The rotator cuff tendinopathy is one of the most common shoulder problems leading to full-thickness rotator cuff tendon tear and, eventually, to degenerative arthritis. Recent research on rotator cuff tendon degeneration has focused on its relationship to cell death. The types of cell death known to be associated with rotator cuff tendon degeneration are apoptosis, necrosis, and autophagic cell death. The increased incidence of cell death in degenerative tendon tissue may affect the rates of collagen synthesis and repair, possibly weakening tendon tissue and increasing the risk of tendon rupture. The biomolecular mechanisms of the degenerative changes leading to apoptotic cell death in rotator cuff tenofibroblasts have been identified as oxidative-stress-related cascade mechanisms. Furthermore, apoptosis, necrosis, and autophagic cell death are all known to be mediated by oxidative stress, a condition in which ROS (reactive oxygen species) are overproduced. Lower levels of oxidative stress trigger apoptosis; higher levels mediate necrosis. Although the signaltransduction pathway leading to autophagy has not yet been fully established, ROS are known to be essential to autophagy. A neuronal theory regarding rotator cuff degeneration has been developed from the findings that glutamate, a neural transmitter, is present in increased concentrations in tendon tissues with tendinopathy and that it induces rat supraspinatus tendon cell death. Recent studies have reported that hypoxia involved in rotator cuff tendon degeneration. Because antioxidants are known to scavenge for intracellular ROS, some studies have been conducted to determine whether antioxidants can reduce cell death in rotator cuff tendon-origin fibroblasts. The first study reported that an antioxidant has the ability to reduce apoptosis in oxidative-stressed rotator cuff tenofibroblasts. The second study reported that antioxidants have both antiapoptotic effects and antinecrotic effects on rotator cuff tendon-origin fibroblasts exposed to an oxidative stimulus. The third study reported that an antioxidant has antiautophagic-cell-death effects on rotator cuff tendon-origin fibroblasts exposed to an oxidative stimulus. The fourth study reported that glutamate markedly increases cell death in rotator cuff tendonorigin fibroblasts. The glutamate-induced cytotoxic effects were reduced by an antioxidant, demonstrating its cytoprotective effects against glutamate-induced tenofibroblast cell death. The fifth study reported that hypoxia significantly increases intracellular ROS and apoptosis. The hypoxia-induced cytotoxic effects were markedly attenuated by antioxidants, demonstrating their cytoprotective effects against hypoxia-induced tenofibroblast cell death. In conclusion, antioxidants have cytoprotective effects on tenofibroblasts exposed in vitro to an oxidative stressor, a neurotransmitter, or hypoxia. These cytoprotective effects result from antiapoptotic, antinecrotic, and antiautophagic actions involving the inhibition of ROS formation. These findings suggest that antioxidants may have therapeutic potential for rotator cuff tendinopathy. Further studies must be conducted in order to apply these in vitro findings to clinical situations.

Summary Statement

The peripheral neuronal phenotype is significantly altered in rotator cuff tendinopathy (RCT) with a clear upregulation of the Glutaminergic system being present in disease.

Purpose: We evaluated the respective roles of acromioplasty and curettage of calcifications in arthroscopic treatment of calcifying tendinopathy of the rotator cuff.

Material and methods: We reviewed 41 cases of calcifying tendinopathy at mean 42 months. We retained for analysis only true calcifications identified at least 12 months after arthroscopy. All patients underwent acromioplasty and 13 underwent calcification curettage. The physical examination searched for subacromial impingement and cuff tendon suffering. The weighted Constant score was determined to assess outcome as excellent, good, fair, or poor. Patient satisfaction was assessed using three subjective questions. We searched for persistent calcification on the AP and Lamy lateral x-rays and quantified acromial resection by measuring the height of the subacromial space, the acromial arrow, and the type of acromion (Bigliani). Ultrasonography was performed to search for cuff lesions. Cuffs were classed as normal, atrophic or torn.

Results: After statistical analysis, the mean Constant score was found to have increased from 55 points to 80 points, with 88% excellent and good results (weighted Constant score > 85%). There was no significant difference between patients with and without calcification curettage (p> 0.1). Patients who were mobilised rapidly had a better outcome (p< 0.005). Subjectively, 88% of the patients were satisfied or very satisfied.These results were not correlated with duration of follow-up. The degree of preoperative calcification did not affect outcome, but persistent calcification (nine cases) had an unfavourable effect on outcome. Nevertheless, 80% of the calcifications without curettage did not resorb after acromioplasty. The type of acromion had an effect on outcome. Acromions which were not flat (type II or III) had an unfavourable influence. The degree of acromial correction had a significant effect on outcome, the Constant score increased proportionally with the height of the subacromial space and inversely with acromial arrow. Ultrasonography disclosed two cuff tears but in elderly subjects, probably due to degeneration.

Conclusion: Curettage of calcifications does not improve outcome of good quality acromioplasty. The stage of the calcification is not an indication for curettage. Furthermore, it appears that the impingement is partly the cause of persistent calcifications since 80% of them disappeared after acromioplasty alone.

Objectives

Emerging evidence indicates that tendon disease is an active process with inflammation that is critical to disease onset and progression. However, the key cytokines responsible for driving and sustaining inflammation have not been identified.

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.