Mechanisms of rotator cuff tendinopathy: Intrinsic, extrinsic, or both?

Published:September 16, 2010DOI://doi.org/10.1016/j.clinbiomech.2010.08.001

      Abstract

      The etiology of rotator cuff tendinopathy is multi-factorial, and has been attributed to both extrinsic and intrinsic mechanisms. Extrinsic factors that encroach upon the subacromial space and contribute to bursal side compression of the rotator cuff tendons include anatomical variants of the acromion, alterations in scapular or humeral kinematics, postural abnormalities, rotator cuff and scapular muscle performance deficits, and decreased extensibility of pectoralis minor or posterior shoulder. A unique extrinsic mechanism, internal impingement, is attributed to compression of the posterior articular surface of the tendons between the humeral head and glenoid and is not related to subacromial space narrowing. Intrinsic factors that contribute to rotator cuff tendon degradation with tensile/shear overload include alterations in biology, mechanical properties, morphology, and vascularity. The varied nature of these mechanisms indicates that rotator cuff tendinopathy is not a homogenous entity, and thus may require different treatment interventions. Treatment aimed at addressing mechanistic factors appears to be beneficial for patients with rotator cuff tendinopathy, however, not for all patients. Classification of rotator cuff tendinopathy into subgroups based on underlying mechanism may improve treatment outcomes.

      Keywords

      Disorders of the rotator cuff (RC) or associated tissues are the most common problem of the shoulder (
      • Chard M.D.
      • Hazleman R.
      • Hazleman B.L.
      • King R.H.
      • Reiss B.B.
      Shoulder disorders in the elderly: a community survey.
      ,
      • van der Windt D.A.
      • Koes B.W.
      • de Jong B.A.
      • Bouter L.M.
      Shoulder disorders in general practice: incidence, patient characteristics, and management.
      ,
      • Vecchio P.
      • Kavanagh R.
      • Hazleman B.L.
      • King R.H.
      Shoulder pain in a community-based rheumatology clinic.
      ). The prevalence of RC disease, specifically partial and full thickness RC tendon tears, has been shown to increase as a function of age starting at 40 years (
      • Iannotti J.P.
      • Zlatkin M.B.
      • Esterhai J.L.
      • Kressel H.Y.
      • Dalinka M.K.
      • Spindler K.P.
      Magnetic resonance imaging of the shoulder. Sensitivity, specificity, and predictive value.
      ,
      • Milgrom C.
      • Schaffler M.
      • Gilbert S.
      • van Holsbeeck M.
      Rotator-cuff changes in asymptomatic adults. The effect of age, hand dominance and gender.
      ,
      • Sher J.S.
      • Uribe J.W.
      • Posada A.
      • Murphy B.J.
      • Zlatkin M.B.
      Abnormal findings on magnetic resonance images of asymptomatic shoulders.
      ,
      • Tempelhof S.
      • Rupp S.
      • Seil R.
      Age-related prevalence of rotator cuff tears in asymptomatic shoulders.
      ), and to exceed as much as 50% by the age of 60 years (
      • Milgrom C.
      • Schaffler M.
      • Gilbert S.
      • van Holsbeeck M.
      Rotator-cuff changes in asymptomatic adults. The effect of age, hand dominance and gender.
      ,
      • Sher J.S.
      • Uribe J.W.
      • Posada A.
      • Murphy B.J.
      • Zlatkin M.B.
      Abnormal findings on magnetic resonance images of asymptomatic shoulders.
      ) Furthermore, RC disease contributes to pain and disability (
      • Bartolozzi A.
      • Andreychik D.
      • Ahmad S.
      Determinants of outcome in the treatment of rotator cuff disease.
      ,
      • Duckworth D.G.
      • Smith K.L.
      • Campbell B.
      • Matsen F.A.
      Self-assessment questionnaires document substantial variability in the clinical expression of rotator cuff tears.
      ,
      • MacDermid J.C.
      • Ramos J.
      • Drosdowech D.
      • Faber K.
      • Patterson S.
      The impact of rotator cuff pathology on isometric and isokinetic strength, function, and quality of life.
      ,
      • Smith K.L.
      • Harryman D.T.
      • Antoniou J.
      • Campbell B.
      • Sidles J.A.
      • Matsen III, F.A.
      A prospective, multipractice study of shoulder function and health status in patients with documented rotator cuff tears [in process citation].
      ), and has an impact on health-related quality of life (
      • MacDermid J.C.
      • Ramos J.
      • Drosdowech D.
      • Faber K.
      • Patterson S.
      The impact of rotator cuff pathology on isometric and isokinetic strength, function, and quality of life.
      ). Randomized trials suggest that the short and long-term outcomes of patients with RC tendinopathy treated with surgery are comparable to conservative treatment that includes exercise or exercise combined with a multimodal rehabilitation program (
      • Brox J.I.
      • Staff P.H.
      • Ljunggren A.E.
      • Brevik J.I.
      Arthroscopic surgery compared with supervised exercises in patients with rotator cuff disease (stage II impingement syndrome).
      ,
      • Brox J.I.
      • Gjengedal E.
      • Uppheim G.
      • Bohmer A.S.
      • Brevik J.I.
      • Ljunggren A.E.
      • et al.
      Arthroscopic surgery versus supervised exercises in patients with rotator cuff disease (stage II impingement syndrome): a prospective, randomized, controlled study in 125 patients with a 2 1/2-year follow-up.
      ,
      • Haahr J.P.
      • Andersen J.H.
      Exercises may be as efficient as subacromial decompression in patients with subacromial stage II impingement: 4–8-years' follow-up in a prospective, randomized study.
      ,
      • Haahr J.P.
      • Ostergaard S.
      • Dalsgaard J.
      • Norup K.
      • Frost P.
      • Lausen S.
      • et al.
      Exercises versus arthroscopic decompression in patients with subacromial impingement: a randomised, controlled study in 90 cases with a one year follow up.
      ). However, regardless of treatment, more than a third of patients do not have a successful outcome with continued persistent pain and disability (
      • Brox J.I.
      • Staff P.H.
      • Ljunggren A.E.
      • Brevik J.I.
      Arthroscopic surgery compared with supervised exercises in patients with rotator cuff disease (stage II impingement syndrome).
      ,
      • Brox J.I.
      • Gjengedal E.
      • Uppheim G.
      • Bohmer A.S.
      • Brevik J.I.
      • Ljunggren A.E.
      • et al.
      Arthroscopic surgery versus supervised exercises in patients with rotator cuff disease (stage II impingement syndrome): a prospective, randomized, controlled study in 125 patients with a 2 1/2-year follow-up.
      ). Given the high prevalence and continued pain despite treatment in patients with RC disease, research to better understand the mechanisms to improve effectiveness of treatment, guide specific treatment choices, and better prognosticate treatment outcomes is necessary.
      RC disease has been classically described as a progressive disorder of the RC tendons which begins with an acute tendinitis, progresses to tendinosis with degeneration and partial thickness tears, and results in full thickness rupture (
      • Neer C.S.
      Impingement lesions.
      ). The diagnostic terms of RC tendinitis and tendinosis represent tendon pathology subsets of RC tendinopathy. RC tendinitis is often used to define both acute and chronic pain associated with, by definition, inflammation. However, histological studies of patients with RC disease have found minimal to no inflammatory cells in the RC tendons (
      • Fukuda H.
      • Hamada K.
      • Yamanaka K.
      Pathology and pathogenesis of bursal-side rotator cuff tears viewed from en bloc histologic sections.
      ) and subacromial bursa (
      • Sarkar K.
      • Uhthoff H.K.
      Ultrastructure of the subacromial bursa in painful shoulder syndromes.
      ). Tendinosis is the diagnostic label for tendon pathology that is degenerative with or without inflammation. In contrast, RC tendinopathy is used to signify a combination of pain and impaired performance associated with RC tendons (
      • Alfredson H.
      Chronic midportion Achilles tendinopathy: an update on research and treatment.
      ,
      • Alfredson H.
      The chronic painful Achilles and patellar tendon: research on basic biology and treatment.
      ). Tendinopathy is a preferred term, to indicate a clinical diagnosis without knowing the specific underlying mechanism or tendon pathology (
      • Almekinders L.C.
      Tendinitis and other chronic tendinopathies.
      ,
      • Fredberg U.
      • Stengaard-Pedersen K.
      Chronic tendinopathy tissue pathology, pain mechanisms, and etiology with a special focus on inflammation.
      ). The focus of this review is RC tendinopathy which includes external or internal impingement, tendinitis, tendinosis with degeneration and partial thickness tendon tears. Full thickness tendon tears are unique and beyond the scope of this review.
      Mechanisms of RC tendinopathy have been classically described as extrinsic, intrinsic or a combination of both. Extrinsic factors are defined as those causing compression of the RC tendons, while intrinsic mechanisms are those associated with degeneration of the RC tendon. Neer proposed an extrinsic mechanism to the etiology RC tendinopathy with compression of the RC tendons and associated tissues within the subacromial space under the anterior aspect of the acromion or surrounding structures (
      • Neer C.S.
      Anterior acromioplasty for the chronic impingement syndrome in the shoulder: a preliminary report.
      ) and coined this subacromial impingement syndrome (
      • Neer C.S.
      Impingement lesions.
      ). The diagnosis of “subacromial impingement” inherently implies an extrinsic compression mechanism due to narrowing of the subacromial space, which may not accurately represent all RC tendon pathology. A unique extrinsic mechanism, internal impingement, has been described particularly in overhead athletes (
      • Burkhart S.S.
      • Morgan C.D.
      • Kibler W.B.
      The disabled throwing shoulder: spectrum of pathology Part III: the SICK scapula, scapular dyskinesis, the kinetic chain, and rehabilitation.
      ,
      • Jobe C.M.
      Posterior superior glenoid impingement: expanded spectrum.
      ,
      • Kibler W.B.
      The role of the scapula in athletic shoulder function.
      ,
      • Kvitne R.S.
      • Jobe F.W.
      The diagnosis and treatment of anterior instability in the throwing athlete.
      ). Internal impingement occurs due to compression of the articular side rather than the bursal side of the RC tendons, between the posterior superior glenoid rim and humerus when the arm is in full external rotation, abduction, and extension (
      • Davidson P.A.
      • Elattrache N.S.
      • Jobe C.M.
      • Jobe F.W.
      Rotator cuff and posterior–superior glenoid labrum injury associated with increased glenohumeral motion: a new site of impingement.
      ,
      • Edelson G.
      • Teitz C.
      Internal impingement in the shoulder.
      ). Although internal impingement can be considered an extrinsic mechanism, narrowing of the subacromial space is not a hallmark finding. In contrast to extrinsic mechanisms of RC tendinopathy, Codman postulated an intrinsic mechanism due to degeneration within the tendon (
      • Codman E.A.
      • Akerson I.B.
      The pathology associated with rupture of the supraspinatus tendon.
      ), confounded by aging (
      • Iannotti J.P.
      • Zlatkin M.B.
      • Esterhai J.L.
      • Kressel H.Y.
      • Dalinka M.K.
      • Spindler K.P.
      Magnetic resonance imaging of the shoulder. Sensitivity, specificity, and predictive value.
      ,
      • Milgrom C.
      • Schaffler M.
      • Gilbert S.
      • van Holsbeeck M.
      Rotator-cuff changes in asymptomatic adults. The effect of age, hand dominance and gender.
      ,
      • Sher J.S.
      • Uribe J.W.
      • Posada A.
      • Murphy B.J.
      • Zlatkin M.B.
      Abnormal findings on magnetic resonance images of asymptomatic shoulders.
      ,
      • Tempelhof S.
      • Rupp S.
      • Seil R.
      Age-related prevalence of rotator cuff tears in asymptomatic shoulders.
      ). Fig. 1 illustrates the mechanisms and the relationships of the varied mechanisms of RC tendinopathy. Despite the debate over the pathogenesis, evidence indicates that the etiology of RC tendinopathy is multi-factorial and likely both intrinsic and extrinsic mechanisms play a role (Table 1).
      Figure thumbnail gr1
      Fig. 1Extrinsic and intrinsic mechanisms of rotator cuff tendinopathy. Lines indicate non-directional evidence of these relationships.
      Table 1Rotator cuff pathological mechanisms.
      Distinguishing featuresIntrinsicExtrinsicExtrinsic-internal impingement
      Conceptual mechanismDegeneration of the tendon where tensile loading exceeds the tendon's intrinsic healing and adaptive responsesCompression of the tendon within the subacromial space from anatomical or biomechanical abnormalitiesCompression of the tendon posteriorly between the humerus and glenoid rim
      PathologyIntratendinous and articular-sided tendon pathology without coracoacromial abnormalitiesBursal-sided tendon pathology with coracoacromial abnormalities more commonArticular-sided pathology without coracoacromial abnormalities. May be related to glenohumeral joint instability.

      1. Extrinsic mechanisms of rotator cuff tendinopathy

      Extrinsic mechanisms of RC tendinopathy that result in bursal-sided RC tendon compression due to narrowing of the subacromial space include anatomical factors, biomechanical factors, or a combination. The subacromial space is the interval between the coracoacromial arch, anterior acromion and the humeral head (
      • Neer C.S.
      • Poppen N.K.
      Supraspinatus outlet [Abstract].
      ). The acromiohumeral distance (AHD), a linear measure between the acromion and the humeral head used to quantify the subacromial space, has been studied in patients with RC disease using magnetic resonance imaging (MRI) (
      • Graichen H.
      • Bonel H.
      • Stammberger T.
      • Haubner M.
      • Rohrer H.
      • Englmeier K.H.
      • et al.
      Three-dimensional analysis of the width of the subacromial space in healthy subjects and patients with impingement syndrome.
      ,
      • Hebert L.J.
      • Moffet H.
      • Dufour M.
      • Moisan C.
      Acromiohumeral distance in a seated position in persons with impingement syndrome.
      ,
      • Saupe N.
      • Pfirrmann C.W.A.
      • Schmid M.R.
      • Jost B.
      • Werner C.M.L.
      • Zanetti M.
      Association between rotator cuff abnormalities and reduced acromiohumeral distance.
      ), ultrasonography (
      • Azzoni R.
      • Cabitza P.
      Sonographic versus radiographic measurement of the subacromial space width.
      ,
      • Azzoni R.
      • Cabitza P.
      • Parrini M.
      Sonographic evaluation of subacromial space.
      ,
      • Cholewinski J.J.
      • Kusz D.J.
      • Wojciechowski P.
      • Cielinski L.S.
      • Zoladz M.P.
      Ultrasound measurement of rotator cuff thickness and acromio-humeral distance in the diagnosis of subacromial impingement syndrome of the shoulder.
      ,
      • Desmeules F.
      • Minville L.
      • Riederer B.
      • Cote C.H.
      • Fremont P.
      Acromio-humeral distance variation measured by ultrasonography and its association with the outcome of rehabilitation for shoulder impingement syndrome.
      ) and radiographs (
      • Norwood L.A.
      • Barrack R.
      • Jacobson K.E.
      Clinical presentation of complete tears of the rotator cuff.
      ,
      • Nove-Josserand L.
      • Edwards T.B.
      • O'Connor D.P.
      • Walch G.
      The acromiohumeral and coracohumeral intervals are abnormal in rotator cuff tears with muscular fatty degeneration.
      ,
      • Petersson C.J.
      • Redlund-Johnell I.
      The subacromial space in normal shoulder radiographs.
      ,
      • Saupe N.
      • Pfirrmann C.W.A.
      • Schmid M.R.
      • Jost B.
      • Werner C.M.L.
      • Zanetti M.
      Association between rotator cuff abnormalities and reduced acromiohumeral distance.
      ,
      • Weiner D.S.
      • Macnab I.
      Superior migration of the humeral head. A radiological aid in the diagnosis of tears of the rotator cuff.
      ). AHD is normally between 7 and 14 mm in healthy shoulders, but is reduced in those with RC tendon tears (
      • Azzoni R.
      • Cabitza P.
      Sonographic versus radiographic measurement of the subacromial space width.
      ,
      • Azzoni R.
      • Cabitza P.
      • Parrini M.
      Sonographic evaluation of subacromial space.
      ,
      • Ellman H.
      • Hanker G.
      • Bayer M.
      Repair of the rotator cuff. End-result study of factors influencing reconstruction.
      ,
      • Golding F.C.
      The shoulder—the forgotten joint.
      ,
      • Weiner D.S.
      • Macnab I.
      Superior migration of the humeral head. A radiological aid in the diagnosis of tears of the rotator cuff.
      ). Furthermore, AHD less than 7 mm with the arm at rest is a predictor indicator of less favorable surgical outcome (
      • Ellman H.
      • Hanker G.
      • Bayer M.
      Repair of the rotator cuff. End-result study of factors influencing reconstruction.
      ,
      • Norwood L.A.
      • Barrack R.
      • Jacobson K.E.
      Clinical presentation of complete tears of the rotator cuff.
      ,
      • Walch G.
      • Marechal E.
      • Maupas J.
      • Liotard J.P.
      Surgical treatment of rotator cuff rupture. Prognostic factors.
      ,
      • Weiner D.S.
      • Macnab I.
      Superior migration of the humeral head. A radiological aid in the diagnosis of tears of the rotator cuff.
      ). However, patients with RC tendinopathy do not consistently present with significant deficits in subacromial space narrowing with the arm at rest (
      • Azzoni R.
      • Cabitza P.
      Sonographic versus radiographic measurement of the subacromial space width.
      ,
      • Desmeules F.
      • Minville L.
      • Riederer B.
      • Cote C.H.
      • Fremont P.
      Acromio-humeral distance variation measured by ultrasonography and its association with the outcome of rehabilitation for shoulder impingement syndrome.
      ). Only measures of subacromial space taken with muscle activation are useful to detect deficits related to biomechanical factors that “functionally” narrow the subacromial space (
      • Graichen H.
      • Bonel H.
      • Stammberger T.
      • Haubner M.
      • Rohrer H.
      • Englmeier K.H.
      • et al.
      Three-dimensional analysis of the width of the subacromial space in healthy subjects and patients with impingement syndrome.
      ). In a series of MRI studies, AHD during active arm elevation was smaller in subjects with RC tendinopathy compared to healthy shoulders (
      • Allmann K.H.
      • Uhl M.
      • Gufler H.
      • Biebow N.
      • Hauer M.P.
      • Kotter E.
      • et al.
      Cine-MR imaging of the shoulder.
      ,
      • Graichen H.
      • Bonel H.
      • Stammberger T.
      • Haubner M.
      • Rohrer H.
      • Englmeier K.H.
      • et al.
      Three-dimensional analysis of the width of the subacromial space in healthy subjects and patients with impingement syndrome.
      ,
      • Hebert L.J.
      • Moffet H.
      • Dufour M.
      • Moisan C.
      Acromiohumeral distance in a seated position in persons with impingement syndrome.
      ). Limited evidence suggests that changes in the subacromial space linear distance or extent of narrowing with arm elevation is a sensitive marker of RC tendinopathy (
      • Cholewinski J.J.
      • Kusz D.J.
      • Wojciechowski P.
      • Cielinski L.S.
      • Zoladz M.P.
      Ultrasound measurement of rotator cuff thickness and acromio-humeral distance in the diagnosis of subacromial impingement syndrome of the shoulder.
      ), and may predict the outcome of rehabilitation (
      • Desmeules F.
      • Minville L.
      • Riederer B.
      • Cote C.H.
      • Fremont P.
      Acromio-humeral distance variation measured by ultrasonography and its association with the outcome of rehabilitation for shoulder impingement syndrome.
      ). Further research that examines changes in subacromial space with active arm elevation in patients with RC tendinopathy is advocated and may be useful to identify the presence of an extrinsic mechanism influencing the articular side of the RC tendons.

      1.1 Anatomical factors

      Anatomical factors that may excessively narrow the subacromial space and outlet to the RC tendons include variations in shape of the acromion (
      • Bigliani L.U.
      • Ticker J.B.
      • Flatow E.L.
      • Soslowsky L.J.
      • Mow V.C.
      The relationship of acromial architecture to rotator cuff disease.
      ,
      • Epstein R.E.
      • Schweitzer M.E.
      • Frieman B.G.
      • Fenlin Jr., J.M.
      • Mitchell D.G.
      Hooked acromion: prevalence on MR images of painful shoulders.
      ,
      • Gill T.J.
      • McIrvin E.
      • Kocher M.S.
      • Homa K.
      • Mair S.D.
      • Hawkins R.J.
      The relative importance of acromial morphology and age with respect to rotator cuff pathology.
      ,
      • Ogawa K.
      • Yoshida A.
      • Inokuchi W.
      • Naniwa T.
      Acromial spur: relationship to aging and morphologic changes in the rotator cuff.
      ), orientation of the slope/angle of the acromion (
      • Aoki M.
      • Ishii S.
      • Usui M.
      The slope of the acromion and rotator cuff impingement.
      ,
      • Edelson J.G.
      The ‘hooked’ acromion revisited.
      ,
      • Toivonen D.A.
      • Tuite M.J.
      • Orwin J.F.
      Acromial structure and tears of the rotator cuff.
      ,
      • Vaz S.
      • Soyer J.
      • Pries P.
      • Clarac J.P.
      Subacromial impingement: influence of coracoacromial arch geometry on shoulder function.
      ) or prominent osseous changes to the inferior aspect of the acromio-clavicular (AC) joint or coracoacromial ligament (
      • Farley T.E.
      • Neumann C.H.
      • Steinbach L.S.
      • Petersen S.A.
      The coracoacromial arch: MR evaluation and correlation with rotator cuff pathology.
      ,
      • Nicholson G.P.
      • Goodman D.A.
      • Flatow E.L.
      • Bigliani L.U.
      The acromion: morphologic condition and age-related changes. A study of 420 scapulas.
      ,
      • Ogawa K.
      • Yoshida A.
      • Inokuchi W.
      • Naniwa T.
      Acromial spur: relationship to aging and morphologic changes in the rotator cuff.
      ). Bigliani et al. described the role of the shape of the acromion as an extrinsic mechanism of RC tendinopathy by describing the morphologic condition of the acromion as a Type I (flat), Type II (curved), or Type III (hooked) (
      • Bigliani L.U.
      • Morrison D.S.
      • April E.W.
      The morphology of the acromion and its relationship to rotator cuff tears [abstract].
      ). An association between acromion shape and severity of RC pathology has been well documented (
      • Bigliani L.U.
      • Ticker J.B.
      • Flatow E.L.
      • Soslowsky L.J.
      • Mow V.C.
      The relationship of acromial architecture to rotator cuff disease.
      ,
      • Epstein R.E.
      • Schweitzer M.E.
      • Frieman B.G.
      • Fenlin Jr., J.M.
      • Mitchell D.G.
      Hooked acromion: prevalence on MR images of painful shoulders.
      ,
      • Gill T.J.
      • McIrvin E.
      • Kocher M.S.
      • Homa K.
      • Mair S.D.
      • Hawkins R.J.
      The relative importance of acromial morphology and age with respect to rotator cuff pathology.
      ,
      • Ogawa K.
      • Yoshida A.
      • Inokuchi W.
      • Naniwa T.
      Acromial spur: relationship to aging and morphologic changes in the rotator cuff.
      ) with trends of a greater prevalence of Type III, or hooked acromion in patients with impingement (
      • Epstein R.E.
      • Schweitzer M.E.
      • Frieman B.G.
      • Fenlin Jr., J.M.
      • Mitchell D.G.
      Hooked acromion: prevalence on MR images of painful shoulders.
      ) and full thickness RC tears (
      • Bigliani L.U.
      • Ticker J.B.
      • Flatow E.L.
      • Soslowsky L.J.
      • Mow V.C.
      The relationship of acromial architecture to rotator cuff disease.
      ,
      • Epstein R.E.
      • Schweitzer M.E.
      • Frieman B.G.
      • Fenlin Jr., J.M.
      • Mitchell D.G.
      Hooked acromion: prevalence on MR images of painful shoulders.
      ,
      • Gill T.J.
      • McIrvin E.
      • Kocher M.S.
      • Homa K.
      • Mair S.D.
      • Hawkins R.J.
      The relative importance of acromial morphology and age with respect to rotator cuff pathology.
      ,
      • Toivonen D.A.
      • Tuite M.J.
      • Orwin J.F.
      Acromial structure and tears of the rotator cuff.
      ). Success of conservative treatment for patients with RC tendinopathy has been related to shape/type of acromion; Morrison et al. found better outcomes in patients with type I acromions (
      • Morrison D.S.
      • Frogameni A.D.
      • Woodworth P.
      Non-operative treatment of subacromial impingement syndrome.
      ). These findings were similar to those of Wang et al., who found 89% of patients with type I acromion had a successful response, 73% with type II, and 58.3% of type III (
      • Wang J.C.
      • Horner G.
      • Brown E.D.
      • Shapiro M.S.
      The relationship between acromial morphology and conservative treatment of patients with impingement syndrome.
      ). Whether acromial shape is congenital (
      • Nicholson G.P.
      • Goodman D.A.
      • Flatow E.L.
      • Bigliani L.U.
      The acromion: morphologic condition and age-related changes. A study of 420 scapulas.
      ) or acquired with age (
      • Bonsell S.
      • Pearsall A.W.T.
      • Heitman R.J.
      • Helms C.A.
      • Major N.M.
      • Speer K.P.
      The relationship of age, gender, and degenerative changes observed on radiographs of the shoulder in asymptomatic individuals.
      ,
      • Edelson J.G.
      The ‘hooked’ acromion revisited.
      ,
      • Speer K.P.
      • Osbahr D.C.
      • Montella B.J.
      • Apple A.S.
      • Mair S.D.
      Acromial morphotype in the young asymptomatic athletic shoulder.
      ,
      • Wang J.C.
      • Shapiro M.S.
      Changes in acromial morphology with age.
      ) remains controversial. Moreover, the acromial shape classification has been questioned because of poor interobserver reliability (
      • Jacobson S.R.
      • Speer K.P.
      • Moor J.T.
      • Janda D.H.
      • Saddemi S.R.
      • MacDonald P.B.
      • et al.
      Reliability of radiographic assessment of acromial morphology.
      ,
      • Zuckerman J.D.
      • Kummer F.J.
      • Cuomo F.
      • Greller M.
      Interobserver reliability of acromial morphology classification: an anatomic study.
      ).
      Measurement of the slope or angle of the acromion is another method to capture the acromial shape, and both have been proposed to cause RC tendon compression (
      • Aoki M.
      • Ishii S.
      • Usui M.
      The slope of the acromion and rotator cuff impingement.
      ,
      • Edelson J.G.
      The ‘hooked’ acromion revisited.
      ,
      • Toivonen D.A.
      • Tuite M.J.
      • Orwin J.F.
      Acromial structure and tears of the rotator cuff.
      ,
      • Vaz S.
      • Soyer J.
      • Pries P.
      • Clarac J.P.
      Subacromial impingement: influence of coracoacromial arch geometry on shoulder function.
      ). A flatter slope or more horizontal position of the acromion is associated with subacromial impingement (
      • Edelson J.G.
      The ‘hooked’ acromion revisited.
      ), degenerative changes of the RC (
      • Aoki M.
      • Ishii S.
      • Usui M.
      The slope of the acromion and rotator cuff impingement.
      ,
      • Toivonen D.A.
      • Tuite M.J.
      • Orwin J.F.
      Acromial structure and tears of the rotator cuff.
      ), subacromial spur formation (
      • Aoki M.
      • Ishii S.
      • Usui M.
      The slope of the acromion and rotator cuff impingement.
      ,
      • Toivonen D.A.
      • Tuite M.J.
      • Orwin J.F.
      Acromial structure and tears of the rotator cuff.
      ), and a greater loss of function in patients with tendinopathy (
      • Vaz S.
      • Soyer J.
      • Pries P.
      • Clarac J.P.
      Subacromial impingement: influence of coracoacromial arch geometry on shoulder function.
      ). Similarly, other anatomical factors like large subacromial spurs, thickening or ossification of the attachment of the coracoacromial ligament (CAL) are associated with RC pathology with bursal-sided partial thickness tears (
      • Ogawa K.
      • Yoshida A.
      • Inokuchi W.
      • Naniwa T.
      Acromial spur: relationship to aging and morphologic changes in the rotator cuff.
      ) and progression to full thickness RC tears (
      • Farley T.E.
      • Neumann C.H.
      • Steinbach L.S.
      • Petersen S.A.
      The coracoacromial arch: MR evaluation and correlation with rotator cuff pathology.
      ,
      • Nicholson G.P.
      • Goodman D.A.
      • Flatow E.L.
      • Bigliani L.U.
      The acromion: morphologic condition and age-related changes. A study of 420 scapulas.
      ,
      • Ogawa K.
      • Yoshida A.
      • Inokuchi W.
      • Naniwa T.
      Acromial spur: relationship to aging and morphologic changes in the rotator cuff.
      ); however, these same osseous changes in CAL have also been documented with age (
      • Edelson J.G.
      The ‘hooked’ acromion revisited.
      ).
      Arthritic changes of the AC joint have also been theorized to contribute to external mechanical impingement of the RC tendons (
      • Neer C.S.
      Anterior acromioplasty for the chronic impingement syndrome in the shoulder: a preliminary report.
      ,
      • Neer C.S.
      Impingement lesions.
      ,
      • Petersson C.J.
      • Gentz C.F.
      Ruptures of the supraspinatus tendon. The significance of distally pointing acromioclavicular osteophytes.
      ). The AC joint undergoes radiographic degeneration with age including narrowing of the joint space and development of osteophytes at the distal clavicle and acromion articulation (
      • Cuomo F.
      • Kummer F.J.
      • Zuckerman J.D.
      • Lyon T.
      • Blair B.
      • Olsen T.
      The influence of acromioclavicular joint morphology on rotator cuff tears.
      ,
      • Nicholson G.P.
      • Goodman D.A.
      • Flatow E.L.
      • Bigliani L.U.
      The acromion: morphologic condition and age-related changes. A study of 420 scapulas.
      ,
      • Petersson C.J.
      Degeneration of the acromioclavicular joint. A morphological study.
      ,
      • Petersson C.J.
      • Redlund-Johnell I.
      Radiographic joint space in normal acromioclavicular joints.
      ). Inferior spurs off the distal clavicle associated with AC joint arthrosis correlate with the presence of RC pathology (
      • Cuomo F.
      • Kummer F.J.
      • Zuckerman J.D.
      • Lyon T.
      • Blair B.
      • Olsen T.
      The influence of acromioclavicular joint morphology on rotator cuff tears.
      ,
      • Petersson C.J.
      • Gentz C.F.
      Ruptures of the supraspinatus tendon. The significance of distally pointing acromioclavicular osteophytes.
      ).
      There is substantial evidence that anatomical variants such as subacromial spurs, AC joint spurs, and acromial shape may contribute biomechanically to an extrinsic mechanism of RC tendinopathy and progressive RC disease; however, the presence of these alone may be insufficient to result in RC tendinopathy.
      • Soslowsky L.J.
      • Thomopoulos S.
      • Esmail A.
      • Flanagan C.L.
      • Iannotti J.P.
      • Williamson III, J.D.
      • et al.
      Rotator cuff tendinosis in an animal model: role of extrinsic and overuse factors.
      ) found that external mechanical compression of RC tendons in rats exposed to normal cage activity did not cause pathological changes, but when combined with overuse activity had a significant effect on tendon injury. Therefore, bony anatomy such as a hooked acromion may not necessarily cause, but predispose an individual to RC tendinopathy. Supporting this theory of a requisite overuse exposure, symptomatic RC disease is more often present in dominant than non-dominant shoulders (
      • Yamaguchi K.
      • Ditsios K.
      • Middleton W.D.
      • Hildebolt C.F.
      • Galatz L.M.
      • Teefey S.A.
      The demographic and morphological features of rotator cuff disease. A comparison of asymptomatic and symptomatic shoulders.
      ).

      1.2 Biomechanical factors

      Biomechanical factors that can lead to extrinsic mechanical RC tendon compression include abnormal scapular and humeral kinematics, postural abnormalities, rotator cuff and scapular muscle performance deficits, and decreased extensibility of pectoralis minor or posterior shoulder tissues. Scapular and humeral kinematic abnormalities can cause dynamic narrowing of the subacromial space leading to RC tendon compression secondary to superior translation of the humeral head (
      • Deutsch A.
      • Altchek D.W.
      • Schwartz E.
      • Otis J.C.
      • Warren R.F.
      Radiologic measurement of superior displacement of the humeral head in the impingement syndrome.
      ,
      • Hallstrom E.
      • Karrholm J.
      Shoulder kinematics in 25 patients with impingement and 12 controls.
      ,
      • Keener J.D.
      • Wei A.S.
      • Kim H.M.
      • Steger-May K.
      • Yamaguchi K.
      Proximal humeral migration in shoulders with symptomatic and asymptomatic rotator cuff tears.
      ,
      • Ludewig P.M.
      • Cook T.M.
      Translations of the humerus in persons with shoulder impingement symptoms.
      ,
      • Paletta Jr., G.A.
      • Warner J.J.
      • Warren R.F.
      • Deutsch A.
      • Altchek D.W.
      Shoulder kinematics with two-plane X-ray evaluation in patients with anterior instability or rotator cuff tearing.
      ,
      • Royer P.J.
      • Kane E.J.
      • Parks K.E.
      • Morrow J.C.
      • Moravec R.R.
      • Christie D.S.
      • et al.
      Fluoroscopic assessment of rotator cuff fatigue on glenohumeral arthrokinematics in shoulder impingement syndrome.
      ) or aberrant scapular motion that causes the acromion to move inferiorly (
      • Ludewig P.M.
      • Cook T.M.
      Alterations in shoulder kinematics and associated muscle activity in people with symptoms of shoulder impingement.
      ). Postural abnormalities, muscle deficits, and soft tissue tightness factors as external mechanisms can directly influence scapular and humeral kinematics.

      1.2.1 Scapular kinematics and influence of posture, muscle deficit and soft tissue tightness

      Scapular kinematic abnormalities have been identified in patients with RC tendinopathy compared to healthy individuals (
      • Endo K.
      • Ikata T.
      • Katoh S.
      • Takeda Y.
      Radiographic assessment of scapular rotational tilt in chronic shoulder impingement syndrome.
      ,
      • Graichen H.
      • Stammberger T.
      • Bonel H.
      • Wiedemann E.
      • Englmeier K.H.
      • Reiser M.
      • et al.
      Three-dimensional analysis of shoulder girdle and supraspinatus motion patterns in patients with impingement syndrome.
      ,
      • Hebert L.J.
      • Moffet H.
      • McFadyen B.J.
      • Dionne C.E.
      Scapular behavior in shoulder impingement syndrome.
      ,
      • Ludewig P.M.
      • Cook T.M.
      Alterations in shoulder kinematics and associated muscle activity in people with symptoms of shoulder impingement.
      ,
      • Lukasiewicz A.C.
      • McClure P.
      • Michener L.
      • Pratt N.
      • Sennett B.
      Comparison of 3-dimensional scapular position and orientation between subjects with and without shoulder impingement.
      ,
      • McClure P.W.
      • Michener L.A.
      • Karduna A.R.
      Shoulder function and 3-dimensional scapular kinematics in people with and without shoulder impingement syndrome.
      ,
      • Warner J.J.
      • Micheli L.J.
      • Arslanian L.E.
      • Kennedy J.
      • Kennedy R.
      Scapulothoracic motion in normal shoulders and shoulders with glenohumeral instability and impingement syndrome. A study using Moire topographic analysis.
      ). Subjects with subacromial impingement generally have decreased scapular posterior tilting (
      • Endo K.
      • Ikata T.
      • Katoh S.
      • Takeda Y.
      Radiographic assessment of scapular rotational tilt in chronic shoulder impingement syndrome.
      ,
      • Ludewig P.M.
      • Cook T.M.
      Alterations in shoulder kinematics and associated muscle activity in people with symptoms of shoulder impingement.
      ,
      • Lukasiewicz A.C.
      • McClure P.
      • Michener L.
      • Pratt N.
      • Sennett B.
      Comparison of 3-dimensional scapular position and orientation between subjects with and without shoulder impingement.
      ), decreased upward rotation (
      • Endo K.
      • Ikata T.
      • Katoh S.
      • Takeda Y.
      Radiographic assessment of scapular rotational tilt in chronic shoulder impingement syndrome.
      ,
      • Ludewig P.M.
      • Cook T.M.
      Alterations in shoulder kinematics and associated muscle activity in people with symptoms of shoulder impingement.
      ,
      • Su K.P.
      • Johnson M.P.
      • Gracely E.J.
      • Karduna A.R.
      Scapular rotation in swimmers with and without impingement syndrome: practice effects.
      ), and increased internal rotation (
      • Endo K.
      • Ikata T.
      • Katoh S.
      • Takeda Y.
      Radiographic assessment of scapular rotational tilt in chronic shoulder impingement syndrome.
      ,
      • Hebert L.J.
      • Moffet H.
      • McFadyen B.J.
      • Dionne C.E.
      Scapular behavior in shoulder impingement syndrome.
      ,
      • Ludewig P.M.
      • Cook T.M.
      Alterations in shoulder kinematics and associated muscle activity in people with symptoms of shoulder impingement.
      ,
      • Warner J.J.
      • Micheli L.J.
      • Arslanian L.E.
      • Kennedy J.
      • Kennedy R.
      Scapulothoracic motion in normal shoulders and shoulders with glenohumeral instability and impingement syndrome. A study using Moire topographic analysis.
      ) compared to healthy subjects. As a result, the anterior aspect of the acromion may fail to move away from the humeral head during arm elevation and in theory contribute to a reduction of subacromial space and external RC compression (
      • Ludewig P.M.
      • Cook T.M.
      Alterations in shoulder kinematics and associated muscle activity in people with symptoms of shoulder impingement.
      ). The anterior aspect of the acromion has been identified as the predominant site of RC compression or impingement (
      • Brossmann J.
      • Preidler K.W.
      • Pedowitz R.A.
      • White L.M.
      • Trudell D.
      • Resnick D.
      Shoulder impingement syndrome: influence of shoulder position on rotator cuff impingement—an anatomic study.
      ,
      • Flatow E.L.
      • Soslowsky L.J.
      • Ticker J.B.
      • Pawluk R.J.
      • Hepler M.
      • Ark J.
      • et al.
      Excursion of the rotator cuff under the acromion. Patterns of subacromial contact.
      ,
      • Lee S.B.
      • Itoi E.
      • O'Driscoll S.W.
      • An K.N.
      Contact geometry at the undersurface of the acromion with and without a rotator cuff tear.
      ,
      • Neer C.S.
      Anterior acromioplasty for the chronic impingement syndrome in the shoulder: a preliminary report.
      ,
      • Neer C.S.
      Impingement lesions.
      ,
      • Yamamoto N.
      • Muraki T.
      • Sperling J.W.
      • Steinmann S.P.
      • Itoi E.
      • Cofield R.H.
      • et al.
      Impingement mechanisms of the Neer and Hawkins signs.
      ). In contrast, increased scapular posterior tilting, upward rotation, and superior translation of the scapula have also been identified in patients with RC tendinopathy compared to asymptomatic subjects (
      • Lukasiewicz A.C.
      • McClure P.
      • Michener L.
      • Pratt N.
      • Sennett B.
      Comparison of 3-dimensional scapular position and orientation between subjects with and without shoulder impingement.
      ,
      • McClure P.W.
      • Michener L.A.
      • Karduna A.R.
      Shoulder function and 3-dimensional scapular kinematics in people with and without shoulder impingement syndrome.
      ). These aberrant patterns are theorized to be a favorable compensatory response to relieve compression of the RC tendons by increasing subacromial space (
      • McClure P.W.
      • Michener L.A.
      • Karduna A.R.
      Shoulder function and 3-dimensional scapular kinematics in people with and without shoulder impingement syndrome.
      ). While variable patterns of abnormal scapular kinematics in patients with RC tendinopathy have emerged, the differences between groups are small in magnitude which casts doubt upon the significance of these findings related to changes in subacromial space and role of abnormal scapular kinematics as an extrinsic mechanism for all patients with RC tendinopathy.
      Interestingly, Graichen et al. suggest that not all patients with RC tendinopathy have altered scapular kinematics, but a subset exists with significant alterations that are greater than 2 standard deviations from the mean of healthy individuals (
      • Graichen H.
      • Stammberger T.
      • Bonel H.
      • Wiedemann E.
      • Englmeier K.H.
      • Reiser M.
      • et al.
      Three-dimensional analysis of shoulder girdle and supraspinatus motion patterns in patients with impingement syndrome.
      ). Moreover, patients with scapular alterations classified with obvious scapular dyskinesis (
      • Tate A.R.
      • McClure P.
      • Kareha S.
      • Irwin D.
      • Barbe M.F.
      A clinical method for identifying scapular dyskinesis, part 2: validity.
      ) compared to less obvious, or subtle, alternations may have meaningful abnormal scapular kinematics that impacts the subacromial space and contribute to an extrinsic mechanism of RC tendinopathy. Silva et al. found a greater reduction in subacromial space in elite tennis players with scapular dyskinesis compared to players without dyskinesis (
      • Silva R.T.
      • Hartmann L.G.
      • Laurino C.F.S.
      • Bilo J.P.R.
      Clinical and ultrasonographic correlation between scapular dyskinesia and subacromial space measurement among junior elite tennis players.
      ); however, the clinical method used to identify scapular dyskinesis and associated reliability was not reported.
      While there is evidence of abnormal scapular kinematics in a subset of patients with RC tendinopathy, the influence of these specific biomechanical alterations on subacromial space remains speculative. Alternatively, passive alterations in scapular position may influence subacromial space (
      • Atalar H.
      • Yilmaz C.
      • Polat O.
      • Selek H.
      • Uras I.
      • Yanik B.
      Restricted scapular mobility during arm abduction: implications for impingement syndrome.
      ,
      • Solem-Bertoft E.
      • Thuomas K.A.
      • Westerberg C.E.
      The influence of scapular retraction and protraction on the width of the subacromial space. An MRI study.
      ). In a study by Atalar et al., limiting scapular motion by externally binding the scapular down to the thorax while the arm is positioned at 90° compared to unrestricted scapula caused a reduction in subacromial space in healthy individuals (
      • Atalar H.
      • Yilmaz C.
      • Polat O.
      • Selek H.
      • Uras I.
      • Yanik B.
      Restricted scapular mobility during arm abduction: implications for impingement syndrome.
      ). In a study by Solem-Bertoft, positioning the scapula of 4 healthy individuals in protraction compared to retraction with sandbags reduced subacromial space (
      • Solem-Bertoft E.
      • Thuomas K.A.
      • Westerberg C.E.
      The influence of scapular retraction and protraction on the width of the subacromial space. An MRI study.
      ). In contrast to these findings, cadaveric study by Karduna et al. found that inducing scapular upward rotation from a neutral position reduced subacromial clearance (
      • Karduna A.R.
      • Kerner P.J.
      • Lazarus M.D.
      Contact forces in the subacromial space: effects of scapular orientation.
      ). Further research is necessary to determine which scapular kinematic alterations are most related to changes in subacromial space and the magnitude of change in scapular kinematics needed to affect the subacromial space.
      The mechanisms responsible for scapular alterations found in subjects with RC tendinopathy have not been clearly defined, but have been theorized to include adaptive shortening of the pectoralis minor muscle (
      • Borstad J.D.
      Resting position variables at the shoulder: evidence to support a posture-impairment association.
      ,
      • Hebert L.J.
      • Moffet H.
      • McFadyen B.J.
      • Dionne C.E.
      Scapular behavior in shoulder impingement syndrome.
      ,
      • Kendall F.P.
      • McCreary E.K.
      • Provance P.G.
      Muscles — testing and function.
      ,
      • Ludewig P.M.
      • Cook T.M.
      Alterations in shoulder kinematics and associated muscle activity in people with symptoms of shoulder impingement.
      ), posterior shoulder tightness (
      • Borich M.R.
      • Bright J.M.
      • Lorello D.J.
      • Cieminski C.J.
      • Buisman T.
      • Ludewig P.M.
      Scapular angular positioning at end range internal rotation in cases of glenohumeral internal rotation deficit.
      ), aberrant scapular and rotator cuff muscle performance (
      • Ludewig P.M.
      • Cook T.M.
      Alterations in shoulder kinematics and associated muscle activity in people with symptoms of shoulder impingement.
      ), and an increase in thoracic spine flexion or kyphosis (
      • Kebaetse M.
      • McClure P.
      • Pratt N.A.
      Thoracic position effect on shoulder range of motion, strength, and three-dimensional scapular kinematics.
      ,
      • Ludewig P.M.
      • Cook T.M.
      Alterations in shoulder kinematics and associated muscle activity in people with symptoms of shoulder impingement.
      ,
      • Wang C.H.
      • McClure P.
      • Pratt N.E.
      • Nobilini R.
      Stretching and strengthening exercises: their effect on three-dimensional scapular kinematics.
      ). Subjects with a relatively shorter pectoralis minor muscle length at rest demonstrate increased scapular internal rotation during arm elevation and decreased scapular posterior tilting at higher arm elevation angles (90° and 120°) when compared with subjects with a relatively longer pectoralis minor muscle length at rest (
      • Borstad J.D.
      • Ludewig P.M.
      The effect of long versus short pectoralis minor resting length on scapular kinematics in healthy individuals.
      ). Similarly, overhead athletes with a loss of glenohumeral internal rotation of 20% or more as compared to their opposite shoulder demonstrate increased scapular anterior tilt at end range glenohumeral internal rotation with the arm abducted or flexed to 90° (
      • Borich M.R.
      • Bright J.M.
      • Lorello D.J.
      • Cieminski C.J.
      • Buisman T.
      • Ludewig P.M.
      Scapular angular positioning at end range internal rotation in cases of glenohumeral internal rotation deficit.
      ). Scapular alterations associated with shortened pectoralis minor length and glenohumeral internal rotation deficit are consistent with previous studies of subjects with RC tendinopathy (
      • Endo K.
      • Ikata T.
      • Katoh S.
      • Takeda Y.
      Radiographic assessment of scapular rotational tilt in chronic shoulder impingement syndrome.
      ,
      • Hebert L.J.
      • Moffet H.
      • McFadyen B.J.
      • Dionne C.E.
      Scapular behavior in shoulder impingement syndrome.
      ,
      • Ludewig P.M.
      • Cook T.M.
      Alterations in shoulder kinematics and associated muscle activity in people with symptoms of shoulder impingement.
      ,
      • Warner J.J.
      • Micheli L.J.
      • Arslanian L.E.
      • Kennedy J.
      • Kennedy R.
      Scapulothoracic motion in normal shoulders and shoulders with glenohumeral instability and impingement syndrome. A study using Moire topographic analysis.
      ). The relationship between pectoralis minor muscle length at rest has been indirectly linked to pain and functional limitations attributed to RC tendinopathy via alterations in scapular kinematics (
      • Borstad J.D.
      • Ludewig P.M.
      The effect of long versus short pectoralis minor resting length on scapular kinematics in healthy individuals.
      ). The extent of pectoralis minor shortening needed to decrease the subacromial space and contribute to an extrinsic mechanism has yet to be determined.
      Aberrant scapular muscle activity has been identified in patients with RC tendinopathy (
      • Cools A.M.
      • Witvrouw E.E.
      • Declercq G.A.
      • Danneels L.A.
      • Cambier D.C.
      Scapular muscle recruitment patterns: trapezius muscle latency with and without impingement symptoms.
      ,
      • Cools A.M.
      • Witvrouw E.E.
      • Declercq G.A.
      • Vanderstraeten G.G.
      • Cambier D.C.
      Evaluation of isokinetic force production and associated muscle activity in the scapular rotators during a protraction–retraction movement in overhead athletes with impingement symptoms.
      ,
      • Cools A.M.
      • Witvrouw E.E.
      • Mahieu N.N.
      • Danneels L.A.
      Isokinetic scapular muscle performance in overhead athletes with and without impingement symptoms.
      ,
      • Cools A.M.
      • Declercq G.A.
      • Cambier D.C.
      • Mahieu N.N.
      • Witvrouw E.E.
      Trapezius activity and intramuscular balance during isokinetic exercise in overhead athletes with impingement symptoms.
      ,
      • Diederichsen L.P.
      • Norregaard J.
      • Dyhre-Poulsen P.
      • Winther A.
      • Tufekovic G.
      • Bandholm T.
      • et al.
      The activity pattern of shoulder muscles in subjects with and without subacromial impingement.
      ,
      • Ludewig P.M.
      • Cook T.M.
      Alterations in shoulder kinematics and associated muscle activity in people with symptoms of shoulder impingement.
      ,
      • Moraes G.F.
      • Faria C.D.
      • Teixeira-Salmela L.F.
      Scapular muscle recruitment patterns and isokinetic strength ratios of the shoulder rotator muscles in individuals with and without impingement syndrome.
      ,
      • Ruwe P.A.
      • Pink M.
      • Jobe F.W.
      • Perry J.
      • Scovazzo M.L.
      The normal and the painful shoulders during the breaststroke. Electromyographic and cinematographic analysis of twelve muscles.
      ,
      • Wadsworth D.J.
      • Bullock-Saxton J.E.
      Recruitment patterns of the scapular rotator muscles in freestyle swimmers with subacromial impingement.
      ) and been directly linked to abnormal scapular kinematics in patients with RC tendinopathy (
      • Ludewig P.M.
      • Cook T.M.
      Alterations in shoulder kinematics and associated muscle activity in people with symptoms of shoulder impingement.
      ). Of particular interest are the relative contributions of the upper and lower serratus anterior muscles and trapezius muscles, found to stabilize the scapula and induce scapular upward rotation, external rotation, and/or posterior tilt (
      • Bagg S.D.
      • Forrest W.J.
      A biomechanical analysis of scapular rotation during arm abduction in the scapular plane.
      ,
      • Johnson G.R.
      • Pandyan A.D.
      The activity in the three regions of the trapezius under controlled loading conditions—an experimental and modelling study.
      ,
      • Kronberg M.
      • Nemeth G.
      • Brostrom L.A.
      Muscle activity and coordination in the normal shoulder. An electromyographic study.
      ) to potentially allow the humeral head to clear the acromion with elevation (
      • McQuade K.J.
      • Dawson J.
      • Smidt G.L.
      Scapulothoracic muscle fatigue associated with alterations in scapulohumeral rhythm kinematics during maximum resistive shoulder elevation.
      ). Individuals with RC tendinopathy have decreased muscle performance of the serratus anterior in terms of force output (
      • Cools A.M.
      • Witvrouw E.E.
      • Declercq G.A.
      • Vanderstraeten G.G.
      • Cambier D.C.
      Evaluation of isokinetic force production and associated muscle activity in the scapular rotators during a protraction–retraction movement in overhead athletes with impingement symptoms.
      ), muscle balance/ratios (
      • Cools A.M.
      • Witvrouw E.E.
      • Declercq G.A.
      • Vanderstraeten G.G.
      • Cambier D.C.
      Evaluation of isokinetic force production and associated muscle activity in the scapular rotators during a protraction–retraction movement in overhead athletes with impingement symptoms.
      ), electromyographical (EMG) activity (
      • Diederichsen L.P.
      • Norregaard J.
      • Dyhre-Poulsen P.
      • Winther A.
      • Tufekovic G.
      • Bandholm T.
      • et al.
      The activity pattern of shoulder muscles in subjects with and without subacromial impingement.
      ,
      • Ludewig P.M.
      • Cook T.M.
      Alterations in shoulder kinematics and associated muscle activity in people with symptoms of shoulder impingement.
      ), and latencies in activation (
      • Moraes G.F.
      • Faria C.D.
      • Teixeira-Salmela L.F.
      Scapular muscle recruitment patterns and isokinetic strength ratios of the shoulder rotator muscles in individuals with and without impingement syndrome.
      ,
      • Wadsworth D.J.
      • Bullock-Saxton J.E.
      Recruitment patterns of the scapular rotator muscles in freestyle swimmers with subacromial impingement.
      ). Similar deficits have been found in the lower trapezius muscle including increased latencies of muscle onset (
      • Cools A.M.
      • Witvrouw E.E.
      • Declercq G.A.
      • Danneels L.A.
      • Cambier D.C.
      Scapular muscle recruitment patterns: trapezius muscle latency with and without impingement symptoms.
      ) and alterations in maximal EMG activity (
      • Cools A.M.
      • Witvrouw E.E.
      • Declercq G.A.
      • Vanderstraeten G.G.
      • Cambier D.C.
      Evaluation of isokinetic force production and associated muscle activity in the scapular rotators during a protraction–retraction movement in overhead athletes with impingement symptoms.
      ,
      • Cools A.M.
      • Declercq G.A.
      • Cambier D.C.
      • Mahieu N.N.
      • Witvrouw E.E.
      Trapezius activity and intramuscular balance during isokinetic exercise in overhead athletes with impingement symptoms.
      ,
      • Diederichsen L.P.
      • Norregaard J.
      • Dyhre-Poulsen P.
      • Winther A.
      • Tufekovic G.
      • Bandholm T.
      • et al.
      The activity pattern of shoulder muscles in subjects with and without subacromial impingement.
      ,
      • Ludewig P.M.
      • Cook T.M.
      Alterations in shoulder kinematics and associated muscle activity in people with symptoms of shoulder impingement.
      ). Relatively small changes in the muscle performance of the scapulothoracic muscles can alter the position of the scapula at a fixed angle of humeral elevation and, in theory, affect the length–tension relationship (point on the length–tension curve) of the RC muscles and the subacromial space.
      Thoracic spine kyphosis posture has been directly linked to alterations in subacromial space (
      • Gumina S.
      • Di Giorgio G.
      • Postacchini F.
      • Postacchini R.
      Subacromial space in adult patients with thoracic hyperkyphosis and in healthy volunteers.
      ), alterations in scapular kinematics (
      • Finley M.A.
      • Lee R.Y.
      Effect of sitting posture on 3-dimensional scapular kinematics measured by skin-mounted electromagnetic tracking sensors.
      ), and thus theorized to contribute to an extrinsic mechanism of RC tendinopathy. An increase in thoracic spine kyphosis/ flexion is associated with a decrease in subacromial space (
      • Gumina S.
      • Di Giorgio G.
      • Postacchini F.
      • Postacchini R.
      Subacromial space in adult patients with thoracic hyperkyphosis and in healthy volunteers.
      ) and a decrease in scapular posterior tilt (
      • Finley M.A.
      • Lee R.Y.
      Effect of sitting posture on 3-dimensional scapular kinematics measured by skin-mounted electromagnetic tracking sensors.
      ,
      • Kebaetse M.
      • McClure P.
      • Pratt N.A.
      Thoracic position effect on shoulder range of motion, strength, and three-dimensional scapular kinematics.
      ). These alterations in scapular kinematics are consistent with those found in patients with RC tendinopathy (
      • Endo K.
      • Ikata T.
      • Katoh S.
      • Takeda Y.
      Radiographic assessment of scapular rotational tilt in chronic shoulder impingement syndrome.
      ,
      • Ludewig P.M.
      • Cook T.M.
      Alterations in shoulder kinematics and associated muscle activity in people with symptoms of shoulder impingement.
      ,
      • Lukasiewicz A.C.
      • McClure P.
      • Michener L.
      • Pratt N.
      • Sennett B.
      Comparison of 3-dimensional scapular position and orientation between subjects with and without shoulder impingement.
      ).

      1.2.2 Humeral kinematics and influence of posture muscle deficits, and soft tissue tightness

      Excessive humeral head migration proximally on the glenoid is theorized to reduce subacromial space and contribute to RC tendon compression. Proximal, or superior, humeral migration and reduction of subacromial space have been used synonymously at times; however, the amount of superior displacement of the humeral head has not been correlated with linear measures or the 3D volume of the subacromial space and may not occur at a 1:1 ratio (refer to Fig. 2). This distinction may be futile in patients with a large RC tendon tears who present dramatic excessive proximal humeral migration with the arm at rest (
      • Keener J.D.
      • Wei A.S.
      • Kim H.M.
      • Steger-May K.
      • Yamaguchi K.
      Proximal humeral migration in shoulders with symptomatic and asymptomatic rotator cuff tears.
      ); however, in patients with RC tendinopathy the changes in subacromial space may only be apparent with active movement (
      • Graichen H.
      • Stammberger T.
      • Bonel H.
      • Wiedemann E.
      • Englmeier K.H.
      • Reiser M.
      • et al.
      Three-dimensional analysis of shoulder girdle and supraspinatus motion patterns in patients with impingement syndrome.
      ). The extent of subacromial space narrowing that occurs with superior humeral head translation on the glenoid may be counteracted with scapular rotation that moves the acromion superiorly or posterior which may increase the subacromial space. Furthermore, a combination of aberrant humeral and scapular kinematics could cause a clinically meaningful reduction of the subacromial space. This relationship requires further study.
      Figure thumbnail gr2
      Fig. 2Superior migration of the humerus on the glenoid (solid line) and diminished subacromial space (dotted line) in patient with a chronic large RC tear.
      Proximal migration of the humerus on the glenoid while the arm is at rest is regarded as a sign of advanced RC disease (
      • Bezer M.
      • Yildirim Y.
      • Akgun U.
      • Erol B.
      • Guven O.
      Superior excursion of the humeral head: a diagnostic tool in rotator cuff tear surgery.
      ,
      • Keener J.D.
      • Wei A.S.
      • Kim H.M.
      • Steger-May K.
      • Yamaguchi K.
      Proximal humeral migration in shoulders with symptomatic and asymptomatic rotator cuff tears.
      ,
      • Norwood L.A.
      • Barrack R.
      • Jacobson K.E.
      Clinical presentation of complete tears of the rotator cuff.
      ,
      • Yamaguchi K.
      • Sher J.S.
      • Andersen W.K.
      • Garretson R.
      • Uribe J.W.
      • Hechtman K.
      • et al.
      Glenohumeral motion in patients with rotator cuff tears: a comparison of asymptomatic and symptomatic shoulders.
      ), and attributed to chronically diminished RC performance to counteract the superior pull of the deltoid (
      • Deutsch A.
      • Altchek D.W.
      • Schwartz E.
      • Otis J.C.
      • Warren R.F.
      Radiologic measurement of superior displacement of the humeral head in the impingement syndrome.
      ). Similar to subacromial space, patients with RC tendinopathy do not exhibit proximal humeral migration on the glenoid with the arm at rest; but rather demonstrate excessive superior–anterior translations of the humeral head with active arm elevation (
      • Deutsch A.
      • Altchek D.W.
      • Schwartz E.
      • Otis J.C.
      • Warren R.F.
      Radiologic measurement of superior displacement of the humeral head in the impingement syndrome.
      ,
      • Hallstrom E.
      • Karrholm J.
      Shoulder kinematics in 25 patients with impingement and 12 controls.
      ,
      • Keener J.D.
      • Wei A.S.
      • Kim H.M.
      • Steger-May K.
      • Yamaguchi K.
      Proximal humeral migration in shoulders with symptomatic and asymptomatic rotator cuff tears.
      ,
      • Ludewig P.M.
      • Cook T.M.
      Translations of the humerus in persons with shoulder impingement symptoms.
      ,
      • Paletta Jr., G.A.
      • Warner J.J.
      • Warren R.F.
      • Deutsch A.
      • Altchek D.W.
      Shoulder kinematics with two-plane X-ray evaluation in patients with anterior instability or rotator cuff tearing.
      ,
      • Royer P.J.
      • Kane E.J.
      • Parks K.E.
      • Morrow J.C.
      • Moravec R.R.
      • Christie D.S.
      • et al.
      Fluoroscopic assessment of rotator cuff fatigue on glenohumeral arthrokinematics in shoulder impingement syndrome.
      ). Patients with RC tendinopathy have presented with a 1.0–1.5 mm greater superior translation (
      • Deutsch A.
      • Altchek D.W.
      • Schwartz E.
      • Otis J.C.
      • Warren R.F.
      Radiologic measurement of superior displacement of the humeral head in the impingement syndrome.
      ,
      • Hallstrom E.
      • Karrholm J.
      Shoulder kinematics in 25 patients with impingement and 12 controls.
      ,
      • Yamaguchi K.
      • Sher J.S.
      • Andersen W.K.
      • Garretson R.
      • Uribe J.W.
      • Hechtman K.
      • et al.
      Glenohumeral motion in patients with rotator cuff tears: a comparison of asymptomatic and symptomatic shoulders.
      ) and 3 mm of greater anterior translation (
      • Ludewig P.M.
      • Cook T.M.
      Translations of the humerus in persons with shoulder impingement symptoms.
      ) with active arm elevation compared to asymptomatic subjects. Biomechanical mechanisms for excessive proximal humeral migration in patients with RC tendinopathy include shortening of the posterior–inferior glenohumeral joint capsule and decreased RC muscle performance.
      Decreased posterior capsule length has been directly linked to excessive anterior–superior humeral translation in cadaveric study (
      • Harryman D.T.
      • Sidles J.A.
      • Clark J.M.
      • McQuade K.J.
      • Gibb T.D.
      • Matsen III, F.A.
      Translation of the humeral head on the glenoid with passive glenohumeral motion.
      ). Glenohumeral internal rotation range of motion (IR ROM) and horizontal adduction at 90° of elevation are reliable clinical measures (
      • Laudner K.G.
      • Stanek J.M.
      • Meister K.
      Assessing posterior shoulder contracture: the reliability and validity of measuring glenohumeral joint horizontal adduction.
      ,
      • Myers J.B.
      • Oyama S.
      • Wassinger C.A.
      • Ricci R.D.
      • Abt J.P.
      • Conley K.M.
      • et al.
      Reliability, precision, accuracy, and validity of posterior shoulder tightness assessment in overhead athletes.
      ,
      • Tyler T.F.
      • Roy T.
      • Nicholas S.J.
      • Gleim G.W.
      Reliability and validity of a new method of measuring posterior shoulder tightness.
      ,
      • Warner J.J.
      • Micheli L.J.
      • Arslanian L.E.
      • Kennedy J.
      • Kennedy R.
      Patterns of flexibility, laxity, and strength in normal shoulders and shoulders with instability and impingement.
      ) that potentially assess posterior capsule length. Content validity for IR ROM has been demonstrated in cadaveric study with a reduction of motion after the posterior–inferior capsule was artificially shortened (
      • Gagey O.J.
      • Boisrenoult P.
      Shoulder capsule shrinkage and consequences on shoulder movements.
      ,
      • Gerber C.
      • Werner C.M.
      • Macy J.C.
      • Jacob H.A.
      • Nyffeler R.W.
      Effect of selective capsulorrhaphy on the passive range of motion of the glenohumeral joint.
      ). Construct validity has been demonstrated for the measure of horizontal adduction range of motion by its ability to identify deficits unique to overhead athletes (
      • Myers J.B.
      • Oyama S.
      • Wassinger C.A.
      • Ricci R.D.
      • Abt J.P.
      • Conley K.M.
      • et al.
      Reliability, precision, accuracy, and validity of posterior shoulder tightness assessment in overhead athletes.
      ). Clinical measures of glenohumeral internal rotation and horizontal adduction range of motion may also be influenced by potential adaptations of the infraspinatus, teres minor, and/or posterior deltoid musculature (
      • Reinold M.M.
      • Wilk K.E.
      • Macrina L.C.
      • Sheheane C.
      • Dun S.
      • Fleisig G.S.
      • et al.
      Changes in shoulder and elbow passive range of motion after pitching in professional baseball players.
      ), or osseous changes of humeral and/or glenoid retroversion (
      • Crockett H.C.
      • Gross L.B.
      • Wilk K.E.
      • Schwartz M.L.
      • Reed J.
      • O'Mara J.
      • et al.
      Osseous adaptation and range of motion at the glenohumeral joint in professional baseball pitchers.
      ,
      • Osbahr D.C.
      • Cannon D.L.
      • Speer K.P.
      Retroversion of the humerus in the throwing shoulder of college baseball pitchers.
      ,
      • Reagan K.M.
      • Meister K.
      • Horodyski M.B.
      • Werner D.W.
      • Carruthers C.
      • Wilk K.
      Humeral retroversion and its relationship to glenohumeral rotation in the shoulder of college baseball players.
      ,
      • Schwab L.M.
      • Blanch P.
      Humeral torsion and passive shoulder range in elite volleyball players.
      ).
      A relationship between the two measures of posterior shoulder tightness, horizontal adduction and IR ROM, have been found in patients with RC tendinopathy (
      • Tyler T.F.
      • Nicholas S.J.
      • Roy T.
      • Gleim G.W.
      Quantification of posterior capsule tightness and motion loss in patients with shoulder impingement.
      ) and asymptomatic professional baseball pitchers (
      • Laudner K.G.
      • Stanek J.M.
      • Meister K.
      Assessing posterior shoulder contracture: the reliability and validity of measuring glenohumeral joint horizontal adduction.
      ). Posterior shoulder tightness has been demonstrated in patients with RC tendinopathy (
      • Myers J.B.
      • Laudner K.G.
      • Pasquale M.R.
      • Bradley J.P.
      • Lephart S.M.
      Glenohumeral range of motion deficits and posterior shoulder tightness in throwers with pathologic internal impingement.
      ,
      • Tyler T.F.
      • Nicholas S.J.
      • Roy T.
      • Gleim G.W.
      Quantification of posterior capsule tightness and motion loss in patients with shoulder impingement.
      ,
      • Warner J.J.
      • Micheli L.J.
      • Arslanian L.E.
      • Kennedy J.
      • Kennedy R.
      Patterns of flexibility, laxity, and strength in normal shoulders and shoulders with instability and impingement.
      ). Furthermore, stretching to address impairments of posterior shoulder tightness has been identified as an important component to rehabilitation for patients with RC tendinopathy (
      • Kuhn J.E.
      Exercise in the treatment of rotator cuff impingement: a systematic review and a synthesized evidence-based rehabilitation protocol.
      ), and change in IR ROM was significantly correlated (r=0.54) with functional improvement in patients undergoing rehabilitation (
      • McClure P.W.
      • Bialker J.
      • Neff N.
      • Williams G.
      • Karduna A.
      Shoulder function and 3-dimensional kinematics in people with shoulder impingement syndrome before and after a 6-week exercise program.
      ). While this mechanism for RC tendinopathy may be prevalent, this is likely not a contributing mechanism of all patients with RC tendinopathy.
      Deficits in RC muscle performance contribute to RC tendinopathy, by leading to proximal migration and subsequent intrinsic breakdown or extrinsic impingement (
      • Chen S.K.
      • Simonian P.T.
      • Wickiewicz T.L.
      • Otis J.C.
      • Warren R.F.
      Radiographic evaluation of glenohumeral kinematics: a muscle fatigue model.
      ,
      • Deutsch A.
      • Altchek D.W.
      • Schwartz E.
      • Otis J.C.
      • Warren R.F.
      Radiologic measurement of superior displacement of the humeral head in the impingement syndrome.
      ,
      • Royer P.J.
      • Kane E.J.
      • Parks K.E.
      • Morrow J.C.
      • Moravec R.R.
      • Christie D.S.
      • et al.
      Fluoroscopic assessment of rotator cuff fatigue on glenohumeral arthrokinematics in shoulder impingement syndrome.
      ). In biomechanical studies, decreased RC muscles force, in particular the infraspinatus has resulted in increased superior humeral head translation and decreased abduction torque (
      • Hurschler C.
      • Wulker N.
      • Mendila M.
      The effect of negative intraarticular pressure and rotator cuff force on glenohumeral translation during simulated active elevation.
      ,
      • Mura N.
      • O'Driscoll S.W.
      • Zobitz M.E.
      • Heers G.
      • Jenkyn T.R.
      • Chou S.M.
      • et al.
      The effect of infraspinatus disruption on glenohumeral torque and superior migration of the humeral head: a biomechanical study.
      ,
      • Sharkey N.A.
      • Marder R.A.
      The rotator cuff opposes superior translation of the humeral head.
      ). Although more recently, the concept that decreased RC muscle performance alone can result in proximal humeral migration has been challenged with an in vivo study. Artificially induced paralysis of the supraspinatus and infraspinatus muscles in 10 healthy individuals resulted in no immediate effects on proximal humeral head translation (
      • Werner C.M.
      • Weishaupt D.
      • Blumenthal S.
      • Curt A.
      • Favre P.
      • Gerber C.
      Effect of experimental suprascapular nerve block on active glenohumeral translations in vivo.
      ). Results of this study suggest that time, or duration of the muscle impairment may also be a factor. Significant decreases in RC muscle peak isometric, concentric, and eccentric torque have been demonstrated in patients with RC tendinopathy compared to asymptomatic subjects (
      • Leroux J.L.
      • Codine P.
      • Thomas E.
      • Pocholle M.
      • Mailhe D.
      • Blotman F.
      Isokinetic evaluation of rotational strength in normal shoulders and shoulders with impingement syndrome.
      ,
      • MacDermid J.C.
      • Ramos J.
      • Drosdowech D.
      • Faber K.
      • Patterson S.
      The impact of rotator cuff pathology on isometric and isokinetic strength, function, and quality of life.
      ,
      • Tyler T.F.
      • Nahow R.C.
      • Nicholas S.J.
      • McHugh M.P.
      Quantifying shoulder rotation weakness in patients with shoulder impingement.
      ,
      • Warner J.J.
      • Micheli L.J.
      • Arslanian L.E.
      • Kennedy J.
      • Kennedy R.
      Patterns of flexibility, laxity, and strength in normal shoulders and shoulders with instability and impingement.
      ). Reddy et al. found a decrease in electromyographic (EMG) activity of the infraspinatus, and subscapularis from 30° to 60° of active elevation and in the infraspinatus muscle alone from 60° to 90° of active elevation in subjects with tendinopathy compared to healthy subjects (
      • Reddy A.S.
      • Mohr K.J.
      • Pink M.M.
      • Jobe F.W.
      Electromyographic analysis of the deltoid and rotator cuff muscles in persons with subacromial impingement.
      ). Diederichsen et al. found decreased infraspinatus EMG muscle activity with resisted external rotation in patients with RC tendinopathy compared to healthy subjects (
      • Diederichsen L.P.
      • Norregaard J.
      • Dyhre-Poulsen P.
      • Winther A.
      • Tufekovic G.
      • Bandholm T.
      • et al.
      The activity pattern of shoulder muscles in subjects with and without subacromial impingement.
      ). However, alterations in muscle activity were also found in the asymptomatic side leading the authors to propose alterations in muscle activity are a factor in the pathogenesis not a result of RC tendinopathy. Lastly, Myers et al. found a decrease in co-activation ratios of the subscapularis–infraspinatus and supraspinatus–infraspinatus muscles with arm elevation from 0 to 30°, and an increase at elevation above 90°in patients with impingement compared to control participants (
      • Myers J.B.
      • Hwang J.H.
      • Pasquale M.R.
      • Blackburn J.T.
      • Lephart S.M.
      Rotator cuff coactivation ratios in participants with subacromial impingement syndrome.
      ). Decreased RC muscle co-activation levels may occur as a result of pain (
      • Myers J.B.
      • Hwang J.H.
      • Pasquale M.R.
      • Blackburn J.T.
      • Lephart S.M.
      Rotator cuff coactivation ratios in participants with subacromial impingement syndrome.
      ) or altered scapular or humeral head position or movement, changing the muscle length–tension relationship and therefore muscle force (
      • Michener L.A.
      • McClure P.W.
      • Karduna A.R.
      Anatomical and biomechanical mechanisms of subacromial impingement syndrome.
      ). Biomechanical consequences of altered RC muscle activity may be an extrinsic mechanism of RC tendinopathy as superior migration may narrow the subacromial space or result in altered stress and intrinsic tendon degradation. Diminished RC muscle performance correlates with patient-rated function and health-related quality of life in patients with RC tendinopathy (
      • MacDermid J.C.
      • Ramos J.
      • Drosdowech D.
      • Faber K.
      • Patterson S.
      The impact of rotator cuff pathology on isometric and isokinetic strength, function, and quality of life.
      ).
      No study has concurrently examined the influence of scapular position on RC muscle activity in patients with RC tendinopathy; however, there is evidence to suggest that a change in scapular position can alter muscle performance (
      • Kebaetse M.
      • McClure P.
      • Pratt N.A.
      Thoracic position effect on shoulder range of motion, strength, and three-dimensional scapular kinematics.
      ,
      • Kibler W.B.
      • Sciascia A.
      • Dome D.
      Evaluation of apparent and absolute supraspinatus strength in patients with shoulder injury using the scapular retraction test.
      ,
      • Tate A.R.
      • McClure P.W.
      • Kareha S.
      • Irwin D.
      Effect of the Scapula Reposition Test on shoulder impingement symptoms and elevation strength in overhead athletes.
      ). Kebaetse et al. found a decrease in isometric abduction muscle force with the arm at 90° concurrent with an increase in scapular anterior tilt in healthy subjects actively assuming a slouched trunk posture compared to an erect posture (
      • Kebaetse M.
      • McClure P.
      • Pratt N.A.
      Thoracic position effect on shoulder range of motion, strength, and three-dimensional scapular kinematics.
      ). Other research has found that passively altering scapular position, as with scapular retraction and scapular reposition tests, influences isometric arm elevation isometric force (
      • Kibler W.B.
      • Sciascia A.
      • Dome D.
      Evaluation of apparent and absolute supraspinatus strength in patients with shoulder injury using the scapular retraction test.
      ,
      • Smith J.
      • Kotajarvi B.R.
      • Padgett D.J.
      • Eischen J.J.
      Effect of scapular protraction and retraction on isometric shoulder elevation strength.
      ,
      • Tate A.R.
      • McClure P.W.
      • Kareha S.
      • Irwin D.
      Effect of the Scapula Reposition Test on shoulder impingement symptoms and elevation strength in overhead athletes.
      ), with an increase noted with reposition and conflicting results with scapular retraction. Changes in muscle force may be due to improved proximal stability or alterations in RC muscle length at the same humeral elevation angle.

      2. Extrinsic mechanisms for the subgroup of internal impingement

      A unique subset of RC tendinopathy with an extrinsic mechanism is internal impingement. Patients with internal impingement tend to present with pain located in the posterior and superior aspects of the shoulder typically while the arm is in abduction and external rotation of the late cocking phase of throwing (
      • Jobe C.M.
      Posterior superior glenoid impingement: expanded spectrum.
      ,
      • Kvitne R.S.
      • Jobe F.W.
      The diagnosis and treatment of anterior instability in the throwing athlete.
      ). In this position, the articular aspect of the RC tendons becomes mechanically impinged between the posterior superior glenoid rim and the humeral head. This is accentuated with further hyperangulation of the humerus to the glenoid with anterior glenohumeral joint instability (
      • Davidson P.A.
      • Elattrache N.S.
      • Jobe C.M.
      • Jobe F.W.
      Rotator cuff and posterior–superior glenoid labrum injury associated with increased glenohumeral motion: a new site of impingement.
      ) or in theory, with a reduction in scapular retraction (
      • Burkhart S.S.
      • Morgan C.D.
      • Kibler W.B.
      The disabled throwing shoulder: spectrum of pathology Part III: the SICK scapula, scapular dyskinesis, the kinetic chain, and rehabilitation.
      ,
      • Kibler W.B.
      The role of the scapula in athletic shoulder function.
      ) and posterior tilt (
      • Laudner K.G.
      • Myers J.B.
      • Pasquale M.R.
      • Bradley J.P.
      • Lephart S.M.
      Scapular dysfunction in throwers with pathologic internal impingement.
      ). Alterations in scapular kinematics were found in a cohort of baseball players with internal impingement, confirmed with arthroscopy, of greater scapular posterior tilt compared to age matched healthy baseball players (
      • Laudner K.G.
      • Myers J.B.
      • Pasquale M.R.
      • Bradley J.P.
      • Lephart S.M.
      Scapular dysfunction in throwers with pathologic internal impingement.
      ). In contrast, a decrease in scapular posterior tilt has been frequently found in patients with RC tendinopathy (
      • Endo K.
      • Ikata T.
      • Katoh S.
      • Takeda Y.
      Radiographic assessment of scapular rotational tilt in chronic shoulder impingement syndrome.
      ,
      • Ludewig P.M.
      • Cook T.M.
      Alterations in shoulder kinematics and associated muscle activity in people with symptoms of shoulder impingement.
      ,
      • Lukasiewicz A.C.
      • McClure P.
      • Michener L.
      • Pratt N.
      • Sennett B.
      Comparison of 3-dimensional scapular position and orientation between subjects with and without shoulder impingement.
      ). Conflicting findings in scapular kinematics may not be due to causative or compensation patterns of RC tendinopathy as previously theorized (
      • Ludewig P.M.
      • Cook T.M.
      Alterations in shoulder kinematics and associated muscle activity in people with symptoms of shoulder impingement.
      ,
      • McClure P.W.
      • Michener L.A.
      • Karduna A.R.
      Shoulder function and 3-dimensional scapular kinematics in people with and without shoulder impingement syndrome.
      ), but may be a result of differences in underlying mechanism. Further study should examine potential differences in mechanisms of this unique subgroup of RC tendinopathy.

      3. Intrinsic mechanisms of rotator cuff tendinopathy

      There is a growing body of evidence to support an intrinsic mechanism. Intrinsic mechanisms of RC tendinopathy influence tendon morphology and performance. Intrinsic factors of RC tendinopathy result in tendon degradation due to the natural process of aging (
      • Iannotti J.P.
      • Zlatkin M.B.
      • Esterhai J.L.
      • Kressel H.Y.
      • Dalinka M.K.
      • Spindler K.P.
      Magnetic resonance imaging of the shoulder. Sensitivity, specificity, and predictive value.
      ,
      • Milgrom C.
      • Schaffler M.
      • Gilbert S.
      • van Holsbeeck M.
      Rotator-cuff changes in asymptomatic adults. The effect of age, hand dominance and gender.
      ,
      • Sher J.S.
      • Uribe J.W.
      • Posada A.
      • Murphy B.J.
      • Zlatkin M.B.
      Abnormal findings on magnetic resonance images of asymptomatic shoulders.
      ,
      • Tempelhof S.
      • Rupp S.
      • Seil R.
      Age-related prevalence of rotator cuff tears in asymptomatic shoulders.
      ), poor vascularity (
      • Biberthaler P.
      • Wiedemann E.
      • Nerlich A.
      • Kettler M.
      • Mussack T.
      • Deckelmann S.
      • et al.
      Microcirculation associated with degenerative rotator cuff lesions. In vivo assessment with orthogonal polarization spectral imaging during arthroscopy of the shoulder.
      ,
      • Brooks C.H.
      • Revell W.J.
      • Heatley F.W.
      A quantitative histological study of the vascularity of the rotator cuff tendon.
      ,
      • Fukuda H.
      • Hamada K.
      • Yamanaka K.
      Pathology and pathogenesis of bursal-side rotator cuff tears viewed from en bloc histologic sections.
      ,
      • Goodmurphy C.W.
      • Osborn J.
      • Akesson E.J.
      • Johnson S.
      • Stanescu V.
      • Regan W.D.
      An immunocytochemical analysis of torn rotator cuff tendon taken at the time of repair.
      ,
      • Rathbun J.B.
      • Macnab I.
      The microvascular pattern of the rotator cuff.
      ,
      • Rudzki J.R.
      • Adler R.S.
      • Warren R.F.
      • Kadrmas W.R.
      • Verma N.
      • Pearle A.D.
      • et al.
      Contrast-enhanced ultrasound characterization of the vascularity of the rotator cuff tendon: age- and activity-related changes in the intact asymptomatic rotator cuff.
      ), altered biology (
      • Kumagai J.
      • Sarkar K.
      • Uhthoff H.K.
      The collagen types in the attachment zone of rotator cuff tendons in the elderly: an immunohistochemical study.
      ,
      • Riley G.P.
      • Harrall R.L.
      • Constant C.R.
      • Chard M.D.
      • Cawston T.E.
      • Hazleman B.L.
      Glycosaminoglycans of human rotator cuff tendons: changes with age and in chronic rotator cuff tendinitis.
      ,
      • Riley G.P.
      • Harrall R.L.
      • Constant C.R.
      • Chard M.D.
      • Cawston T.E.
      • Hazleman B.L.
      Tendon degeneration and chronic shoulder pain: changes in the collagen composition of the human rotator cuff tendons in rotator cuff tendinitis.
      ), and inferior mechanical properties resulting in damage with tensile or shear loads (
      • Bey M.J.
      • Song H.K.
      • Wehrli F.W.
      • Soslowsky L.J.
      Intratendinous strain fields of the intact supraspinatus tendon: the effect of glenohumeral joint position and tendon region.
      ,
      • Huang C.Y.
      • Wang V.M.
      • Pawluk R.J.
      • Bucchieri J.S.
      • Levine W.N.
      • Bigliani L.U.
      • et al.
      Inhomogeneous mechanical behavior of the human supraspinatus tendon under uniaxial loading.
      ,
      • Lake S.P.
      • Miller K.S.
      • Elliott D.M.
      • Soslowsky L.J.
      Effect of fiber distribution and realignment on the nonlinear and inhomogeneous mechanical properties of human supraspinatus tendon under longitudinal tensile Loading.
      ,
      • Reilly P.
      • Amis A.A.
      • Wallace A.L.
      • Emery R.J.
      Mechanical factors in the initiation and propagation of tears of the rotator cuff. Quantification of strains of the supraspinatus tendon in vitro.
      ). A genetic component for the development of RC disease has also been identified (
      • Harvie P.
      • Ostlere S.J.
      • Teh J.
      • McNally E.G.
      • Clipsham K.
      • Burston B.J.
      • et al.
      Genetic influences in the aetiology of tears of the rotator cuff. Sibling risk of a full-thickness tear.
      ) and theorized to be related to polymorphism of collagen genes such as found with Achilles tendinopathy (
      • Mokone G.G.
      • Gajjar M.
      • September A.V.
      • Schwellnus M.P.
      • Greenberg J.
      • Noakes T.D.
      • et al.
      The guanine–thymine dinucleotide repeat polymorphism within the tenascin-C gene is associated with achilles tendon injuries.
      ); however, no specific genotype has yet to be identified as a risk factor for the development of RC disease (
      • September A.V.
      • Schwellnus M.P.
      • Collins M.
      Tendon and ligament injuries: the genetic component.
      ). Furthermore, RC tendinopathy with an intrinsic mechanism may lead to a reduction in subacromial space creating an interaction of intrinsic and extrinsic mechanisms.
      The morphology of the RC tendons has been studied in detail. The RC tendon near their insertions have been shown to interdigitate; specifically, the supraspinatus tendon consists of five axial plane layers from the bursal to articular side (
      • Clark J.M.
      • Harryman D.T.
      Tendons, ligaments, and capsule of the rotator cuff. Gross and microscopic anatomy.
      ) in the critical zone where pathology is most prevalent (
      • Codman E.A.
      The shoulder: rupture of the supraspinatus tendon and other lesion in or about the subacromial bursa.
      ). RC tendinopathy can include symptomatic tendon pathology with degeneration and partial thickness tears that extend through several, but not all layers. It is commonly described as occurring in 3 regions: bursal sided, mid-substance, and articular sided. Furthermore, pathology that occurs within the mid-substance and articular-sided layers without bursal-side involvement is further support for the intrinsic mechanisms of RC tendinopathy (
      • Fukuda H.
      • Hamada K.
      • Yamanaka K.
      Pathology and pathogenesis of bursal-side rotator cuff tears viewed from en bloc histologic sections.
      ,
      • Hashimoto T.
      • Nobuhara K.
      • Hamada T.
      Pathologic evidence of degeneration as a primary cause of rotator cuff tear.
      ).

      3.1 Age-related degenerative changes

      Codman first proposed an underlying degenerative process within the tendon which precedes supraspinatus tendinopathy and tears (
      • Codman E.A.
      • Akerson I.B.
      The pathology associated with rupture of the supraspinatus tendon.
      ).
      • Neer C.S.
      Impingement lesions.
      described RC disease as a continuum of pathology with 3 stages characterized by age: less than 25 years for stage I, between 25 and 40 years for stage II, and greater than 40 years of age for stage III respectively. Although Neer's theory is biased by an extrinsic mechanism, age was included as an important factor for RC disease. The prevalence of tendon degeneration including partial and full thickness tears increases as a function of age starting at 40 years (
      • Iannotti J.P.
      • Zlatkin M.B.
      • Esterhai J.L.
      • Kressel H.Y.
      • Dalinka M.K.
      • Spindler K.P.
      Magnetic resonance imaging of the shoulder. Sensitivity, specificity, and predictive value.
      ,
      • Milgrom C.
      • Schaffler M.
      • Gilbert S.
      • van Holsbeeck M.
      Rotator-cuff changes in asymptomatic adults. The effect of age, hand dominance and gender.
      ,
      • Sher J.S.
      • Uribe J.W.
      • Posada A.
      • Murphy B.J.
      • Zlatkin M.B.
      Abnormal findings on magnetic resonance images of asymptomatic shoulders.
      ,
      • Tempelhof S.
      • Rupp S.
      • Seil R.
      Age-related prevalence of rotator cuff tears in asymptomatic shoulders.
      ). Additionally, a prospective study has shown RC disease is progressive and leads to pain and disability in more than 50% of previously asymptomatic individuals in less than 4 years (
      • Yamaguchi K.
      • Tetro A.M.
      • Blam O.
      • Evanoff B.A.
      • Teefey S.A.
      • Middleton W.D.
      Natural history of asymptomatic rotator cuff tears: a longitudinal analysis of asymptomatic tears detected sonographically.
      ).
      Age has been shown to have a negative impact on tendon properties. Evidence from biomechanical studies suggest that there is a reduced toe region of a stress–strain curve, decreased elasticity, and decreased overall tensile strength of tendons with age (
      • Woo S.L.
      • An K.N.
      • Frank C.B.
      • Livesay G.A.
      • Ma C.B.
      • Zeminski J.
      • et al.
      Anatomy, biology, and biomechanics of tendon and ligament.
      ). Histological study of RC tendons have shown calcification and fibrovascular proliferation degenerative changes in elderly subjects without history of shoulder ailments that were not present in younger subjects, both without a history of shoulder ailments (
      • Kumagai J.
      • Sarkar K.
      • Uhthoff H.K.
      The collagen types in the attachment zone of rotator cuff tendons in the elderly: an immunohistochemical study.
      ). Also, with age, there is a decrease in total glycosaminoglycan (GAGs) and proteoglycans (PGs) content in the supraspinatus tendon (
      • Riley G.P.
      • Harrall R.L.
      • Constant C.R.
      • Chard M.D.
      • Cawston T.E.
      • Hazleman B.L.
      Glycosaminoglycans of human rotator cuff tendons: changes with age and in chronic rotator cuff tendinitis.
      ). An overall reduction of collagen content and an increased proportion of weaker, more irregularly arranged type III collagen has been found with aging (
      • Kumagai J.
      • Sarkar K.
      • Uhthoff H.K.
      The collagen types in the attachment zone of rotator cuff tendons in the elderly: an immunohistochemical study.
      ); however, there is conflicting evidence that these changes in the supraspinatus are not age related but attributed to inferior healing response from microtrauma to the tendon (
      • Bank R.A.
      • TeKoppele J.M.
      • Oostingh G.
      • Hazleman B.L.
      • Riley G.P.
      Lysylhydroxylation and non-reducible crosslinking of human supraspinatus tendon collagen: changes with age and in chronic rotator cuff tendinitis.
      ,
      • Riley G.P.
      • Harrall R.L.
      • Constant C.R.
      • Chard M.D.
      • Cawston T.E.
      • Hazleman B.L.
      Glycosaminoglycans of human rotator cuff tendons: changes with age and in chronic rotator cuff tendinitis.
      ,
      • Riley G.P.
      • Harrall R.L.
      • Constant C.R.
      • Chard M.D.
      • Cawston T.E.
      • Hazleman B.L.
      Tendon degeneration and chronic shoulder pain: changes in the collagen composition of the human rotator cuff tendons in rotator cuff tendinitis.
      ). There is no consensus whether changes in the tendon are primarily due to aging or a secondary consequence of reduced mechanical properties that make the tendon more susceptible to injury with repetitive motion. Regardless, age related changes to the tendon appear to be a significant factor in the intrinsic pathoetiology of RC tendinopathy.

      3.2 Vascularity

      A deficient vascular supply of the human RC tendons has been implicated in the pathogenesis and mechanism of RC tendinopathy. Codman first described the ‘critical zone’, an area within the supraspinatus tendon approximately 1 cm from the insertion on the greater tubercle with decreased vascularity and the most common site for RC tendon injury (
      • Codman E.A.
      The shoulder: rupture of the supraspinatus tendon and other lesion in or about the subacromial bursa.
      ). Furthermore, this hypovascular zone and resultant diminished healing capacity predisposes one to RC tendinopathy (
      • Biberthaler P.
      • Wiedemann E.
      • Nerlich A.
      • Kettler M.
      • Mussack T.
      • Deckelmann S.
      • et al.
      Microcirculation associated with degenerative rotator cuff lesions. In vivo assessment with orthogonal polarization spectral imaging during arthroscopy of the shoulder.
      ,
      • Brooks C.H.
      • Revell W.J.
      • Heatley F.W.
      A quantitative histological study of the vascularity of the rotator cuff tendon.
      ,
      • Fukuda H.
      • Hamada K.
      • Yamanaka K.
      Pathology and pathogenesis of bursal-side rotator cuff tears viewed from en bloc histologic sections.
      ,
      • Goodmurphy C.W.
      • Osborn J.
      • Akesson E.J.
      • Johnson S.
      • Stanescu V.
      • Regan W.D.
      An immunocytochemical analysis of torn rotator cuff tendon taken at the time of repair.
      ,
      • Rathbun J.B.
      • Macnab I.
      The microvascular pattern of the rotator cuff.
      ,
      • Rudzki J.R.
      • Adler R.S.
      • Warren R.F.
      • Kadrmas W.R.
      • Verma N.
      • Pearle A.D.
      • et al.
      Contrast-enhanced ultrasound characterization of the vascularity of the rotator cuff tendon: age- and activity-related changes in the intact asymptomatic rotator cuff.
      ) and tends to worsen with age (
      • Rudzki J.R.
      • Adler R.S.
      • Warren R.F.
      • Kadrmas W.R.
      • Verma N.
      • Pearle A.D.
      • et al.
      Contrast-enhanced ultrasound characterization of the vascularity of the rotator cuff tendon: age- and activity-related changes in the intact asymptomatic rotator cuff.
      ). However, this notion has been challenged with in vivo studies that found no apparent region of avascularity in the critical zone (
      • Levy O.
      • Relwani J.
      • Zaman T.
      • Even T.
      • Venkateswaran B.
      • Copeland S.
      Measurement of blood flow in the rotator cuff using laser Doppler flowmetry.
      ,
      • Longo U.G.
      • Franceschi F.
      • Ruzzini L.
      • Rabitti C.
      • Morini S.
      • Maffulli N.
      • et al.
      Histopathology of the supraspinatus tendon in rotator cuff tears.
      ,
      • Matthews T.J.
      • Hand G.C.
      • Rees J.L.
      • Athanasou N.A.
      • Carr A.J.
      Pathology of the torn rotator cuff tendon. Reduction in potential for repair as tear size increases.
      ) or evidence that hypovascularity is limited to the articular side and not the bursal side of the tendon (
      • Lohr J.F.
      • Uhthoff H.K.
      The microvascular pattern of the supraspinatus tendon.
      ,
      • Rudzki J.R.
      • Adler R.S.
      • Warren R.F.
      • Kadrmas W.R.
      • Verma N.
      • Pearle A.D.
      • et al.
      Contrast-enhanced ultrasound characterization of the vascularity of the rotator cuff tendon: age- and activity-related changes in the intact asymptomatic rotator cuff.
      ).
      Research suggests an increased vascular response, or neovascularization, in regions of degenerative changes and smaller tendon tears such as with chronic RC tendinopathy (
      • Fukuda H.
      • Hamada K.
      • Yamanaka K.
      Pathology and pathogenesis of bursal-side rotator cuff tears viewed from en bloc histologic sections.
      ,
      • Goodmurphy C.W.
      • Osborn J.
      • Akesson E.J.
      • Johnson S.
      • Stanescu V.
      • Regan W.D.
      An immunocytochemical analysis of torn rotator cuff tendon taken at the time of repair.
      ,
      • Hashimoto T.
      • Nobuhara K.
      • Hamada T.
      Pathologic evidence of degeneration as a primary cause of rotator cuff tear.
      ,
      • Kumagai J.
      • Sarkar K.
      • Uhthoff H.K.
      The collagen types in the attachment zone of rotator cuff tendons in the elderly: an immunohistochemical study.
      ,
      • Levy O.
      • Relwani J.
      • Zaman T.
      • Even T.
      • Venkateswaran B.
      • Copeland S.
      Measurement of blood flow in the rotator cuff using laser Doppler flowmetry.
      ,
      • Rathbun J.B.
      • Macnab I.
      The microvascular pattern of the rotator cuff.
      ), that is theorized to be a healing response to tissue microtrauma (
      • Levy O.
      • Relwani J.
      • Zaman T.
      • Even T.
      • Venkateswaran B.
      • Copeland S.
      Measurement of blood flow in the rotator cuff using laser Doppler flowmetry.
      ,
      • Rathbun J.B.
      • Macnab I.
      The microvascular pattern of the rotator cuff.
      ). In contrast, tendinopathy that progresses to complete tendon tears have been shown to be avascular (
      • Biberthaler P.
      • Wiedemann E.
      • Nerlich A.
      • Kettler M.
      • Mussack T.
      • Deckelmann S.
      • et al.
      Microcirculation associated with degenerative rotator cuff lesions. In vivo assessment with orthogonal polarization spectral imaging during arthroscopy of the shoulder.
      ,
      • Fukuda H.
      • Hamada K.
      • Yamanaka K.
      Pathology and pathogenesis of bursal-side rotator cuff tears viewed from en bloc histologic sections.
      ,
      • Matthews T.J.
      • Hand G.C.
      • Rees J.L.
      • Athanasou N.A.
      • Carr A.J.
      Pathology of the torn rotator cuff tendon. Reduction in potential for repair as tear size increases.
      ,
      • Rathbun J.B.
      • Macnab I.
      The microvascular pattern of the rotator cuff.
      ). It is unclear whether this avascular condition is a cause of progressive tendinopathy or a consequence of a complete tear. In subjects with RC tendinopathy, imaging with laser or ultrasound color Doppler has been used to detect the presence of neovascularization in vivo (
      • Alfredson H.
      • Ohberg L.
      • Forsgren S.
      Is vasculo-neural ingrowth the cause of pain in chronic Achilles tendinosis? An investigation using ultrasonography and colour Doppler, immunohistochemistry, and diagnostic injections.
      ,
      • Levy O.
      • Relwani J.
      • Zaman T.
      • Even T.
      • Venkateswaran B.
      • Copeland S.
      Measurement of blood flow in the rotator cuff using laser Doppler flowmetry.
      ). Levy et al. found subjects with acute RC tendinopathy (impingement without tear) had hypovascularity in the supraspinatus tendon compared to subjects without RC disease, while those with chronic RC tears had hypervascularity near the degenerative changes (
      • Levy O.
      • Relwani J.
      • Zaman T.
      • Even T.
      • Venkateswaran B.
      • Copeland S.
      Measurement of blood flow in the rotator cuff using laser Doppler flowmetry.
      ). The role of vascularity in the intrinsic mechanism of symptomatic RC tendinopathy has not been fully elucidated, however it does appear to be a factor that is influenced by and/or influences the extent and duration of tendon pathology.

      3.3 Impact of alterations in tendon matrix on mechanical properties

      The composition and organization of the tendon matrix dictate the morphology and mechanical properties of tendons. Tendons are composed of proteins, collagen, and cells referred to as tenocytes. Collagen fibers in tendons are composed predominately of type I molecules in tight and parallel fiber bundles and a small proportion (<5%) of type III collagen fibers that are thinner, weaker, and more irregularly arranged (
      • Kumagai J.
      • Sarkar K.
      • Uhthoff H.K.
      The collagen types in the attachment zone of rotator cuff tendons in the elderly: an immunohistochemical study.
      ,
      • Riley G.P.
      • Harrall R.L.
      • Constant C.R.
      • Chard M.D.
      • Cawston T.E.
      • Hazleman B.L.
      Tendon degeneration and chronic shoulder pain: changes in the collagen composition of the human rotator cuff tendons in rotator cuff tendinitis.
      ). The collagens within the RC tendon matrix are stabilized by formations of cross-links, specifically hydroxylyslypyridinoline and lysylpyridinoline (
      • Bank R.A.
      • TeKoppele J.M.
      • Oostingh G.
      • Hazleman B.L.
      • Riley G.P.
      Lysylhydroxylation and non-reducible crosslinking of human supraspinatus tendon collagen: changes with age and in chronic rotator cuff tendinitis.
      ). Within the RC tendons of elderly samples, the distribution of collagen types has been shown to vary with greater proportion of type II and III collagen near the insertional fibrocartilagenous region compared to more proximal tendon (
      • Kumagai J.
      • Sarkar K.
      • Uhthoff H.K.
      The collagen types in the attachment zone of rotator cuff tendons in the elderly: an immunohistochemical study.
      ). Since type III collagen fibrils are considered more extensible than type I fibers and tend to be more irregularly arranged, authors theorized that the insertional region of the supraspinatus may be subjected to greater non-linear stresses than other RC tendons. In agreement with this theory, Lake et al. quantified the degree of collagen fiber alignment in different longitudinal sections of the supraspinatus tendon and demonstrated a highly inhomogeneous tissue with a relatively low degree of fiber alignment in the region near the tendon to bone insertion (
      • Lake S.P.
      • Miller K.S.
      • Elliott D.M.
      • Soslowsky L.J.
      Effect of fiber distribution and realignment on the nonlinear and inhomogeneous mechanical properties of human supraspinatus tendon under longitudinal tensile Loading.
      ). These changes correlated with diminished mechanical properties in this region. Furthermore, histological evidence of inferior tissue organization, greater disorganization in the mid-substance and/or the articular side compared to more regularly arranged collagen on the bursal-side layers of the RC tendons has been proposed to weaken the tendon and precede complete tendon tear (
      • Fukuda H.
      • Hamada K.
      • Yamanaka K.
      Pathology and pathogenesis of bursal-side rotator cuff tears viewed from en bloc histologic sections.
      ,
      • Hashimoto T.
      • Nobuhara K.
      • Hamada T.
      Pathologic evidence of degeneration as a primary cause of rotator cuff tear.
      ).
      The intrinsic mechanism of RC tendinopathy assumes the demands placed on the tendon cells at some point exceeds the ability to effectively repair structural deficits (
      • Riley G.
      The pathogenesis of tendinopathy. A molecular perspective.
      ) resulting in breakdown and eventually pain. Studies that have examined alterations in RC tendon matrix have found no differences in total GAG concentration and PG content (
      • Riley G.P.
      • Harrall R.L.
      • Constant C.R.
      • Chard M.D.
      • Cawston T.E.
      • Hazleman B.L.
      Glycosaminoglycans of human rotator cuff tendons: changes with age and in chronic rotator cuff tendinitis.
      ), but a reduction in total collagen content and an increased proportion of type III collagen fibers (
      • Riley G.P.
      • Harrall R.L.
      • Constant C.R.
      • Chard M.D.
      • Cawston T.E.
      • Hazleman B.L.
      Tendon degeneration and chronic shoulder pain: changes in the collagen composition of the human rotator cuff tendons in rotator cuff tendinitis.
      ) in patients with chronic RC tendinopathy compared to cadaveric samples of normal tendon. Additionally, greater tenocyte apoptosis (cell death) has been found in tendons of patients with chronic RC tendinopathy as compared to normal tendons (
      • Tuoheti Y.
      • Itoi E.
      • Pradhan R.L.
      • Wakabayashi I.
      • Takahashi S.
      • Minagawa H.
      • et al.
      Apoptosis in the supraspinatus tendon with stage II subacromial impingement.
      ,
      • Yuan J.
      • Murrell G.A.
      • Wei A.Q.
      • Wang M.X.
      Apoptosis in rotator cuff tendonopathy.
      ). These matrix alterations are concurrent with morphology characterized by an irregular tendon contour and reduced tendon thickness (
      • Selkowitz D.M.
      • Chaney C.
      • Stuckey S.J.
      • Vlad G.
      The effects of scapular taping on the surface electromyographic signal amplitude of shoulder girdle muscles during upper extremity elevation in individuals with suspected shoulder impingement syndrome.
      ,
      • Teefey S.A.
      • Hasan S.A.
      • Middleton W.D.
      • Patel M.
      • Wright R.W.
      • Yamaguchi K.
      Ultrasonography of the rotator cuff. A comparison of ultrasonographic and arthroscopic findings in one hundred consecutive cases.
      ,
      • Teefey S.A.
      • Rubin D.A.
      • Middleton W.D.
      • Hildebolt C.F.
      • Leibold R.A.
      • Yamaguchi K.
      Detection and quantification of rotator cuff tears. Comparison of ultrasonographic, magnetic resonance imaging, and arthroscopic findings in seventy-one consecutive cases.
      ,
      • Wiener S.N.
      • Seitz Jr., W.H.
      Sonography of the shoulder in patients with tears of the rotator cuff: accuracy and value for selecting surgical options.
      ). Cholewinski et al. found thinning of the RC tendons in patients with chronic unilateral (>6 months) subacromial impingement compared to an asymptomatic individuals without a history of shoulder injury (
      • Cholewinski J.J.
      • Kusz D.J.
      • Wojciechowski P.
      • Cielinski L.S.
      • Zoladz M.P.
      Ultrasound measurement of rotator cuff thickness and acromio-humeral distance in the diagnosis of subacromial impingement syndrome of the shoulder.
      ).
      In contrast, an accumulation of GAGs and disorganization of the collagen fibers, which is theorized to cause tendon thickening in RC tendinopathy, has been demonstrated within 12 weeks of the onset of injury (
      • Scott A.
      • Cook J.L.
      • Hart D.A.
      • Walker D.C.
      • Duronio V.
      • Khan K.M.
      Tenocyte responses to mechanical loading in vivo: a role for local insulin-like growth factor 1 signaling in early tendinosis in rats.
      ). The supraspinatus appears to have higher rates of collagen matrix turnover compared to other tendons and accelerates in the presence of RC pathology (
      • Bank R.A.
      • TeKoppele J.M.
      • Oostingh G.
      • Hazleman B.L.
      • Riley G.P.
      Lysylhydroxylation and non-reducible crosslinking of human supraspinatus tendon collagen: changes with age and in chronic rotator cuff tendinitis.
      ). In an animal model, tendon cells in the supraspinatus become more chondroid and increase proliferation in an acute injury (
      • Scott A.
      • Cook J.L.
      • Hart D.A.
      • Walker D.C.
      • Duronio V.
      • Khan K.M.
      Tenocyte responses to mechanical loading in vivo: a role for local insulin-like growth factor 1 signaling in early tendinosis in rats.
      ).
      • Joensen J.
      • Couppe C.
      • Bjordal J.M.
      Increased palpation tenderness and muscle strength deficit in the prediction of tendon hypertrophy in symptomatic unilateral shoulder tendinopathy: an ultrasonographic study.
      ) found that increased RC tendon thickness of greater than or equal to 0.80 mm compared to the asymptomatic shoulder was associated with RC tendinopathy. The conflicting findings of tendon thickness in this study compared to those of tendon thinning by
      • Cholewinski J.J.
      • Kusz D.J.
      • Wojciechowski P.
      • Cielinski L.S.
      • Zoladz M.P.
      Ultrasound measurement of rotator cuff thickness and acromio-humeral distance in the diagnosis of subacromial impingement syndrome of the shoulder.
      ) may be attributed to the duration of symptoms. Inclusion criteria for
      • Joensen J.
      • Couppe C.
      • Bjordal J.M.
      Increased palpation tenderness and muscle strength deficit in the prediction of tendon hypertrophy in symptomatic unilateral shoulder tendinopathy: an ultrasonographic study.
      ) were greater than 1 month with 30% of the subjects having pain less than 3 months in duration compared to an inclusion criteria of pain greater than 6 months in duration in the study by Cholewinski et al. (mean duration was 7 months, range 6–48 months). Overall, tendon morphology has been suggested to vary based on the duration of tendon injury. An acute injury exhibits increased diffuse tendon thickness associated with matrix changes of a healing response (
      • Malliaras P.
      • Purdam C.
      • Maffulli N.
      • Cook J.L.
      Temporal sequence of gray-scale ultrasound changes and their relationship with neovascularity and pain in the patellar tendon.
      ) while a more chronic tendinopathy demonstrates focal defects and tendon thinning associated with degeneration.

      3.4 Tensile tissue overload: inhomogeneous mechanical properties

      Another proposed intrinsic mechanism of RC tendinopathy is related to the response of the tendons to tensile load, or mechanical properties of the supraspinatus tendon (
      • Bey M.J.
      • Song H.K.
      • Wehrli F.W.
      • Soslowsky L.J.
      Intratendinous strain fields of the intact supraspinatus tendon: the effect of glenohumeral joint position and tendon region.
      ,
      • Hashimoto T.
      • Nobuhara K.
      • Hamada T.
      Pathologic evidence of degeneration as a primary cause of rotator cuff tear.
      ,
      • Huang C.Y.
      • Wang V.M.
      • Pawluk R.J.
      • Bucchieri J.S.
      • Levine W.N.
      • Bigliani L.U.
      • et al.
      Inhomogeneous mechanical behavior of the human supraspinatus tendon under uniaxial loading.
      ,
      • Reilly P.
      • Amis A.A.
      • Wallace A.L.
      • Emery R.J.
      Mechanical factors in the initiation and propagation of tears of the rotator cuff. Quantification of strains of the supraspinatus tendon in vitro.
      ). Lower ultimate strain values (
      • Bey M.J.
      • Song H.K.
      • Wehrli F.W.
      • Soslowsky L.J.
      Intratendinous strain fields of the intact supraspinatus tendon: the effect of glenohumeral joint position and tendon region.
      ,
      • Huang C.Y.
      • Wang V.M.
      • Pawluk R.J.
      • Bucchieri J.S.
      • Levine W.N.
      • Bigliani L.U.
      • et al.
      Inhomogeneous mechanical behavior of the human supraspinatus tendon under uniaxial loading.
      ) and greater tissue stiffness (
      • Nakajima T.
      • Rokuuma N.
      • Hamada K.
      • Tomatsu T.
      • Fukuda H.
      Histologic and biomechanical characteristics of the supraspinatus tendon: reference to rotator cuff tearing.
      ) to longitudinal loading have been found on the articular side of the supraspinatus tendon near the insertion as compared to the bursal side; although, this was in conflict with results of studies by other investigators who found no differences in mechanical properties between articular (deep) and bursal sided (superficial), but lack of homogeneity between the anterior and posterior supraspinatus to longitudinal loads (
      • Itoi E.
      • Berglund L.J.
      • Grabowski J.J.
      • Schultz F.M.
      • Growney E.S.
      • Morrey B.F.
      • et al.
      Tensile properties of the supraspinatus tendon.
      ,
      • Lake S.P.
      • Miller K.S.
      • Elliott D.M.
      • Soslowsky L.J.
      Effect of fiber distribution and realignment on the nonlinear and inhomogeneous mechanical properties of human supraspinatus tendon under longitudinal tensile Loading.
      ). Moreover, loading the tendon at various arm positions may result in strain differentials between the articular and bursal side of the supraspinatus. Greater strain has been shown on the supraspinatus tendon articular side with the arm positioned at the beginning of elevation (angles <30° abduction (
      • Bey M.J.
      • Song H.K.
      • Wehrli F.W.
      • Soslowsky L.J.
      Intratendinous strain fields of the intact supraspinatus tendon: the effect of glenohumeral joint position and tendon region.
      ,
      • Huang C.Y.
      • Wang V.M.
      • Pawluk R.J.
      • Bucchieri J.S.
      • Levine W.N.
      • Bigliani L.U.
      • et al.
      Inhomogeneous mechanical behavior of the human supraspinatus tendon under uniaxial loading.
      ) and 62° abduction (
      • Huang C.Y.
      • Wang V.M.
      • Pawluk R.J.
      • Bucchieri J.S.
      • Levine W.N.
      • Bigliani L.U.
      • et al.
      Inhomogeneous mechanical behavior of the human supraspinatus tendon under uniaxial loading.
      )) while Reilly et al. found a progressive increase in articular-sided strain with elevation (angles 0 to 120° abduction) (
      • Reilly P.
      • Amis A.A.
      • Wallace A.L.
      • Emery R.J.
      Mechanical factors in the initiation and propagation of tears of the rotator cuff. Quantification of strains of the supraspinatus tendon in vitro.
      ). Greater bursal-sided strain was found when the glenohumeral joint is at mid-ranges (90°) (
      • Huang C.Y.
      • Wang V.M.
      • Pawluk R.J.
      • Bucchieri J.S.
      • Levine W.N.
      • Bigliani L.U.
      • et al.
      Inhomogeneous mechanical behavior of the human supraspinatus tendon under uniaxial loading.
      ). While there is inconsistency with the specific results and methods used among these studies, intratendinous degradation is theorized to result from shearing between various portions of RC, specifically the supraspinatus tendon (
      • Fukuda H.
      • Hamada K.
      • Yamanaka K.
      Pathology and pathogenesis of bursal-side rotator cuff tears viewed from en bloc histologic sections.
      ,
      • Lee S.B.
      • Nakajima T.
      • Luo Z.P.
      • Zobitz M.E.
      • Chang Y.W.
      • An K.N.
      The bursal and articular sides of the supraspinatus tendon have a different compressive stiffness.
      ) potentially due to the distinct mechanical characteristics and force differentials incurred with various loads (
      • Bey M.J.
      • Song H.K.
      • Wehrli F.W.
      • Soslowsky L.J.
      Intratendinous strain fields of the intact supraspinatus tendon: the effect of glenohumeral joint position and tendon region.
      ,
      • Huang C.Y.
      • Wang V.M.
      • Pawluk R.J.
      • Bucchieri J.S.
      • Levine W.N.
      • Bigliani L.U.
      • et al.
      Inhomogeneous mechanical behavior of the human supraspinatus tendon under uniaxial loading.
      ,
      • Lake S.P.
      • Miller K.S.
      • Elliott D.M.
      • Soslowsky L.J.
      Effect of fiber distribution and realignment on the nonlinear and inhomogeneous mechanical properties of human supraspinatus tendon under longitudinal tensile Loading.
      ,
      • Nakajima T.
      • Rokuuma N.
      • Hamada K.
      • Tomatsu T.
      • Fukuda H.
      Histologic and biomechanical characteristics of the supraspinatus tendon: reference to rotator cuff tearing.
      ,
      • Reilly P.
      • Amis A.A.
      • Wallace A.L.
      • Emery R.J.
      Mechanical factors in the initiation and propagation of tears of the rotator cuff. Quantification of strains of the supraspinatus tendon in vitro.
      ). Intrasubstance degeneration in the supraspinatus initiates mid-substance tendon tears and propagates with continued loading to an articular side tendon tear before complete tendon failure (
      • Reilly P.
      • Amis A.A.
      • Wallace A.L.
      • Emery R.J.
      Supraspinatus tears: propagation and strain alteration.
      ). Biomechanical consequences of complex longitudinal and transverse inhomogenous tendon properties would be exacerbated in combination with extrinsic factors such as repetitive tensile loading induced with daily activities such as lifting or pulling or the strain incurred with the follow through phase of overhead sports.
      Other factors than collagen fiber alignment, such as tendon geometry can influence the mechanical properties. Alterations in tendon geometry including tendon irregularity and thinning have been demonstrated in patients with degenerative RC pathology (
      • Cholewinski J.J.
      • Kusz D.J.
      • Wojciechowski P.
      • Cielinski L.S.
      • Zoladz M.P.
      Ultrasound measurement of rotator cuff thickness and acromio-humeral distance in the diagnosis of subacromial impingement syndrome of the shoulder.
      ) which could influence its mechanical properties. Thickening of the tendon associated with an acute healing response to injury may create greater area to distribute forces; however, tendon thinning associated with degenerative or chronic tendinopathy would reduce the surface area for the same load conditions thus may perpetuate injury. A weak correlation has been shown between supraspinatus tendon thickness and in vivo mechanical properties (
      • Bey M.J.
      • Song H.K.
      • Wehrli F.W.
      • Soslowsky L.J.
      Intratendinous strain fields of the intact supraspinatus tendon: the effect of glenohumeral joint position and tendon region.
      ). There also is a strong correlation between the extent of RC tendon degenerative changes and tensile strength; as tendon degeneration increases the tensile strength decreases (
      • Sano H.
      • Ishii H.
      • Yeadon A.
      • Backman D.S.
      • Brunet J.A.
      • Uhthoff H.K.
      Degeneration at the insertion weakens the tensile strength of the supraspinatus tendon: a comparative mechanical and histologic study of the bone-tendon complex.
      ). However, both of these studies examined the mechanical properties of cadaveric tissue samples. However in patients with RC tendinopathy, a decrease in tendon thickness has been shown to be associated with a decrease in muscle performance (
      • Joensen J.
      • Couppe C.
      • Bjordal J.M.
      Increased palpation tenderness and muscle strength deficit in the prediction of tendon hypertrophy in symptomatic unilateral shoulder tendinopathy: an ultrasonographic study.
      ).

      4. Subgroups of patients with tendinopathy based on mechanism

      Subgroups of RC tendinopathy may exist, based on intrinsic and extrinsic mechanism that may serve to facilitate treatment decision-making for patients with RC tendinopathy. In a cadaver study, bursal-sided tendon degeneration with partial thickness tears were always associated with attritional lesions on the coracoacromial ligament and anterior third of the acromion (
      • Ozaki J.
      • Fujimoto S.
      • Nakagawa Y.
      • Masuhara K.
      • Tamai S.
      Tears of the rotator cuff of the shoulder associated with pathological changes in the acromion. A study in cadavera.
      ); however, this was not true of articular-sided RC pathology in which the undersurface of the acromion was almost always normal. Similarly in patients, milder pathological changes of the undersurface of the acromion and less severe RC degenerative changes were found in patients with articular-sided RC pathology compared to bursal sided (
      • Ko J.Y.
      • Huang C.C.
      • Chen W.J.
      • Chen C.E.
      • Chen S.H.
      • Wang C.J.
      Pathogenesis of partial tear of the rotator cuff: a clinical and pathologic study.
      ). It appears there is a link between pathoanatomy and mechanism of RC tendinopathy; articular-sided degenerative changes of the tendons are primarily associated with an intrinsic mechanism, and bursal-sided pathologies of the tendons are more associated with an extrinsic mechanism. As each of these distinct mechanisms progress, they may increasingly overlap. A patient with primary extrinsic compression mechanism of RC tendinopathy may progress with degenerative changes to the RC tendons over time. Alternatively, a patient with primary intrinsic degenerative mechanism of RC tendinopathy may progressively lose stabilizing function of the RC resulting in excessive superior humeral migration and extrinsic compression.
      The literature suggests using the link between pathology and mechanism to drive treatment choices. For surgical treatment of RC tendinopathy attributable to an intrinsic mechanism, debridement of the RC without acromioplasty has been advocated (
      • Budoff J.E.
      • Nirschl R.P.
      • Guidi E.J.
      Debridement of partial-thickness tears of the rotator cuff without acromioplasty. Long-term follow-up and review of the literature.
      ,