The puzzling pathophysiology of frozen shoulders – a scoping review

Abstract

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. Level of evidence Level V.

MR Imaging Biomarkers for Clinical Impairment and Disease Progression in Patients with Shoulder Adhesive Capsulitis: A Prospective Study

“…Conversely, thin IGHL (3 mm or lower) was associated with clinical worsening. This could be related to collagen accumulation in the joint capsule in late disease phases [39,40]. As AC is a disease with a self-limited course, a thicker IGHL could be an indicator of a late disease phase and hence be associated with a favorable outcome.…”

Clinical Guidelines in the Management of Frozen Shoulder: An Update!

“…The tissue samples from FS reveal dense collagen matrix and high population of fibroblasts and contractile myofibroblasts, a process similar to Dupuytren's contracture, with the fibrotic process predominantly limited to anterior capsule [22,23]. An early immune response with elevated levels of alarmins, binding to the receptor of advance glycation end products and accrued irreversible crosslinks between various collagen protein molecules through glycosylation is observed at the beginning of the cascade [24,25]. Increased expression of vascular endothelial growth factors (especially in diabetics with high glycosylated haemoglobin), nerve growth factor receptor and neoangiogenesis are also noted, and that may help explain severe pain and stiffness in patients with FS [26,27].…”

A Central Nervous System Focused Treatment Program for People with Frozen Shoulder: A Feasibility Study

“…The pathophysiology of FS is a complex and multifactorial process encompassing several mechanisms such as an upregulation of grown factors and inflammatory cytokines, which stimulate fibroblast proliferation and differentiation into myofibroblasts. This in turn leads to an imbalance of extracellular matrix turnover and a resultant stiff and thickened glenohumeral capsule with an abundance of type III collagen [ 4 ]. Accumulation of advanced glycation end products (AGEs) has also been shown in people with FS [ 5 ].…”