Aims. Rotator cuff tear (RCT) is the leading cause of shoulder pain, primarily associated with age-related tendon degeneration. This study aimed to elucidate the potential differential gene expressions in tendons across different age groups, and to investigate their roles in tendon degeneration. Methods. Linear regression and differential expression (DE) analyses were performed on two transcriptome profiling datasets of torn supraspinatus tendons to identify age-related genes. Subsequent functional analyses were conducted on these candidate genes to explore their potential roles in tendon ageing. Additionally, a secondary DE analysis was performed on candidate genes by comparing their expressions between lesioned and normal tendons to explore their correlations with RCTs. Results. We identified 49 genes in torn supraspinatus tendons associated with advancing age. Among them, five age-related genes showed DE in lesioned tendons compared to normal tendons. Functional analyses and previous studies have highlighted their specific enrichments in biological functions, such as muscle development (e.g. myosin heavy chain 3 (MYH3)), transcription regulation (e.g. CCAAT enhancer binding brotein delta (CEBPD)), and metal ion homeostasis (e.g. metallothionein 1X (MT1X)). Conclusion. This study uncovered molecular aspects of tendon ageing and their potential links to RCT development, offering insights for targeted interventions. These findings enhance our understanding of the mechanisms of tendon degeneration, allowing potential strategies to be made for reducing the incidence of RCT. Cite this article: Bone Joint Res 2024;13(9):474–484

Aims

A revision for periprosthetic joint infection (PJI) in total hip arthroplasty (THA) has a major effect on the patient’s quality of life, including walking capacity. The objective of this case control study was to investigate the histological and ultrastructural changes to the gluteus medius tendon (GMED) in patients revised due to a PJI, and to compare it with revision THAs without infection performed using the same lateral approach.

Aims

Dislocation of the hip remains a major complication after periacetabular tumour resection and endoprosthetic reconstruction. The position of the acetabular component is an important modifiable factor for surgeons in determining the risk of postoperative dislocation. We investigated the significance of horizontal, vertical, and sagittal displacement of the hip centre of rotation (COR) on postoperative dislocation using a CT-based 3D model, as well as other potential risk factors for dislocation.

Tendon is a bradytrophic and hypovascular tissue, hence, healing remains a major challenge. The molecular key events involved in successful repair have to be unravelled to develop novel strategies that reduce the risk of unfavourable outcomes such as non-healing, adhesion formation, and scarring. This review will consider the diverse pathophysiological features of tendon-derived cells that lead to failed healing, including misrouted differentiation (e.g. de- or transdifferentiation) and premature cell senescence, as well as the loss of functional progenitors. Many of these features can be attributed to disturbed cell-extracellular matrix (ECM) or unbalanced soluble mediators involving not only resident tendon cells, but also the cross-talk with immigrating immune cell populations. Unrestrained post-traumatic inflammation could hinder successful healing. Pro-angiogenic mediators trigger hypervascularization and lead to persistence of an immature repair tissue, which does not provide sufficient mechano-competence. Tendon repair tissue needs to achieve an ECM composition, structure, strength, and stiffness that resembles the undamaged highly hierarchically ordered tendon ECM. Adequate mechano-sensation and -transduction by tendon cells orchestrate ECM synthesis, stabilization by cross-linking, and remodelling as a prerequisite for the adaptation to the increased mechanical challenges during healing. Lastly, this review will discuss, from the cell biological point of view, possible optimization strategies for augmenting Achilles tendon (AT) healing outcomes, including adapted mechanostimulation and novel approaches by restraining neoangiogenesis, modifying stem cell niche parameters, tissue engineering, the modulation of the inflammatory cells, and the application of stimulatory factors.

Cite this article: Bone Joint Res 2022;11(8):561–574.

Aims

Failure of healing is a well-known problem after repair of the rotator cuff. This study aimed to investigate if early repair of trauma-related full-thickness rotator cuff tears (FTRCTs) could prevent this failure.

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.

Objectives. Triamcinolone acetonide (TA) is widely used for the treatment of rotator cuff injury because of its anti-inflammatory properties. However, TA can also produce deleterious effects such as tendon degeneration or rupture. These harmful effects could be prevented by the addition of platelet-rich plasma (PRP), however, the anti-inflammatory and anti-degenerative effects of the combined use of TA and PRP have not yet been made clear. The objective of this study was to determine how the combination of TA and PRP might influence the inflammation and degeneration of the rotator cuff by examining rotator cuff-derived cells induced by interleukin (IL)-1ß. Methods. Rotator cuff-derived cells were seeded under inflammatory stimulation conditions (with serum-free medium with 1 ng/ml IL-1ß for three hours), and then cultured in different media: serum-free (control group), serum-free + TA (0.1mg/ml) (TA group), serum-free + 10% PRP (PRP group), and serum-free + TA (0.1mg/ml) + 10% PRP (TA+PRP group). Cell morphology, cell viability, and expression of inflammatory and degenerative mediators were assessed. Results. Exposure to TA significantly decreased cell viability and changed the cell morphology; these effects were prevented by the simultaneous administration of PRP. Compared with the control group, expression levels of inflammatory genes and reactive oxygen species production were reduced in the TA, PRP, and TA+PRP groups. PRP significantly decreased the expression levels of degenerative marker genes. Conclusions. The combination of TA plus PRP exerts anti-inflammatory and anti-degenerative effects on rotator cuff-derived cells stimulated by IL-1ß. This combination has the potential to relieve the symptoms of rotator cuff injury. Cite this article: T. Muto, T. Kokubu, Y. Mifune, A. Inui, R. Sakata, Y. Harada, F. Takase, M. Kurosaka. Effects of platelet-rich plasma and triamcinolone acetonide on interleukin-1ß-stimulated human rotator cuff-derived cells. Bone Joint Res 2016;5:602–609. DOI: 10.1302/2046-3758.512.2000582

If a modular convertible total shoulder system is used as a primary implant for an anatomical total shoulder arthroplasty, failure of the prosthesis or the rotator cuff can be addressed by converting it to a reverse shoulder arthroplasty (RSA), with retention of the humeral stem and glenoid baseplate. This has the potential to reduce morbidity and improve the results.

In a retrospective study of 14 patients (15 shoulders) with a mean age of 70 years (47 to 83) we reviewed the clinical and radiological outcome of converting an anatomical shoulder arthroplasty (ASA) to a RSA using a convertible prosthetic system (SMR system, Lima, San Daniele, Italy).

The mean operating time was 64 minutes (45 to 75). All humeral stems and glenoid baseplates were found to be well-fixed and could be retained. There were no intra-operative or early post-operative complications and no post-operative infection.

The mean follow-up was 43 months (21 to 83), by which time the mean visual analogue scale for pain had decreased from 8 pre-operatively to 1, the mean American Shoulder and Elbow Surgeons Score from 12 to 76, the mean Oxford shoulder score from 3 to 39, the mean Western Ontario Osteoarthritis of the Shoulder Score from 1618 to 418 and the mean Subjective shoulder value from 15 to 61.

On radiological review, one patient had a lucency around the humeral stem, two had stress shielding. There were no fatigue fractures of the acromion but four cases of grade 1 scapular notching.

The use of a convertible prosthetic system to revise a failed ASA reduces morbidity and minimises the rate of complications. The mid-term clinical and radiological results of this technique are promising.

Cite this article: Bone Joint J 2015;97-B:1662–7.

Objectives. To investigate the appropriate dose and interval for the administration of triamcinolone acetonide (TA) in treating tendinopathy to avoid adverse effects such as tendon degeneration and rupture. Methods. Human rotator cuff-derived cells were cultured using three media: regular medium (control), regular medium with 0.1 mg/mL of TA (low TA group), and with 1.0 mg/mL of TA (high TA group). The cell morphology, apoptosis, and viability were assessed at designated time points. Results. In the low TA group, the cells became flattened and polygonal at seven days then returned to normal at 21 days. The cell apoptosis ratio and messenger ribonucleic acid expression of caspase-3, 7, 8, and 9 increased, and viability was reduced in the low and high groups at seven days. In the low TA group, apoptosis and viability returned to normal at 21 days, however, in the high TA group, the cell morphology, apoptosis ratio, caspase-3, 7, 8, and 9 and viability did not return by day 21. Re-administration was performed in the low TA group at 7-, 14-, and 21-day intervals, and cell viability did not return to the control level at the 7- and 14-day intervals. Conclusion. A 0.1 mg/mL dose of TA temporarily decreased cell viability and increased cell apoptosis, which was recovered at 21 days, however, 1 mg/mL of TA caused irreversible damage to cell morphology and viability. An interval > three weeks was needed to safely re-administer TA. These findings may help determine the appropriate dose and interval for TA injection therapy. Cite this article: Bone Joint Res 2014;3:328–34

Aims

We performed a systematic review of the literature to determine whether earlier surgical repair of acute rotator cuff tear (ARCT) leads to superior post-operative clinical outcomes.

This study reports the clinical and sonographic outcome of arthroscopic rotator cuff repair in patients aged ≥ 70 years and aimed to determine factors associated with re-tear. A total of 69 consecutive repairs were performed in 68 patients with a mean age of 77 years (70 to 86). Constant-Murley scores were collected pre-operatively and at one year post-operatively. The integrity of the repair was assessed using ultrasound. Re-tear was detected in 20 of 62 patients (32%) assessed with ultrasound. Age at operation was significantly associated with re-tear free survival (p = 0.016). The mean pre-operative Constant score was 23 (sd 14), which increased to 58 (sd 20) at one year post-operatively (paired t-test, p < 0.001). Male gender was significantly associated with a higher score at one year (p = 0.019).

We conclude that arthroscopic rotator cuff repair in patients aged ≥ 70 years is a successful procedure. The gender and age of the patient are important factors to consider when planning management.

Cite this article: Bone Joint J 2013;95-B:199–205.

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.

The effect of timing of a manipulation under anaesthetic (MUA) and injection of corticosteroid and local anaesthetic for the treatment of frozen shoulder has attracted little attention to date. All studies describe a period of conservative treatment before proceeding to an MUA. Delay has been associated with a poorer outcome.

We present a retrospective review of a prospectively collected, single-surgeon, consecutive series of 246 patients with a primary frozen shoulder treated by MUA within four weeks of presentation. The mean duration of presenting symptoms was 28 weeks (6 to 156), and time to initial post-operative assessment was 26 days (5 to 126). The Oxford shoulder score (OSS) improved by a mean of 16 points (Wilcoxon signed-ranks test, p < 0.001) with a mean OSS at this time of 43 (7 to 48). Linear regression analysis showed no correlation between the duration of presenting symptoms and OSS at initial follow-up (R2 < 0.001) or peri-operative change in OSS (R2 < 0.001) or OSS at long-term follow-up (R2 < 0.03). Further analysis at a mean of 42 months (8 to 127) revealed a sustained improvement with a mean OSS of 44 (16 to 48).

A good outcome follows an MUA and injection of corticosteroid and local anaesthetic in patients with primary frozen shoulder, independent of the duration of the presenting symptoms, and this improvement is maintained in the long term.

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.

The aim of this study was to investigate genetic influences on the development and progression of tears of the rotator cuff. From a group of siblings of patients with a tear of the rotator cuff and of controls studied five years earlier, we determined the prevalence of tears of the rotator cuff with and without associated symptoms using ultrasound and the Oxford Shoulder Score.

In the five years since the previous assessment, three of 62 (4.8%) of the sibling group and one of the 68 (1.5%) controls had undergone shoulder surgery. These subjects were excluded from the follow-up.

Full-thickness tears were found in 39 of 62 (62.9%) siblings and in 15 of 68 (22.1%) controls (p = 0.0001). The relative risk of full-thickness tears in siblings as opposed to controls was 2.85 (95% confidence interval (CI) 1.75 to 4.64), compared to 2.42 (95% CI 1.77 to 3.31) five years earlier. Full-thickness tears associated with pain were found in 30 of 39 (76.9%) tears in the siblings and in eight of 15 (53.3%) tears in the controls (p = 0.045). The relative risk of pain associated with a full-thickness tear in the siblings as opposed to the controls was 1.44 (95% CI 2.04 to 8.28) (p = 0.045).

In the siblings group ten of 62 (16.1%) had progressed in terms of tear size or development compared to one of 68 (1.5%) in the control group which had increased in size.

Full-thickness rotator cuff tears in siblings are significantly more likely to progress over a period of five years than in a control population. This implies that genetic factors have a role, not only in the development but also in the progression of full-thickness tears of the rotator cuff.

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.

We have conducted a prospective study to assess the mid-term clinical results following arthroscopic repair of the rotator cuff. Patients were evaluated using the Constant score, subjective satisfaction levels and post-operative ultrasound scans.

Of 115 consecutive patients who underwent arthroscopic repair of the rotator cuff at our institution, 102 were available for follow-up. The mean period of follow-up was for 35.8 months (24 to 73). The mean age of the patients was 57.3 years (23 to 78). There were 18 small (≤ 1 cm in diameter), 44 medium (1 cm to 3 cm in diameter), 34 large (3 cm to 5 cm in diameter) and six massive (> 5 cm in diameter) tears. There was a statistically significant increase in the size of the tear with increasing age (p = 0.0048).

The mean pre-operative Constant score was 41.4 points (95% confidence interval, 37.9 to 44.9), which improved to 84.5 (95% confidence interval, 82.2 to 86.9). A significant inverse association (p = 0.0074), was observed between the size of the tear and the post-operative Constant score, with patients having smaller tears attaining higher Constant scores after repair. Post-operatively, 80 patients (78.4%) were able to resume their occupations and 84 (82.4%) returned to their pre-injury leisure activities. Only eight (7.8%) of 102 patients were not satisfied with the outcome.

Recurrent tears were detected by ultrasound in 19 (18.6%) patients, and were generally smaller than the original ones. Patients with recurrent tears experienced a mean improvement of 31.6 points (95% confidence interval, 23.6 to 39.6) in their post-operative Constant scores. Those with intact repairs had significantly improved (p < 0.0001) Constant scores (mean improvement 46.3 points, 95% confidence interval, 41.9 to 50.6). Patient satisfaction was high in 94 cases (92%), irrespective of the outcome of the Constant score. Recurrent tears appear to be linked to age-related degeneration.

Arthroscopic repair of the rotator cuff leads to high rates of satisfaction (92%) and good functional results, albeit with a recurrence rate of 18.6% (19 of 102).