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Bone & Joint Research
Vol. 13, Issue 10 | Pages 596 - 610
21 Oct 2024
Toegel S Martelanz L Alphonsus J Hirtler L Gruebl-Barabas R Cezanne M Rothbauer M Heuberer P Windhager R Pauzenberger L

Aims. This study aimed to define the histopathology of degenerated humeral head cartilage and synovial inflammation of the glenohumeral joint in patients with omarthrosis (OmA) and cuff tear arthropathy (CTA). Additionally, the potential of immunohistochemical tissue biomarkers in reflecting the degeneration status of humeral head cartilage was evaluated. Methods. Specimens of the humeral head and synovial tissue from 12 patients with OmA, seven patients with CTA, and four body donors were processed histologically for examination using different histopathological scores. Osteochondral sections were immunohistochemically stained for collagen type I, collagen type II, collagen neoepitope C1,2C, collagen type X, and osteocalcin, prior to semiquantitative analysis. Matrix metalloproteinase (MMP)-1, MMP-3, and MMP-13 levels were analyzed in synovial fluid using enzyme-linked immunosorbent assay (ELISA). Results. Cartilage degeneration of the humeral head was associated with the histological presentation of: 1) pannus overgrowing the cartilage surface; 2) pores in the subchondral bone plate; and 3) chondrocyte clusters in OmA patients. In contrast, hyperplasia of the synovial lining layer was revealed as a significant indicator of inflammatory processes predominantly in CTA. The abundancy of collagen I, collagen II, and the C1,2C neoepitope correlated significantly with the histopathological degeneration of humeral head cartilage. No evidence for differences in MMP levels between OmA and CTA patients was found. Conclusion. This study provides a comprehensive histological characterization of humeral cartilage and synovial tissue within the glenohumeral joint, both in normal and diseased states. It highlights synovitis and pannus formation as histopathological hallmarks of OmA and CTA, indicating their roles as drivers of joint inflammation and cartilage degradation, and as targets for therapeutic strategies such as rotator cuff reconstruction and synovectomy. Cite this article: Bone Joint Res 2024;13(10):596–610


Bone & Joint Research
Vol. 13, Issue 4 | Pages 169 - 183
15 Apr 2024
Gil-Melgosa L Llombart-Blanco R Extramiana L Lacave I Abizanda G Miranda E Agirre X Prósper F Pineda-Lucena A Pons-Villanueva J Pérez-Ruiz A

Aims

Rotator cuff (RC) injuries are characterized by tendon rupture, muscle atrophy, retraction, and fatty infiltration, which increase injury severity and jeopardize adequate tendon repair. Epigenetic drugs, such as histone deacetylase inhibitors (HDACis), possess the capacity to redefine the molecular signature of cells, and they may have the potential to inhibit the transformation of the fibro-adipogenic progenitors (FAPs) within the skeletal muscle into adipocyte-like cells, concurrently enhancing the myogenic potential of the satellite cells.

Methods

HDACis were added to FAPs and satellite cell cultures isolated from mice. The HDACi vorinostat was additionally administered into a RC injury animal model. Histological analysis was carried out on the isolated supra- and infraspinatus muscles to assess vorinostat anti-muscle degeneration potential.


Bone & Joint Research
Vol. 10, Issue 5 | Pages 298 - 306
1 May 2021
Dolkart O Kazum E Rosenthal Y Sher O Morag G Yakobson E Chechik O Maman E

Aims

Rotator cuff (RC) tears are common musculoskeletal injuries which often require surgical intervention. Noninvasive pulsed electromagnetic field (PEMF) devices have been approved for treatment of long-bone fracture nonunions and as an adjunct to lumbar and cervical spine fusion surgery. This study aimed to assess the effect of continuous PEMF on postoperative RC healing in a rat RC repair model.

Methods

A total of 30 Wistar rats underwent acute bilateral supraspinatus tear and repair. A miniaturized electromagnetic device (MED) was implanted at the right shoulder and generated focused PEMF therapy. The animals’ left shoulders served as controls. Biomechanical, histological, and bone properties were assessed at three and six weeks.


Bone & Joint Research
Vol. 8, Issue 3 | Pages 118 - 125
1 Mar 2019
Doi N Izaki T Miyake S Shibata T Ishimatsu T Shibata Y Yamamoto T

Objectives

Indocyanine green (ICG) fluorescence angiography is an emerging technique that can provide detailed anatomical information during surgery. The purpose of this study is to determine whether ICG fluorescence angiography can be used to evaluate the blood flow of the rotator cuff tendon in the clinical setting.

Methods

Twenty-six patients were evaluated from October 2016 to December 2017. The participants were categorized into three groups based on their diagnoses: the rotator cuff tear group; normal rotator cuff group; and adhesive capsulitis group. After establishing a posterior standard viewing portal, intravenous administration of ICG at 0.2 mg/kg body weight was performed, and fluorescence images were recorded. The time from injection of the drug to the beginning of enhancement of the observed area was measured. The hypovascular area in the rotator cuff was evaluated, and the ratio of the hypovascular area to the anterolateral area of the rotator cuff tendon was calculated (hypovascular area ratio).


The Bone & Joint Journal
Vol. 96-B, Issue 5 | Pages 574 - 579
1 May 2014
Talbot CL Ring J Holt EM

We present a review of claims made to the NHS Litigation Authority (NHSLA) by patients with conditions affecting the shoulder and elbow, and identify areas of dissatisfaction and potential improvement. Between 1995 and 2012, the NHSLA recorded 811 claims related to the shoulder and elbow, 581 of which were settled. This comprised 364 shoulder (64%), and 217 elbow (36%) claims. A total of £18.2 million was paid out in settled claims. Overall diagnosis, mismanagement and intra-operative nerve injury were the most common reasons for litigation. The highest cost paid out resulted from claims dealing with incorrect, missed or delayed diagnosis, with just under £6 million paid out overall. Fractures and dislocations around the shoulder and elbow were common injuries in this category. All 11 claims following wrong-site surgery that were settled led to successful payouts.

This study highlights the diagnoses and procedures that need to be treated with particular vigilance. Having an awareness of the areas that lead to litigation in shoulder and elbow surgery will help to reduce inadvertent risks to patients and prevent dissatisfaction and possible litigation.

Cite this article: Bone Joint J 2014; 96-B:574–9.


The Bone & Joint Journal
Vol. 95-B, Issue 7 | Pages 935 - 941
1 Jul 2013
Moor BK Bouaicha S Rothenfluh DA Sukthankar A Gerber C

We hypothesised that a large acromial cover with an upwardly tilted glenoid fossa would be associated with degenerative rotator cuff tears (RCTs), and conversely, that a short acromion with an inferiorly inclined glenoid would be associated with glenohumeral osteoarthritis (OA). This hypothesis was tested using a new radiological parameter, the critical shoulder angle (CSA), which combines the measurements of inclination of the glenoid and the lateral extension of the acromion (the acromion index).

The CSA was measured on standardised radiographs of three groups: 1) a control group of 94 asymptomatic shoulders with normal rotator cuffs and no OA; 2) a group of 102 shoulders with MRI-documented full-thickness RCTs without OA; and 3) a group of 102 shoulders with primary OA and no RCTs noted during total shoulder replacement. The mean CSA was 33.1° (26.8° to 38.6°) in the control group, 38.0° (29.5° to 43.5°) in the RCT group and 28.1° (18.6° to 35.8°) in the OA group. Of patients with a CSA > 35°, 84% were in the RCT group and of those with a CSA < 30°, 93% were in the OA group.

We therefore concluded that primary glenohumeral OA is associated with significantly smaller degenerative RCTs with significantly larger CSAs than asymptomatic shoulders without these pathologies. These findings suggest that individual quantitative anatomy may imply biomechanics that are likely to induce specific types of degenerative joint disorders.

Cite this article: Bone Joint J 2013;95-B:935–41.


Bone & Joint Research
Vol. 2, Issue 7 | Pages 132 - 139
1 Jul 2013
Ketola S Lehtinen J Rousi T Nissinen M Huhtala H Konttinen YT Arnala I

Objectives

To report the five-year results of a randomised controlled trial examining the effectiveness of arthroscopic acromioplasty in the treatment of stage II shoulder impingement syndrome.

Methods

A total of 140 patients were randomly divided into two groups: 1) supervised exercise programme (n = 70, exercise group); and 2) arthroscopic acromioplasty followed by a similar exercise programme (n = 70, combined treatment group).


The Bone & Joint Journal
Vol. 95-B, Issue 7 | Pages 942 - 946
1 Jul 2013
Dattani R Ramasamy V Parker R Patel VR

There is little published information on the health impact of frozen shoulder. The purpose of this study was to assess the functional and health-related quality of life outcomes following arthroscopic capsular release (ACR) for contracture of the shoulder. Between January 2010 and January 2012 all patients who had failed non-operative treatment including anti-inflammatory medication, physiotherapy and glenohumeral joint injections for contracture of the shoulder and who subsequently underwent an ACR were enrolled in the study. A total of 100 patients were eligible; 68 underwent ACR alone and 32 had ACR with a subacromial decompression (ASD). ACR resulted in a highly significant improvement in the range of movement and functional outcome, as measured by the Oxford shoulder score and EuroQol EQ-5D index. The mean cost of a quality-adjusted life year (QALY) for an ACR and ACR with an ASD was £2563 and £3189, respectively. . ACR is thus a cost-effective procedure that can restore relatively normal function and health-related quality of life in most patients with a contracture of the shoulder within six months after surgery; and the beneficial effects are not related to the duration of the presenting symptoms. Cite this article: Bone Joint J 2013;95-B:942–6


The Bone & Joint Journal
Vol. 95-B, Issue 6 | Pages 721 - 731
1 Jun 2013
Sewell MD Al-Hadithy N Le Leu A Lambert SM

The sternoclavicular joint (SCJ) is a pivotal articulation in the linked system of the upper limb girdle, providing load-bearing in compression while resisting displacement in tension or distraction at the manubrium sterni. The SCJ and acromioclavicular joint (ACJ) both have a small surface area of contact protected by an intra-articular fibrocartilaginous disc and are supported by strong extrinsic and intrinsic capsular ligaments. The function of load-sharing in the upper limb by bulky periscapular and thoracobrachial muscles is extremely important to the longevity of both joints. Ligamentous and capsular laxity changes with age, exposing both joints to greater strain, which may explain the rising incidence of arthritis in both with age. The incidence of arthritis in the SCJ is less than that in the ACJ, suggesting that the extrinsic ligaments of the SCJ provide greater stability than the coracoclavicular ligaments of the ACJ.

Instability of the SCJ is rare and can be difficult to distinguish from medial clavicular physeal or metaphyseal fracture-separation: cross-sectional imaging is often required. The distinction is important because the treatment options and outcomes of treatment are dissimilar, whereas the treatment and outcomes of ACJ separation and fracture of the lateral clavicle can be similar. Proper recognition and treatment of traumatic instability is vital as these injuries may be life-threatening. Instability of the SCJ does not always require surgical intervention. An accurate diagnosis is required before surgery can be considered, and we recommend the use of the Stanmore instability triangle. Most poor outcomes result from a failure to recognise the underlying pathology.

There is a natural reluctance for orthopaedic surgeons to operate in this area owing to unfamiliarity with, and the close proximity of, the related vascular structures, but the interposed sternohyoid and sternothyroid muscles are rarely injured and provide a clear boundary to the medial retroclavicular space, as well as an anatomical barrier to unsafe intervention.

This review presents current concepts of instability of the SCJ, describes the relevant surgical anatomy, provides a framework for diagnosis and management, including physiotherapy, and discusses the technical challenges of operative intervention.

Cite this article: Bone Joint J 2013;95-B:721–31.


The Bone & Joint Journal
Vol. 95-B, Issue 5 | Pages 660 - 663
1 May 2013
Ghosh S Singh VK Jeyaseelan L Sinisi M Fox M

In adults with brachial plexus injuries, lack of active external rotation at the shoulder is one of the most common residual deficits, significantly compromising upper limb function. There is a paucity of evidence to address this complex issue. We present our experience of isolated latissimus dorsi (LD) muscle transfer to achieve active external rotation. This is a retrospective review of 24 adult post-traumatic plexopathy patients who underwent isolated latissimus dorsi muscle transfer to restore external rotation of the shoulder between 1997 and 2010. All patients were male with a mean age of 34 years (21 to 57). All the patients underwent isolated LD muscle transfer using a standard technique to correct external rotational deficit. Outcome was assessed for improvement in active external rotation, arc of movement, muscle strength and return to work. The mean improvement in active external rotation from neutral was 24° (10° to 50°). The mean increase in arc of rotation was 52° (38° to 55°). Mean power of the external rotators was 3.5 Medical Research Council (MRC) grades (2 to 5).

A total of 21 patients (88%) were back in work by the time of last follow up. Of these, 13 had returned to their pre-injury occupation. Isolated latissimus dorsi muscle transfer provides a simple and reliable method of restoring useful active external rotation in adults with brachial plexus injuries with internal rotational deformity.

Cite this article: Bone Joint J 2013;95-B:660–3.


The Bone & Joint Journal
Vol. 95-B, Issue 4 | Pages 523 - 529
1 Apr 2013
Henseler JF Nagels J van der Zwaal P Nelissen RGHH

Surgical repair of posterosuperior rotator cuff tears has a poorer outcome and a higher rate of failure compared with repairs of supraspinatus tears. In this prospective cohort study 28 consecutive patients with an irreparable posterosuperior rotator cuff tear after failed conservative or surgical treatment underwent teres major tendon transfer. Their mean age was 60 years (48 to 71) and the mean follow-up was 25 months (12 to 80). The mean active abduction improved from 79° (0° to 150°) pre-operatively to 105° (20° to 180°) post-operatively (p = 0.011). The mean active external rotation in 90° abduction improved from 25° (0° to 70°) pre-operatively to 55° (0° to 90°) post-operatively (p < 0.001). The mean Constant score improved from 43 (18 to 78) pre-operatively to 65 (30 to 86) post-operatively (p < 0.001). The median post-operative VAS (0 to 100) for pain decreased from 63 (0 to 96) pre-operatively to 5 (0 to 56) post-operatively (p < 0.001).

In conclusion, teres major transfer effectively restores function and relieves pain in patients with irreparable posterosuperior rotator cuff tears and leads to an overall clinical improvement in a relatively young and active patient group with limited treatment options.

Cite this article: Bone Joint J 2013;95-B:523–9.


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 12 | Pages 1666 - 1669
1 Dec 2012
Gulotta LV Choi D Marinello P Wright T Cordasco FA Craig EV Warren RF

Reverse total shoulder replacement (RTSR) depends on adequate deltoid function for a successful outcome. However, the anterior deltoid and/or axillary nerve may be damaged due to prior procedures or injury. The purpose of this study was to determine the compensatory muscle forces required for scapular plane elevation following RTSR when the anterior deltoid is deficient. The soft tissues were removed from six cadaver shoulders, except for tendon attachments. After implantation of the RTSR, the shoulders were mounted on a custom-made shoulder simulator to determine the mean force in each muscle required to achieve 30° and 60° of scapular plane elevation. Two conditions were tested: 1) Control with an absent supraspinatus and infraspinatus; and 2) Control with anterior deltoid deficiency. Anterior deltoid deficiency resulted in a mean increase of 195% in subscapularis force at 30° when compared with the control (p = 0.02). At 60°, the subscapularis force increased a mean of 82% (p < 0.001) and the middle deltoid force increased a mean of 26% (p = 0.04).

Scapular plane elevation may still be possible following an RTSR in the setting of anterior deltoid deficiency. When the anterior deltoid is deficient, there is a compensatory increase in the force required by the subscapularis and middle deltoid. Attempts to preserve the subscapularis, if present, might maximise post-operative function.


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 11 | Pages 1534 - 1539
1 Nov 2012
Karataglis D Papadopoulos P Boutsiadis A Fotiadou A Ditsios K Hatzokos I Christodoulou A

This study evaluates the position of the long head of biceps tendon using ultrasound following simple tenotomy, in patients with arthroscopically repaired rotator cuff tears.

In total, 52 patients with a mean age of 60.7 years (45 to 75) underwent arthroscopic repair of the rotator cuff and simple tenotomy of the long head of biceps tendon. At two years post-operatively, ultrasound revealed that the tendon was inside the bicipital groove in 43 patients (82.7%) and outside in nine (17.3%); in six of these it was lying just outside the groove and in the remaining three (5.8%) it was in a remote position with a positive Popeye Sign. A dynamic ultrasound scan revealed that the tenotomised tendons had adhered to the surrounding tissues (autotenodesis).The initial condition of the tendon influenced its final position (p < 0.0005). The presence of a Popeye sign was statistically influenced by the pre-operative co-existence of supraspinatus and subscapularis tears (p < 0.0001).

It appears that the natural history of the tenotomised long head of biceps tendon is to tenodese itself inside or just outside the bicipital groove, while its pre-operative condition and coexistent subscapularis tears play a significant role in the occurrence of a Popeye sign.


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 9 | Pages 1253 - 1259
1 Sep 2012
Sewell MD Higgs DS Al-Hadithy N Falworth M Bayley I Lambert SM

Scapulothoracic fusion (STF) for painful winging of the scapula in neuromuscular disorders can provide effective pain relief and functional improvement, but there is little information comparing outcomes between patients with dystrophic and non-dystrophic conditions. We performed a retrospective review of 42 STFs in 34 patients with dystrophic and non-dystrophic conditions using a multifilament trans-scapular, subcostal cable technique supported by a dorsal one-third semi-tubular plate. There were 16 males and 18 females with a mean age of 30 years (15 to 75) and a mean follow-up of 5.0 years (2.0 to 10.6). The mean Oxford shoulder score improved from 20 (4 to 39) to 31 (4 to 48). Patients with non-dystrophic conditions had lower overall functional scores but achieved greater improvements following STF. The mean active forward elevation increased from 59° (20° to 90°) to 97° (30° to 150°), and abduction from 51° (10° to 90°) to 83° (30° to 130°) with a greater range of movement achieved in the dystrophic group. Revision fusion for nonunion was undertaken in five patients at a mean time of 17 months (7 to 31) and two required revision for fracture. There were three pneumothoraces, two rib fractures, three pleural effusions and six nonunions. The main risk factors for nonunion were smoking, age and previous shoulder girdle surgery.

STF is a salvage procedure that can provide good patient satisfaction in 82% of patients with both dystrophic and non-dystrophic pathologies, but there was a relatively high failure rate (26%) when poor outcomes were analysed. Overall function was better in patients with dystrophic conditions which correlated with better range of movement; however, patients with non-dystrophic conditions achieved greater functional improvement.


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 9 | Pages 1260 - 1264
1 Sep 2012
Raiss P Lin A Mizuno N Melis B Walch G

A total of 12 epileptic patients (14 shoulders) with recurrent seizures and anterior dislocations of the shoulder underwent a Latarjet procedure and were reviewed at a mean of 8.3 years (1 to 20) post-operatively. Mean forward flexion decreased from 165° (100° to 180°) to 160° (90° to 180°) (p = 0.5) and mean external rotation from 54° (10° to 90°) to 43° (5° to 75°) (p = 0.058). The mean Rowe score was 76 (35 to 100) at the final follow-up. Radiologically, all shoulders showed a glenoid-rim defect and Hill-Sachs lesions pre-operatively. Osteo-arthritic changes of the glenohumeral joint were observed in five shoulders (36%) pre-operatively and in eight shoulders (57%) post-operatively. Re-dislocation during a seizure occurred in six shoulders (43%). Five of these patients underwent revision surgery using a bone buttress from the iliac crest and two of these patients re-dislocated due to a new seizure. . Due to the unacceptably high rate of re-dislocation after surgery in these patients, the most important means of reducing the incidence of further dislocation is the medical management of the seizures. The Latarjet procedure should be reserved for the well-controlled patient with epilepsy who has recurrent anterior dislocation of the shoulder during activities of daily living


Bone & Joint Research
Vol. 1, Issue 7 | Pages 158 - 166
1 Jul 2012
Dean BJF Franklin SL Carr AJ

Introduction

The pathogenesis of rotator cuff disease (RCD) is complex and not fully understood. This systematic review set out to summarise the histological and molecular changes that occur throughout the spectrum of RCD.

Methods

We conducted a systematic review of the scientific literature with specific inclusion and exclusion criteria.


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 6 | Pages 799 - 804
1 Jun 2012
Hems TEJ Mahmood F

We reviewed 101 patients with injuries of the terminal branches of the infraclavicular brachial plexus sustained between 1997 and 2009. Four patterns of injury were identified: 1) anterior glenohumeral dislocation (n = 55), in which the axillary and ulnar nerves were most commonly injured, but the axillary nerve was ruptured in only two patients (3.6%); 2) axillary nerve injury, with or without injury to other nerves, in the absence of dislocation of the shoulder (n = 20): these had a similar pattern of nerve involvement to those with a known dislocation, but the axillary nerve was ruptured in 14 patients (70%); 3) displaced proximal humeral fracture (n = 15), in which nerve injury resulted from medial displacement of the humeral shaft: the fracture was surgically reduced in 13 patients; and 4) hyperextension of the arm (n = 11): these were characterised by disruption of the musculocutaneous nerve. There was variable involvement of the median and radial nerves with the ulnar nerve being least affected.

Surgical intervention is not needed in most cases of infraclavicular injury associated with dislocation of the shoulder. Early exploration of the nerves should be considered in patients with an axillary nerve palsy without dislocation of the shoulder and for musculocutaneous nerve palsy with median and/or radial nerve palsy. Urgent operation is needed in cases of nerve injury resulting from fracture of the humeral neck to relieve pressure on nerves.


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 5 | Pages 577 - 583
1 May 2012
Smith CD Guyver P Bunker TD

The outcome of an anatomical shoulder replacement depends on an intact rotator cuff. In 1981 Grammont designed a novel large-head reverse shoulder replacement for patients with cuff deficiency. Such has been the success of this replacement that it has led to a rapid expansion of the indications. We performed a systematic review of the literature to evaluate the functional outcome of each indication for the reverse shoulder replacement. Secondary outcome measures of range of movement, pain scores and complication rates are also presented.


Bone & Joint Research
Vol. 1, Issue 5 | Pages 78 - 85
1 May 2012
Entezari V Della Croce U DeAngelis JP Ramappa AJ Nazarian A Trechsel BL Dow WA Stanton SK Rosso C Müller A McKenzie B Vartanians V Cereatti A

Objectives. Cadaveric models of the shoulder evaluate discrete motion segments using the glenohumeral joint in isolation over a defined trajectory. The aim of this study was to design, manufacture and validate a robotic system to accurately create three-dimensional movement of the upper body and capture it using high-speed motion cameras. Methods. In particular, we intended to use the robotic system to simulate the normal throwing motion in an intact cadaver. The robotic system consists of a lower frame (to move the torso) and an upper frame (to move an arm) using seven actuators. The actuators accurately reproduced planned trajectories. The marker setup used for motion capture was able to determine the six degrees of freedom of all involved joints during the planned motion of the end effector. Results. The testing system demonstrated high precision and accuracy based on the expected versus observed displacements of individual axes. The maximum coefficient of variation for displacement of unloaded axes was less than 0.5% for all axes. The expected and observed actual displacements had a high level of correlation with coefficients of determination of 1.0 for all axes. Conclusions. Given that this system can accurately simulate and track simple and complex motion, there is a new opportunity to study kinematics of the shoulder under normal and pathological conditions in a cadaveric shoulder model


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 1 | Pages 1 - 9
1 Jan 2012
Robinson CM Seah KTM Chee YH Hindle P Murray IR

Frozen shoulder is commonly encountered in general orthopaedic practice. It may arise spontaneously without an obvious predisposing cause, or be associated with a variety of local or systemic disorders. Diagnosis is based upon the recognition of the characteristic features of the pain, and selective limitation of passive external rotation. The macroscopic and histological features of the capsular contracture are well-defined, but the underlying pathological processes remain poorly understood. It may cause protracted disability, and imposes a considerable burden on health service resources. Most patients are still managed by physiotherapy in primary care, and only the more refractory cases are referred for specialist intervention. Targeted therapy is not possible and treatment remains predominantly symptomatic. However, over the last ten years, more active interventions that may shorten the clinical course, such as capsular distension arthrography and arthroscopic capsular release, have become more popular.

This review describes the clinical and pathological features of frozen shoulder. We also outline the current treatment options, review the published results and present our own treatment algorithm.