Factors affecting the onset and progression of rotator cuff tears in the general population

While previous studies have revealed factors affecting the progression of rotator cuff tear (RCT), none have yet described factors affecting its onset. The purpose of this longitudinal observational study was to analyze factors affecting the RCT onset and progression in the general population. The present study included 185 shoulders from 93 participants who completed all the examinations in both 2012 and 2017. Participants received a questionnaire with age, gender, arm dominance, and presence of pain at rest, in motion, and at night. The range of motion (ROM), simple shoulder test (SST) were also examined. Anteroposterior radiograph of the shoulder joint was performed to evaluate the degree of osteoarthritic changes by the Samilson-Prieto (S-P) classification. The degree of RCT was examined by ultrasonography. There were 132 shoulders without RCT and 53 with RCT in 2012. RCT occurred in 21 of 132 shoulders, and the factor affecting the RCT onset was S-P grade 2 osteoarthritic change in 2012 (odds ratio [OR] 10.10). RCT progressed in 22 of 53 shoulders, and the factor affecting RCT progression was the presence of motion pain in 2012 (OR 13.76). These results added new knowledge regarding the natural course of RCT onset and progression.


Scientific Reports
| (2021) 11:1858 | https://doi.org/10.1038/s41598-020-79867-x www.nature.com/scientificreports/ Study protocol. Participants completed a questionnaire including hand dominance, profession, a visual analog scale (VAS) for pain, and the Simple Shoulder Test (SST). In this questionnaire, "profession" was divided into manual labor (e.g. farming, forestry, construction) and non-manual labor (e.g. office worker, clerk, housewife), and the participants evaluated their shoulder pain at rest, in motion, and at night. According to a previous study 13 , if the pain VAS was more than 35, the participants were considered to have pain. After the questionnaire had been completed, participants underwent a standardized measurement of the active range of motion (ROM) in flexion (Flex), abduction (Abd), and external rotation (ER). According to a previous study 14 , one trained orthopaedic surgeon performed standardized ultrasound examinations to determine the tear type (partialthickness or full-thickness) and the affected tendons (subscapularis [SSc], supraspinatus [SSP], infraspinatus [ISP]). The probe was applied at the lesser tuberosity (LT) and the superior and middle facet of the greater tuberosity (GT). The state and size of the RCT were evaluated as follows: no tear, partial-thickness SSP tear, fullthickness SSP tear, and SSP and ISP tears. The presence of SSc tear was independently evaluated. These tests were performed in both 2012 and 2017.

Radiographic analyses. A trained radiation technologist performed radiographs in an anteroposterior
glenoid view, and the image data were saved in the Digital Imaging and Communications in Medicine (DICOM) format. To achieve blinding from the evaluator, the image data were given another ID which is independent of the ID associated with the participant, and two independent observers (S.H and I. T) evaluated the image separately using the blinding ID. Each radiograph was graded using the Samilson and Prieto (S-P) classification of glenohumeral osteoarthritis 15 . This classification system grades shoulders for osteophyte formation as follows: 0, no osteophytes ( Fig. 1); 1, slight osteophyte (< 3 mm) formation (Fig. 2); 2, moderate osteophyte (3 to 7 mm) formation (Fig. 3); and 3, severe osteophyte (> 8 mm) formation with glenohumeral narrowing. As we showed in our previous study 16 , the interclass coefficient against intraclass reliability was 0.83, while that against intertester reliability was 0.80 in 2012. The data in 2017 were evaluated by the same method, and the interclass coefficient against intraclass reliability was 0.86, while that against intertester reliability was 0.82. After the reliability in 2017 was confirmed, the findings for 2012 and 2017 were combined and analyzed.
Statistical analyses. We divided the shoulders into two groups according to the presence of RCT in 2012 (with and without RCT). The differences between the groups in age, ROM, and SST score were analyzed by an independent t-test, and the gender difference, affected arm (dominant or non-dominant), manual labor, presence of pain (at rest, in motion, and at night), and S-P grade were analyzed by chi-squared test. Longitudinal changes in the ROM and the SST score were analyzed by a paired t-test, and the presence of pain, the presence of SSC tear, the size of RCT, and the S-P grade were analyzed by the

Results
One hundred and eighty-five shoulders were divided into those without RCT (n = 132) and with RCT (n = 53).
In 2012, the group of shoulders without RCT showed a significantly lower age, lower prevalence of dominant arm, higher ROM of flexion and abduction, and lower prevalence of pain at night than the group of shoulders with RCT (Table 1). Shoulders were divided into two groups according to the RCT status in 2012, and the ROM and S-P grade significantly deteriorated between 2012 and 2017 in both groups (Tables 2, 3). A post-hoc analysis of the McNemar-Bowker test revealed a significant difference in the change of the S-P grade from 0 to 1 (p < 0.01 in shoulders without RCT, p = 0.047 in shoulders with RCT). Furthermore, significant deterioration of the SST score and progression of RCT occurred in shoulders with RCT (Table 3). A post-hoc analysis revealed a significant difference in the change of RCT size from SSP to SSP and ISP (p < 0.01).
Among shoulders without RCT, RCT onset occurred in 21 of 132 shoulders (15.9%). Compared to the No change group, the Onset group showed significantly higher age, higher S-P grade in 2012 (Table 4). A post-hoc analysis revealed that the onset group had more S-P grade 2 shoulders than the no change group (p = 0.006). A stepwise logistic regression analysis revealed that S-P grade 2 in 2012 (odds ratio [OR] 10.10, 95% confidence interval [CI] 1.56-65.51) was an independent risk factor of RCT onset in 2017. www.nature.com/scientificreports/ Among shoulders with RCT, RCT progression occurred in 22 of 53 shoulders (41.5%). Compared to the No progression group, the RCT progression group showed a significantly lower ROM of abduction and external rotation, a higher prevalence of pain in motion in 2012 (Table 5). A stepwise logistic regression analysis revealed that the presence of pain in motion in 2012 (OR 13.76, 95% CI 1.49-126.85) was an independent risk factor of RCT progression in 2017.

Discussion
To our knowledge, the present study is the first longitudinal observational study to evaluate the risk factor of RCT onset or progression in the general population.
Previous studies have reported a high incidence of RCT in the elderly population and assumed that the age 1,2 , gender 3 , smoking 4,5 , and posture 6 were causes of RCT onset. However, since these studies lacked longitudinal observation, the actual risk factors of RCT onset have been unclear. The present study also showed that the age in 2012 was significantly higher in the group of shoulders with RCT than in the group without RCT. Furthermore, the subanalysis demonstrated that the age in 2012 was significantly higher in the Onset group than in the No change group and that osteoarthritic change in 2012 was more severe in the RCT onset group than those in the No change group. However, a logistic regression analysis demonstrated that moderate osteoarthritic change (S-P grade 2) was the only independent risk factor of RCT onset in shoulders without RCT.
Regarding the relationship between osteoarthritis (OA) of the shoulder joint and RCT, previous studies have shown that RCT can originate OA. RCT results in various bony changes, such as the formation of a subacromial spur in the early stage and acetabulization of the acromion, chondral defects, and loss of joint space in the late stage 17 . Regarding these degenerative changes associated with RCT, a previous study pointed out the influence of instability due to rotator cuff dysfunction 18 , and previous cadaveric studies have confirmed that the rotator cuff counterbalances the translation of the humeral head, even in simple motion [19][20][21] . In addition, a recent study reported that the progression of osteoarthritic changes in the shoulder joint with RCT, as evaluated by the S-P grade, was affected by the repaired cuff integrity 22 . However, repetitive instability in the shoulder joint without www.nature.com/scientificreports/ RCT also results in osteoarthritic changes, such as the formation of osteophytes 15 . Therefore, the presence of moderate osteoarthritic changes (S-P grade 2) without RCT in the present study may reflect existing rotator cuff dysfunction, and such dysfunction may result in repetitive minor damage to the rotator cuff and might be a risk factor for RCT onset. Previous studies have also reported a high incidence of RCT progression in asymptomatic and symptomatic shoulders with RCT 7-9,12,23,24 . In those reports, the rate of RCT progression defined as an increase in tear size exceeding 5 mm ranged from 11.6% to 69.9% at 20 to 61 months and a systematic review of Kwong et al. 12 showed that 40.6% of asymptomatic RCT cases had progressed during a mean follow-up period of 46.8 months compared with 34.1% of symptomatic RCT cases at 37.8 months. These results suggested that the rate of RCT progression is similar between asymptomatic and symptomatic RCT. The present study found that RCT progression occurred in 41.5% of 53 shoulders, and the rate of RCT progression in the present study was consistent with that in previous studies.
Regarding risk factors of RCT progression, previous studies reported that an older age 11,24 , the presence of a subacromial spur 11 , full-thickness tear [9][10][11]24 , middle-sized tear 10 , and smoking 10 were independent risk factors of RCT progression. Previous studies that included asymptomatic patients showed that RCT progression influenced new pain development [7][8][9] , while those that included symptomatic patients showed that the pain degree and prevalence did not change over time 10,11 . Since these studies included only symptomatic or asymptomatic patients and the definition of symptomatic and asymptomatic differed among studies, they were unable to clarify the effect of the detail and degree of shoulder pain on RCT progression. In contrast, the present study included all participants, regardless of the presence or absence of pain, and collected data on pain in different situations (at rest, in motion, and at night) with a clear definition (VAS > 35). As a result, the presence of pain in motion was found to be the only independent risk factor of RCT progression in shoulders with RCT. Since shoulder pain is suspected to arise from a combination of pathologies, such as impingement, and intra-articular inflammation, including synovitis or bursitis [25][26][27] , the determination of the cause of shoulder pain is a clinical challenge. Although the present study lacked data on the presence of impingement sign, our findings suggest that shoulder impingement itself or disturbance of the normal shoulder motion due to pain in motion exerted repetitive damage to the torn rotator cuff.
Several limitations associated with the present study warrant mention. First, since the participants in the present study consisted of voluntary participants only, there may be some potential selection bias. Second, the small number of participants and the lack of detailed background information such as ROM in IR, rheumatoid arthritis, sports level, smoking status or the presence of diabetes mellitus may have hidden potential risk factors for RCT progression. Third, since the present study included both shoulders from the same person, there may have been some potential bias. Fourth, since the present study evaluated the participants in 2012 and 2017, whether the RCT progressed within the first 1 or 2 years or progressed little by little over 5-years was unclear. Therefore, some of the risk factors in the present study may merely be associated with an acute progression. Further studies are therefore needed to clarify the risk factors influencing RCT progression in the general population.

Conclusion
In summary, the present study revealed that the shoulder ROM deteriorated regardless of the presence of RCT and that the state of osteoarthritic changes progressed. S-P grade 2 osteoarthritic change was an independent risk factor for RCT onset, and the presence of pain in motion was an independent risk factor for RCT progression in the next 5 years. These results add new knowledge regarding the natural course of RCT onset and progression. www.nature.com/scientificreports/ Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creat iveco mmons .org/licen ses/by/4.0/.