The role of inflammatory cells and their products in tendinopathy is not completely understood. Pro-inflammatory cytokines are upregulated after oxidative and other forms of stress. Based on observations that increased cytokine expression has been demonstrated in cyclically-loaded tendon cells we hypothesised that because of their role in oxidative stress and apoptosis, pro-inflammatory cytokines may be present in rodent and human models of tendinopathy. A rat supraspinatus tendinopathy model produced by running overuse was investigated at the genetic level by custom micro-arrays. Additionally, samples of torn supraspinatus tendon and matched intact subscapularis tendon were collected from patients undergoing arthroscopic shoulder surgery for rotator-cuff tears and control samples of subscapularis tendon from ten patients with normal rotator cuffs undergoing arthroscopic stabilisation of the shoulder were also obtained. These were all evaluated using semiquantitative reverse transcription polymerase chain-reaction and immunohistochemistry. We identified significant upregulation of pro-inflammatory cytokines and apoptotic genes in the rodent model (p = 0.005). We further confirmed significantly increased levels of cytokine and apoptotic genes in human supraspinatus and subscapularis tendon harvested from patients with rotator cuff tears (p = 0.0008). These findings suggest that pro-inflammatory cytokines may play a role in tendinopathy and may provide a target for preventing tendinopathies

Abstract. Shoulder replacements have evolved and current 4th generation implants allow intraoperative flexibility to perform anatomic, reverse, trauma, and revision shoulder arthroplasty. Despite high success rates with shoulder arthroplasty, complication rates high as 10–15% have been reported and progressive glenoid loosening remains a concern. Objectives. To report medium term outcomes following 4th generation VAIOS® shoulder replacement. Methods. We retrospectively analysed prospectively collected data following VAIOS® shoulder arthroplasty performed by the senior author between 2014–2020. This included anatomical (TSR), reverse(rTSR), revision and trauma shoulder replacements. The primary outcome was implant survival (Kaplan-Meier analysis). Secondary outcomes were Oxford Shoulder Scores (OSS), radiological outcomes and complications. Results. 172 patients met our inclusion criteria with 114 rTSR, 38 anatomical TSR, and 20 hemiarthroplasty. Reverse TSR- 55 primary, 31 revision, 28 for trauma. Primary rTSR- 0 revisions, average 3.35-year follow-up. Revision rTSR-1 revision (4.17%), average 3.52-year follow-up. Trauma rTSR- 1 revision (3.57%), average 4.56-year follow-up OSS: Average OSS improved from 15.39 to 33.8 (Primary rTSR) and from 15.11 to 29.1 (Revision rTSR). Trauma rTSR-Average post-operative OSS was 31.4 Anatomical TSR38 patients underwent primary anatomical TSR, 8 were revisions following hemiarthroplasty. In 16/38 patients, glenoid bone loss was addressed by bone grafting before implantation of the metal back glenoid component. Mean age at time of surgery was 68.3 years (53 – 81 years). Mean follow-up was 34 months (12 – 62 months). The average Oxford shoulder score improved from 14 (7–30) to 30 (9–48). There were 3 revisions (7.8%); two following subscapularis failure requiring revision conversion to reverse shoulder replacement and one for glenoid graft failure. Conclusions. The medium-term results of the VAIOS® system suggest much lower revision rates across multiple configurations of the system than previously reported, as well as a low incidence of scapular notching. This system allows conversion to rTSR during primary and revision surgery

The objective was to seek evidence of hypoxia in early human tendinopathy and thereafter, to explore mechanisms whereby tissue hypoxia may regulate apoptosis, inflammatory mediators and matrix regulation in human tenocytes. Fifteen torn supraspinatus tendon (established pathology) and matched intact subscapularis tendon (representing ‘early pathology’) biopsies were collected from patients undergoing arthroscopic shoulder surgery. Control samples of subscapularis tendon were collected from 10 patients undergoing arthroscopic stabilisation surgery. Markers of hypoxia were quantified by immunohistochemical methods. Human tendon-derived primary cells were derived from hamstring tendon tissue obtained during hamstring tendon ACL reconstruction. The impact of hypoxia upon tenocyte biology ex vivo was measured using quantitative RT-PCR, multiplex cytokine assays, apoptotic proteomic profiling, immunohistochemistry and annexin V FACS staining. Increased expression of HIF 1a, Bcl-2 and clusterin (hypoxic and apoptotic markers) was detected in subscapularis tendon samples compared to both matched torn samples and non matched control samples (p<0.01). Hypoxic tenocytes exhibited increased production of proinflammatory cytokines (p<0.001), altered matrix regulation (p<0.01) with increased production of Collagen type III operating through a MAPK dependent pathway. Finally, hypoxia increased expression of several mediators of apoptosis and thereby promoted tenocyte apoptosis. Hypoxia promotes expression of proinflammatory cytokines, key apoptotic mediators and drives matrix component synthesis towards a collagen type III profile by human tenocytes. We propose hypoxic cell injury as a critical pathophysiological mechanism in early tendinopathy offering novel therapeutic opportunities in the management of tendon disorders

Objectives . The effects of disease progression and common tendinopathy treatments on the tissue characteristics of human rotator cuff tendons have not previously been evaluated in detail owing to a lack of suitable sampling techniques. This study evaluated the structural characteristics of torn human supraspinatus tendons across the full disease spectrum, and the short-term effects of subacromial corticosteroid injections (SCIs) and subacromial decompression (SAD) surgery on these structural characteristics. . Methods . Samples were collected inter-operatively from supraspinatus tendons containing small, medium, large and massive full thickness tears (n = 33). Using a novel minimally invasive biopsy technique, paired samples were also collected from supraspinatus tendons containing partial thickness tears either before and seven weeks after subacromial SCI (n = 11), or before and seven weeks after SAD surgery (n = 14). Macroscopically normal subscapularis tendons of older patients (n = 5, mean age = 74.6 years) and supraspinatus tendons of younger patients (n = 16, mean age = 23.3) served as controls. Ultra- and micro-structural characteristics were assessed using atomic force microscopy and polarised light microscopy respectively. . Results. Significant structural differences existed between torn and control groups. Differences were identifiable early in the disease spectrum, and increased with increasing tear size. Neither SCI nor SAD surgery altered the structural properties of partially torn tendons seven weeks after treatment. . Conclusions . These findings may suggest the need for early clinical intervention strategies for torn rotator cuff tendons in order to prevent further degeneration of the tissue as tear size increases. Further work is required to establish the long-term abilities of SCI and SAD to prevent, and even reverse, such degeneration. Cite this article: Bone Joint Res 2014;3:252–61

Alarmins- also referred to as damage associated molecular patterns (DAMPS)- are endogenous molecules mobilized in response to tissue damage known to activate the innate immune system and regulate tissue repair and remodelling. The molecular mechanisms that regulate inflammatory and remodelling pathways in tendinopathy are largely unknown therefore identifying early immune effectors is essential to understanding the pathology. S100A8 and S100A9 are low molecular weight calcium binding proteins primarily released by activated phagocytes in an inflammatory setting and also secreted as a heterodimeric complex that exhibits cytokine like functions. Based on our previous investigations we sought evidence of S100A8/A9 expression in human tendinopathy and thereafter, to explore mechanisms whereby S100 proteins may regulate inflammatory mediators and matrix regulation in human tenocytes. Torn supraspinatus tendon (established pathology) and matched intact subscapularis tendon (representing ‘early pathology’) biopsies were collected from patients undergoing arthroscopic shoulder surgery. Control samples of subscapularis tendon were collected from patients undergoing arthroscopic stabilisation surgery. S100A8/A9 expression was analysed at transcript and protein level using quantitative RT-PCR and immunohistochemistry, respectively. Primary human tenocytes were cultured from hamstring tendon tissue obtained during hamstring tendon ACL reconstruction. The in vitro effect of recombinant human S100 A8/A9 on primary human tenocytes was measured using quantitative RT-PCR and ELISA. Immunohistochemistry of tendinopathic tissues demonstrated the presence of S100 A8/A9 in diseased tissues compared to control tissue. In addition, early pathological diseased tissue indicated greater S100A9 expression compared with established diseased pathology. These findings were reflected by data obtained at transcript level from diseased tissues. Recombinant human S100A8, A9 and A8/A9 complex led to significant increase in expression of inflammatory mediators, including IL-6 in vitro. Further analysis via quantitative RT-PCR demonstrated recombinant S100A8, A9 and A8/A9 complex treatment on tenocytes, in vitro, had no direct effect on the expression of genes involved in matrix remodelling. The presence of S100A8 and S100A9 in early tendinopathic lesions suggests expression is upregulated in response to cellular damage. S100A8 and S100A9 are endogenous ligands of Toll-like receptors (TLRs) and receptor for advanced glycation end products (RAGE). These receptors have known regulatory effects on immune mediated cytokine production. We propose S100A8 and S100A9 as active alarmins in the early stages of tendinopathy and thus targeting of its downstream signalling may offer novel therapeutic approaches in the management of human tendon disorders

Summary Statement. Reverse shoulder design philosophy can impact external rotation moment arms. Lateralizing the humerus can increase the external rotator moment arms relative to normal anatomy. Introduction. The design of reverse shoulders continues to evolve. These devices are unique in that they are not meant to reproduce the healthy anatomy. The reversal of the fulcurm in these devices impacts every muscle that surrounds the joint. This study is focused on analyzing the moment arms for the rotator cuff muscles involved in internal and external rotation for a number of reverse shoulder design philosophies. Methods. Four of the most common design philosophies were chosen. The first, a Grammont style prosthesis, with a center of rotation (COR) on the glenoid face and a humeral cup countersunk into the proximal humerus (MGMH). The second concept is the MGMH design lateralised by a 10mm bone graft (BIO). The third concept has a lateralised glenosphere COR and a humeral component inside the proximal humerus (LGMH). The fourth design has a medialised COR with a humeral component placed on top of the humerus (MGLH). This places the humerus further lateral than the previous designs. For each component set, a representative implant was modeled based on published specifications. Each design was implanted into the same digital bone models (consisting of a humerus, scapula, clavicle, and ribcage) following the manufacturer's recommended surgical technique. The muscles analyzed were the posterior-deltoid (PD), subscapularis (SSC), infraspinatus (IS), and teres minor (TM). These muscles were allowed to wrap around the bone of the scapula and proximal humerus through the range of motion. All muscle origin and insertion points were kept constant throughout the analysis. The assemblies were externally rotated from an initial position of 45° internal rotation to 45° of external rotation of the humerus with the arm at 0° of abduction. The moment arms for all muscles were compared to those calculated for the anatomic shoulder. Results. All the rotator cuff muscles displayed a similar trend with the reverse shoulder. The external rotators all had similar moment arm values at neutral (IS∼22mm, TM∼20mm), but increased at rates proportional to their humeral offsets with external rotation (IS-MGLH 32.3mm, LGMH 27.5mm, MGMH and BIO 26.25mm; TM-MGLH 31.3mm, LGMH 27.8mm, MGMH and BIO 26.5mm). The SSC internal rotation moment arm remains roughly constant at 20mm for the anatomic shoulder, but varies widely from 45° external to 45° internal rotation with the different designs (MGLH 31.4mm to 6.7mm; MGMH 25.1mm to 11.2mm; LGMH 26.2mm to 10.8mm; BIO 25.4mm to 4.8mm). The PD moment arm is increased relative to the anatomic shoulder during external rotation for the MGLH design (9.3mm vs. 7.4mm). The other designs exhibit a decrease in the moment arm of this muscle relative to the anatomic design (LGMH 7.3mm, MGMH 5.8mm, BIO 6.4mm). Discussion. The lateral offset between the center of humeral axis and the muscle insertion on the humerus dominates the external rotation moment arm value through this range of motion. This is evident by the increase in the moment arms with external rotation for the different reverse shoulder designs. The increase in external rotation efficiency for the external rotators and PD could play a critical role in post-operative external rotation strength and motion

The aim of this study was to investigate the occurrence of tissue hypoxia and apoptosis at different stages of tendinopathy and tears of the rotator cuff.

We studied tissue from 24 patients with eight graded stages of either impingement (mild, moderate and severe) or tears of the rotator cuff (partial, small, medium, large and massive) and three controls. Biopsies were analysed using three immunohistochemical techniques, namely antibodies against HIF-1α (a transcription factor produced in a hypoxic environment), BNip3 (a HIF-1α regulated pro-apoptotic protein) and TUNEL (detecting DNA fragmentation in apoptosis).

The HIF-1α expression was greatest in mild impingement and in partial, small, medium and large tears. BNip3 expression increased significantly in partial, small, medium and large tears but was reduced in massive tears. Apoptosis was increased in small, medium, large and massive tears but not in partial tears.

These findings reveal evidence of hypoxic damage throughout the spectrum of pathology of the rotator cuff which may contribute to loss of cells by apoptosis. This provides a novel insight into the causes of degeneration of the rotator cuff and highlights possible options for treatment.

Objectives

Rotator cuff tears are among the most common and debilitating upper extremity injuries. Chronic cuff tears result in atrophy and an infiltration of fat into the muscle, a condition commonly referred to as ‘fatty degeneration’. While stem cell therapies hold promise for the treatment of cuff tears, a suitable immunodeficient animal model that could be used to study human or other xenograft-based therapies for the treatment of rotator cuff injuries had not previously been identified.

Wear of polyethylene is associated with aseptic loosening of orthopaedic implants and has been observed in hip and knee prostheses and anatomical implants for the shoulder. The reversed shoulder prostheses have not been assessed as yet. We investigated the volumetric polyethylene wear of the reversed and anatomical Aequalis shoulder prostheses using a mathematical musculoskeletal model. Movement and joint stability were achieved by EMG-controlled activation of the muscles. A non-constant wear factor was considered. Simulated activities of daily living were estimated from in vivo recorded data.

After one year of use, the volumetric wear was 8.4 mm³ for the anatomical prosthesis, but 44.6 mm³ for the reversed version. For the anatomical prosthesis the predictions for contact pressure and wear were consistent with biomechanical and clinical data. The abrasive wear of the polyethylene in reversed prostheses should not be underestimated, and further analysis, both experimental and clinical, is required.

This study evaluated the effect on movement under load of three different techniques for re-attachment of the tuberosities of the humerus using test sawbones. In the first, the tuberosities were attached both to the shaft and to each other, with one cerclage suture through the anterior hole in the prosthesis. The second technique was identical except for omission of the cerclage suture and in the third the tuberosities were attached to the prosthesis and to the shaft. An orthogonal photogrammetric system allowed all segments to be tracked in a 3D axis system. The humeri were incrementally-loaded in abduction, and the 3D linear and angular movements of all segments were calculated. Displacement between the tuberosities and the shaft was measured.

The first and second techniques were the most stable constructs, with the third allowing greater separation of fragments and angular movement. Separation at the midpoint of the tuberosities was significantly greater using the latter technique (p < 0.05). The cerclage suture added no further stability to the fixation.

Our aim was to determine the most repeatable three-dimensional measurement of glenoid orientation and to compare it between shoulders with intact and torn rotator cuffs. Our null hypothesis was that glenoid orientation in the scapulae of shoulders with a full-thickness tear of the rotator cuff was the same as that in shoulders with an intact rotator cuff.

We studied 24 shoulders in cadavers, 12 with an intact rotator cuff and 12 with a full-thickness tear. Two different observers used a three-dimensional digitising system to measure glenoid orientation in the scapular plane (ie glenoid inclination) using six different techniques. Glenoid version was also measured. The overall precision of the measurements revealed an error of less than 0.6°.

Intraobserver reliability (correlation coefficients of 0.990 and 0.984 for each observer) and interobserver reliability (correlation coefficient of 0.985) were highest for measurement of glenoid inclination based on the angle obtained from a line connecting the superior and inferior points of the glenoid and that connecting the most superior point of the glenoid and the most superior point on the body of the scapula. There were no differences in glenoid inclination (p = 0.34) or glenoid version (p = 0.12) in scapulae from shoulders with an intact rotator cuff and those with a full-thickness tear. Abnormal glenoid orientation was not present in shoulders with a torn rotator cuff.