) with frozen shoulder as the disease population. Three male and 5 female frozen shoulder patients had a mean age of 52 years (range, 41-60). Six shoulder instability patients (5 male and 1 female) had a mean age of 23 years (range, 16-40). Eight rotator cuff tear patients (5 male and 3 female) had a mean age of 58 years (range, 52-71) in the control populations. The mean duration of symptoms before shoulder surgeries was 5

Discussion

This study has found increased immunoreactivity of AGEs in frozen shoulder capsules compared with control capsules. Histologic features of all H&E-stained frozen shoulder capsule slides included densely packed collagen fibers, fibroblastic hypercellularity, and increased vascularization. In addition, increased numbers of adipocytes were noted in frozen shoulder capsules compared with control capsules.

Our study used tissue from shoulder conditions other than frozen shoulder because it would have

Conclusion

This study highlights a potential role for AGEs in the pathogenesis of frozen shoulder. As far as we can determine, this paper is the first to consider whether AGEs are involved in the frozen shoulders of patients regardless of their diabetic status. In addition, we have also found increased numbers of adipocytes in the capsular tissues of frozen shoulder patients compared with capsular tissues of rotator cuff tears and shoulder instability patients. The overexpression of AGEs may explain the

Disclaimer

The authors, their immediate families, and any research foundation with which they are affiliated have not received any financial payments or other benefits from any commercial entity related to the subject of this article.

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