Risk Factors for Rotator Cuff Disease: An Experimental Study on Intact Human Subscapularis Tendons

Although several studies revealed a multifactorial pathogenesis of degenerative rotator cuff disorders, the impact and interaction of extrinsic variables is still poorly understood. Thus, this study aimed at uncovering the effect of patient- and pathology-specific risk factors that may contribute to degeneration of the rotator cuff tendons. Between 2015 and 2018, 54 patients who underwent arthroscopic shoulder surgery at three specialized shoulder clinics were prospectively included. Using tendon samples harvested from the macroscopically intact subscapularis (SSC) tendon, targeted messenger RNA expression profile analysis was performed in the first cohort (n = 38). Furthermore, histological analyses were conducted on tendon tissue samples obtained from a second cohort (n = 16). Overall, both study cohorts were comparable concerning patient demographics. Results were then analyzed with respect to specific extrinsic factors, such as patient age, body mass index, current as well as previous professions and sport activities, smoking habit, and systemic metabolic diseases. While patient age, sports-activity level, and preexisting rotator cuff lesions were considered to contribute most strongly to tendinopathogenesis, no further coherences were found. With regards to gene expression analysis, change in expression correlated most strongly with patient age and severity of the rotator cuff pathology. Further, chronic disorders increased overall gene expression variation. Taken together, our study provides further evidence that tendon degeneration is the consequence of a multifactorial process and pathological changes of the supraspinatus tendon affect the quality of SSC tendon and most likely vice versa. Therefore, the rotator cuff tendons need to be considered as a unit when managing rotator cuff pathologies. © 2019 The Authors. Journal of Orthopaedic Research^® published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society J Orthop Res 38:182–191, 2020     

Correlation between Severity of Synovitis and Clinical Features in Rotator Cuff Tears

BackgroundRotator cuff tears can be asymptomatic in some cases; however, even when the tear size is small, clinical symptoms can be very severe. This suggests that symptoms of rotator cuff tears are related to factors other than the size. Although synovitis has been cited as one of the factors, there is no grading system for synovitis in rotator cuff tears. Moreover, there are few studies that evaluated the relationship between synovitis and clinical features in patients with rotator cuff tears.MethodsPatients with medium-sized rotator cuff tears, who were scheduled for arthroscopic repair, were recruited for this study. The glenohumeral joint was divided into 4 quarters. Then, vascularity and hypertrophy of the joint were graded in each quarter using a modified scoring system. Clinical assessment was performed preoperatively and at 3 months and 6 months after surgery. Finally, correlation between the severity of synovitis and clinical features was analyzed.ResultsThe intraobserver correlation coefficient was 0.815 to 0.918 and the interobserver correlation coefficient was 0.779 to 0.992 for the single measurement. Vascularity was significantly correlated with the range of motion, strength, and constant score within 6 months after surgery. Hypertrophy was correlated with the range of motion within 6 months after surgery.ConclusionsSynovitis in the shoulder with rotator cuff tears can be graded by using our modified scoring system. The severity of synovitis was closely related to the clinical features after surgery. Therefore, when treating patients with rotator cuff tears, treatment of synovitis should also be considered.     

Aged Mice Demonstrate Greater Muscle Degeneration of Chronically Injured Rotator Cuff

Massive tears of the rotator cuff (RC) are often associated with progressive and irreversible muscle degeneration due to fibrosis, fatty infiltration, and muscle atrophy. RC tears are common in individuals older than 60 years and the repair of these tears is amongst the most prevalent of orthopedic procedures. However, most current models of this injury are established in young animals, which may not accurately recapitulate the clinical condition. In this study, we used a murine model of massive RC tears to evaluate age-related muscle degeneration following chronic injury. The expression of the fibro-adipogenic genes encoding collagen type III and leptin was higher in aged RC compared with matched injured young tissue at 2 weeks post-injury, and development of fibrosis was accelerated in aged mice within 5 days post-injury. Furthermore, the synthesis of collagens type I and III and fat tissue accumulation were significantly higher in injured RCs of aged mice. Similar frequency of fibro-adipogenic PDGFRβ⁺PDGFRα⁺ progenitor cells was measured in non-injured RC of aged and young mice, but PDGFRβ⁺PDGFRα⁺ cells contributed to significantly larger fibrotic lesions in aged RCs within 2 weeks post-injury, implying a more robust fibrotic environment in the aged injured muscle. Altogether, these findings demonstrate age-dependent differences in RC response to chronic injury with a more profound fibro-adipogenic change in aged muscles. Clinically, cell therapies for muscular pathologies should not only consider the cell type being transplanted but also the recipient milieu into which these cells are seeded. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:320-328, 2020     

Arthroscopic Intratendinous Repair of the Delaminated Partial-Thickness Rotator Cuff Tear in Overhead Athletes

A distinct type of partial-thickness rotator cuff tear has been observed in overhead athletes, characterized by partial failure of the undersurface of the posterior supraspinatus and anterior infraspinatus tendons with intratendinous delamination. We present a technique of percutaneous intratendinous repair using nonabsorbable mattress sutures designed for the management of articular-side delaminated partial-thickness tears. After tear evaluation and preparation, the torn rotator cuff undersurface is held in a reduced position with a grasper through an anterolateral rotator interval portal while viewing intra-articularly. Two spinal needles are then placed percutaneously through the full thickness of the torn and intact rotator cuff. A polydioxanone suture is passed through each needle, retrieved out the anterior portal, and used to shuttle a single nonabsorbable No. 2 suture through the tissue, creating a mattress suture. Multiple mattress sutures can be placed as dictated by tear size and morphology, with suture retrieval and knot securing then proceeding in the subacromial space. We have adopted this approach with the goals of anatomically re-establishing the rotator cuff insertion and sealing the area of intratendinous delamination while preventing significant alteration to the anatomy of the rotator cuff insertion, which could lead to motion deficits, internal impingement, and potential tear recurrence.     

Rotator Cuff Tear Susceptibility Is Associated With Variants in Genes Involved in Tendon Extracellular Matrix Homeostasis

Rotator cuff tears (RCT) is a multifactorial disease with genetic factors contributing for the disease etiology. We hypothesized that genetic variants in genes involved in extracellular matrix (ECM) homeostasis may alter susceptibility to RCT. We evaluated 20 polymorphisms of genes involved in ECM homeostasis in 211 cases of full-thickness tears of the supraspinatus (N_females = 130; N_males = 81) and 567 age-matched controls (N_females = 317; N_males = 250). Multivariate logistic regressions were carried out with age, gender, genetic ancestry (based on the analysis of 61 biallelic short insertion/deletion polymorphisms), and common co-morbidities (diabetes, dyslipidemia, and smoking habits) as covariates. We observed that carriers of the rare allele of both studied variants of TGFB1, as well as their G/A (rs1800470/rs1800469) haplotype, were less susceptible to RCT (p < 0.05). In contrast, carriers of the G allele of MMP9 rs17576 (p = 0.014) or G/G haplotype (rs17576/rs17577; p < 0.001) had an increased risk for tendon tears. The presence of the T allele of MMP2 rs2285053 (p = 0.033), the T allele of MMP3 rs679620 (p = 0.024), and the TT-genotype of TIMP2 rs2277698 (p = 0.01) was associated with susceptibility to tears, especially in females. In males, the A allele of COL5A1 rs3196378 (p = 0.032) and the G allele of TGFBR1 rs1590 (p = 0.039) were independent risk factors for RCT. The C/T COL5A1 (rs3196378/rs11103544) haplotype was associated with a reduced risk of tears in males (p = 0.03). In conclusion, we identified the genetic variants associated with RCT susceptibility, thereby reinforcing the role of genes involved in the structure and homeostasis of the ECM of tendons in disease development. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:192–201, 2020     

自体腘绳肌腱修复兔巨大肩袖缺损的实验研究

目的研究自体腘绳肌腱修复兔巨大肩袖缺损腱骨愈合的早期实验效果。方法将40只成年雄性新西兰大白兔随机分为3组,分别为正常组(n=8)、模型组(n=8)和实验组(n=24)。正常组相同方式饲养但不予手术处理;模型组将大白兔双前肢肱骨头大结节处切取1.5 cm×1.0 cm的肩袖组织缺损,不予缝合修补后直接缝合皮肤;实验组在模型组的基础上用自体腘绳肌腱修复巨大肩袖缺损。实验组分别于术后第8、16、24周时安乐死8只大白兔后取出双肩标本。将标本处理后分别进行组织形态学分析和生物力学研究测试。结果组织形态学分析结果显示:实验组术后24周腱骨界面胶原纤维明显增多,腱骨隧道连接处可见Sharpey纤维、纤维软骨细胞及纤维软骨等腱骨愈合成分。生物力学研究结果显示实验组肌腱最大负荷随时间延长呈持续增大趋势(各时间点之间比较,P<0.05),术后24周可以获得较强的力学强度。结论应用自体腘绳肌腱修复兔巨大肩袖缺损可以获得良好的腱骨愈合。     

MicroRNA Profiling Reveals Distinct Signatures in Degenerative Rotator Cuff Pathologies

MicroRNAs (miRNAs) have emerged as key regulators orchestrating a wide range of inflammatory and fibrotic diseases. However, the role of miRNAs in degenerative shoulder joint disorders is poorly understood. The aim of this explorative case-control study was to identify pathology-related, circulating miRNAs in patients with chronic rotator cuff tendinopathy and degenerative rotator cuff tears (RCT). In 2017, 15 patients were prospectively enrolled and assigned to three groups based on the diagnosed pathology: (i) no shoulder pathology, (ii) chronic rotator cuff tendinopathy, and (iii) degenerative RCTs. In total, 14 patients were included. Venous blood samples (“liquid biopsies”) were collected from each patient and serum levels of 187 miRNAs were determined. Subsequently, the change in expression of nine candidate miRNAs was verified in tendon biopsy samples, collected from patients who underwent arthroscopic shoulder surgery between 2015 and 2018. Overall, we identified several miRNAs to be progressively deregulated in sera from patients with either chronic rotator cuff tendinopathy or degenerative RCTs. Importantly, for the several of these miRNAs candidates repression was also evident in tendon biopsies harvested from patients who were treated for a supraspinatus tendon tear. As similar expression profiles were determined for tendon samples, the newly identified systemic miRNA signature has potential as novel diagnostic or prognostic biomarkers for degenerative rotator cuff pathologies. © 2019 The Authors. Journal of Orthopaedic Research^® published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. Inc. J Orthop Res 38:202–211, 2020     

Correlation between Rotator Cuff Tears and Repeated Subacromial Steroid Injections: A Case-Controlled Study

INTRODUCTION

Concern exists regarding potential damage to the rotator cuff from repeated corticosteroid injections into the subacromial space.

PATIENTS AND METHODS

In this retrospective, case-controlled study, 230 consecutive patients presenting to three orthopaedic units with subacromial impingement and investigated as an end-point with magnetic resonance imaging (MRI) of the shoulder were divided into groups having received less than three or three or more subacromial injections of corticosteroids.

RESULTS

With no significant difference in age and sex distribution, analysis by MRI showed no significant difference between the two groups in the incidence of rotator cuff tear (P < 1.0).

CONCLUSIONS

This suggests that corticosteroid use in patients with subacromial impingement should not be considered a causative factor in rotator cuff tears.