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The Journal of Bone & Joint Surgery British Volume
Vol. 82-B, Issue 5 | Pages 768 - 773
1 Jul 2000
Bunker TD Reilly J Baird KS Hamblen DL

Frozen shoulder is a chronic fibrosing condition of the capsule of the joint. The predominant cells involved are fibroblasts and myofibroblasts which lay down a dense matrix of type-I and type-III collagen within the capsule. This subsequently contracts leading to the typical features of pain and stiffness. Cytokines and growth factors regulate the growth and function of the fibroblasts of connective tissue and remodelling of the matrix is controlled by the matrix metalloproteinases (MMPs) and their inhibitors. Our aim was to determine whether there was an abnormal expression or secretion of cytokines, growth factors and MMPs in tissue samples from 14 patients with frozen shoulder using the reverse transcription/polymerase chain reaction (RT/PCR) technique and to compare the findings with those in tissue from four normal control shoulders and from five patients with Dupuytren’s contracture. Tissue from frozen shoulders demonstrated the presence of mRNA for a large number of cytokines and growth factors although the frequency was only slightly higher than in the control tissue. The frequency for a positive signal for the proinflammatory cytokines Il-1β and TNF-α and TNF-β, was not as great as in the Dupuytren’s tissue. The presence of mRNA for fibrogenic growth factors was, however, more similar to that obtained in the control and Dupuytren’s tissue. This correlated with the histological findings which in most specimens showed a dense fibrous tissue response with few cells other than mature fibroblasts and with very little evidence of any active inflammatory cell process. Positive expressions of the mRNA for the MMPs were also increased, together with their natural inhibitor TIMP. The notable exception compared with control and Dupuytren’s tissue was the absence of MMP-14, which is known to be a membrane-type MMP required for the activation of MMP-2 (gelatinase A). Understanding the control mechanisms which play a part in the pathogenesis of frozen shoulder may lead to the development of new regimes of treatment for this common, protracted and painful chronic fibrosing condition


The Journal of Bone & Joint Surgery British Volume
Vol. 80-B, Issue 5 | Pages 907 - 908
1 Sep 1998
Hutchinson JW Tierney GM Parsons SL Davis TRC

In a series of 12 patients with inoperable gastric carcinoma who had treatment with a synthetic matrix metalloproteinase inhibitor (Marimastat) for more than one month, six developed a frozen shoulder or a condition resembling Dupuytren’s disease. This suggests that the matrix metalloproteinases, a family of naturally occurring proteinases, may be involved in the pathogenesis of these two conditions. Our observation opens avenues for further research which could lead to local or systemic therapeutic interventions for frozen shoulder and Dupuytren’s disease


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_2 | Pages 130 - 130
2 Jan 2024
Dvorak N
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In-vitro models of disease are valuable tools for studying disease and analysing response to therapeutics. Recently, advances in patient-derived organoid (PDO) models have been shown to faithfully recapitulate structure, function, and therapeutic response for a wide range of tissues. Frozen shoulder is a rare example of a chronic inflammatory fibrotic disease which is self-limiting, unlike many other soft tissue fibrotic disorders. As no in-vitro 3D models or in-vivo animal models exist for frozen shoulder, establishing an organoid model which recapitulates core diseases features may give insight into fibrosis resolution. Consequently, using biocompatible hydrogels, primary capsular fibroblasts, monocyte-derived macrophages and HUVEC cells, we generated stable PDO cultures which exhibited key disease phenotypes, including vascularization, increased stiffness, and an expanded lining layer over 21 days of culture. Through further investigation of cell-matrix and cell-cell interactions in the organoid model, we intend to unpack the differences between resolving and non-resolving fibrotic disease and uncover clinically relevant therapeutic targets for fibrosis


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_2 | Pages 86 - 86
1 Mar 2021
Bommireddy L Granville E Davies-Jones G Gogna R Clark DI
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Abstract. Objectives. Clavicle fractures are common, yet debate exists regarding which patients would benefit from conservative versus operative management. Traditionally shortening greater than 2cm has been accepted as an indicator for surgery. However, clavicle length varies between individuals. In a cadaveric study clavicle shortening greater than 15% was suggested to affect outcomes. There is no clinical correlation of this in the literature. In this study we investigate outcomes following middle third clavicle fractures and the effect of percentage shortening on union rates. Methods. We identified a consecutive series of adults with primary midshaft clavicle fractures presenting to our institution from April 2015-March 2017. Clinical records and radiographs were reviewed to elicit outcomes. Time to union was measured against factors including; percentage shortening, displacement, comminution and smoking. Statistical significance was calculated. Results. 127 patients were identified, of whom 90 were managed conservatively and 37 operatively. Fractures were displaced in 86 patients (68%). Mean age was 41.7 years (range 18–89). Mean time to union for displaced fractures was longer than for undisplaced at 13.4 and 8.9 weeks respectively (p=0.0948). Displaced fractures treated operatively had mean time to union of 12.8 weeks, three weeks shorter than those managed conservatively (p=0.0470). Mean time to union for fractures with >15% shortening was 16.0 weeks, nearly double the 8.7 weeks with <15% shortening (p= 0.0241). Smokers had 8 weeks longer time to union (p=0.0082). Nonunion rate was 10% in fractures managed conservatively and 0% in those treated operatively. Complications following operative management were plate removal (13.5%), frozen shoulder (8.1%) and infection (2.9%). Conclusions. Nonunion rate is higher in fractures managed conservatively. Shortening >15% leads to significantly longer union time and should therefore be used as an indicator for surgery. Displacement and smoking also lengthen time to union and should be considered in the operative decision process. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_1 | Pages 85 - 85
1 Jan 2017
Edwards T Patel B Brandford-White H Banfield D Thayaparan A Woods D
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Clavicular hook plates have been used over the last decade in the treatment of lateral clavicular fractures with good rates of union reported throughout the literature. Fewer studies have reported the functional outcome of these patients and some have reported potential soft tissue damage post plate removal. We aimed to review the functional outcomes alongside union rates in patients treated with hook plates for lateral clavicular fractures. In this retrospective case series, 21 patients with traumatic lateral third clavicular fractures were included. 15 had Neer type II fractures, 4 Neer type III fractures, 1 patient had a Neer type I fracture and 1 radiograph was not able to be classified. All patients were treated with clavicular hook plates at the same district general hospital by five experienced surgeons between March 2010 and February 2015 adhering to the same surgical protocol. All patients had standard physiotherapy and post operative follow up. Plates were removed when radiological union was achieved in all but one patient who had the plate removed before union was achieved due to prolonged non-union. Patients were followed up post plate removal and evaluated clinically using the Oxford Shoulder Score. Their post plate radiographs were assessed by an independent radiologist and bony union documented. 21 patients were included. Mean age was 40 (range 14–63) with a male:female ratio of 17:4. Mean follow up was 5 months post injury (1–26 months). The hook plate remained in situ for a mean time of 4.3 months (2–16 months). One patient developed a post-operative wound infection treated with antibiotics, 2 patients developed adhesive capsulitis, one patient had not achieved bony union prior to hook plate removal at 16 months, however did achieve union 2 months post plate removal, two patients required revision plating. All patients achieved bony union eventually with good alignment and no displacement of the acromioclavicular joint seen on the most recent post operative radiographs. Post plate removal Oxford Shoulder Scores indicated good shoulder function with a mean score of 41.5 (maximum score possible 48 and the range of scores for our cohort was 30–47). Our data would support the use of hook plates in the treatment of lateral clavicular fractures. All patients achieved union eventually with good alignment and this was reflected in the good functional outcome scores. This study is limited in its small cohort and short-term follow up. More research is required to examine the long term consequences of hook plate surgery in a larger patient population


Bone & Joint Research
Vol. 7, Issue 5 | Pages 362 - 372
1 May 2018
Ueda Y Inui A Mifune Y Sakata R Muto T Harada Y Takase F Kataoka T Kokubu T Kuroda R

Objectives

The aim of this study was to investigate the effect of hyperglycaemia on oxidative stress markers and inflammatory and matrix gene expression within tendons of normal and diabetic rats and to give insights into the processes involved in tendinopathy.

Methods

Using tenocytes from normal Sprague-Dawley rats, cultured both in control and high glucose conditions, reactive oxygen species (ROS) production, cell proliferation, messenger RNA (mRNA) expression of NADPH oxidase (NOX) 1 and 4, interleukin-6 (IL-6), matrix metalloproteinase (MMP)-2, tissue inhibitors of matrix metalloproteinase (TIMP)-1 and -2 and type I and III collagens were determined after 48 and 72 hours in vitro. In an in vivo study, using diabetic rats and controls, NOX1 and 4 expressions in Achilles tendon were also determined.