The puzzling pathophysiology of frozen shoulders - a scoping review

T Kraal, J Lübbers, M P J van den Bekerom, J Alessie, Y van Kooyk, D Eygendaal, R C T Koorevaar

Research output: Contribution to journalArticleAcademicpeer-review


PURPOSE: The pathophysiology of frozen shoulders is a complex and multifactorial process. The purpose of this review is to scope the currently available knowledge of the pathophysiology of frozen shoulders.

METHODS: A systematic search was conducted in Medline, Embase and the Cochrane library. Original articles published between 1994 and October 2020 with a substantial focus on the pathophysiology of frozen shoulders were included.

RESULTS: Out of 827 records, 48 original articles were included for the qualitative synthesis of this review. Glenohumeral capsular biopsies were reported in 30 studies. Fifteen studies investigated were classified as association studies. Three studies investigated the pathophysiology in an animal studies. A state of low grade inflammation, as is associated with diabetes, cardiovascular disease and thyroid disorders, predisposes for the development of frozen shoulder. An early immune response with elevated levels of alarmins and binding to the receptor of advance glycation end products is present at the start of the cascade. Inflammatory cytokines, of which transforming growth factor-β1 has a prominent role, together with mechanical stress stimulates Fibroblast proliferation and differentiation into myofibroblasts. This leads to an imbalance of extracellular matrix turnover resulting in a stiff and thickened glenohumeral capsule with abundance of type III collagen.

CONCLUSION: This scoping review outlines the complexity of the pathophysiology of frozen shoulder. A comprehensive overview with background information on pathophysiologic mechanisms is given. Leads are provided to progress with research for clinically important prognostic markers and in search for future interventions.


Original languageEnglish
Article number91
Pages (from-to)91
JournalInternational Orthopaedics
Issue number1
Publication statusPublished - Dec 2020

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