Is Muscle Weakness a Risk Factor of the Development of Rotator Cuff Tendinopathy – A Systematic Review

Underlying muscle weakness may explain the inconsistency in the development of rotator cuff tendinopathy in population with similar activity levels. This systematic review aims to assess existing prospective studies to evaluate whether muscle weakness is a risk factor to the development of rotator cuff tendinopathy. A systematic search was performed using the PRISMA guidelines. Prospective studies measuring muscle strength or stiffness and the incidence of rotator cuff tendinopathy will be included. Quality assessment was performed with the Newcastle-Ottawa Quality Assessment Scale. Results The search yielded 6 studies, with a total of 523 trained overhead athletes followed up for 1 season. External and internal rotation strength was described as protective factors for the development of rotator cuff tendinopathy, with an odds ratio of 0.940 (p < 0.05) and 0.946 (p < 0.01) respectively for each N/m increased in force generated. Limited range of motion of <106 o for shoulder external rotation was also described as a risk factor with an odds ratio of 1.12 (p < 0.001). Imbalance between external and internal rotation strength was reported as a risk factor for shoulder injuries in 2 studies, with a relative risk of 2.57 (p < 0.05) reported in 1 of them. Supraspinatus weakness was also reported as a risk factor for shoulder injuries in 1 study, with no odds ratio or relative risk provided. Due to insucient data, combination into a meta-analysis was not possible. supraspinatus with more groups, time, clearly

underlying muscle weakness.

Methods
Systemic search was carried out in PubMed, CINAHL, and Scopus from inception to May 13 th , 2020. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statements was used as guidelines in the performance of the systematic review. (20) Our study have been registered to the PROSPERO database, under the registration number CRD42020197927. The searched keywords are shown in Table I. Supplementary searches were carried out by hand searching the reference lists of the included studies. Muscle weak* Newcastle-Ottawa Quality Assessment Scale was used to assess the quality of included studies. Out of a full score of 9, studies scoring ≥7 indicates high methodological quality, 6 indicates intermediate quality, and ≤5 indicates low quality. The assessment of study quality was performed in a standardized manner independently by two reviewers (CKK, MCK). Disagreements were resolved by consensus between the 2 reviewers. A third reviewer (FSC) was available to resolve further disagreements. Intra-class correlation coe cient (ICC) 2-way mixed-effects analysis was calculated using SPSS Version 20 for Windows (SPSS Inc., Chicago, IL) to measure the inter-rater agreement between 2 reviewers for the quality assessment. 10 (n/a) 10 n/a n/a n/a ER ra motio

Studies included
The systematic search resulted in 13,789 studies, which 663 were suitable for abstract review. Results were further screened down to 12 studies for full text review. Six studies were included while the remainder were excluded as the entity of investigation was not rotator cuff tendinopathy, or prospective measurements of muscle weakness was not documented.
Six included studies prospectively documented muscle weakness or stiffness, and the incidence of rotator cuff tendinopathy in a total of 523 patients. 105 patients developed shoulder injuries during the follow-up period, of which 70 were diagnosed as rotator cuff tendinopathy. However, statistical association between muscle weakness or stiffness and the incidence of tendinopathy was only calculated in two out of the six studies (23,26). The other four demonstrated the association between muscle weakness or stiffness against shoulder injuries in general (21,22,24,25). The documentation of previous injuries were also inconsistent. Of the two studies which documented for previous injuries, 19 out of 24 cases of shoulder injuries had an injury history. All included studies had a follow-up period of 1 season, approximately 6 months depending on the schedule of speci c leagues. The studied population of all 6 studies were trained overhead athletes participating in either volleyball (23,24), baseball (25,26), or handball (21,22). Exact training load, in terms of hours per week, was not comparable due to inconsistent documentation among studies. Participants were free of shoulder pain at the beginning of studies, but other aspects of the past medical history were not documented. The diagnosis of tendinopathy also varied among the studies. Four studies did not provide the diagnostic criteria of rotator cuff tendinopathy (21,22,24,25), while 2 studies described the diagnosis to be made clinically and con rmed with radiological evidence. (23,26) Methodological quality assessment The results of quality assessment with the Newcastle-Ottawa Scale for Cohort Studies are included in Table II. Among 6 included studies, there were 4 of high methodological quality, and 2 with low quality. The criteria regarding the demonstration of an absence of the outcome of interest at the start of the study was not achieved in all included studies, as the absence of rotator cuff tendinopathy was only recorded from self-reporting questionnaires, without the support of clinical or radiological testing. The intra-class correlation coe cient for the inter-rater agreement between 2 reviewers was 0.960 (95% CI 0.733-0.994).
Studies reporting rotator cuff strength and stiffness as risk factors to the development of rotator cuff tendinopathy One included study discussed isometric internal and external rotation strength (IR & ER), with an isokinetic dynamometer, as a possible risk factor to the development of rotator cuff tendinopathy.
ER strength was described as a protective factor. An odds ratio of 0.940 (p < 0.05) for each 1 N/m increased in maximal force generated eccentrically at 60 o of shoulder abduction (23).
IR strength was also described as a protective factor. An odds ratio of 0.946 (p < 0.01) was reported for each N/m increased in maximal force generated eccentrically at 60 o of shoulder abduction (23) The signi cance of ER range of motion, hand measured with a goniometer, was reported in one study (26). An odds ratio of 1.12 (p < 0.001) was reported for a dominant arm ER range of < 106 o .
Due to insu cient number of studies, combination into a meta-analysis was not possible. The authors were contacted in request for necessary raw data for calculation, but no additional data were provided.

Studies reporting rotator cuff strength and stiffness as risk factors to the development of shoulder injuries
Five studies discussed isometric rotator cuff strength, with an isokinetic dynamometer, as a possible risk factor to the development of shoulder injuries, of which 70 out of 105 cases were diagnosed as rotator cuff tendinopathies.
On top of the studies mentioned in the previous paragraph, Imbalance between ER and IR strength was mentioned in two studies. However, the de nition for muscle imbalance varied. In one study, imbalance was de ned as a signi cant strength difference between IR and ER strength, with no relative risk or odds ratio provided. (24) In the other study, a cut off of < 69% of IR/ER ratio was adapted, and a relative risk of 2.57 (p < 0.05) was reported for athletes with muscle imbalance. (22) ER and supraspinatus weakness was reported in one study with no odds ratio or relative risk provided. (25) Due to insu cient number of studies, combination into a meta-analysis was not possible. The authors were contacted in request for necessary raw data for calculation, but no additional data were provided.

Discussion
According to our systematic search, IR weakness, ER weakness, and limited range of ER at the glenohumeral joint have been reported to be associated with the development of rotator cuff tendinopathy. Supraspinatus weakness and imbalance in IR/ER strength have also been reported as a risk factor in the development of shoulder injuries.
Limited evidence support that weakness and stiffness of the rotator cuff muscles are risk factors to the development of rotator cuff tendinopathy Our ndings showed the signi cance of pre-injury muscle strength and stiffness on the incidence of tendinopathy. The reported risk factors include weakness of the shoulder external rotators, weakness of the internal rotators, and a small range of motion for external rotation at the glenohumeral joint. It was demonstrated in previous studies that these muscle changes, in the absence of pain, may increase the risk of newly developing rotator cuff tendinopathies in the upcoming season.
Other risk factors such as a low IR/ER ratio and supraspinatus weakness were also mentioned in included studies. Although the signi cance of these factors were associated with shoulder injuries, rotator cuff tendinopathies make up 70 out of 105 total cases of shoulder injuries included. There is a possibility that the risk factors may also be valid for the development of rotator cuff tendinopathy, but the calculations were unfortunately not commenced in our included studies (22,24,25).
Risk factors were classi ed into ve evidence levels in a previous systematic review on rotator cuff tendinopathy. (27,28) Using the same method, evidence supporting that weakness and stiffness of rotator cuff muscles are risk factors to the development of rotator cuff tendinopathy could be classi ed as limited evidence. Very limited evidence support that a low IR/ER ratio and supraspinatus weakness are risk factors to the development of rotator cuff tendinopathy.
Hypothesis on how muscle weakness may lead to rotator cuff tendinopathy Tendon loading, in terms of tension or compression to the tendon, is one of the risk factors leading the development to tendinopathy. this suggestion is supported by previous in vitro studies, demonstrating that tension or compression of tendon cells will lead to apoptosis and increased expression of in ammatory markers.(5,6,29) As mentioned in the introduction, several mechanisms have been proposed by various groups to explain how muscle weakness may lead to increased loading. Strength in the rotator cuff muscles are crucial in counteracting the deltoid muscle, keeping the humeral head adhered to the glenoid.(8) with weakened or fatigued rotator cuff muscles, humeral head elevation may occur, decreasing the size of sub-acromial space, leading to compression of the supraspinatus tendon.(9,10) Another possible mechanism was described in a previous study suggesting that IR and ER strength is crucial for the deceleration of arm swinging movements. (11) It was illustrated that the requirement for ER strength is increased to effectively decelerate an arm from forceful IR. Imbalance in athletes with repetitive arm swings is hypothesized lead to strains and tears to the tendon. (12) Muscle weakness may not be an isolated problem Associated factors such as muscle stiffness posture, and movement patterns may provide more insights on the causes of muscle weakness, as well as a direction on how to effectively correct it. Unfortunately, it was demonstrated in our systematic search that the association of these factors to the development of rotator cuff tendinopathy is under-investigated, with only one existing study discussing the signi cance of shoulder range of motion to the development of rotator cuff tendinopathy. (26) This study demonstrated that limited ER range of the shoulder is associated with the development of rotator cuff tendinopathy.
Unfortunately, whether range of motion was active or passively measured was not described. This piece of information suggests a cause of the underlying muscle weakness. Limited range in ER may imply stiffness of internal rotators such as pectoralis major, teres major, and subscapularis, latissimus dorsi, and deltoid muscles. Considering the concept of reciprocal inhibition, tightness in this muscle group would lead to weakness in ER muscles, which is also consistent with our result demonstrating that a weakened ER compared with IR strength is associated with the development of rotator cuff tendinopathy. (8) This nding provide evidence that muscle weakness is not the only muscle change which may lead to the development of rotator cuff tendinopathy.
Could the history of a previous injury be a confounding factor As shown in Table 1, the history of previous injuries were inconsistently recorded in the included studies. Of the two studies which documented for injury history, 19 out of 24 cases of shoulder injury also had a history of previous shoulder injury. However, current evidence is inconclusive whether the history of a previous shoulder injury may act as a confounding factor between rotator cuff weakness and the development of rotator cuff tendinopathies.
Rotator cuff tendinopathies are described to be persistent and recurring.(30) However, A previous systematic review on the risk factors on the development of rotator cuff tendinopathy have not been able to identify existing studies on whether a previous injury history is a risk factor to the development of future rotator cuff tendinopathies. (27) Also, rotator cuff tendinopathies are well known to present as shoulder weakness (31), but little is known on whether a previous injury would lead to residual weaknesses.
One of our included studies have attempted to address this issue. (21) According to this study, 47% of 108 athletes were documented for previous shoulder injury. However, it was shown in the study that previous injury was not a signi cant risk factor to development of new injury (p=0.28). There were also no signi cant difference in isokinetic results between players with and without previous injuries (p>0.05) (21). The signi cance of previous injuries were not assessed in the other included studies.

Clinical relevance
Rotator cuff tendinopathy affects a huge population, leading to disability and heavy socioeconomical impacts. (3) The results from this study provided an insight on how we may attempt to decrease such burden via primary prevention. It was demonstrated that not only in absolute strength, but imbalance in external and IR strength of the shoulder may contribute to the development of rotator cuff tendinopathy. Therefore, screening programs can be conducted in high risk groups, such as athletes competing in overhead sports, to identify individuals who are at a further high risk of the development of rotator cuff tendinopathy, and indicated for correction of muscle imbalance. There is a possibility that correction of muscle imbalance in existing cases of tendinopathy may also improve symptom control by modifying mechanical load to the tendon. However, its effectiveness on symptom control is yet to be investigated.
Regarding the method to correct muscle imbalance, it is to be acknowledged that a successful protocol would include, but is not limited to training of the weakened muscle. As mentioned in previous sections, muscle tightness would lead to reciprocal inhibition of the antagonist muscle. Attempts to relief muscle stiffness may augment the effectiveness of training to restore muscle imbalances. This provides a rationale to some existing treatments to tendinopathy, including eccentric exercises to train weak muscles, soft tissue release to relax tightened muscles. Systematic reviews on the effectiveness of these treatments alone have shown promising but inconclusive results on symptom relief of tendinopathy. (14,32,33) However, the effectiveness of combined treatment of muscle relaxation followed by training have not been investigated in rotator cuff tendinopathies, which opens a direction of future clinical trials.

Limitations
All included cohort studies recruited patients in the athletic population. Therefore, the signi cance of muscle imbalance on the development of rotator cuff tendinopathy in the general public is currently unclear.
Rotator cuff tendinopathy observed in the included studies also presented in a rather sub-acute manner, developing in one season time. In comparison, tendinopathy in the general public is more known as a chronic degenerative disease with failed healing.(4) One explanation can be that weakness in the rotator cuff leads to an unfavorable mechanical environment, causing subclinical microtraumas chronically. Tendinitis would then develop as an acute on chronic condition from triggers such as an intense competitive season.
This hypothesis is particularly relevant as participants in the included cohort studies were painless at the beginning of follow-up, but no con rmatory imaging tests were done to con rm the absence of tendinopathy. Muscle weakness or stiffness could therefore be a result of adaptation to painless cases of tendinopathy, which its existence was previously described in an MRI study. (34) The diagnostic criteria of rotator cuff tendinopathy was also not clearly documented in several included studies (21,22,24,25), providing a potential source of inconsistency.
Athletes in the included studies also varied in age, gender, and sports participated. These factors may explain the inconsistencies between the results of our included studies.

Future study
With a goal to develop screening programs and lower injury risk, future studies could be directed in three steps. To further investigate and provide more details on the pro le of muscle weaknesses that may lead to rotator cuff tendinopathy, to investigate on the most effective method to correct muscle weakness, and at last to investigate whether correction of muscle weakness would lead to a decrease in injury risk.
Unfortunately, existing evidence is still far from achieving step one. The signi cance of muscle weakness or stiffness have only been investigated on rotator cuff muscles, while there have been hypothesis that muscles of the spine, chest, and back may also have an impact on shoulder injuries. (35) Results from this review have also pointed out several limitations on the existing cohort studies, and that a future cohort could further improve on the existing evidence with a longer follow-up time, clearly documented injury history, and a stringent diagnosis to rotator cuff tendinopathy.
Prospective investigations on muscle stiffness, posture, and movement patterns may also be fruitful, as it may provide a cause to the existing muscle imbalance, as well as provide an insight on how this problem could be more effectively corrected.

Conclusions
Limited evidence support that weakness of the external rotators, weakness in the internal rotators, and limited range of motion in external rotation are risk factors to the development of rotator cuff tendinopathy. Very limited evidence support that imbalance in external rotator and internal rotator strength, and supraspinatus weakness are risk factors for rotator cuff tendinopathies. Existing evidence on whether muscle weakness is a risk factor to the development of rotator cuff tendinopathy is limited, despite having great potentials in providing insights on the development of screening programs to lower the risk of this disease. Future cohort studies may improve on existing evidence with investigations on more muscle groups, a longer follow-up time, clearly documented injury history, and a stringent diagnosis to rotator cuff tendinopathy.
Abbreviations IR: Internal rotation; ER: External rotation; ICC: Intra-class correlation coe cient; PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses