Pathology of the torn rotator cuff tendon. Reduction in potential for repair as tear size increases

We have studied cellular and vascular changes in different stages of full thickness tears of the rotator cuff. We examined biopsies from the supraspinatus tendon in 40 patients with chronic rotator cuff tears who were undergoing surgery and compared them with biopsies from four uninjured subscapularis tendons. Morphological and immunocytochemical methods using monoclonal antibodies directed against leucocytes, macrophages, mast cells, proliferative and vascular markers were used. Histological changes indicative of repair and inflammation were most evident in small sized rotator cuff tears with increased fibroblast cellularity and intimal hyperplasia, together with increased expression of leucocyte and vascular markers. These reparative and inflammatory changes diminished as the size of the rotator cuff tear increased. Marked oedema and degeneration was seen in large and massive tears, which more often showed chondroid metaplasia and amyloid deposition. There was no association between the age of the patient and the duration of symptoms. In contrast, large and massive tears showed no increase in the number of inflammatory cells and blood vessels. Small sized rotator cuff tears retained the greatest potential to heal, showing increased fibroblast cellularity, blood vessel proliferation and the presence of a significant inflammatory component. Tissue from large and massive tears is of such a degenerative nature that it may be a significant cause of re-rupture after surgical repair and could make healing improbable in this group.     

Fibrous cartilage in the rotator cuff: A pathogenetic mechanism of tendon tear?

There is no consensus on the pathogenesis of rotator cuff tears. Fibrous cartilage has been hypothesized to develop in some tendons as a result of shear or compressive forces, resulting in a tissue less capable of resisting normal tensile load and more prone to tearing. To test the hypothesis that metaplastic fibrocartilage in the rotator cuff could be involved in the pathogenic mechanism of its tear, samples from 34 acute and chronic torn rotator cuffs were subjected to histologic and immunohistologic study for the presence and type of cartilage (hyaline, fibrous, or elastic) in the area of the lesion and surrounding tissues. Detection of type I and II collagen, S-100 protein, and chondroitin sulfate allowed areas of fibrous cartilage to be seen in all samples, suggesting that the characteristic of rotator cuff tendons to work both in tension and in compression may stimulate fibrocartilaginous metaplasia and lead to a complete tear.     

Glenohumeral articular cartilage changes in rotator cuff disease

This study aims to clarify the natural history of glenohumeral articular cartilage changes in rotator cuff disease. We assessed 33 cadaveric shoulder joints, examining the rotator cuffs for macroscopic tears and the articular surfaces for degenerative changes. Ten specimens had tears of the rotator cuff. Articular degenerative changes were noted in 23 joints. Articular cartilage degeneration was almost twice as frequent in the group with rotator cuff tears (10/10 shoulders) as in those without tears (13/23 shoulders). This difference was statistically significant. This strong correlation between tears of the rotator cuff and articular degeneration has not been documented previously, other than in the extreme situation of massive cuff tears and cuff-tear arthropathy. This is deserving of further study because it may have implications for surgical management.     

The association between retraction of the torn rotator cuff and increasing expression of hypoxia inducible factor 1α and vascular endothelial growth factor expression: an immunohistological study

Background  

Differing levels of tendon retraction are found in full-thickness rotator cuff tears. The pathophysiology of tendon degeneration and retraction is unclear. Neoangiogenesis in tendon parenchyma indicates degeneration. Hypoxia inducible factor 1α (HIF) and vascular endothelial growth factor (VEGF) are important inducers of neoangiogenesis. Rotator cuff tendons rupture leads to fatty muscle infiltration (FI) and muscle atrophy (MA). The aim of this study is to clarify the relationship between HIF and VEGF expression, neoangiogenesis, FI, and MA in tendon retraction found in full-thickness rotator cuff tears.     

Apoptosis in rotator cuff tendonopathy.

The aim of this study was to investigate the involvement of apoptosis (programmed cell death) in the pathogenesis of rotator cuff disorders. The edges of torn supraspinatus rotator cuff tendons were collected from patients with rotator cuff tear (n = 25). Samples of the intra-articular portion of subscapularis tendons were collected from patients without rotator cuff tear as control (n = 6). To minimize individual variance, we also collected six pairs of supraspinatus tendon and subscapularis tendon from six patients with rotator cuff tears. Apoptosis was detected by in situ DNA end labelling assay and DNA laddering assay. Immunohistochemical staining was performed to identify cells undergoing apoptosis. Control subscapularis tendon had normal morphology. Tendon from torn supraspinatus rotator cuff showed significant mucoid degeneration. Within the areas of degeneration, there were large numbers of apoptotic cells. The percentage of apoptotic cells in the degenerative rotator cuff (34%) was significantly higher than that in controls (13%) (p < 0.001). The excessive apoptosis detected in degenerative rotator cuff tissue was confirmed by DNA laddering assays. This is the first report of excessive apoptosis in degenerating rotator cuff tendon. Cells undergoing apoptosis in rotator cuff were mainly fibroblast-like cells. These finding indicate that apoptosis may play an important role in the pathogenesis of rotator cuff degeneration.     

The results of repair of massive tears of the rotator cuff

BACKGROUND: Massive tears of the tendons of the rotator cuff cause atrophy and fatty degeneration of the rotator cuff muscles and painful loss of function of the shoulder. Repair of massive rotator cuff tears is often followed by retears of the tendons, additional muscular degeneration, and a poor clinical outcome. The purposes of this study were to determine whether a new method of repair of rotator cuff tendons can yield a lower retear rate and a better clinical outcome than previously reported methods, to assess the muscular changes following repair of massive tears of the musculotendinous units, and to correlate findings on magnetic resonance imaging with the clinical results. METHODS: Twenty-nine massive rotator cuff tears involving complete detachment of at least two tendons were repaired operatively with use of a new laboratory-tested technique in a prospective study. At least two years (average, thirty-seven months; range, twenty-four to sixty-one months) postoperatively, twenty-seven patients were evaluated clinically and with magnetic resonance imaging to determine the clinical outcome, the integrity of the repair, and the condition of the rotator cuff muscles. RESULTS: The age and gender-adjusted Constant score improved from an average of 49 percent preoperatively to an average of 85 percent postoperatively, corresponding to a subjective shoulder value of 78 percent of that of a normal shoulder. Pain-free flexion improved from an average of 92 degrees to an average of 142 degrees, and abduction improved from an average of 82 degrees to an average of 137 degrees. Pain decreased and performance of activities of daily living improved significantly (p < 0.05). The seventeen patients who had a structurally successful repair all had an excellent clinical outcome. Muscle atrophy could not be reversed except in successfully repaired supraspinatus musculotendinous units. Fatty degeneration increased in all muscles. CONCLUSIONS: The method of repair of massive rotator cuff tears that was used in this study yielded a comparatively low retear rate and good-to-excellent clinical results; however, the repair did not result in substantial reversal of muscular atrophy and fatty degeneration. Retears occurred more often in patients who had had a shorter interval between the onset of the symptoms and the operation (p < 0.05). Patients who had a retear had improvement of the shoulder compared with the preoperative state, but they had less improvement than did those who had a successful repair.     

Editorial Commentary: Does the Morphology of the Acromion Explain All Rotator Cuff Tears?

Given the high prevalence of rotator cuff tears and their socioeconomic impact, surgeons and researchers have tried to understand their etiology and pathomechanism for almost hundred years. Articles about tendon degeneration with increasing age dominate the literature, and numerous factors contributing to tendon degeneration have been identified. One of them, the lateral extension of the acromion, as quantitated using the acromion index or the critical shoulder angle, has become very popular in the last few years. Other big tendons in the human body, such as the distal biceps tendon, the Achilles tendon, or the patellar tendon, are also subject to degenerative changes, but they normally do not lose their continuity without a relevant trauma. This raises 2 questions: What makes the rotator cuff different from the other tendons, and why are there not more rotator cuff tears related to a trauma? What we do know is that risk factors for rotator cuff tear include trauma, dominant arm, and age, whereas the effect of a large acromion is more ambiguous.     

Editorial Commentary: Monitoring Tendon and Muscle Recovery After Rotator Cuff Repair Using Diagnostic Ultrasound Demonstrates that Early Repair is Beneficial for Many Patients With Reparable Tears

Rotator cuff repair is performed to effect healing of the enthesis; to restore shoulder comfort, strength, and function; to prevent tear propagation; and to prevent progression of atrophic muscle changes (fatty degeneration, fatty infiltration, and fatty atrophy) that eventually occur. Non-retracted and moderately retracted rotator cuff tears usually heal after repair, and muscle atrophy may recover over time. It follows that early rotator cuff repair is beneficial for many patients with chronic but reparable rotator cuff tears. Diagnostic ultrasound can provide quantitative information about the recovery of both muscle and tendon and represents a viable alternative to magnetic resonance imaging for evaluating healing after rotator cuff repair.     

Lysophosphatidic acid‐induced RhoA signaling and prolonged macrophage infiltration worsens fibrosis and fatty infiltration following rotator cuff tears

Previous studies have suggested that macrophage‐mediated chronic inflammation is involved in the development of rotator cuff muscle atrophy and degeneration following massive tendon tears. Increased RhoA signaling has been reported in chronic muscle degeneration, such as muscular dystrophy. However, the role of RhoA signaling in macrophage infiltration and rotator muscle degeneration remains unknown. Using a previously established rat model of massive rotator cuff tears, we found RhoA signaling is upregulated in rotator cuff muscle following a massive tendon‐nerve injury. This increase in RhoA expression is greatly potentiated by the administration of a potent RhoA activator, lysophosphatidic acid (LPA), and is accompanied by increased TNFα and TGF‐β1 expression in rotator cuff muscle. Boosting RhoA signaling with LPA significantly worsened rotator cuff muscle atrophy, fibrosis, and fatty infiltration, accompanied with massive monocytic infiltration of rotator cuff muscles. Co‐staining of RhoA and the tissue macrophage marker CD68 showed that CD68+ tissue macrophages are the dominant cell source of increased RhoA signaling in rotator cuff muscles after tendon tears. Taken together, our findings suggest that LPA‐mediated RhoA signaling in injured muscle worsens the outcomes of atrophy, fibrosis, and fatty infiltration by increasing macrophage infiltraion in rotator cuff muscle. Clinically, inhibiting RhoA signaling may represent a future direction for developing new treatments to improve muscle quality following massive rotator cuff tears. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1539–1547, 2017.

     

Histologic evidence of degeneration at the insertion of 3 rotator cuff tendons: a comparative study with human cadaveric shoulders

We determined on histologic examination the degree of degeneration at the insertion of 3 rotator cuff tendons in 76 cadaveric shoulders, 17 of which had a partial tear of the supraspinatus. Fiber thinning, the presence of granulation tissue, and incomplete tearing of fibers, all evidence of degeneration, were quantified separately for each tendon. Among the shoulders that were intact on macroscopy, no significant difference in degeneration score could be found. In all 3 tendons degeneration was more prominent on the articular sides compared with the bursal sides (P < .0001). The degeneration score of partially torn supraspinatus was significantly higher than that of the intact tendons (P < .0001). The extent of granulation tissue, 1 criterion of degeneration, seemed to contribute mostly to this difference. Intrinsic degeneration occurred foremost in the articular side of the rotator cuff and might constitute the primary cause of rotator cuff tearing.     

Intermethod agreement and interobserver correlation of radiologic acromiohumeral distance measurements

The acromiohumeral distance (AHD) measured on conventional, true anteroposterior radiographs taken with the patient standing and the arm held in neutral rotation can predict the presence or absence of a large, chronic rotator cuff tears, and narrowing of the acromiohumeral distance can predict irreparability of rotator cuff tears. The relation between AHD measured on conventional radiographs and the integrity of the rotator cuff tendons is well known. Conversely, the correlation between the AHD on conventional radiographs and that measured on magnetic resonance imaging (MRI) or computed tomography (CT) scans is unknown. It has also not been determined which method correlates better with fatty infiltration of the rotator cuff muscles and might thereby be a better prognostic value for the outcome of rotator cuff repair. Conventional radiographs, plus MRI and or CT studies taken at the same time of patients with rotator cuff tears, shoulder instability, primary glenohumeral osteoarthritis, or idiopathic frozen shoulder, were randomly selected, and the AHD was measured both on conventional radiographs and on MRI or CT. The values were correlated with the stage of fatty degeneration of the rotator cuff muscles in the cases of rotator cuff tears. The AHD on conventional radiographs was larger than on MRI and CT, and correlation of the values measured (conventional radiography vs MRI and CT) could be demonstrated. For rotator cuff diseases, a significant but moderate correlation (r = 0.6; P < .05) between conventional and MRI was identified, and the conventional values were approximately 0.6 mm greater than the corresponding MRI values. It is, therefore, possible to use the AHD read on MRI or CT studies for prognostic reasons, provided the values obtained are converted accordingly and remembering that the correlation of the values is only moderate.     

Histological analysis of the coracoacromial arch: Correlation between age-related changes and rotator cuff tears

The purpose of this study was to analyze age-related changes in the coracoacromial arch and correlate these degenerative changes with rotator cuff tears. We obtained 80 shouldes from 40 cadavers. The mean age at death was 58.4 years. We performed a gross examination of the rotator cuff and the acromion and histological examination of the coracoacromial ligament. The statistical significance of any difference for each group considered was determined by Student's t-test. The rotator cuff was normal in 66 specimens; there was an articular-side partial tear in 4 cases, a bursal-side partial tear in 6 cases, and a full-thickness tear in 4 cases. Age was correlated with increasing incidence and severity of cuff tears. We noted age-related degenerative changes in the coracoacromial ligament, degeneration of the acromial bone-ligament junction, and acromial spur formation. Anterior acromial spur was not related to the morphology of the acromion. We observed an increased incidence of bursal-side and complete cuff tears when the acromion was curved or beaked. Degenerative changes in the undersurface of the acromion were also present when the rotator cuff was normal. Bursal-side and complete cuff tears were associated with severe degenerative changes in the acromion in 100% of cases. Articular-side cuff tears were not related either to acromial morphology or degenerative changes in the coracoacromial arch. The association between cuff tears and acromial spur was more evident in the presence of a type III acromion. Our results would suggest that the incidence and severity of rotator cuff tears are correlated with aging and with the morphology of the acromion. Rotator cuff tears that involve the bursal side are often associated with changes in the coracoacromial ligament and the undersurface of the acromion. However, degenerative changes in the coracoacromial arch are always related to aging, also in the presence of a normal rotator cuff. Articular-side partial tears do not cause damage to the undersurface of the acromion.     

Clinical and structural outcomes of nonoperative management of massive rotator cuff tears

BACKGROUND: The natural history of massive rotator cuff tears is not well known. The purpose of this study was to determine the clinical and structural mid-term outcomes in a series of nonoperatively managed massive rotator cuff tears. METHODS: Nineteen consecutive patients (twelve men and seven women; average age, sixty-four years) with a massive rotator cuff tear, documented by magnetic resonance imaging, were identified retrospectively. There were six complete tears of two rotator cuff tendons and thirteen complete tears of three rotator cuff tendons. All patients were managed exclusively with nonoperative means. Nonoperative management was chosen when a patient had low functional demands and relatively few symptoms and/or if he or she refused to have surgery. For the purpose of this study, patients were examined clinically and with standard radiographs and magnetic resonance imaging. RESULTS: After a mean duration of follow-up of forty-eight months, the mean relative Constant score was 83% and the mean subjective shoulder value was 68%. The score for pain averaged 11.5 points on a 0 to 15-point visual analogue scale in which 15 points represented no pain. The active range of motion did not change over time. Forward flexion and abduction averaged 136 degrees; external rotation, 39 degrees; and internal rotation, 66 degrees. Glenohumeral osteoarthritis progressed (p = 0.014), the acromiohumeral distance decreased (p = 0.005), the size of the tendon tear increased (p = 0.003), and fatty infiltration increased by approximately one stage in all three muscles (p = 0.001). Patients with a three-tendon tear showed more progression of osteoarthritis (p = 0.01) than did patients with a two-tendon tear. Four of the eight rotator cuff tears that were graded as reparable at the time of the diagnosis became irreparable at the time of final follow-up. CONCLUSIONS: Patients with a nonoperatively managed, moderately symptomatic massive rotator cuff tear can maintain satisfactory shoulder function for at least four years despite significant progression of degenerative structural joint changes. There is a risk of a reparable tear progressing to an irreparable tear within four years.     

Graft Augmentation of Repairable Rotator Cuff Tears: An Algorithmic Approach Based on Healing Rates

We provide our algorithm for tissue augmentation of rotator cuff repairs based on the current available evidence regarding rotator cuff healing. A variety of factors are associated with healing following rotator cuff repair. Increasing tear size and retraction as well as severe fatty degeneration have been associated with worsening rates of tendon healing. Given the correlation between tendon healing and postoperative outcomes, it is important to identify patients at high risk for failure and to modify their treatment accordingly to minimize the risk of early biomechanical failure and maximize the potential for structural healing. One approach that may be used to improve healing is tissue augmentation. Tissue augmentation is the use of tissue patches and scaffolds to provide rotator cuff reinforcement. Surgical management for rotator cuff tears (RCTs) continues to be a challenging task in orthopaedic surgery today. Appropriate treatment measures require an in depth understanding and consideration of the patient’s prognostic factors such as age, fatty infiltration of the rotator cuff muscles, bone mineral density, rotator cuff retraction, anteroposterior tear size, work activity, and degenerative changes of the joint. Using these factors within the Rotator Cuff Healing Index, we can determine a patient’s surgical treatment that will yield the maximum healing rate. For nonarthritic RCTs, joint-preserving strategies should be first-line treatment options. For young, active patients with a reparable RCT and minimal fatty infiltration, a complete repair can be effective. For young patients with irreparable RCTs, superior capsular reconstructions, and tendon transfers are viable options. For elderly patients with low work activity, an irreparable RCT and significant fatty infiltration, a partial repair with or without graft augmentation can be attempted if minimal to no arthritic changes are seen.Level of EvidenceLevel V, expert opinion.     

Matrix Metalloproteases 1 and 3 Promoter Gene Polymorphism Is Associated With Rotator Cuff Tear

Clinical Orthopaedics and Related Research® - Studies suggest that the collagen degeneration and disordered arrangement of collagen fibers in rotator cuff tears are associated with an increase...     

Association of Superoxide-Induced Oxidative Stress With Rotator Cuff Tears in Human Patients

Rotator cuff degeneration is one of the factors contributing to rotator cuff tears. Oxidative stress is involved in tendon degeneration, and superoxide-induced oxidative stress plays a pathological role in regulating the balance between oxidation and reduction. The role of oxidative stress in rotator cuff tears, however, is unclear. This study, therefore, aimed to investigate the contribution of superoxide-induced oxidative stress to rotator cuff tears. Seventy patients were recruited and divided into two groups: patients with (Ruptured group) and those without (Unruptured group) a rotator cuff tear. Specimens from both groups were collected during surgery. Degeneration morphology was classified according to the degeneration score. Superoxide-induced oxidative stress was assessed according to dihydroethidium (DHE) relative fluorescence intensity, capacity for antioxidation according to superoxide dismutase (SOD) activity, and the balance between oxidation and reduction based on the redox ratio. Data were compared between groups. Correlations between the degeneration score and the oxidative stress factors were calculated. Degeneration score and DHE relative fluorescence intensity were significantly higher in the Ruptured than the Unruptured group. The SOD activity was not significantly different between groups. Degeneration score was positively correlated with both DHE relative fluorescence intensity and SOD activity. Thus, superoxide-induced oxidative stress and tendon degeneration were greater in rotator cuff tear tissues than in those with no tear, suggesting that oxidative imbalance may be involved in degenerative rotator cuff tears. Clinical Relevance: Understanding the mechanisms of superoxide-induced oxidative stress may lead to targeted tissue therapy for degenerative rotator cuff tears. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:212–218, 2020     

Localised deposition of amyloid in tears of the rotator cuff

Age-related localised deposition of amyloid in connective tissue has been found in degenerative articular and periarticular tissue. Biopsies of the supraspinatus tendon of 28 patients undergoing repair of the rotator cuff were analysed histologically for the presence of localised deposition of amyloid. There was a long history of impingement in 20 patients, and eight patients had suffered an acute traumatic tear with no preceding symptoms. Localised deposition of amyloid identified by Congo Red staining was detected in 16 samples (57%). Amyloid was present in 14 (70%) of the degenerative tears, but in only two (25%) of the acute tears. Immunohistochemical staining showed that the amyloid deposits were positive for P component, but negative for kappa and lambda light chains, prealbumin, and beta2 microglobulin. Critical electrolyte staining revealed highly-sulphated glycosaminoglycans at sites of deposition of amyloid. The presence of localised deposition of amyloid in tears of the rotator cuff is likely to represent irreversible structural changes. These findings support the theory that impingement and tears are due to intrinsic degenerative changes within the tendons of the rotator cuff.     

Degenerative change and rotator cuff tears

Summary In order to determine the effects of friction and rubbing in the development of rotator cuff tear, we studied 160 shoulders of 80 cadavers (age at death 43–93 years, mean 69.3 years). Seventy-two cadavers were fixed with formalin and eight were fresh cadavers. The surface of the cuff and the undersurface of the acromion were observed macroscopically. Eight shoulders of fresh cadavers were examined by scanning electron microscopy. Ninety-eight specimens (61%) showed degenerative changes of the supraspinatus tendon. The number of tendons with degeneration and tear increased from the fifth to sixth decade of life, and the size of the tear increased with age. However, there was no sustained increase in the incidence with aging from the age of 60 to 90 years, and the percentage with degenerative changes of the cuff remained at approximately 60% in each decade. Ninety-six specimens (60%) showed degeneration of the subacromial surface. The percentage with degeneration of the undersurface of the acromion remained at approximately 60% from the sixth to ninth decade. There was a significant correlation between the severity of the changes in the rotator cuff and the subacromial surface. Scanning electron microscopy showed changes suggesting effects of friction and rubbing on the rotator cuff, such as regularly arranged wool-like spherical structures on the surface of the tendon and rounded ruptured ends of the tendon fibers. These results indicate that degenerative change of the rotator cuff is aggravated by a friction and rubbing mechanism with the undersurface of the acromion and leads to development of a complete tear.